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Sample records for copper target downstream

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

    Energy Technology Data Exchange (ETDEWEB)

    Ekdahl, Carl [Los Alamos National Laboratory; Schulze, Martin E [Los Alamos National Laboratory

    2008-01-01

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

  3. Tantalum/Copper X-Ray Targets

    Science.gov (United States)

    Waters, William J.; Edmonds, Brian

    1993-01-01

    Lewis Research Center developed unique solution to subsidiary problem of fabrication of x-ray target. Plasma spraying enabled fabrication of lightweight, high-performance targets. Power settings, atmosphere-control settings, rate of deposition, and other spraying parameters developed. Thin coats of tantalum successfully deposited on copper targets. Targets performed successfully in tests and satisfied all criteria expressed in terms of critical parameters. Significantly reduces projected costs of fabrication of targets and contributes to development of improved, long-lived, lightweight x-ray system.

  4. Influence of Copper Ore Comminution in HPGR on Downstream Minerallurgical Processes

    Directory of Open Access Journals (Sweden)

    Saramak D.

    2017-09-01

    Full Text Available Crushing processes taking place in high-pressure grinding rolls devices (HPGR are currently one of the most efficient methods of hard ore size reduction in terms of the energy consumption. The HPGR products are characterized by a fine particle size and the micro-cracks formation in individual particles, which appears in downstream grinding processes, decreasing their energy consumption. The purpose of the paper was to analyze the effectiveness of a ball mill grinding process and flotation operations depending on the changeable conditions of run of the HPGR crushing process. The research programme carried out included crushing tests in the laboratory scale HPGR device at various settings of the operating pressure volume and selected qualitative properties of the feed material (i.e. particle size distribution. On the basis of obtained results the models, defining the grinding process effectiveness as a function of changeable conditions of HPGR process run, were determined. Based on these models the optimal grinding time in a ball mill was specified which is, in turn, the basis for optimization of operation the technological comminution circuits for a given material type. The obtained results proved that the application of HPGR devices in given copper ore comminution circuit may improve the effectiveness of downstream grinding process what leads to improvement of the entire circuit work efficiency through decreasing the process energy consumption and enhancing the product size reduction.

  5. Molecular imaging and therapy targeting copper metabolism in hepatocellular carcinoma.

    Science.gov (United States)

    Wachsmann, Jason; Peng, Fangyu

    2016-01-07

    Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Significant efforts have been devoted to identify new biomarkers for molecular imaging and targeted therapy of HCC. Copper is a nutritional metal required for the function of numerous enzymatic molecules in the metabolic pathways of human cells. Emerging evidence suggests that copper plays a role in cell proliferation and angiogenesis. Increased accumulation of copper ions was detected in tissue samples of HCC and many other cancers in humans. Altered copper metabolism is a new biomarker for molecular cancer imaging with position emission tomography (PET) using radioactive copper as a tracer. It has been reported that extrahepatic mouse hepatoma or HCC xenografts can be localized with PET using copper-64 chloride as a tracer, suggesting that copper metabolism is a new biomarker for the detection of HCC metastasis in areas of low physiological copper uptake. In addition to copper modulation therapy with copper chelators, short-interference RNA specific for human copper transporter 1 (hCtr1) may be used to suppress growth of HCC by blocking increased copper uptake mediated by hCtr1. Furthermore, altered copper metabolism is a promising target for radionuclide therapy of HCC using therapeutic copper radionuclides. Copper metabolism has potential as a new theranostic biomarker for molecular imaging as well as targeted therapy of HCC.

  6. Combating trastuzumab resistance by targeting SRC, a common node downstream of multiple resistance pathways

    OpenAIRE

    Zhang, Siyuan; Huang, Wen-Chien; Li, Ping; Guo, Hua; Poh, Say-Bee; Brady, Samuel W.; Xiong, Yan; Tseng, Ling-Ming; Li, Shau-Hsuan; Ding, Zhaoxi; Sahin, Aysegul A.; Esteva, Francisco J; Hortobagyi, Gabriel N.; Yu, Dihua

    2011-01-01

    Trastuzumab is a successful rationally designed ERBB2-targeted therapy. However, about half of individuals with ERBB2-overexpressing breast cancer do not respond to trastuzumab-based therapies, owing to various resistance mechanisms. Clinically applicable regimens for overcoming trastuzumab resistance of different mechanisms are not yet available. We show that the nonreceptor tyrosine kinase c-SRC (SRC) is a key modulator of trastuzumab response and a common node downstream of multiple trastu...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  8. 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

  9. 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...

  10. Targeting Protein Kinase C Downstream of Growth Factor and Adhesion Signalling

    Directory of Open Access Journals (Sweden)

    Catríona M. Dowling

    2015-07-01

    Full Text Available The signaling outputs of Receptor Tyrosine Kinases, G-protein coupled receptors and integrins converge to mediate key cell process such as cell adhesion, cell migration, cell invasion and cell proliferation. Once activated by their ligands, these cell surface proteins recruit and direct a diverse range of proteins to disseminate the appropriate response downstream of the specific environmental cues. One of the key groups of proteins required to regulate these activities is the family of serine/threonine intracellular kinases called Protein Kinase Cs. The activity and subcellular location of PKCs are mediated by a series of tightly regulated events and is dependent on several posttranslational modifications and the availability of second messengers. Protein Kinase Cs exhibit both pro- and anti-tumorigenic effects making them an interesting target for anti-cancer treatment.

  11. Targeting Protein Kinase C Downstream of Growth Factor and Adhesion Signalling

    Energy Technology Data Exchange (ETDEWEB)

    Dowling, Catríona M., E-mail: Catriona.Dowling@ul.ie; Kiely, Patrick A., E-mail: Catriona.Dowling@ul.ie [Department of Life Sciences, Materials and Surface Science Institute and Stokes Institute, University of Limerick, Limerick 78666 (Ireland); Health Research Institute (HRI), University of Limerick, Limerick 78666 (Ireland)

    2015-07-15

    The signaling outputs of Receptor Tyrosine Kinases, G-protein coupled receptors and integrins converge to mediate key cell process such as cell adhesion, cell migration, cell invasion and cell proliferation. Once activated by their ligands, these cell surface proteins recruit and direct a diverse range of proteins to disseminate the appropriate response downstream of the specific environmental cues. One of the key groups of proteins required to regulate these activities is the family of serine/threonine intracellular kinases called Protein Kinase Cs. The activity and subcellular location of PKCs are mediated by a series of tightly regulated events and is dependent on several posttranslational modifications and the availability of second messengers. Protein Kinase Cs exhibit both pro- and anti-tumorigenic effects making them an interesting target for anti-cancer treatment.

  12. Protein kinases: mechanisms and downstream targets in inflammation-mediated obesity and insulin resistance.

    Science.gov (United States)

    Nandipati, Kalyana C; Subramanian, Saravanan; Agrawal, Devendra K

    2017-02-01

    Obesity-induced low-grade inflammation (metaflammation) impairs insulin receptor signaling. This has been implicated in the development of insulin resistance. Insulin signaling in the target tissues is mediated by stress kinases such as p38 mitogen-activated protein kinase, c-Jun NH2-terminal kinase, inhibitor of NF-kB kinase complex β (IKKβ), AMP-activated protein kinase, protein kinase C, Rho-associated coiled-coil containing protein kinase, and RNA-activated protein kinase. Most of these kinases phosphorylate several key regulators in glucose homeostasis. The phosphorylation of serine residues in the insulin receptor and IRS-1 molecule results in diminished enzymatic activity in the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. This has been one of the key mechanisms observed in the tissues that are implicated in insulin resistance especially in type 2 diabetes mellitus (T2-DM). Identifying the specific protein kinases involved in obesity-induced chronic inflammation may help in developing the targeted drug therapies to minimize the insulin resistance. This review is focused on the protein kinases involved in the inflammatory cascade and molecular mechanisms and their downstream targets with special reference to obesity-induced T2-DM.

  13. Proliferating cell nuclear antigen (Pcna) as a direct downstream target gene of Hoxc8

    Energy Technology Data Exchange (ETDEWEB)

    Min, Hyehyun; Lee, Ji-Yeon; Bok, Jinwoong; Chung, Hyun Joo [Department of Anatomy, Embryology Laboratory, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Kim, Myoung Hee, E-mail: mhkim1@yuhs.ac [Department of Anatomy, Embryology Laboratory, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of)

    2010-02-19

    Hoxc8 is a member of Hox family transcription factors that play crucial roles in spatiotemporal body patterning during embryogenesis. Hox proteins contain a conserved 61 amino acid homeodomain, which is responsible for recognition and binding of the proteins onto Hox-specific DNA binding motifs and regulates expression of their target genes. Previously, using proteome analysis, we identified Proliferating cell nuclear antigen (Pcna) as one of the putative target genes of Hoxc8. Here, we asked whether Hoxc8 regulates Pcna expression by directly binding to the regulatory sequence of Pcna. In mouse embryos at embryonic day 11.5, the expression pattern of Pcna was similar to that of Hoxc8 along the anteroposterior body axis. Moreover, Pcna transcript levels as well as cell proliferation rate were increased by overexpression of Hoxc8 in C3H10T1/2 mouse embryonic fibroblast cells. Characterization of 2.3 kb genomic sequence upstream of Pcna coding region revealed that the upstream sequence contains several Hox core binding sequences and one Hox-Pbx binding sequence. Direct binding of Hoxc8 proteins to the Pcna regulatory sequence was verified by chromatin immunoprecipitation assay. Taken together, our data suggest that Pcna is a direct downstream target of Hoxc8.

  14. Vacuum calculation of the TBID (Target Beam Instrumentation Downstream) for CNGS

    CERN Document Server

    Chiggiato, P

    2006-01-01

    For the TBID (Target Beam Instrumentation Downstream) monitor of CNGS (CERN Neutrinos to Gran Sasso) a design identical to that of the TBIU (Target Beam Instrumentation Upstream) monitor of the SPS targets has been adopted. However the vacuum solution implemented in the SPS, namely ion pumping, cannot be trivially applied to CNGS; in fact the high radioactivity level expected for the latter could damage the electrical cables in the about 10 years of expected activity and hinder or delay any human intervention. In this note the possibility of NEG pumping, without any electrical feeding, is considered. The getter should ensure the demanded pressure limit of 10-4 Torr in conditions that are very harsh: temperature up to 150°C, 0.1 A electron bombardment and proton bombardment during the 10 years of working of the monitor. It is shown that the beam induced CH4 pumping speed is not enough at the beginning of the operation to ensure the pressure requirements. In addition, in the worst scenario when a uniform ele...

  15. Novel downstream molecular targets of SIRT1 in melanoma: a quantitative proteomics approach.

    Science.gov (United States)

    Singh, Chandra K; George, Jasmine; Nihal, Minakshi; Sabat, Grzegorz; Kumar, Raj; Ahmad, Nihal

    2014-04-15

    Melanoma is one of the most lethal forms of skin cancer and its incidence is continuing to rise in the United States. Therefore, novel mechanism and target-based strategies are needed for the management of this disease. SIRT1, a NAD(+)-dependent class III histone deacetylase, has been implicated in a variety of physiological processes and pathological conditions. We recently demonstrated that SIRT1 is upregulated in melanoma and its inhibition by a small-molecule, tenovin-1, inhibits cell proliferation and clonogenic survival of melanoma cells, possibly via activating p53. Here, we employed a gel free quantitative proteomics approach to identify the downstream effectors and targets of SIRT1 in melanoma. The human malignant melanoma, G361 cells were treated with tenovin-1 followed by protein extraction, in liquid trypsin digestion, and peptide analyses using nanoLC-MS/MS. A total of 1091 proteins were identified, of which 20 proteins showed significant differential expression with 95% confidence interval. These proteins were subjected to gene ontology and Ingenuity Pathway Analysis (IPA) to obtain the information regarding their biological and molecular functions. Real-Time qRT-PCR validation showed that five of these (PSAP, MYO1B, MOCOS, HIS1H4A and BUB3) were differentially expressed at mRNA levels. Based on their important role in cell cycle regulation, we selected to focus on BUB family proteins (BUB3, as well as BUB1 and BUBR1) for subsequent validation. The qRT-PCR and immunoblot analyses showed that tenovin-1 inhibition of SIRT1 resulted in a downregulation of BUB3, BUB1 and BUBR1 in multiple melanoma cell lines. Since tenovin-1 is an inhibitor of both SIRT1 and SIRT2, we employed lentivirus mediated silencing of SIRT1 and SIRT2 in G361 cells to determine if the observed effects on BUB family proteins are due to SIRT1- or SIRT2- inhibition. We found that only SIRT1 inhibition resulted in a decrease in BUB3, BUB1 and BUBR1. Our study identified the mitotic

  16. Targeting the cis-dimerization of LINGO-1 with low MW compounds affects its downstream signalling.

    Science.gov (United States)

    Cobret, L; De Tauzia, M L; Ferent, J; Traiffort, E; Hénaoui, I; Godin, F; Kellenberger, E; Rognan, D; Pantel, J; Bénédetti, H; Morisset-Lopez, S

    2015-02-01

    The transmembrane protein LINGO-1 is a negative regulator in the nervous system mainly affecting axonal regeneration, neuronal survival, oligodendrocyte differentiation and myelination. However, the molecular mechanisms regulating its functions are poorly understood. In the present study, we investigated the formation and the role of LINGO-1 cis-dimers in the regulation of its biological activity. LINGO-1 homodimers were identified in both HEK293 and SH-SY5Y cells using co-immunoprecipitation experiments and BRET saturation analysis. We performed a hypothesis-driven screen for identification of small-molecule protein-protein interaction modulators of LINGO-1 using a BRET-based assay, adapted for screening. The compound identified was further assessed for effects on LINGO-1 downstream signalling pathways using Western blotting analysis and AlphaScreen technology. LINGO-1 was present as homodimers in primary neuronal cultures. LINGO-1 interacted homotypically in cis-orientation and LINGO-1 cis-dimers were formed early during LINGO-1 biosynthesis. A BRET-based assay allowed us to identify phenoxybenzamine as the first conformational modulator of LINGO-1 dimers. In HEK-293 cells, phenoxybenzamine was a positive modulator of LINGO-1 function, increasing the LINGO-1-mediated inhibition of EGF receptor signalling and Erk phosphorylation. Our data suggest that LINGO-1 forms constitutive cis-dimers at the plasma membrane and that low MW compounds affecting the conformational state of these dimers can regulate LINGO-1 downstream signalling pathways. We propose that targeting the LINGO-1 dimerization interface opens a new pharmacological approach to the modulation of its function and provides a new strategy for drug discovery. © 2014 The British Pharmacological Society.

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

    Science.gov (United States)

    Kristensen, Dorte E; Albers, Peter H; Prats, Clara; Baba, Otto; Birk, Jesper B; Wojtaszewski, Jørgen F P

    2015-01-01

    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 demonstrated. We hypothesized that AMPK subunits 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 vastus lateralis muscle from healthy men before and after two exercise trials: (1) continuous cycling (CON) for 30 min at 69 ± 1% peak rate of O2 consumption () or (2) interval cycling (INT) for 30 min with 6 × 1.5 min high-intensity bouts peaking at 95 ± 2% . 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. In type I vs. II fibres phosphoregulation after CON was similar (AMPKThr172, ACCSer221, TBC1D1Ser231 and GS2+2a) or lower (TBC1D4Ser704). Following INT, phosphoregulation in type I vs. II fibres was lower (AMPKThr172, TBC1D1Ser231, TBC1D4Ser704 and ACCSer221) or higher (GS2+2a). Exercise-induced glycogen degradation in type I vs. II fibres was similar (CON) or lower (INT). In conclusion, a differentiated response to exercise of metabolic signalling/effector proteins in human type I and II fibres was evident during interval exercise. This could be important for exercise type-specific adaptations, i.e. insulin sensitivity and mitochondrial density, and highlights the potential for new discoveries when investigating fibre type-specific signalling. PMID:25640469

  18. Parathyroid hormone-related peptide is a downstream target for ras and src activation.

    Science.gov (United States)

    Li, X; Drucker, D J

    1994-03-04

    Neoplastic transformation may be associated with the development of paraneoplastic syndromes that complicate the management of patients with malignant disease. One of these syndromes, humoral hypercalcemia of malignancy, has been shown to be attributable to increased secretion of a parathyroid hormone-related peptide (PTHrP). The gene encoding PTHrP is expressed at low levels in a growth factor-dependent manner in normal tissues, and the mechanisms underlying selective tumor-associated induction of PTHrP gene expression remain unclear. Here we show that cellular transformation by the EJ-Ha-ras and v-src oncogenes is associated with a marked increase in PTHrP gene expression. Ha-ras- and v-src-transfected NRK 49F cells and ras-transfected RCB 2.2 cell lines secreted increased amounts of immunoreactive PTHrP. Northern blot analysis also demonstrated increased levels of PTHrP mRNA transcripts in oncogene-transfected stable cell lines. No significant change in the half-life of PTHrP mRNA transcripts was detected in Ha-ras- and v-src-transformed cells. In contrast, nuclear run-on assays demonstrated an increased rate of PTHrP gene transcription in oncogene-transformed cells. These observations demonstrate that the gene encoding PTHrP is a downstream target for ras and src, potentially providing a molecular basis for understanding the activation of PTHrP gene expression in malignancy-associated hypercalcemia.

  19. 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

  20. Activated Ras alters lens and corneal development through induction of distinct downstream targets

    Directory of Open Access Journals (Sweden)

    Reneker Lixing

    2010-01-01

    results suggest that Ras activation a induces distinct sets of downstream targets in the lens and cornea resulting in distinct cellular responses and b is sufficient for initiation but not completion of lens fiber differentiation.

  1. Inhibition of copper uptake in yeast reveals the copper transporter Ctr1p as a potential molecular target of saxitoxin.

    Science.gov (United States)

    Cusick, Kathleen D; Minkin, Steven C; Dodani, Sheel C; Chang, Christopher J; Wilhelm, Steven W; Sayler, Gary S

    2012-03-06

    Saxitoxin is a secondary metabolite produced by several species of dinoflagellates and cyanobacteria which targets voltage-gated sodium and potassium channels in higher vertebrates. However, its molecular target in planktonic aquatic community members that co-occur with the toxin producers remains unknown. Previous microarray analysis with yeast identified copper and iron-homeostasis genes as being differentially regulated in response to saxitoxin. This study sought to identify the molecular target in microbial cells by comparing the transcriptional profiles of key copper and iron homeostasis genes (CTR1, FRE1, FET3, CUP1, CRS5) in cells exposed to saxitoxin, excess copper, excess iron, an extracellular Cu(I) chelator, or an intracellular Cu(I) chelator. Protein expression and localization of Ctr1p (copper transporter), Fet3p (multicopper oxidase involved in high-affinity iron uptake), and Aft1p (iron regulator) were also compared among treatments. Combined transcript and protein profiles suggested saxitoxin inhibited copper uptake. This hypothesis was confirmed by intracellular Cu(I) imaging with a selective fluorescent probe for labile copper. On the basis of the combined molecular and physiological results, a model is presented in which the copper transporter Ctr1p serves as a molecular target of saxitoxin and these observations are couched in the context of the eco-evolutionary role this toxin may serve for species that produce it.

  2. Basic helix-loop-helix transcription factor TCF21 is a downstream target of the male sex determining gene SRY.

    Directory of Open Access Journals (Sweden)

    Ramji K Bhandari

    Full Text Available The cascade of molecular events involved in mammalian sex determination has been shown to involve the SRY gene, but specific downstream events have eluded researchers for decades. The current study identifies one of the first direct downstream targets of the male sex determining factor SRY as the basic-helix-loop-helix (bHLH transcription factor TCF21. SRY was found to bind to the Tcf21 promoter and activate gene expression. Mutagenesis of SRY/SOX9 response elements in the Tcf21 promoter eliminated the actions of SRY. SRY was found to directly associate with the Tcf21 promoter SRY/SOX9 response elements in vivo during fetal rat testis development. TCF21 was found to promote an in vitro sex reversal of embryonic ovarian cells to induce precursor Sertoli cell differentiation. TCF21 and SRY had similar effects on the in vitro sex reversal gonadal cell transcriptomes. Therefore, SRY acts directly on the Tcf21 promoter to in part initiate a cascade of events associated with Sertoli cell differentiation and embryonic testis development.

  3. NF-kB activation and its downstream target genes expression after heavy ions exposure

    Science.gov (United States)

    Chishti, Arif Ali; Baumstark-Khan, Christa; Hellweg, Christine; Schmitz, Claudia; Koch, Kristina; Feles, Sebastian

    2016-07-01

    To enable long-term human space flight cellular radiation response to densely ionizing radiation needs to be better understood for developing appropriate countermeasures to mitigate acute effects and late radiation risks for the astronaut. The biological effectiveness of accelerated heavy ions (which constitute the most important radiation type in space) with high linear energy transfer (LET) for effecting DNA damage response pathways as a gateway to cell death or survival is of major concern not only for space missions but also for new regimes of tumor radiotherapy. In the current research study, the contribution of NF-κB in response to space-relevant radiation qualities was determined by a NF-κB reporter cell line (HEK-pNF-κB-d2EGFP/Neo L2). The NF-κB dependent reporter gene expression (d2EGFP) after ionizing radiation (X-rays and heavy ions) exposure was evaluated by flow cytometry. Because of differences in the extent of NF-κB activation after X-irradiation and heavy ions exposure, it was expected that radiation quality (LET) might play an important role in the cellular radiation response. In addition, the biological effectiveness (RBE) of NF-κB activation and reduction of cellular survival was examined for heavy ions having a broad range of LET (˜0.3 - 9674 keV/µm). Furthermore, the effect of LET on NF-κB target gene expression was analyzed by real time reverse transcriptase quantitative PCR (RT-qPCR). In this study it was proven that NF-κB activation and NF-κB dependent gene expression comprises an early step in cellular radiation response. Taken together, this study clearly demonstrates that NF-κB activation and NF-κB-dependent gene expression by heavy ions are highest in the LET range of ˜50-200 keV/μupm. The up-regulated chemokines and cytokines (CXCL1, CXCL2, CXCL10, IL-8 and TNF) might be important for cell-cell communication among hit as well as unhit cells (bystander effect). The results obtained suggest the NF-κB pathway to be a

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  5. Comparison of the toxicity of two chelated copper algaecides and copper sulfate to non-target fish.

    Science.gov (United States)

    Closson, K R; Paul, E A

    2014-12-01

    New pesticide products are reviewed by the United States Environmental Protection Agency for possible effects to non-target aquatic organisms. The required toxicity data are for the active ingredient only, and fail to include toxicity of the mixture of other ingredients found in these pesticides. These ingredients may increase the toxicity of the active ingredient to non-target organisms. Our study compares the toxicity of two formulations of chelated copper algaecides with each other, and to a copper sulfate algaecide. We were particularly interested in the effects of a surfactant that is present in one of the formulations. We found that copper becomes less toxic to fish (e.g. fathead minnow 48-h LC50 = 0.90 mg/L) when it is chelated, providing an additional margin of safety to non-target fish compared to copper sulfate. However, inclusion of a surfactant to the formulation resulted in increased toxicity (e.g. fathead minnow 48-h LC50 = 0.30 mg/L).

  6. 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.

  7. Combination of Chemical Genetics and Phosphoproteomics for Kinase Signaling Analysis Enables Confident Identification of Cellular Downstream Targets*

    Science.gov (United States)

    Oppermann, Felix S.; Grundner-Culemann, Kathrin; Kumar, Chanchal; Gruss, Oliver J.; Jallepalli, Prasad V.; Daub, Henrik

    2012-01-01

    Delineation of phosphorylation-based signaling networks requires reliable data about the underlying cellular kinase-substrate interactions. We report a chemical genetics and quantitative phosphoproteomics approach that encompasses cellular kinase activation in combination with comparative replicate mass spectrometry analyses of cells expressing either inhibitor-sensitive or resistant kinase variant. We applied this workflow to Plk1 (Polo-like kinase 1) in mitotic cells and induced cellular Plk1 activity by wash-out of the bulky kinase inhibitor 3-MB-PP1, which targets a mutant kinase version with an enlarged catalytic pocket while not interfering with wild-type Plk1. We quantified more than 20,000 distinct phosphorylation sites by SILAC, approximately half of which were measured in at least two independent experiments in cells expressing mutant and wild-type Plk1. Based on replicate phosphorylation site quantifications in both mutant and wild-type Plk1 cells, our chemical genetic proteomics concept enabled stringent comparative statistics by significance analysis of microarrays, which unveiled more than 350 cellular downstream targets of Plk1 validated by full concordance of both statistical and experimental data. Our data point to hitherto poorly characterized aspects in Plk1-controlled mitotic progression and provide a largely extended resource for functional studies. We anticipate the described strategies to be of general utility for systematic and confident identification of cellular protein kinase substrates. PMID:22199227

  8. Combination of chemical genetics and phosphoproteomics for kinase signaling analysis enables confident identification of cellular downstream targets.

    Science.gov (United States)

    Oppermann, Felix S; Grundner-Culemann, Kathrin; Kumar, Chanchal; Gruss, Oliver J; Jallepalli, Prasad V; Daub, Henrik

    2012-04-01

    Delineation of phosphorylation-based signaling networks requires reliable data about the underlying cellular kinase-substrate interactions. We report a chemical genetics and quantitative phosphoproteomics approach that encompasses cellular kinase activation in combination with comparative replicate mass spectrometry analyses of cells expressing either inhibitor-sensitive or resistant kinase variant. We applied this workflow to Plk1 (Polo-like kinase 1) in mitotic cells and induced cellular Plk1 activity by wash-out of the bulky kinase inhibitor 3-MB-PP1, which targets a mutant kinase version with an enlarged catalytic pocket while not interfering with wild-type Plk1. We quantified more than 20,000 distinct phosphorylation sites by SILAC, approximately half of which were measured in at least two independent experiments in cells expressing mutant and wild-type Plk1. Based on replicate phosphorylation site quantifications in both mutant and wild-type Plk1 cells, our chemical genetic proteomics concept enabled stringent comparative statistics by significance analysis of microarrays, which unveiled more than 350 cellular downstream targets of Plk1 validated by full concordance of both statistical and experimental data. Our data point to hitherto poorly characterized aspects in Plk1-controlled mitotic progression and provide a largely extended resource for functional studies. We anticipate the described strategies to be of general utility for systematic and confident identification of cellular protein kinase substrates.

  9. Rbfox proteins regulate microRNA biogenesis by sequence-specific binding to their precursors and target downstream Dicer.

    Science.gov (United States)

    Chen, Yu; Zubovic, Lorena; Yang, Fan; Godin, Katherine; Pavelitz, Tom; Castellanos, Javier; Macchi, Paolo; Varani, Gabriele

    2016-05-19

    Rbfox proteins regulate tissue-specific splicing by targeting a conserved GCAUG sequence within pre-mRNAs. We report here that sequence-specific binding of the conserved Rbfox RRM to miRNA precursors containing the same sequence motif in their terminal loops, including miR-20b and miR-107, suppresses their nuclear processing. The structure of the complex between precursor miR-20b and Rbfox RRM shows the molecular basis for recognition, and reveals changes in the stem-loop upon protein binding. In mammalian cells, Rbfox2 downregulates mature miR-20b and miR-107 levels and increases the expression of their downstream targets PTEN and Dicer, respectively, suggesting that Rbfox2 indirectly regulates many more cellular miRNAs. Thus, some of the widespread cellular functions of Rbfox2 protein are attributable to regulation of miRNA biogenesis, and might include the mis-regulation of miR-20b and miR-107 in cancer and neurodegeneration. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

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

    Science.gov (United States)

    Roeseler, David A; Sachdev, Shrikesh; Buckley, Desire M; Joshi, Trupti; Wu, Doris K; Xu, Dong; Hannink, Mark; Waters, Samuel T

    2012-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Ray, Heather J; Niswander, Lee A

    2016-04-01

    The transcription factor grainyhead-like 2 (GRHL2) is expressed in non-neural ectoderm (NNE) and Grhl2 loss results in fully penetrant cranial neural tube defects (NTDs) in mice. GRHL2 activates expression of several epithelial genes; however, additional molecular targets and functional processes regulated by GRHL2 in the NNE remain to be determined, as well as the underlying cause of the NTDs in Grhl2 mutants. Here, we find that Grhl2 loss results in abnormal mesenchymal phenotypes in the NNE, including aberrant vimentin expression and increased cellular dynamics that affects the NNE and neural crest cells. The resulting loss of NNE integrity contributes to an inability of the cranial neural folds to move toward the midline and results in NTD. Further, we identified Esrp1, Sostdc1, Fermt1, Tmprss2 and Lamc2 as novel NNE-expressed genes that are downregulated in Grhl2 mutants. Our in vitro assays show that they act as suppressors of the epithelial-to-mesenchymal transition (EMT). Thus, GRHL2 promotes the epithelial nature of the NNE during the dynamic events of neural tube formation by both activating key epithelial genes and actively suppressing EMT through novel downstream EMT suppressors. © 2016. Published by The Company of Biologists Ltd.

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

    Directory of Open Access Journals (Sweden)

    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

  15. MMP14 as a novel downstream target of VEGFR2 in migratory glioma-tropic neural stem cells

    Directory of Open Access Journals (Sweden)

    Nikita G. Alexiades

    2015-11-01

    Full Text Available Neural stem cell (NSC-based carriers have been presented as promising therapeutic tools for the treatment of infiltrative brain tumors due to their intrinsic tumor homing property. They have demonstrated the ability to migrate towards distant tumor microsatellites and effectively deliver the therapeutic payload, thus significantly improving survival in experimental animal models for brain tumor. Despite such optimistic results, the efficacy of NSC-based anti-cancer therapy has been limited due to the restricted tumor homing ability of NSCs. To examine this issue, we investigated the mechanisms of tumor-tropic migration of an FDA-approved NSC line, HB1.F3.CD, by performing a gene expression analysis. We identified vascular endothelial growth factor-A (VEGFA and membrane-bound matrix metalloproteinase (MMP14 as molecules whose expression are significantly elevated in migratory NSCs. We observed increased expression of VEGF receptor 2 (VEGFR2 in the focal adhesion complexes of migratory NSCs, with downstream activation of VEGFR2-dependent kinases such as p-PLCγ, p-FAK, and p-Akt, a signaling cascade reported to be required for cellular migration. In an in vivo orthotopic glioma xenograft model, analysis of the migratory trail showed that NSCs maintained expression of VEGFR2 and preferentially migrated within the perivascular space. Knockdown of VEGFR2 via shRNAs led to significant downregulation of MMP14 expression, which resulted in inhibited tumor-tropic migration. Overall, our results suggest, the involvement of VEGFR2-regulated MMP14 in the tumor-tropic migratory behavior of NSCs. Our data warrant investigation of MMP14 as a target for enhancing the migratory properties of NSC carriers and optimizing the delivery of therapeutic payloads to disseminated tumor burdens.

  16. Immunohistochemical analysis of phosphorylated mammalian target of rapamycin and its downstream signaling components in invasive breast cancer.

    Science.gov (United States)

    Ma, Bin-Lin; Shan, Mei-Hui; Sun, Gang; Ren, Guang-Hui; Dong, Chao; Yao, Xuemei; Zhou, Mei

    2015-10-01

    The present study aimed to investigate whether the mammalian target of rapamycin (mTOR) signaling pathway is activated in invasive breast cancer. The expression levels of phosphorylated (p)‑mTOR at ser2448 were detected, as well as the expression levels of its downstream signaling molecules: Eukaryotic translation initiation factor 4E‑binding protein 1 (4E‑BP1), and p70 ribosomal protein S6 kinase 1 (S6K1). The correlation between p‑mTOR, p‑4E‑BP1, p‑S6K1, and the clinicopathological parameters of breast cancer were also determined. p‑mTOR, p‑4E‑BP1 and p‑S6K1 expression was detected in 285 breast cancer tumor samples and adjacent normal tissue samples using immunohistochemistry. The expression levels and the location of the proteins were analyzed and compared in the various tissue samples. Multivariate Cox regression was used to analyze the clinicopathological factors and prognosis associated with the tissue samples. The disease‑free survival rate was examined using survival analyses and Log‑rank tests. The results of the present study indicated that the expression levels of p‑mTOR, p‑4E‑BP1, and p‑S6K1 were significantly higher in breast cancer tissue, as compared with normal tissue (Pbreast cancer tissue samples, as compared with normal tissue samples (P0.05). Thus suggesting that these markers are not adequate risk factors for disease free survival (P>0.05). In conclusion, the results of the present study suggested that p‑mTOR, p‑4E‑BP1, and p‑S6K1 are activated in invasive breast cancer. In addition, the exclusive expression of p‑4E‑BP1 and p‑S6K1 in the cytoplasm may be characteristic of progressive breast cancer. However, p‑mTOR, p‑4E‑BP1, and p‑S6K1 are not prognostic factors for breast cancer.

  17. p300 and p53 levels determine activation of HIF-1 downstream targets in invasive breast cancer

    NARCIS (Netherlands)

    Vleugel, M.M.; Shvarts, D.; Wall, E. van der; Diest, P.J. van

    2006-01-01

    In previous studies, we noted that overexpression of hypoxia-inducible factor (HIF)–1a in breast cancer, especially the diffuse form, does not always lead to functional activation of its downstream genes. Transcriptional activity of HIF-1 may be repressed by p53 through competition

  18. 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.

    2009-01-01

    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 < 0.05; n = 6) in both types of tissue recombinants despite the absence of epithelial PR in wt-S + ko-E grafts. Conversely, 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. PMID:19372202

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

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Zhenqin, E-mail: zqxiong@sjtu.edu.cn; Gu, Hanyang; Gong, Shenjie

    2015-09-15

    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{sup 4} and 7.0 × 10{sup 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.

  20. Novel Drugs Targeting the Epidermal Growth Factor Receptor and Its Downstream Pathways in the Treatment of Colorectal Cancer: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Amartej Merla

    2012-01-01

    Full Text Available Colorectal cancer is the second most common malignancy among men and women in the United States, and the 5-year survival rate remains poor despite recent advances in chemotherapy and targeted agents. The mainstay of therapy for advanced disease remains the cytotoxic chemotherapy including 5-FU, irinotecan, and oxaliplatin. The USFDA approval and introduction of targeted therapies, including cetuximab and panitumumab (monoclonal antibodies targeting the epidermal growth factor receptor (EGFR and bevacizumab (monoclonal antibody targeting the vascular epithelial growth factor (VEGF, has improved the median survival of patients with metastatic colorectal cancer to around 24 months. Clearly, better and more efficacious drugs are needed, and target-specific agents remain the future of cancer treatment. On this front, rapid advances are being made, which are likely to change the future of the management of metastatic colorectal cancer. However, absence of specific biomarkers for the use of targeted agents, in the subset of population who will benefit from the treatment, remains a major drawback. In this paper, we review agents that are in phases 1 and 2 clinical development, specifically targeting the EGFR and its subsequent downstream pathways.

  1. Advances in revealing the molecular targets downstream of oxidative stress-induced proapoptotic kinase signaling in diabetic embryopathy.

    Science.gov (United States)

    Wang, Fang; Reece, E Albert; Yang, Peixin

    2015-08-01

    Preexisting maternal diabetes is a high-risk factor of diabetic embryopathy, such as neural tube defects and congenital heart defects. Maternal diabetes significantly increases the production of reactive oxygen species, resulting in oxidative stress and diabetic embryopathy. Multiple cellular and metabolic factors contribute to these processes. Forkhead box O (FoxO)-3a has been demonstrated as a key transcription factor in the signaling transduction pathways responsible for maternal diabetes-induced birth defects. Apoptosis signal-regulating kinase 1 (ASK1) activated by oxidative stress stimulates nuclear translocation of FoxO3a, resulting in the overexpression of tumor necrosis factor receptor 1-associated death domain protein, which, in turn, leads to caspase-8 activation and apoptosis. Maternal diabetes-activated c-Jun N-terminal kinase (JNK)-1/2, downstream effectors of ASK1, can be blocked by superoxide dismutase-1 overexpression, suggesting that oxidative stress is responsible for JNK1/2 signaling activation. Deletion of JNK1/2 significantly suppressed the activity of FoxO3a. These observations indicate that maternal diabetes-induced oxidative stress stimulates the activation of ASK1, JNK1/2, FoxO3a, tumor necrosis factor receptor 1-associated death domain protein, caspase-8 cleavage, and finally, apoptosis and diabetic embryopathy. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Identification of several potential chromatin binding sites of HOXB7 and its downstream target genes in breast cancer.

    Science.gov (United States)

    Heinonen, Henna; Lepikhova, Tatiana; Sahu, Biswajyoti; Pehkonen, Henna; Pihlajamaa, Päivi; Louhimo, Riku; Gao, Ping; Wei, Gong-Hong; Hautaniemi, Sampsa; Jänne, Olli A; Monni, Outi

    2015-11-15

    HOXB7 encodes a transcription factor that is overexpressed in a number of cancers and encompasses many oncogenic functions. Previous results have shown it to promote cell proliferation, angiogenesis, epithelial-mesenchymal transition, DNA repair and cell survival. Because of its role in many cancers and tumorigenic processes, HOXB7 has been suggested to be a potential drug target. However, HOXB7 binding sites on chromatin and its targets are poorly known. The aim of our study was to identify HOXB7 binding sites on breast cancer cell chromatin and to delineate direct target genes located nearby these binding sites. We found 1,504 HOXB7 chromatin binding sites in BT-474 breast cancer cell line that overexpresses HOXB7. Seventeen selected binding sites were validated by ChIP-qPCR in several breast cancer cell lines. Furthermore, we analyzed expression of a large number of genes located nearby HOXB7 binding sites and found several new direct targets, such as CTNND2 and SCGB1D2. Identification of HOXB7 chromatin binding sites and target genes is essential to understand better the role of HOXB7 in breast cancer and mechanisms by which it regulates tumorigenic processes. © 2015 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

  3. Effect of target-fixture geometry on shock-wave compacted copper powders

    Science.gov (United States)

    Kim, Wooyeol; Ahn, Dong-Hyun; Yoon, Jae Ik; Park, Lee Ju; Kim, Hyoung Seop

    2018-01-01

    In shock compaction with a single gas gun system, a target fixture is used to safely recover a powder compact processed by shock-wave dynamic impact. However, no standard fixture geometry exists, and its effect on the processed compact is not well studied. In this study, two types of fixture are used for the dynamic compaction of hydrogen-reduced copper powders, and the mechanical properties and microstructures are investigated using the Vickers microhardness test and electron backscatter diffraction, respectively. With the assistance of finite element method simulations, we analyze several shock parameters that are experimentally hard to control. The results of the simulations indicate that the target geometry clearly affects the characteristics of incident and reflected shock waves. The hardness distribution and the microstructure of the compacts also show their dependence on the geometry. With the results of the simulations and the experiment, it is concluded that the target geometry affects the shock wave propagation and wave interaction in the specimen.

  4. Neutron energy spectrum from 120 GeV protons on a thick copper target

    Energy Technology Data Exchange (ETDEWEB)

    Shigyo, Nobuhiro; /Kyushu U.; Sanami, Toshiya; /KEK, Tsukuba; Kajimoto, Tsuyoshi; /Kyushu U.; Iwamoto, Yosuke; /JAEA, Ibaraki; Hagiwara, Masayuki; Saito, Kiwamu; /KEK, Tsukuba; Ishibashi, Kenji; /Kyushu U.; Nakashima, Hiroshi; Sakamoto, Yukio; /JAEA, Ibaraki; Lee, Hee-Seock; /Pohang Accelerator Lab.; Ramberg, Erik; /Fermilab

    2010-08-01

    Neutron energy spectrum from 120 GeV protons on a thick copper target was measured at the Meson Test Beam Facility (MTBF) at Fermi National Accelerator Laboratory. The data allows for evaluation of neutron production process implemented in theoretical simulation codes. It also helps exploring the reasons for some disagreement between calculation results and shielding benchmark data taken at high energy accelerator facilities, since it is evaluated separately from neutron transport. The experiment was carried out using a 120 GeV proton beam of 3E5 protons/spill. Since the spill duration was 4 seconds, protoninduced events were counted pulse by pulse. The intensity was maintained using diffusers and collimators installed in the beam line to MTBF. The protons hit a copper block target the size of which is 5cm x 5cm x 60 cm long. The neutrons produced in the target were measured using NE213 liquid scintillator detectors, placed about 5.5 m away from the target at 30{sup o} and 5 m 90{sup o} with respect to the proton beam axis. The neutron energy was determined by time-of-flight technique using timing difference between the NE213 and a plastic scintillator located just before the target. Neutron detection efficiency of NE213 was determined on basis of experimental data from the high energy neutron beam line at Los Alamos National Laboratory. The neutron spectrum was compared with the results of multiparticle transport codes to validate the implemented theoretical models. The apparatus would be applied to future measurements to obtain a systematic data set for secondary particle production on various target materials.

  5. Antibody cross-linking and target elution protocols used for immunoprecipitation significantly modulate signal-to noise ratio in downstream 2D-PAGE analysis

    Directory of Open Access Journals (Sweden)

    Slupphaug Geir

    2011-08-01

    Full Text Available Abstract Background Immunoprecipitation and subsequent 2D-PAGE/mass spectrometry are powerful tools to study post-translational protein modifications. Often disregarded in this workflow is the impact of the chemical cross-linker upon antibody affinity, as well as incomplete elution of primary target protein in buffers commonly used in 2D-PAGE. This may impede detection of non-abundant protein isoforms. Results Here we have compared cross-linking of antibodies to Dynabeads® Protein A by using DMP or BS3, as well as the efficiency of various target elution buffers prior to 2D-PAGE separation. BS3 cross-linking generally resulted in less non-specific binding than DMP, whereas DMP cross-linking gave overall higher yield of target protein. Regardless of the cross-linker used, incomplete elution of target protein was observed with conventional glycine- or urea-based buffers. Conversely, complete elution was obtained with 2% hot SDS and subsequent dilution in urea buffer containing 4% CHAPS, to 0.2% final SDS yielded perfectly focused gels suitable for mass spectrometry analysis. Conclusion Careful choice of Ig cross-linker as well as efficient elution of target protein in SDS prior to downstream 2D-PAGE may be key factors to analyze low-abundance proteins enriched by magnetic bead immunoprecipitation.

  6. The histone demethylase KDM3A, and its downstream target MCAM, promote Ewing Sarcoma cell migration and metastasis.

    Science.gov (United States)

    Sechler, M; Parrish, J K; Birks, D K; Jedlicka, P

    2017-07-20

    Ewing Sarcoma is the second most common solid pediatric malignant neoplasm of bone and soft tissue. Driven by EWS/Ets, or rarely variant, oncogenic fusions, Ewing Sarcoma is a biologically and clinically aggressive disease with a high propensity for metastasis. However, the mechanisms underpinning Ewing Sarcoma metastasis are currently not well understood. In the present study, we identify and characterize a novel metastasis-promotional pathway in Ewing Sarcoma, involving the histone demethylase KDM3A, previously identified by our laboratory as a new cancer-promoting gene in this disease. Using global gene expression profiling, we show that KDM3A positively regulates genes and pathways implicated in cell migration and metastasis, and demonstrate, using functional assays, that KDM3A promotes migration in vitro and experimental, post-intravasation, metastasis in vivo. We further identify the melanoma cell adhesion molecule (MCAM) as a novel KDM3A target gene in Ewing Sarcoma, and an important effector of KDM3A pro-metastatic action. Specifically, we demonstrate that MCAM depletion, like KDM3A depletion, inhibits cell migration in vitro and experimental metastasis in vivo, and that MCAM partially rescues impaired migration due to KDM3A knock-down. Mechanistically, we show that KDM3A regulates MCAM expression both through a direct mechanism, involving modulation of H3K9 methylation at the MCAM promoter, and an indirect mechanism, via the Ets1 transcription factor. Finally, we identify an association between high MCAM levels in patient tumors and poor survival, in two different Ewing Sarcoma clinical cohorts. Taken together, our studies uncover a new metastasis-promoting pathway in Ewing Sarcoma, with therapeutically targetable components.

  7. LRF is an essential downstream target of GATA1 in erythroid development and regulates BIM-dependent apoptosis

    Science.gov (United States)

    Maeda, Takahiro; Ito, Keisuke; Merghoub, Taha; Poliseno, Laura; Hobbs, Robin M.; Wang, Guocan; Dong, Lin; Maeda, Manami; Dore, Louis C.; Zelent, Arthur; Luzzatto, Lucio; Teruya-Feldstein, Julie; Weiss, Mitchell J.; Pandolfi, Pier Paolo

    2011-01-01

    SUMMARY GATA-1-dependent transcription is essential for erythroid differentiation and maturation. Suppression of programmed cell death is also thought to be critical for this process; however, the link between these two features of erythropoiesis has remained elusive. Here, we show that the POZ-Krüppel family transcription factor, LRF (also known as Zbtb7a/Pokemon), is a direct target of GATA1 and plays an essential anti-apoptotic role during terminal erythroid differentiation. We find that loss of Lrf leads to lethal anemia in embryos, due to increased apoptosis of late stage erythroblasts. This programmed cell death is Arf- and p53-independent and is instead mediated by up-regulation of the pro-apoptotic factor Bim. We identify Lrf as a direct repressor of Bim transcription. In strong support of this mechanism, genetic Bim-loss delays the lethality of Lrf-deficient embryos and rescues their anemia-phenotype. Thus, our data defines a key transcriptional cascade for effective erythropoiesis, whereby GATA-1 suppresses BIM-mediated apoptosis via LRF. PMID:19853566

  8. Copper matrix composites as heat sink materials for water-cooled divertor target

    Directory of Open Access Journals (Sweden)

    Jeong-Ha You

    2015-12-01

    Full Text Available According to the recent high heat flux (HHF qualification tests of ITER divertor target mock-ups and the preliminary design studies of DEMO divertor target, the performance of CuCrZr alloy, the baseline heat sink material for DEMO divertor, seems to only marginally cover the envisaged operation regime. The structural integrity of the CuCrZr heat sink was shown to be affected by plastic fatigue at 20 MW/m². The relatively high neutron irradiation dose expected for the DEMO divertor target is another serious concern, as it would cause significant embrittlement below 250 °C or irradiation creep above 350 °C. Hence, an advanced design concept of the divertor target needs to be devised for DEMO in order to enhance the HHF performance so that the structural design criteria are fulfilled for full operation scenarios including slow transients. The biggest potential lies in copper-matrix composite materials for the heat sink. In this article, three promising Cu-matrix composite materials are reviewed in terms of thermal, mechanical and HHF performance as structural heat sink materials. The considered candidates are W particle-reinforced, W wire-reinforced and SiC fiber-reinforced Cu matrix composites. The comprehensive results of recent studies on fabrication technology, design concepts, materials properties and the HHF performance of mock-ups are presented. Limitations and challenges are discussed.

  9. An electrophysiological investigation of reinforcement effects in attention deficit/hyperactivity disorder: Dissociating cue sensitivity from down-stream effects on target engagement and performance

    Directory of Open Access Journals (Sweden)

    Georgia Chronaki

    2017-12-01

    Full Text Available Objective: Neural hypo-sensitivity to cues predicting positive reinforcement has been observed in ADHD using the Monetary Incentive Delay (MID task. Here we report the first study using an electrophysiological analogue of this task to distinguish between (i cue related anticipation of reinforcement and downstream effects on (ii target engagement and (iii performance in a clinical sample of adolescents with ADHD and controls. Methods: Thirty-one controls and 32 adolescents with ADHD aged 10–16 years performed the electrophysiological (e-MID task − in which preparatory cues signal whether a response to an upcoming target will be reinforced or not − under three conditions; positive reinforcement, negative reinforcement (response cost and no consequence (neutral. We extracted values for both cue-related potentials known to be, both, associated with response preparation and modulated by reinforcement (Cue P3 and Cue CNV and target-related potentials (target P3 and compared these between ADHD and controls. Results: ADHD and controls did not differ on cue-related components on neutral trials. Against expectation, adolescents with ADHD displayed Cue P3 and Cue CNV reinforcement-related enhancement (versus neutral trials compared to controls. ADHD individuals displayed smaller target P3 amplitudes and slower and more variable performance − but effects were not modulated by reinforcement contingencies. When age, IQ and conduct problems were controlled effects were marginally significant but the pattern of results did not change. Discussion: ADHD was associated with hypersensitivity to positive (and marginally negative reinforcement reflected on components often thought to be associated with response preparation − however these did not translate into improved attention to targets. In the case of ADHD, upregulated CNV may be a specific marker of hyper-arousal rather than an enhancement of anticipatory attention to upcoming targets

  10. 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.

  11. MicroRNA-409-5p is upregulated in breast cancer and its downregulation inhibits cancer development through downstream target of RSU1.

    Science.gov (United States)

    Yu, Hong; Xing, Hua; Han, Wei; Wang, Yali; Qi, Tianyang; Song, Changlong; Xu, Zheli; Li, Hongjun; Huang, Yinghui

    2017-05-01

    We investigated the expression and function of miR-409-5p in human breast cancer. Quantitative real-time polymerase chain reaction was conducted to evaluate endogenous miR-409-5p expression in breast cancer tumors and breast cancer cell lines. Lentiviral transduction was performed to stably downregulate miR-409-5p in breast cancer cell lines MDA-MB-231 and MCF-7 and cells. The effects of miR-409-5p downregulation on breast cancer proliferation, migration, and xenograft development were then evaluated. Downstream target gene of miR-409-5p, Ras suppressor protein 1, was examined by dual-luciferase activity assay, quantitative real-time polymerase chain reaction, and western blot in lentiviral-transduced breast cancer cells. Ras suppressor protein 1 was also inhibited in miR-409-5p-downregulated breast cancer cells to examine its functional effect on breast cancer proliferation and migration. MiR-409-5p was aberrantly upregulated in both breast cancer tumors and cell lines. Lentiviral transduction successfully downregulated endogenous miR-409-5p expression as well as suppressed proliferation, migration, and xenograft development in MDA-MB-231 and MCF-7 cells. Ras suppressor protein 1 was confirmed to be directly targeted by miR-409-5p in breast cancer cells. Small interfering RNA-mediated Ras suppressor protein 1 inhibition reversely promoted cancer proliferation and migration in miR-409-5p-downregualted breast cancer cells. MiR-409-5p is downregulated in breast cancer and its inhibition has anti-cancer effect on breast cancer development both in vitro and in vivo. The regulatory effect of miR-409-5p inhibition is likely through the inverse upregulation of Ras suppressor protein 1 in breast cancer.

  12. 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.

  13. Diagnosis of abnormal biliary copper excretion by positron emission tomography with targeting of (64)Copper-asialofetuin complex in LEC rat model of Wilson's disease.

    Science.gov (United States)

    Bahde, Ralf; Kapoor, Sorabh; Bhargava, Kuldeep K; Palestro, Christopher J; Gupta, Sanjeev

    2014-01-01

    Identification by molecular imaging of key processes in handling of transition state metals, such as copper (Cu), will be of considerable clinical value. For instance, the ability to diagnose Wilson's disease with molecular imaging by identifying copper excretion in an ATP7B-dependent manner will be very significant. To develop highly effective diagnostic approaches, we hypothesized that targeting of radiocopper via the asialoglycoprotein receptor will be appropriate for positron emission tomography, and examined this approach in a rat model of Wilson's disease. After complexing (64)Cu to asialofetuin we studied handling of this complex compared with (64)Cu in healthy LEA rats and diseased homozygous LEC rats lacking ATP7B and exhibiting hepatic copper toxicosis. We analyzed radiotracer clearance from blood, organ uptake, and biliary excretion, including sixty minute dynamic positron emission tomography recordings. In LEA rats, (64)Cu-asialofetuin was better cleared from blood followed by liver uptake and greater biliary excretion than (64)Cu. In LEC rats, (64)Cu-asialofetuin activity cleared even more rapidly from blood followed by greater uptake in liver, but neither (64)Cu-asialofetuin nor (64)Cu appeared in bile. Image analysis demonstrated rapid visualization of liver after (64)Cu-asialofetuin administration followed by decreased liver activity in LEA rats while liver activity progressively increased in LEC rats. Image analysis resolved this difference in hepatic activity within one hour. We concluded that (64)Cu-asialofetuin complex was successfully targeted to the liver and radiocopper was then excreted into bile in an ATP7B-dependent manner. Therefore, hepatic targeting of radiocopper will be appropriate for improving molecular diagnosis and for developing drug/cell/gene therapies in Wilson's disease.

  14. An in-vivo study for targeted delivery of copper-organic complex to breast cancer using chitosan polymer nanoparticles.

    Science.gov (United States)

    Pramanik, Arindam; Laha, Dipranjan; Dash, Sandeep Kumar; Chattopadhyay, Sourav; Roy, Somenath; Das, Dipak Kumar; Pramanik, Panchanan; Karmakar, Parimal

    2016-11-01

    We have developed a strategy for targeted delivery of metal-diketo complex, "bis(2,4-pentanedionato) copper(II)" to breast cancer cells both in-vitro and in-vivo. This metal-organic complex induced ROS and subsequently DNA damage as well as mitochondrial membrane depolarization was observed. The mitochondria rupture further triggered apoptosis. For in-vitro targeting strategies, two different approaches were employed, folic acid or her-2 specific peptide (KCCYSL) was attached to stearic acid-modified polymeric Chitosan nanoparticles loaded with metal-organic complex "bis(2,4-pentanedionato)copper(II)". This was tested on two pairs of isogenic cells (FR+/FR- MCf-7 and her2+ /her2- MCF-7) and it was observed that cells expressing the receptor were susceptible to the drug whereas non-expressing isogenic cells were almost un-affected. During in-vivo studies, mice receiving targeted delivery of bis(2,4-pentanedionato) copper (II) had increased survivability and reduced tumor volume compared to non-targeted drug delivery. During toxicity studies for liver enzymes it was also found that the mice receiving targeted drug did not show any sign of liver damage as well as other histology changes. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Monochromatic flash x-ray generator utilizing copper-target diode

    Science.gov (United States)

    Sato, Eiichi; Sagae, Michiaki; Komatsu, Makoto; Germer, Rudolf; Tanaka, Etsuro; Mori, Hidezo; Kawai, Toshiaki; Ichimaru, Toshio; Sato, Shigehiro; Ojima, Hidenori; Takayama, Kazuyoshi; Ido, Hideaki

    2005-03-01

    High-voltage condensers in a polarity-inversion two-stage Marx surge generator are charged from -50 to -70 kV using a power supply, and the electric charges in the condensers are discharged to an x-ray tube after closing the gap switches in the surge generator using a trigger device. The x-ray tube is a demountable diode, and the turbomolecular pump evacuates air from the tube with a pressure of approximately 1 mPa. Clean copper Kα lines are produced using a 10-μm-thick nickel filter, since the tube utilizes a disk cathode and a rod target, and bremsstrahlung rays are not emitted in the opposite direction to that of electron acceleration. The peak tube voltage increased with increasing charging voltage. At a charging voltage of -70 kV, the peak tube voltage and current were 140 kV and 0.8 kA, respectively. The pulse widths were approximately 30 ns, and the maximum dimension of the x-ray source was 3.0 mm in diameter. The number of generator-produced Kα photons was approximately 2.5x106 photons/cm2 at 0.5 m per pulse.

  16. Electrochemical detection of protein by using magnetic graphene-based target enrichment and copper nanoparticles-assisted signal amplification.

    Science.gov (United States)

    Zhao, Jing; Lv, Yun; Kang, Mingyang; Wang, Keming; Xiang, Yang

    2015-11-21

    In this paper, we propose a new method for protein detection by making use of magnetic graphene for enrichment and separation of the targets and duplex DNA-templated copper nanoparticles for amplification of electrochemical signals. Because the binding of the target protein (e.g. folate receptor) and small molecule (e.g. folate) can protect complementary DNA (cDNA) from exonuclease III-catalyzed degradation, duplex DNA from the hybridization of probe DNA and cDNA can act as the template for the formation of copper nanoparticles (CuNPs). Afterward, CuNPs-coated DNA can be enriched on the surface of magnetic graphene through the 3'-overhanging end of probe DNA, and then separated from the reaction mixture with the aid of magnet. As a result, copper ions released from acid-dissolution of CuNPs can catalyze the oxidation of o-phenylenediamine (OPD) by dissolved oxygen, resulting in an amplified electrochemical response. Our method can sensitively detect target protein over a wide linear range and with a low detection limit of 7.8 pg mL(-1), which can easily distinguish the targets even in complex serum samples. Therefore, this method may be promising for the clinical diagnosis of protein biomarkers by changing the recognition elements in the future.

  17. CCAAT-enhancer-binding Protein β (C/EBPβ) and Downstream Human Placental Growth Hormone Genes Are Targets for Dysregulation in Pregnancies Complicated by Maternal Obesity*

    Science.gov (United States)

    Vakili, Hana; Jin, Yan; Menticoglou, Savas; Cattini, Peter A.

    2013-01-01

    Human chorionic somatomammotropin (CS) and placental growth hormone variant (GH-V) act as metabolic adaptors in response to maternal insulin resistance, which occurs in “normal” pregnancy. Maternal obesity can exacerbate this “resistance,” suggesting that CS, GH-V, or transcription factors that regulate their production might be targets. The human CS genes, hCS-A and hCS-B, flank the GH-V gene. A significant decrease in pre-term placental CS/GH-V RNA levels was observed in transgenic mice containing the CS/GH-V genes in a model of high fat diet (HFD)-induced maternal obesity. Similarly, a decrease in CS/GH-V RNA levels was detected in term placentas from obese (body mass index (BMI) ≥ 35 kg/m2) versus lean (BMI 20–25 kg/m2) women. A specific decrease in transcription factor CCAAT-enhancer-binding protein β (C/EBPβ) RNA levels was also seen with obesity; C/EBPβ is required for mouse placenta development and is expressed, like CS and GH-V, in syncytiotrophoblasts. Binding of C/EBPβ to the CS gene downstream enhancer regions, which by virtue of their position distally flank the GH-V gene, was reduced in placenta chromatin from mice on a HFD and in obese women; a corresponding decrease in RNA polymerase II associated with CS/GH-V promoters was also observed. Detection of decreased endogenous CS/GH-V RNA levels in human placental tumor cells treated with C/EBPβ siRNA is consistent with a direct effect. These data provide evidence for CS/GH-V dysregulation in acute HFD-induced obesity in mouse pregnancy and chronic obesity in human pregnancy and implicate C/EBPβ, a factor associated with CS regulation and placental development. PMID:23782703

  18. CCAAT-enhancer-binding protein β (C/EBPβ) and downstream human placental growth hormone genes are targets for dysregulation in pregnancies complicated by maternal obesity.

    Science.gov (United States)

    Vakili, Hana; Jin, Yan; Menticoglou, Savas; Cattini, Peter A

    2013-08-02

    Human chorionic somatomammotropin (CS) and placental growth hormone variant (GH-V) act as metabolic adaptors in response to maternal insulin resistance, which occurs in "normal" pregnancy. Maternal obesity can exacerbate this "resistance," suggesting that CS, GH-V, or transcription factors that regulate their production might be targets. The human CS genes, hCS-A and hCS-B, flank the GH-V gene. A significant decrease in pre-term placental CS/GH-V RNA levels was observed in transgenic mice containing the CS/GH-V genes in a model of high fat diet (HFD)-induced maternal obesity. Similarly, a decrease in CS/GH-V RNA levels was detected in term placentas from obese (body mass index (BMI) ≥ 35 kg/m(2)) versus lean (BMI 20-25 kg/m(2)) women. A specific decrease in transcription factor CCAAT-enhancer-binding protein β (C/EBPβ) RNA levels was also seen with obesity; C/EBPβ is required for mouse placenta development and is expressed, like CS and GH-V, in syncytiotrophoblasts. Binding of C/EBPβ to the CS gene downstream enhancer regions, which by virtue of their position distally flank the GH-V gene, was reduced in placenta chromatin from mice on a HFD and in obese women; a corresponding decrease in RNA polymerase II associated with CS/GH-V promoters was also observed. Detection of decreased endogenous CS/GH-V RNA levels in human placental tumor cells treated with C/EBPβ siRNA is consistent with a direct effect. These data provide evidence for CS/GH-V dysregulation in acute HFD-induced obesity in mouse pregnancy and chronic obesity in human pregnancy and implicate C/EBPβ, a factor associated with CS regulation and placental development.

  19. Ammonium tetrathiomolybdate treatment targets the copper transporter ATP7A and enhances sensitivity of breast cancer to cisplatin

    OpenAIRE

    Chisholm, Cristine L.; Wang, Haitao; Wong, Ada Hang-Heng; Vazquez-Ortiz, Guelaguetza; Chen, Weiping; Xu, Xiaoling; Deng, Chu-Xia

    2016-01-01

    Cisplatin is an effective breast cancer drug but resistance often develops over prolonged chemotherapy. Therefore, we performed a candidate approach RNAi screen in combination with cisplatin treatment to identify molecular pathways conferring survival advantages. The screen identified ATP7A as a therapeutic target. ATP7A is a copper ATPase transporter responsible for intercellular movement and sequestering of cisplatin. Pharmaceutical replacement for ATP7A by ammonium tetrathiomolybdate (TM) ...

  20. Human topoisomerase IB is a target of a thiosemicarbazone copper(II) complex.

    Science.gov (United States)

    Vutey, Venn; Castelli, Silvia; D'Annessa, Ilda; Sâmia, Luciana B P; Souza-Fagundes, Elaine M; Beraldo, Heloisa; Desideri, Alessandro

    2016-09-15

    The human topoisomerase IB inhibition and the antiproliferative activity of 3-(4-bromophenyl)-1-pyridin-2-ylprop-2-en-1-one thiosemicarbazone HPyCT4BrPh alone and its copper(II) complex [Cu(PyCT4BrPh)Cl] was investigated. [Cu(PyCT4BrPh)Cl] inhibits both the DNA cleavage and religation step of the enzyme, whilst the ligand alone does not display any effect. In addition we show that coordination to copper(II) improves the cytotoxicity of HPyCT4BrPh against THP-1 leukemia and MCF-7 breast cancer cells. The data indicate that the copper(II) thiosemicarbazone complex may hit human topoisomerase IB and that metal coordination can be useful to improve cytotoxicity of this versatile class of compounds. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Copper Test

    Science.gov (United States)

    ... Tests G6PD Gamma-Glutamyl Transferase (GGT) Gastrin Gastrointestinal Pathogens Panel Genetic Tests for Targeted Cancer Therapy Glucose ... hepatic). Copper is found in many foods including nuts, chocolate, mushrooms, shellfish, whole grains, dried fruits, and ...

  2. Interactions of 160 GeV/Nucleon $^{207}$Pb Nuclei in Emulsion Chambers with Copper and Lead Targets

    CERN Multimedia

    2002-01-01

    % EMU13 \\\\ \\\\ Nuclear emulsions will be used as targets and trackers to investigate the interactions of $^{207}$Pb nuclei in emulsion, copper and lead targets; specifically (i) the pseudorapidity distributions of charged particles including analysis of particle fluctuations in pseudorapidity and azimuthal angle distributions, (ii) the transverse momentum distribution of $\\alpha$ fragments from the projectile nucleus. \\\\ \\\\Several emulsion chambers with different geometry and targets will be exposed to the $^{207}$Pb beam. Each chamber will be irradiated with the beam of low density $^{207}$Pb ions (several hundred per cm$^2$). Interactions with small impact parameter, characterized by high multiplicity and disruption of the projectile nucleus will be found with high efficiency. Measurements in the emulsion will include the number and emission angles of charged particles produced and the emission angles of $\\alpha$ fragments from the projectile nucleus.

  3. Structure and Properties of Nanoparticles Fabricated by Laser Ablation of Bulk Metal Copper Targets in Water and Ethanol

    Science.gov (United States)

    Goncharova, D. A.; Lapin, I. N.; Savelyev, E. S.; Svetlichnyi, V. A.

    2017-11-01

    Colloidal solutions of nanoparticles (NPs) are prepared by nanosecond pulsed laser ablation (upon exposure to Nd:YAG laser radiation at a wavelength of 1064 nm with a pulse duration of 7 ns) of a copper target in water and ethyl alcohol. Their composition, structure, and optical properties are investigated. It is shown that monovalent Cu2O NPs are mainly formed in water, whereas metal Cu NPs are mainly formed in ethanol. The nonlinear transmission of colloids at wavelengths of 532 and 1064 nm is investigated. It is established that they effectively limit the nanosecond laser pulse power at a wavelength of 532 nm.

  4. Upstream to downstream: a multiple-assessment-point approach for targeting non-point-source priority management areas at large watershed scale

    Science.gov (United States)

    Chen, L.; Zhong, Y.; Wei, G.; Shen, Z.

    2014-04-01

    The identification of priority management areas (PMAs) is essential for the control of non-point-source (NPS) pollution, especially for a large-scale watershed. However, previous studies have typically focused on small-scale catchments adjacent to specific assessment points; thus, the interactions between multiple river points remain poorly understood. In this study, a multiple-assessment-point PMA (MAP-PMA) framework was proposed by integrating the upstream sources and the downstream transport aspects of NPS pollution. Daning River watershed was taken as a case study in this paper, which has demonstrated that the integration of the upstream input changes was vital for the final PMAs map, especially for downstream areas. Contrary to conventional wisdom, this research recommended that the NPS pollutants could be best controlled among the upstream high-level PMAs when protecting the water quality of the entire watershed. The MAP-PMA framework provided a more cost-effective tool for the establishment of conservation practices, especially for a large-scale watershed.

  5. Impact of the 7 TeV/c Large Hadron Collider proton beam on a copper target

    CERN Document Server

    Tahir, N A; Goddard, B; Hoffmann, Dieter H H; Kain, V; Lomonosov, I V; Piriz, A R; Schmidt, R; Shutov, A; Temporal, M

    2005-01-01

    The Large Hadron Collider (LHC) will allow for collision between two 7 TeV/c proton beams, each comprising 2808 bunches with 1.1*10/sup 11 / protons per bunch, traveling in opposite direction. The bunch length is 0.5 ns and two neighboring bunches are separated by 25 ns so that the duration of the entire beam is about 89 mu s. The beam power profile in the transverse direction is a Gaussian with a standard deviation of 0.2 mm. The energy stored in each beam is about 350 MJ that is sufficient to melt 500 kg of copper. In case of a failure in the machine protection systems, the entire beam could impact directly onto an accelerator equipment. A first estimate of the scale of damage resulting from such a failure has been assessed for a solid copper target hit by the beam by carrying out three- dimensional energy deposition calculations and two-dimensional numerical simulations of the hydrodynamic and thermodynamic response of the target. This work has shown that the penetration depth of the LHC protons will be be...

  6. A Copper(II) Phenanthroline Metallopeptide That Targets and Disrupts Mitochondrial Function in Breast Cancer Stem Cells.

    Science.gov (United States)

    Laws, Kristine; Bineva-Todd, Ganka; Eskandari, Arvin; Lu, Chunxin; O'Reilly, Nicola; Suntharalingam, Kogularamanan

    2018-01-02

    The breast cancer stem cell (CSC) and bulk breast cancer cell potency of a series of metallopeptides containing dichloro(1,10-phenanthroline)copper(II) and various organelle-targeting peptide sequences is reported. The mitochondria-targeting metallopeptide 1 exploits the higher mitochondrial load in breast CSCs over the corresponding non-CSCs and the vulnerability of breast CSCs to mitochondrial damage to potently and selectively kill breast CSCs. Strikingly, 1 reduces the formation and size of mammospheres to a greater extent than salinomycin, an established CSC-potent agent. Mechanistic studies show that 1 enters CSC mitochondria, induces mitochondrial dysfunction, generates reactive oxygen species (ROS), activates JNK and p38 pathways, and prompts apoptosis. To the best of our knowledge, 1 is the first metallopeptide to selectivity kill breast CSCs in vitro. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Targeted water soluble copper-tetrazolate complexes: interactions with biomolecules and catecholase like activities.

    Science.gov (United States)

    Saha, Manideepa; Das, Mriganka; Nasani, Rajendar; Choudhuri, Indrani; Yousufuddin, Muhammed; Nayek, Hari Pada; Shaikh, Mobin M; Pathak, Biswarup; Mukhopadhyay, Suman

    2015-12-14

    Two new mononuclear water soluble copper(II) complexes, [Cu{(5-pyrazinyl)tetrazolate}2(1,10-phenanthroline)] 1 and [Cu{(5-pyrazinyl)tetrazolate}(1,10-phenanthroline)2](NO3)0.5(N3)0.5 2, have been synthesized using the metal mediated [2 + 3] cycloaddition reaction between copper bound azide and pyrazinecarbonitrile. The interactions of these copper tetrazolate complexes 1 and 2 with biomolecules like DNA and bovine serum albumin (BSA) are studied and the catecholase like catalytic activity of compound 2 is also explored. Structural determination reveals that both compounds 1 and 2 are octahedral in nature. Screening tests were conducted to quantify the binding ability of complexes (1 and 2) towards DNA and it was revealed that complex 2 has a stronger affinity to bind to CT-DNA. DFT studies indicated that a lower HOMO-LUMO energy gap between the DNA fragment and metal complexes might be the reason for this type of stronger interaction. DNA cleavage activity was explored by gel-electrophoresis and moderate to strong DNA cleavage properties were observed in the presence and absence of co-reagents. Inhibition of cleavage in the presence of sodium azide indicates the propagation of the activity through the production of singlet molecular oxygen. Furthermore enzyme kinetic studies reflect that complex 2 is also effective in mimicking catecholase like activities. An ESI-MS spectral study indicates the probable involvement of dimeric species [(phen)2Cu-(OH)2-Cu(phen)2](2+) in the catalytic cycle.

  8. Copper(I) targeting in the Alzheimer's disease context: a first example using the biocompatible PTA ligand.

    Science.gov (United States)

    Atrián-Blasco, E; Cerrada, E; Conte-Daban, A; Testemale, D; Faller, P; Laguna, M; Hureau, C

    2015-08-01

    Copper(I) coordinating ligands in the Alzheimer's disease context have remained unexplored, despite the biological relevance of this redox state of the copper ion. Here, we show that the PTA ligand can remove copper from Aβ, prevent reactive oxygen species production and oligomer formation, two deleterious events in the disease's etiology.

  9. Eta Production at High Transverse Momentum by Negative 520 GeV/c Pions Incident on Beryllium and Copper Targets

    Energy Technology Data Exchange (ETDEWEB)

    Roser, Robert Martin [Univ. of Rochester, NY (United States)

    1994-01-01

    This thesis presents a measurement of the production of high transverse momentum 17 mesons by a 520 GeV /c $\\sqrt{s}$ = 31.2) $\\pi^-$ beam using data collected during the 1990 fixed target run of Fermilab experiment E706. E706 is a second generation fixed target experiment designed to measure direct-photon production in hadron-nucleus collisions. These data provide a clean test of perturbative QCD and serve as a valuable tool for probing hadronic structure. The $\\gamma\\gamma$ decay mode of the $\\eta$ meson was studied using data from a highly segmented electromagnetic lead liquid argon sampling calorimeter. Results are presented for inclusive $\\eta$ production by $\\pi^-$ beams on both beryllium and copper targets. The $\\eta$ to $\\pi^0$ production ratio and the nuclear dependence of the $\\eta$ production cross section are also reported. These results are for $\\eta$'s in the transverse momentum range 3.5 to 9 Ge V / c and the center of mass rapidity range -0.75 to 0.75, and are the highest energy results ever obtained for inclusive $\\eta$ production using a $\\pi^-$ beam.

  10. miR-2478 inhibits TGFβ1 expression by targeting the transcriptional activation region downstream of the TGFβ1 promoter in dairy goats.

    Science.gov (United States)

    Li, Zhuanjian; Lan, Xianyong; Han, Ruili; Wang, Jing; Huang, Yongzhen; Sun, Jiajie; Guo, Wenjiao; Chen, Hong

    2017-02-15

    In a previous study, miR-2478 was demonstrated to be up-regulated in dairy goat mammary glands during peak lactation compared with the dry period. However, the detailed mechanisms by which miR-2478 regulates physiological lactation and mammary gland development in dairy goats remain unclear. In this study, we used bioinformatics analysis and homologous cloning to predict the target genes of miR-2478 and selected INSR, FBXO11, TGFβ1 and ING4 as candidate target genes of miR-2478. Subsequently, by targeting the 5'UTR of the TGFβ1 gene, we verified that miR-2478 significantly inhibited TGFβ1 transcription and the Pearson's correlation coefficient between miR-2478 expression and TGFβ1 expression was -0.98. Furthermore, we identified the potential promoter and transcription factor binding regions of TGFβ1 and analyzed the potential mechanisms of interaction between miR-2478 and TGFβ1. Dual-luciferase reporter assays revealed that two regions, spanning from -904 to -690 bp and from -79 to +197 bp, were transcription factor binding regions of TGFβ1. Interesting, the miR-2478 binding sequence was determined to span from +123 to +142 bp in the TGFβ1 gene promoter. Thus, our results have demonstrated that miR-2478 binds to the core region of the TGFβ1 promoter and that it affects goat mammary gland development by inhibiting TGFβ1 transcription.

  11. Copper nanoparticles differentially target testis of the catfish, Clarias batrachus: in vivo and in vitro study

    Directory of Open Access Journals (Sweden)

    Raju Murugananthkumar

    2016-11-01

    Full Text Available Present study examined the impact of copper (Cu as nanoparticle (Cu-NPs and soluble form (CuSO4 in adult male catfish Clarias batrachus. Following treatment, upregulation of transcripts of several testis-related genes and increased androgen levels were evident. Though profound promotional effect was seen at gene and androgen levels, structural analysis revealed completely different scenario. Histological observations of testis showed disruption of basal lamina, distinct spermatogonium and enlarged spermatocytes in the treated groups. Quite alarmingly, transmission electron microscopic analysis showed damage of testicular lumen with irregular basal lamina and distinctive spermatocytes. In addition, Sertoli cells and erythrocytes exhibited damage after Cu treatments. Cytotoxic effects of Cu in catfish primary testis and TM3 Leydig cells showed cytotoxicity which is correlated well with morphological and flow cytometric analysis. Taken together, the results demonstrated that low dose of Cu/Cu-NPs can be detrimental to catfish testicular recrudescence vis-à-vis reproduction and the toxic effect manifest drastically in in vitro cultures.

  12. Oligodendroglial Argonaute protein Ago2 associates with molecules of the Mbp mRNA localization machinery and is a downstream target of Fyn kinase

    Directory of Open Access Journals (Sweden)

    Christina eMüller

    2015-08-01

    Full Text Available Oligodendrocytes myelinate neuronal axons in the central nervous system (CNS facilitating rapid transmission of action potentials by saltatory conduction. Myelin Basic Protein (MBP is an essential component of myelin and its absence results in severe hypomyelination in the CNS of rodents. Mbp mRNA is not translated immediately after exit from the nucleus in the cytoplasm, but is transported to the plasma membrane in RNA transport granules in a translationally silenced state. We have previously identified the small non-coding RNA 715 (sncRNA715 as an inhibitor of Mbp translation associated with RNA granules. Argonaute (Ago proteins and small RNAs form the minimal core of the RNA induced silencing complex (RISC and together recognize target mRNAs to be translationally inhibited or degraded. Recently, tyrosine phosphorylation of Ago2 was reported to be a regulator of small RNA binding. The oligodendroglial non-receptor tyrosine kinase Fyn is activated by neuronal signals and stimulates the translation of Mbp mRNA at the axon-glial contact site. Here we analyzed the expression of Ago proteins in oligodendrocytes, if they associate with Mbp mRNA transport granules and are tyrosine phosphorylated by Fyn. We show that all Ago proteins (Ago1-4 are expressed by oligodendrocytes and that Ago2 colocalizes with hnRNP A2 in granular cytoplasmic structures. Ago2 associates with hnRNP A2, Mbp mRNA, sncRNA715 and Fyn kinase and is tyrosine phosphorylated in response to Fyn activity. Our findings suggest an involvement of Ago2 in the translational regulation of Mbp. The identification of Ago proteins as Fyn targets will foster further research to understand in more molecular detail how Fyn activity regulates Mbp translation.

  13. microRNA-340-5p Functions Downstream of Cardiotrophin-1 to Regulate Cardiac Eccentric Hypertrophy and Heart Failure via Target Gene Dystrophin.

    Science.gov (United States)

    Zhou, Jian; Gao, Jie; Zhang, Xiaoya; Liu, Yan; Gu, Song; Zhang, Xitao; An, Xiangguang; Yan, Jun; Xin, Yue; Su, Pixiong

    2015-01-01

    Pathological cardiac hypertrophy inevitably leads to the unfavorable outcomes of heart failure (HF) or even sudden death. microRNAs are key regulation factors participating in many pathophysiological processes. Recently, we observed upregulation of microRNA-340-5p (miR-340) in failing human hearts because of dilated cardiomyopathy, but the functional consequence of miR-340 remains to be clarified.We transfected neonatal cardiomyocytes with miR-340 and found fetal gene expression including Nppa, Nppb and Myh7. We also observed eccentric hypertrophy development upon treatment which was analogous to the phenotype after cardiotrophin-1 (CT-1) stimulation. As a potent inducer of cardiac eccentric hypertrophy, treatment by IL-6 family members CT-1 and leukemia inhibitory factor (LIF) led to the elevation of miR-340. Knockdown of miR-340 using antagomir attenuated fetal gene expression and hypertrophy formation, which means miR-340 could convey the hypertrophic signal of CT-1. To demonstrate the initial factor of miR-340 activation, we constructed a volume overloaded abdominal aorta-inferior vena cava fistula rat HF model. miR-340 and CT-1 were found to be up-regulated in the left ventricle. Dystrophin (DMD), a putative target gene of miR-340 which is eccentric hypertrophy-susceptible, was decreased in this HF model upon Western blotting and immunohistochemistry tests. Luciferase assay constructed in two seed sequence of DMD gene 3'UTR showed decreased luciferase activities, and miR-340 transfected cells resulted in the degradation of DMD.miR-340 is a pro-eccentric hypertrophy miRNA, and its expression is dependent on volume overload and cytokine CT-1 activation. Cardiomyocyte structure protein DMD is a target of miR-340.

  14. Information Extraction and Interpretation Analysis of Mineral Potential Targets Based on ETM+ Data and GIS technology: A Case Study of Copper and Gold Mineralization in Burma

    Science.gov (United States)

    Wenhui, Du; Gongwen, Wang; Yongqing, Chen; Nana, Guo; Yinglong, Hao; Pengfei, Zhao

    2014-03-01

    Mineralization-alteration and structure information extraction plays important roles in mineral resource prospecting and assessment using remote sensing data and the Geographical Information System (GIS) technology. Choosing copper and gold mines in Burma as example, the authors adopt band ratio, threshold segmentation and principal component analysis (PCA) to extract the hydroxyl alteration information using ETM+ remote sensing images. Digital elevation model (DEM) (30m spatial resolution) and ETM+ data was used to extract linear and circular faults that are associated with copper and gold mineralization. Combining geological data and the above information, the weights of evidence method and the C-A fractal model was used to integrate and identify the ore-forming favourable zones in this area. Research results show that the high grade potential targets are located with the known copper and gold deposits, and the integrated information can be used to the next exploration for the mineral resource decision-making.

  15. Production of copper-64 and gallium-68 with a medical cyclotron using liquid targets

    Science.gov (United States)

    Alves, F.; Alves, V. H. P.; Do Carmo, S. J. C.; Neves, A. C. B.; Silva, M.; Abrunhosa, A. J.

    2017-06-01

    This work describes the production of two clinically relevant metal radioisotopes 64Cu and 68Ga with a medical cyclotron by the irradiation of liquid targets. New results are presented for the implementation of this methodology in a fully automated system, using commercially available equipment. Liquid target solutions containing enriched 64Ni and 68Zn were loaded, bombarded and transferred to synthesis modules where a purified solution containing the desired radiometal is obtained and can then be used to further radiolabeling within only one hour after End-Of-Bombardment (EOB). Typical production runs using enriched material lead to the production of 5 GBq and 6 GBq (0.14 MBq/(μAh ṡ mg) and 1.5 MBq/(μAh ṡ mg)) of 64Cu and 68Ga; although the technique can be used to obtain up to 25 GBq and 40 GBq, respectively, by simply scaling up the amount of the enriched material. Purified solutions containing 64Cu and 68Ga were obtained within 30 min after EOB and used to produce 64Cu-ATSM and 68Ga-DOTA-NOC, respectively, with quality parameters suitable for human use.

  16. Biotin Decorated Gold Nanoparticles for Targeted Delivery of a Smart-Linked Anticancer Active Copper Complex: In Vitro and In Vivo Studies.

    Science.gov (United States)

    Pramanik, Anup K; Siddikuzzaman; Palanimuthu, Duraippandi; Somasundaram, Kumaravel; Samuelson, Ashoka G

    2016-12-21

    The synthesis and anticancer activity of a copper(II) diacetyl-bis(N4-methylthiosemicarbazone) complex and its nanoconjugates are reported. The copper(II) complex is connected to a carboxylic acid group through a cleavable disulfide link to enable smart delivery. The copper complex is tethered to highly water-soluble 20 nm gold nanoparticles (AuNPs), stabilized by amine terminated lipoic acid-polyethylene glycol (PEG). The gold nanoparticle carrier was further decorated with biotin to achieve targeted action. The copper complex and the conjugates with and without biotin, were tested against HeLa and HaCaT cells. They show very good anticancer activity against HeLa cells, a cell line derived from cervical cancer and are less active against HaCaT cells. Slow and sustained release of the complex from conjugates is demonstrated through cleavage of disulfide linker in the presence of glutathione (GSH), a reducing agent intrinsically present in high concentrations within cancer cells. Biotin appended conjugates do not show greater activity than conjugates without biotin against HeLa cells. This is consistent with drug uptake studies, which suggests similar uptake profiles for both conjugates in vitro. However, in vivo studies using a HeLa cell xenograft tumor model shows 3.8-fold reduction in tumor volume for the biotin conjugated nanoparticle compared to the control whereas the conjugate without biotin shows only 2.3-fold reduction in the tumor volume suggesting significant targeting.

  17. 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.

  18. Rapid and ultrasensitive detection of microRNA by target-assisted isothermal exponential amplification coupled with poly (thymine)-templated fluorescent copper nanoparticles

    Science.gov (United States)

    Park, Kwan Woo; Batule, Bhagwan S.; Kang, Kyoung Suk; Park, Ki Soo; Park, Hyun Gyu

    2016-10-01

    We devised a novel method for rapid and ultrasensitive detection of target microRNA (miRNA) by employing target-assisted isothermal exponential amplification (TAIEA) combined with poly (thymine)-templated fluorescent copper nanoparticles (CuNPs) as signaling probes. The target miRNA hybridizes to the unimolecular template DNA and works as a primer for the extension reaction to form double-stranded product, which consequently generates two nicking endonuclease recognition sites. By simultaneous nicking and displacement reactions, exponential amplification generates many poly (thymine) strands as final products, which are employed for the synthesis of fluorescent CuNPs. Based on the fluorescent signal from CuNPs, target miRNA is detected as low as 0.27 fM around 1 h of total analysis time. The diagnostic capability of this system has been successfully demonstrated by reliably detecting target miRNA from different cell lysates, showing its great potential towards real clinical applications.

  19. Effects of inhibitors of vascular endothelial growth factor receptor 2 and downstream pathways of receptor tyrosine kinases involving phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin or mitogen-activated protein kinase in canine hemangiosarcoma cell lines.

    Science.gov (United States)

    Adachi, Mami; Hoshino, Yuki; Izumi, Yusuke; Sakai, Hiroki; Takagi, Satoshi

    2016-07-01

    Canine hemangiosarcoma (HSA) is a progressive malignant neoplasm with no current effective treatment. Previous studies showed that receptor tyrosine kinases and molecules within their downstream pathways involving phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (m-TOR) or mitogen-activated protein kinase (MAPK) were overexpressed in canine, human, and murine tumors, including HSA. The present study investigated the effects of inhibitors of these pathways in canine splenic and hepatic HSA cell lines using assays of cell viability and apoptosis. Inhibitors of the MAPK pathway did not affect canine HSA cell viability. However, cell viability was significantly reduced by exposure to inhibitors of vascular endothelial growth factor receptor 2 and the PI3K/Akt/m-TOR pathway; these inhibitors also induced apoptosis in these cell lines. These results suggest that these inhibitors reduce the proliferation of canine HSA cells by inducing apoptosis. Further study of these inhibitors, using xenograft mouse models of canine HSA, are warranted to explore their potential for clinical application.

  20. Alterations in the synthesis of IL-1β, TNF-α, IL-6 and their downstream targets RANKL and OPG by mouse calvarial osteoblasts in vitro: inhibition of bone resorption by cyclic mechanical strain

    Directory of Open Access Journals (Sweden)

    Salvador eGarcía-López

    2013-10-01

    Full Text Available Mechanical strain is an important determinant of bone mass and architecture, and the aim of this investigation was to further understand the role of the cell-cell signalling molecules, IL1-β, TNF-α and IL-6 in the mechanobiology of bone. Mouse calvarial osteoblasts in monolayer culture were subjected to a cyclic out-of-plane deformation of 0.69% for 6 s, every 90 s for 2‒48 h, and the levels of each cytokine plus their downstream targets RANKL and OPG measured in culture supernatants by ELISAs. Mouse osteoblasts constitutively synthesized IL-1β, TNF-α and IL-6, the production of which was significantly up-regulated in all three by cyclic mechanical strain. RANKL and OPG were also constitutively synthesized; mechanical deformation however, resulted in a down-regulation of RANKL and an up-regulation OPG synthesis. We next tested whether the immunoreactive RANKL and OPG were biologically active in an isolated osteoclast resorption pit assay - this showed that culture supernatants from mechanically-deformed cells significantly inhibited osteoclast-mediated resorptive activity across the 48 h time-course. These findings are counterintuitive, because IL-1β, TNF-α and IL-6 have well-established reputations as bone resorptive agents. Nevertheless, they are pleiotropic molecules with multiple biological activities, underlining the complexity of the biological response of osteoblasts to mechanical deformation, and the need to understand cell-cell signalling in terms of cytokine networks. It is also important to recognize that osteoblasts cultured in vitro are deprived of the mechanical stimuli to which they are exposed in vivo - in other words, the cells are in a physiological default state that in the intact skeleton leads to decreased bone strains below the critical threshold required to maintain normal bone structure.

  1. ανβ3-targeted Copper Nanoparticles Incorporating an Sn 2 Lipase-Labile Fumagillin Prodrug for Photoacoustic Neovascular Imaging and Treatment

    Science.gov (United States)

    Zhang, Ruiying; Pan, Dipanjan; Cai, Xin; Yang, Xiaoxia; Senpan, Angana; Allen, John S.; Lanza, Gregory M.; Wang, Lihong V.

    2015-01-01

    Photoacoustic (PA) tomography enables multiscale, multicontrast and high-resolution imaging of biological structures. In particular, contrast-enhanced PA imaging offers high-sensitivity noninvasive imaging of neovessel sprout formation and nascent tubules, which are important biomarkers of malignant tumors and progressive atherosclerotic disease. While gold nanoparticles or nanorods have been used as PA contrast agents, we utilized high-density copper oleate small molecules encapsulated within a phospholipid surfactant (CuNPs) to generate a soft nanoparticle with PA contrast comparable to that from gold. Within the NIR window, the copper nanoparticles provided a 4-fold higher signal than that of blood. ανβ3-integrin targeting of CuNPs in a MatrigelTM angiogenesis mouse model demonstrated prominent (p<0.05) PA contrast enhancement of the neovasculature compared with mice given nontargeted or competitively inhibited CuNPs. Furthermore, incorporation of a Sn 2 lipase-labile fumagillin prodrug into the CuNP outer lipid membrane produced marked antiangiogenesis in the same model when targeted to the ανβ3-integrin, providing proof of concept in vivo for the first targeted PA - drug delivery agent. PMID:25553103

  2. DARHT-II Downstream Beam Transport Beamline

    Energy Technology Data Exchange (ETDEWEB)

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

    2000-08-01

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

  3. Site-specific antibody-liposome conjugation through copper-free click chemistry: a molecular biology approach for targeted photodynamic therapy (Conference Presentation)

    Science.gov (United States)

    Obaid, Girgis; Wang, Yucheng; Kuriakose, Jerrin; Broekgaarden, Mans; Alkhateeb, Ahmed; Bulin, Anne-Laure; Hui, James; Tsourkas, Andrew; Hasan, Tayyaba

    2016-03-01

    Nanocarriers, such as liposomes, have the ability to potentiate photodynamic therapy (PDT) treatment regimens by the encapsulation of high payloads of photosensitizers and enhance their passive delivery to tumors through the enhanced permeability and retention effect. By conjugating targeting moieties to the surface of the liposomal nanoconstructs, cellular selectivity is imparted on them and PDT-based therapies can be performed with significantly higher dose tolerances, as off-target toxicity is simultaneously reduced.1 However, the maximal benefits of conventional targeted nanocarriers, including liposomes, are hindered by practical limitations including chemical instability, non-selective conjugation chemistry, poor control over ligand orientation, and loss of ligand functionality following conjugation, amongst others.2 We have developed a robust, physically and chemically stable liposomal nanoplatform containing benzoporphyrin derivative photosensitizer molecules within the phospholipid bilayer and an optimized surface density of strained cyclooctyne moieties for `click' conjugation to azido-functionalized antibodies.3 The clinical chimeric anti-EGFR antibody Cetuximab is site-specifically photocrosslinked to a recombinant bioengineered that recognizes the antibody's Fc region, containing a terminal azide.4 The copper-free click conjugation of the bioengineered Cetuximab derivative to the optimized photosensitizing liposome provides exceptional control over the antibody's optimal orientation for cellular antigen binding. Importantly, the reaction occurs rapidly under physiological conditions, bioorthogonally (selectively in the presence of other biomolecules) and without the need for toxic copper catalysis.3 Such state-of-the-art conjugation strategies push the boundaries of targeted photodynamic therapy beyond the limitations of traditional chemical coupling techniques to produce more robust and effective targeted therapeutics with applications beyond

  4. Numerical simulations of energy deposition caused by 50 MeV—50 TeV proton beams in copper and graphite targets

    Directory of Open Access Journals (Sweden)

    Y. Nie

    2017-08-01

    Full Text Available The conceptual design of the Future Circular Collider (FCC is being carried out actively in an international collaboration hosted by CERN, for the post–Large Hadron Collider (LHC era. The target center-of-mass energy of proton-proton collisions for the FCC is 100 TeV, nearly an order of magnitude higher than for LHC. The existing CERN accelerators will be used to prepare the beams for FCC. Concerning beam-related machine protection of the whole accelerator chain, it is critical to assess the consequences of beam impact on various accelerator components in the cases of controlled and uncontrolled beam losses. In this paper, we study the energy deposition of protons in solid copper and graphite targets, since the two materials are widely used in magnets, beam screens, collimators, and beam absorbers. Nominal injection and extraction energies in the hadron accelerator complex at CERN were selected in the range of 50 MeV–50 TeV. Three beam sizes were studied for each energy, corresponding to typical values of the betatron function. Specifically for thin targets, comparisons between fluka simulations and analytical Bethe equation calculations were carried out, which showed that the damage potential of a few-millimeter-thick graphite target and submillimeter-thick copper foil can be well estimated directly by the Bethe equation. The paper provides a valuable reference for the quick evaluation of potential damage to accelerator elements over a large range of beam parameters when beam loss occurs.

  5. Estimating the Causal Impact of Proximity to Gold and Copper Mines on Respiratory Diseases in Chilean Children: An Application of Targeted Maximum Likelihood Estimation

    Directory of Open Access Journals (Sweden)

    Ronald Herrera

    2017-12-01

    Full Text Available In a town located in a desert area of Northern Chile, gold and copper open-pit mining is carried out involving explosive processes. These processes are associated with increased dust exposure, which might affect children’s respiratory health. Therefore, we aimed to quantify the causal attributable risk of living close to the mines on asthma or allergic rhinoconjunctivitis risk burden in children. Data on the prevalence of respiratory diseases and potential confounders were available from a cross-sectional survey carried out in 2009 among 288 (response: 69 % children living in the community. The proximity of the children’s home addresses to the local gold and copper mine was calculated using geographical positioning systems. We applied targeted maximum likelihood estimation to obtain the causal attributable risk (CAR for asthma, rhinoconjunctivitis and both outcomes combined. Children living more than the first quartile away from the mines were used as the unexposed group. Based on the estimated CAR, a hypothetical intervention in which all children lived at least one quartile away from the copper mine would decrease the risk of rhinoconjunctivitis by 4.7 percentage points (CAR: − 4.7 ; 95 % confidence interval ( 95 % CI: − 8.4 ; − 0.11 ; and 4.2 percentage points (CAR: − 4.2 ; 95 % CI: − 7.9 ; − 0.05 for both outcomes combined. Overall, our results suggest that a hypothetical intervention intended to increase the distance between the place of residence of the highest exposed children would reduce the prevalence of respiratory disease in the community by around four percentage points. This approach could help local policymakers in the development of efficient public health strategies.

  6. Abnormal Copper Homeostasis: Mechanisms and Roles in Neurodegeneration

    OpenAIRE

    Mario Manto

    2014-01-01

    As a cofactor of proteins and enzymes involved in critical molecular pathways in mammals and low eukaryotes, copper is a transition metal essential for life. The intra-cellular and extra-cellular metabolism of copper is under tight control, in order to maintain free copper concentrations at very low levels. Copper is a critical element for major neuronal functions, and the central nervous system is a major target of disorders of copper metabolism. Both the accumulation of copper and copper d...

  7. Interaction of Super Proton Synchrotron beam with solid copper target: Simulations of future experiments at HiRadMat facility at CERN

    CERN Document Server

    Tahir, N A; Brugger, M; Assmann, R; Shutov, A; Lomonosov, I V; Fortov, V E; Piriz, A R; Deutsch, C; Hoffmann, D H H

    2009-01-01

    In this paper we present numerical simulations of interaction of 450 GeV/c proton beam that is generated by Super Proton Synchrotron (SPS) at CERN, with a solid copper target. These simulations have been carried out using a two-dimensional hydrodynamic computer code, BIG2. This study has been done to assess the damage caused by these highly relativistic protons to equipment including collimators, absorbers and others in case of an uncontrolled accidental release of the beam. In fact a dedicated experimental facility named HiRadMat is under construction at CERN that will allow one to study these problems experimentally. The simulations presented in this paper will be very useful in designing these experiments and later to interpret the experimental results.

  8. Protons and electrons generated from a 5-{mu}m thick copper tape target irradiated by s-, circularly-, and p-polarized 55-fs laser pulses

    Energy Technology Data Exchange (ETDEWEB)

    Li, Z. [Advanced Photon Research Center, Japan Atomic Energy Agency, Umeimidai 8-1, Kizu, Kyoto 619-0215 (Japan); National Institute of Radiological Sciences, Anagawa 4-9-1, Inage, Chiba 263-8555 (Japan)], E-mail: lizhong@sinap.ac.cn; Daido, H. [Advanced Photon Research Center, Japan Atomic Energy Agency, Umeimidai 8-1, Kizu, Kyoto 619-0215 (Japan); Fukumi, A. [Advanced Photon Research Center, Japan Atomic Energy Agency, Umeimidai 8-1, Kizu, Kyoto 619-0215 (Japan); National Institute of Radiological Sciences, Anagawa 4-9-1, Inage, Chiba 263-8555 (Japan); Bulanov, S.V.; Sagisaka, A.; Ogura, K.; Yogo, A.; Nishiuchi, M.; Orimo, S.; Mori, M. [Advanced Photon Research Center, Japan Atomic Energy Agency, Umeimidai 8-1, Kizu, Kyoto 619-0215 (Japan); Oishi, Y.; Nayuki, T.; Fujii, T.; Nemoto, K. [Central Research Institute of Electric Power Industry, Nagasaka 2-6-1, Yokosuka, Kanagawa 240-0196 (Japan); Nakamura, S.; Noda, A. [Institute of Chemical Research, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan); Choi, I.W.; Sung, J.H.; Ko, D.-K.; Lee, J. [Advanced Photonics Research Institute, Gwangju Institute of Science and Technology, Gwangju 500-712 (Korea, Republic of)

    2007-10-01

    The angular distribution and energy spectra of energetic protons emitted from a 5-{mu}m thick copper tape target irradiated by p-, circularly-, and s-polarized 55-fs laser pulses with intensity of 8-9x10{sup 18} W/cm{sup 2} are measured. The protons are found in the rear target normal direction while the hot electrons are found in the laser propagation direction. The maximum energy of protons is equal to 1.34 MeV for p-polarized irradiation. The energy spectrum of protons depends strongly on the total amount of electrons but it does not so strongly depend on the electron angular distribution under our experiment conditions. Two-dimensional particle in cell simulations also show the maximal proton acceleration for the p-polarized pulse, less efficient acceleration for the circular polarization, and lower acceleration efficiency in the case of the s-polarization, which is related to the electron acceleration efficiency at the front side of the target.

  9. Copper transport.

    Science.gov (United States)

    Linder, M C; Wooten, L; Cerveza, P; Cotton, S; Shulze, R; Lomeli, N

    1998-05-01

    In adult humans, the net absorption of dietary copper is approximately 1 mg/d. Dietary copper joins some 4-5 mg of endogenous copper flowing into the gastrointestinal tract through various digestive juices. Most of this copper returns to the circulation and to the tissues (including liver) that formed them. Much lower amounts of copper flow into and out of other major parts of the body (including heart, skeletal muscle, and brain). Newly absorbed copper is transported to body tissues in two phases, borne primarily by plasma protein carriers (albumin, transcuprein, and ceruloplasmin). In the first phase, copper goes from the intestine to the liver and kidney; in the second phase, copper usually goes from the liver (and perhaps also the kidney) to other organs. Ceruloplasmin plays a role in this second phase. Alternatively, liver copper can also exit via the bile, and in a form that is less easily reabsorbed. Copper is also present in and transported by other body fluids, including those bathing the brain and central nervous system and surrounding the fetus in the amniotic sac. Ceruloplasmin is present in these fluids and may also be involved in copper transport there. The concentrations of copper and ceruloplasmin in milk vary with lactational stage. Parallel changes occur in ceruloplasmin messenger RNA expression in the mammary gland (as determined in pigs). Copper in milk ceruloplasmin appears to be particularly available for absorption, at least in rats.

  10. Numerical simulations of energy deposition caused by 50 MeV—50 TeV proton beams in copper and graphite targets

    CERN Document Server

    Nie, Y; Chetvertkova, V; Rosell-Tarrago, G; Burkart, F; Wollmann, D

    2017-01-01

    The conceptual design of the Future Circular Collider (FCC) is being carried out actively in an international collaboration hosted by CERN, for the post–Large Hadron Collider (LHC) era. The target center-of-mass energy of proton-proton collisions for the FCC is 100 TeV, nearly an order of magnitude higher than for LHC. The existing CERN accelerators will be used to prepare the beams for FCC. Concerning beam-related machine protection of the whole accelerator chain, it is critical to assess the consequences of beam impact on various accelerator components in the cases of controlled and uncontrolled beam losses. In this paper, we study the energy deposition of protons in solid copper and graphite targets, since the two materials are widely used in magnets, beam screens, collimators, and beam absorbers. Nominal injection and extraction energies in the hadron accelerator complex at CERN were selected in the range of 50 MeV–50 TeV. Three beam sizes were studied for each energy, corresponding to typical values ...

  11. DARHT-II Downstream Transport Beamline

    Energy Technology Data Exchange (ETDEWEB)

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

    2001-06-06

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

  12. Copper hypersensitivity

    DEFF Research Database (Denmark)

    Fage, Simon W; Faurschou, Annesofie; Thyssen, Jacob P

    2014-01-01

    hypersensitivity, a database search of PubMed was performed with the following terms: copper, dermatitis, allergic contact dermatitis, contact hypersensitivity, contact sensitization, contact allergy, patch test, dental, IUD, epidemiology, clinical, and experimental. Human exposure to copper is relatively common...

  13. Large-angle production of charged pions by 3 GeV/c - 12 GeV/c protons on carbon, copper and tin targets

    CERN Document Server

    Catanesi, M.G.; Ellis, Malcolm; Robbins, S.; Soler, F.J.P.; Gossling, C.; Bunyatov, S.; Krasnoperov, A.; Popov, B.; Serdiouk, V.; Tereschenko, V.; Di Capua, E.; Vidal-Sitjes, G.; Artamonov, A.; Arce, P.; Giani, S.; Gilardoni, S.; Gorbunov, P.; Grant, A.; Grossheim, A.; Gruber, P.; Ivanchenko, V.; Kayis-Topaksu, A.; Panman, J.; Papadopoulos, I.; Pasternak, J.; Tcherniaev, E.; Tsukerman, I.; Veenhof, R.; Wiebusch, C.; Zucchelli, P.; Blondel, A.; Borghi, S.; Campanelli, M.; Morone, M.C.; Prior, G.; Schroeter, R.; Engel, R.; Meurer, C.; Kato, I.; Gastaldi, U.; Mills, G.B.; Graulich, J.S.; Gregoire, G.; Bonesini, M.; Ferri, F.; Paganoni, M.; Paleari, F.; Kirsanov, M.; Bagulya, A.; Grichine, V.; Polukhina, M.; Palladino, V.; Coney, L.; Schmitz, D.; Barr, G.; De Santo, A.; Pattison, C.; Zuber, K.; Bobisut, F.; Gibin, D.; Guglielmi, A.; Mezzetto, M.; Dumarchez, J.; Vannucci, F.; Dore, U.; Orestano, D.; Pastore, F.; Tonazzo, A.; Tortora, L.; Booth, C.; Buttar, C.; Hodgson, P.; howlett, L.; Bogomilov, M.; Chizhov, M.; Kolev, D.; Tsenov, R.; Piperov, Stefan; Temnikov, P.; Apollonio, M.; Chimenti, P.; Giannini, G.; Santin, G.; Burguet-Castell, J.; Cervera-Villanueva, A.; Gomez-Cadenas, J.J.; Martin-Albo, J.; Novella, P.; Sorel, M.; Tornero, A.

    2008-01-01

    A measurement of the double-differential $\\pi^{\\pm}$ production cross-section in proton--carbon, proton--copper and proton--tin collisions in the range of pion momentum $100 \\MeVc \\leq p < 800 \\MeVc$ and angle $0.35 \\rad \\le \\theta <2.15 \\rad$ is presented. The data were taken with the HARP detector in the T9 beam line of the CERN PS. The pions were produced by proton beams in a momentum range from 3 \\GeVc to 12 \\GeVc hitting a target with a thickness of 5% of a nuclear interaction length. The tracking and identification of the produced particles was done using a small-radius cylindrical time projection chamber (TPC) placed in a solenoidal magnet. An elaborate system of detectors in the beam line ensured the identification of the incident particles. Results are shown for the double-differential cross-sections at four incident proton beam momenta (3 \\GeVc, 5 \\GeVc, 8 \\GeVc and 12 \\GeVc).

  14. Extensive Literature Search on the “Effects of Copper intake levels in the gut microbiota profile of target animals, in particular piglets"

    DEFF Research Database (Denmark)

    Jensen, Bent Borg

    . The overallconclusion from the studies with piglets and growing pigs is that copper, even at low concentrations(coliform bacteria seems to be affected by low copper concentrations...... and coliform bacteria, to reduce the pH in gizzard content and to producesevere gizzard erosion...

  15. 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)

  16. Auxin perception and downstream events.

    Science.gov (United States)

    Strader, Lucia C; Zhao, Yunde

    2016-10-01

    Auxin responses have been arbitrarily divided into two categories: genomic and non-genomic effects. Genomic effects are largely mediated by SCFTIR1/AFB-Aux/IAA auxin receptor complexes whereas it has been postulated that AUXIN BINDING PROTEIN 1 (ABP1) controls the non-genomic effects. However, the roles of ABP1 in auxin signaling and plant development were recently called into question. In this paper, we present recent progress in understanding the SCFTIR1/AFB-Aux/IAA pathway. In more detail, we discuss the current understanding of ABP1 research and provide an updated view of ABP1-related genetic materials. Further, we propose a model in which auxin efflux carriers may play a role in auxin perception and we briefly describe recent insight on processes downstream of auxin perception. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Copper (II)

    African Journals Online (AJOL)

    CLEMENT O BEWAJI

    ABSTRACT: A Schiff base was prepared from the reaction of 2 - amino - 3 – methylbutanoic acid and 2, 4 - pentanedione. The reaction of the prepared Schiff base with ethanolic solution of copper (II) chloride formed diaquo bis( N – 2 – amino – 3 - methylbutyl - 2, 4 - pentanedionato) copper (II) complex. The Schiff base is ...

  18. 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.

  19. The link between copper and Wilson's disease.

    Science.gov (United States)

    Purchase, Rupert

    2013-01-01

    Wilson's disease (hepatolenticular degeneration) is a rare inherited autosomal recessive disorder of copper metabolism leading to copper accumulation in the liver and extrahepatic organs such as the brain and cornea. Patients may present with combinations of hepatic, neurological and psychiatric symptoms. Copper is the therapeutic target for the treatment of Wilson's disease. But how did copper come to be linked with Wilson's disease? The answer encompasses a study of enzootic neonatal ataxia in lambs in the 1930s, the copper-chelating properties of British Anti-Lewisite, and the chemical analysis for copper of the organs of deceased Wilson's disease patients in the mid-to-late 1940s. Wilson's disease is one of a number of copper-related disorders where loss of copper homeostasis as a result of genetic, nutritional or environmental factors affects human health.

  20. Targeting copper(II)-induced oxidative stress and the acetylcholinesterase system in Alzheimer's disease using multifunctional tacrine-coumarin hybrid molecules.

    Science.gov (United States)

    Hamulakova, Slavka; Poprac, Patrik; Jomova, Klaudia; Brezova, Vlasta; Lauro, Peter; Drostinova, Lenka; Jun, Daniel; Sepsova, Vendula; Hrabinova, Martina; Soukup, Ondrej; Kristian, Pavol; Gazova, Zuzana; Bednarikova, Zuzana; Kuca, Kamil; Valko, Marian

    2016-08-01

    Alzheimer's disease is a multifactorial disease that is characterized mainly by Amyloid-β (A-β) deposits, cholinergic deficit and extensive metal (copper, iron)-induced oxidative stress. In this work we present details of the synthesis, antioxidant and copper-chelating properties, DNA protection study, cholinergic activity and amyloid-antiaggregation properties of new multifunctional tacrine-7-hydroxycoumarin hybrids. The mode of interaction between copper(II) and hybrids and interestingly, the reduction of Cu(II) to Cu(I) species (for complexes Cu-5e-g) were confirmed by EPR measurements. EPR spin trapping on the model Fenton reaction, using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin trap, demonstrated a significantly suppressed formation of hydroxyl radicals for the Cu-5e complex in comparison with free copper(II). This suggests that compound 5e upon coordination to free copper ion prevents the Cu(II)-catalyzed decomposition of hydrogen peroxide, which in turn may alleviate oxidative stress-induced damage. Protective activity of hybrids 5c and 5e against DNA damage in a Fenton system (copper catalyzed) was found to be in excellent agreement with the EPR spin trapping study. Compound 5g was the most effective in the inhibition of acetylcholinesterase (hAChE, IC50=38nM) and compound 5b was the most potent inhibitor of butyrylcholinesterase (hBuChE, IC50=63nM). Compound 5c was the strongest inhibitor of A-β1-40 aggregation, although a significant inhibition (>50%) was detected for compounds 5b, 5d, 5e and 5g. Collectively, these results suggest that the design and investigation of multifunctional agents containing along with the acetylcholinesterase inhibitory segment also an antioxidant moiety capable of alleviating metal (copper)-induced oxidative stress, may be of importance in the treatment of Alzheimer's disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. The Intestinal Copper Exporter CUA-1 Is Required for Systemic Copper Homeostasis in Caenorhabditis elegans.

    Science.gov (United States)

    Chun, Haarin; Sharma, Anuj Kumar; Lee, Jaekwon; Chan, Jefferson; Jia, Shang; Kim, Byung-Eun

    2017-01-06

    Copper plays key catalytic and regulatory roles in biochemical processes essential for normal growth, development, and health. Defects in copper metabolism cause Menkes and Wilson's disease, myeloneuropathy, and cardiovascular disease and are associated with other pathophysiological states. Consequently, it is critical to understand the mechanisms by which organisms control the acquisition, distribution, and utilization of copper. The intestinal enterocyte is a key regulatory point for copper absorption into the body; however, the mechanisms by which intestinal cells transport copper to maintain organismal copper homeostasis are poorly understood. Here, we identify a mechanism by which organismal copper homeostasis is maintained by intestinal copper exporter trafficking that is coordinated with extraintestinal copper levels in Caenorhabditis elegans Specifically, we show that CUA-1, the C. elegans homolog of ATP7A/B, localizes to lysosome-like organelles (gut granules) in the intestine under copper overload conditions for copper detoxification, whereas copper deficiency results in a redistribution of CUA-1 to basolateral membranes for copper efflux to peripheral tissues. Worms defective in gut granule biogenesis exhibit defects in copper sequestration and increased susceptibility to toxic copper levels. Interestingly, however, a splice isoform CUA-1.2 that lacks a portion of the N-terminal domain is targeted constitutively to the basolateral membrane irrespective of dietary copper concentration. Our studies establish that CUA-1 is a key intestinal copper exporter and that its trafficking is regulated to maintain systemic copper homeostasis. C. elegans could therefore be exploited as a whole-animal model system to study regulation of intra- and intercellular copper trafficking pathways. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Copper Test

    Science.gov (United States)

    ... Pregnancy hCG Tumor Marker HDL Cholesterol Heavy Metals Helicobacter pylori Testing Hematocrit Hemoglobin Hemoglobin A1c Hemoglobinopathy Evaluation ... or trying to get more copper in my diet? In most cases, a regular diet satisfies the ...

  3. Studies of copper transport in mammalian cells using copper radioisotopes

    Energy Technology Data Exchange (ETDEWEB)

    Camakaris, J.; Voskoboinik, I.; Brooks, H.; Greenough, M. [University of Melbourne, Parkville, VIC (Australia). Department of Genetics; Smith, S. [Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW (Australia). Radiopharmaceuticals Division; Mercer, J. [Deakin University, Clayton, VIC (Australia). Centre of Cellular and Molecular Biology

    1998-12-31

    The trace element copper poses a major problem for all organisms. It is essential as a number of vital enzymes require it. Copper deficiency can lead to neurological disorders, osteoporosis and weakening of arteries. However Cu is also highly toxic and homeostatic mechanisms have evolved to maintain Cu at levels which satisfy requirements but do not cause toxicity. Toxicity is mediated by the oxidative capacity of Cu and its ability to generate toxic free radicals. There are several acquired and inherited diseases due to either Cu toxicity or Cu deficiency. The study of these diseases facilitates identification of genes and proteins involved in copper homeostasis, and this in turn will provide rational therapeutic approaches. Using the copper radioisotopes {sup 64}Cu (t1/2 = 12.8 hr) and {sup 67}Cu (t1/2 = 61 hr) we have developed a number of systems for studying copper transport in mammalian cells. These include investigation of copper uptake, copper efflux and ligand blot assays for Cu-binding proteins. Our studies have focused on Menkes disease which is an inherited and usually lethal copper deficiency disorder in humans. We have demonstrated that the Menkes protein is directly involved as a copper efflux pump in mammalian cells. Using cells overexpressing the Menkes protein we have provided the first biochemical evidence that this functions as a Cu translocating (across the membrane) P-type ATPase (Voskoboinik et al., FEBS Letters, in press). These studies were carried out using purified plasma membrane vesicles. We are now carrying out structure- function studies on this protein using targeted mutations and assaying using the radiocopper vesicle assay. Recently we have commenced studies on the role of amyloid precursor protein (APP) in copper transport and relationship of this to Alzheimers disease

  4. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2002-07-15

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

  6. Thin films preparation by rf-sputtering of copper/iron ceramic targets with Cu/Fe=1: From nanocomposites to delafossite compounds

    OpenAIRE

    Mugnier, Emmanuelle; Barnabé, Antoine; Presmanes, Lionel; Tailhades, Philippe

    2008-01-01

    In the Cu–Fe–O phase diagram, delafossite CuFeO2 is obtained for the CuI oxidation state and for the Cu/Fe=1 ratio. By decreasing the oxygen content, copper/spinel oxide composite can be obtained because of the reduction and the disproponation of cuprous ions. Many physical properties as for instance, electrical, optical, catalytic properties can then be affected by the control of the oxygen stoichiometry. In rf-sputtering technique, the bombardment energies on the substrate can be c...

  7. Copper metallothioneins.

    Science.gov (United States)

    Calvo, Jenifer; Jung, Hunmin; Meloni, Gabriele

    2017-04-01

    Metallothioneins (MTs) are a class of low molecular weight and cysteine-rich metal binding proteins present in all the branches of the tree of life. MTs efficiently bind with high affinity several essential and toxic divalent and monovalent transition metals by forming characteristic polynuclear metal-thiolate clusters within their structure. MTs fulfil multiple biological functions related to their metal binding properties, with essential roles in both Zn(II) and Cu(I) homeostasis as well as metal detoxification. Depending on the organism considered, the primary sequence, and the specific physiological and metabolic status, Cu(I)-bound MT isoforms have been isolated, and their chemistry and biology characterized. Besides the recognized role in the biochemistry of divalent metals, it is becoming evident that unique biological functions in selectively controlling copper levels, its reactivity as well as copper-mediated biochemical processes have evolved in some members of the MT superfamily. Selected examples are reviewed to highlight the peculiar chemical properties and biological functions of copper MTs. © 2016 IUBMB Life, 69(4):236-245, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

  8. 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.

  9. Downstream bioprocess characterisation within microfluidic devices

    DEFF Research Database (Denmark)

    Marques, Marco; Krühne, Ulrich; Szita, Nicolas

    2016-01-01

    Miniaturising bioprocess unit operation steps is a well-established approach to find novel routes for process intensification and improved process economics. While a number of microbioreactors have been presented over the last 15 years, miniaturised downstream unit operations (mDUO) are less...

  10. Measuring Iranian Petroleum Downstream Supply Chain Management Performance; : A Combination of Analytical Hierarchy Process and Balance Score Card

    OpenAIRE

    Norouzi, Saba

    2013-01-01

    Petroleum downstream is a strategic and important industry for any nation. It supplies most of transport and travel needs and provides petrochemical business raw material, which is one of the infrastructure industries. Considering the importance of petroleum downstream and due to a very volatile crude and product market, one of the industry’s main targets is to meet customers’ requirements with administrating downstream supply chain efficiently. Supply chain management (SCM) is a strategic to...

  11. Copper and Copper Proteins in Parkinson's Disease

    OpenAIRE

    Sergio Montes; Susana Rivera-Mancia; Araceli Diaz-Ruiz; Luis Tristan-Lopez; Camilo Rios

    2014-01-01

    Copper is a transition metal that has been linked to pathological and beneficial effects in neurodegenerative diseases. In Parkinson’s disease, free copper is related to increased oxidative stress, alpha-synuclein oligomerization, and Lewy body formation. Decreased copper along with increased iron has been found in substantia nigra and caudate nucleus of Parkinson’s disease patients. Copper influences iron content in the brain through ferroxidase ceruloplasmin activity; therefore decreased pr...

  12. A new, simple and precise method for measuring cyclotron proton beam energies using the activity vs. depth profile of zinc-65 in a thick target of stacked copper foils.

    Science.gov (United States)

    Asad, A H; Chan, S; Cryer, D; Burrage, J W; Siddiqui, S A; Price, R I

    2015-11-01

    The proton beam energy of an isochronous 18MeV cyclotron was determined using a novel version of the stacked copper-foils technique. This simple method used stacked foils of natural copper forming 'thick' targets to produce Zn radioisotopes by the well-documented (p,x) monitor-reactions. Primary beam energy was calculated using the (65)Zn activity vs. depth profile in the target, with the results obtained using (62)Zn and (63)Zn (as comparators) in close agreement. Results from separate measurements using foil thicknesses of 100, 75, 50 or 25µm to form the stacks also concurred closely. Energy was determined by iterative least-squares comparison of the normalized measured activity profile in a target-stack with the equivalent calculated normalized profile, using 'energy' as the regression variable. The technique exploits the uniqueness of the shape of the activity vs. depth profile of the monitor isotope in the target stack for a specified incident energy. The energy using (65)Zn activity profiles and 50-μm foils alone was 18.03±0.02 [SD] MeV (95%CI=17.98-18.08), and 18.06±0.12MeV (95%CI=18.02-18.10; NS) when combining results from all isotopes and foil thicknesses. When the beam energy was re-measured using (65)Zn and 50-μm foils only, following a major upgrade of the ion sources and nonmagnetic beam controls the results were 18.11±0.05MeV (95%CI=18.00-18.23; NS compared with 'before'). Since measurement of only one Zn monitor isotope is required to determine the normalized activity profile this indirect yet precise technique does not require a direct beam-current measurement or a gamma-spectroscopy efficiency calibrated with standard sources, though a characteristic photopeak must be identified. It has some advantages over published methods using the ratio of cross sections of monitor reactions, including the ability to determine energies across a broader range and without need for customized beam degraders. Copyright © 2015 Elsevier Ltd. All rights

  13. 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.

  14. Antwerp Copper Plates

    DEFF Research Database (Denmark)

    Wadum, Jørgen

    1999-01-01

    In addition to presenting a short history of copper paintings, topics detail artists’ materials and techniques, as well as aspects of the copper industry, including mining, preparation and trade routes.......In addition to presenting a short history of copper paintings, topics detail artists’ materials and techniques, as well as aspects of the copper industry, including mining, preparation and trade routes....

  15. 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.

  16. Copper and copper proteins in Parkinson's disease.

    Science.gov (United States)

    Montes, Sergio; Rivera-Mancia, Susana; Diaz-Ruiz, Araceli; Tristan-Lopez, Luis; Rios, Camilo

    2014-01-01

    Copper is a transition metal that has been linked to pathological and beneficial effects in neurodegenerative diseases. In Parkinson's disease, free copper is related to increased oxidative stress, alpha-synuclein oligomerization, and Lewy body formation. Decreased copper along with increased iron has been found in substantia nigra and caudate nucleus of Parkinson's disease patients. Copper influences iron content in the brain through ferroxidase ceruloplasmin activity; therefore decreased protein-bound copper in brain may enhance iron accumulation and the associated oxidative stress. The function of other copper-binding proteins such as Cu/Zn-SOD and metallothioneins is also beneficial to prevent neurodegeneration. Copper may regulate neurotransmission since it is released after neuronal stimulus and the metal is able to modulate the function of NMDA and GABA A receptors. Some of the proteins involved in copper transport are the transporters CTR1, ATP7A, and ATP7B and the chaperone ATOX1. There is limited information about the role of those biomolecules in the pathophysiology of Parkinson's disease; for instance, it is known that CTR1 is decreased in substantia nigra pars compacta in Parkinson's disease and that a mutation in ATP7B could be associated with Parkinson's disease. Regarding copper-related therapies, copper supplementation can represent a plausible alternative, while copper chelation may even aggravate the pathology.

  17. Copper and Copper Proteins in Parkinson's Disease

    Science.gov (United States)

    Rivera-Mancia, Susana; Diaz-Ruiz, Araceli; Tristan-Lopez, Luis; Rios, Camilo

    2014-01-01

    Copper is a transition metal that has been linked to pathological and beneficial effects in neurodegenerative diseases. In Parkinson's disease, free copper is related to increased oxidative stress, alpha-synuclein oligomerization, and Lewy body formation. Decreased copper along with increased iron has been found in substantia nigra and caudate nucleus of Parkinson's disease patients. Copper influences iron content in the brain through ferroxidase ceruloplasmin activity; therefore decreased protein-bound copper in brain may enhance iron accumulation and the associated oxidative stress. The function of other copper-binding proteins such as Cu/Zn-SOD and metallothioneins is also beneficial to prevent neurodegeneration. Copper may regulate neurotransmission since it is released after neuronal stimulus and the metal is able to modulate the function of NMDA and GABA A receptors. Some of the proteins involved in copper transport are the transporters CTR1, ATP7A, and ATP7B and the chaperone ATOX1. There is limited information about the role of those biomolecules in the pathophysiology of Parkinson's disease; for instance, it is known that CTR1 is decreased in substantia nigra pars compacta in Parkinson's disease and that a mutation in ATP7B could be associated with Parkinson's disease. Regarding copper-related therapies, copper supplementation can represent a plausible alternative, while copper chelation may even aggravate the pathology. PMID:24672633

  18. [Copper and copper alloys. Technology updates].

    Science.gov (United States)

    Loconsolo, V; Crespi, M

    2012-01-01

    The correlations between copper and copper alloys and human health have been the subject of some recent and extensive scientific researches. The voluntary risks evaluation, which anticipated the EU REACH Directive application, has shown that copper is a "safe" product for human health and for environment. In addition, it could be of great help thanks to its antibacterial properties. Copper tube can contribute in a relevant way to the prevention of water systems pollution by Legionella. Also the spreading of nosocomial infections is significantly contrasted by the use of copper and copper alloys for the production of articles intended for being frequently touched by people. The Environmental Protection Agency of the United States has in fact "registered" as antibacterial over 350 of copper alloys.

  19. Mitochondrial Ferredoxin Determines Vulnerability of Cells to Copper Excess.

    Science.gov (United States)

    Vallières, Cindy; Holland, Sara L; Avery, Simon V

    2017-10-19

    The essential micronutrient copper is tightly regulated in organisms, as environmental exposure or homeostasis defects can cause toxicity and neurodegenerative disease. The principal target(s) of copper toxicity have not been pinpointed, but one key effect is impaired supply of iron-sulfur (FeS) clusters to the essential protein Rli1 (ABCE1). Here, to find upstream FeS biosynthesis/delivery protein(s) responsible for this, we compared copper sensitivity of yeast-overexpressing candidate targets. Overexpression of the mitochondrial ferredoxin Yah1 produced copper hyper-resistance. 55Fe turnover assays revealed that FeS integrity of Yah1 was particularly vulnerable to copper among the test proteins. Furthermore, destabilization of the FeS domain of Yah1 produced copper hypersensitivity, and YAH1 overexpression rescued Rli1 dysfunction. This copper-resistance function was conserved in the human ferredoxin, Fdx2. The data indicate that the essential mitochondrial ferredoxin is an important copper target, determining a tipping point where plentiful copper supply becomes excessive. This knowledge could help in tackling copper-related diseases. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. COPPER-64 Production Studies with Natural Zinc Targets at Deuteron Energy up to 19 Mev and Proton Energy from 141 Down to 31 Mev

    Science.gov (United States)

    Bonardi, Mauro L.; Birattari, Claudio; Groppi, Flavia; Song Mainard, Hae; Zhuikov, Boris L.; Kokhanyuk, Vladimir M.; Lapshina, Elena V.; Mebel, Michail V.; Menapace, Enzo

    2004-07-01

    High specific activity no-carrier-added 64Cu is a β-/β+ emitting radionuclide of increasing interest for PET imaging, as well as systemic and targeted radioimmunotherapy of tumors. Its peculiarity of intense Auger emitter is still under investigation. The cross-sections for production of 64Cu from Zn target of natural isotopic composition were measured in the deuteron energy range from threshold up to 19 MeV and proton energy range from 141 down to 31 MeV. The stacked-foil technique was used at both K=38 cyclotron of JRC-Ispra of CEC, Italy and 160 MeV intersection point of INR proton-LINAC in Troitsk, Russia. Several Ga, Zn, Cu, Ni, Co, V, Fe and Mn radionuclides were detected in Zn targets at the EOB. Optimized irradiation conditions are reported as a function of deuteron energy and energy loss into the Zn target, as well as target irradiation time and cooling time after radiochemistry. The activity of n.c.a. 64Cu was measured through its only γ emission of 1346 keV (i.e. 0.473 % intensity) both by instrumental and radiochemical methods, due to the non-specificity of annihilation radiation at 511 keV. To this last purpose, it was necessary to carry out a selective radiochemical separation of GaIII radionuclides by liquid/liquid extraction from the bulk of irradiated Zn targets and other spallation products, which remained in the 7 M HCl aqueous phase. Anion exchange chromatography tests had been carried out to separate the 64Cu from all others radionuclides in n.c.a. form. Theoretical calculations of cross-sections were performed with codes EMPIRE II and PENELOPE for deuteron reactions and CEF model and HMS-ALICE hybrid model for proton reactions. The theoretical results are presented and compared with the experimental values.

  1. A facile, sensitive, and highly specific trinitrophenol assay based on target-induced synergetic effects of acid induction and electron transfer towards DNA-templated copper nanoclusters.

    Science.gov (United States)

    Li, Haiyin; Chang, Jiafu; Hou, Ting; Ge, Lei; Li, Feng

    2016-11-01

    Reliable, selective and sensitive approaches for trinitrophenol (TNP) detection are highly desirable with respect to national security and environmental protection. Herein, a simple and novel fluorescent strategy for highly sensitive and specific TNP assay has been successfully developed, which is based on the quenching of the fluorescent poly(thymine)-templated copper nanoclusters (DNA-CuNCs), through the synergetic effects of acid induction and electron transfer. Upon the addition of TNP, donor-acceptor complexes between the electron-deficient nitro-groups in TNP and the electron-donating DNA templates are formed, resulting in the close proximity between TNP and CuNCs. Moreover, the acidity of TNP contributes to the pH decrease of the system. These factors combine to dramatically quench the fluorescence of DNA-CuNCs, providing a "signal-off" strategy for TNP sensing. The as-proposed strategy demonstrates high sensitivity for TNP assay, and a detection limit of 0.03μM is obtained, which is lower than those reported by using organic fluorescent materials. More significantly, this approach shows outstanding selectivity over a number of TNP analogues, such as 2,4,6-trinitrotoluene (TNT), 2,4-dinitrotoluene (DNT), 2,4-dinitrophenol (DNP), 3-nitrophenol (NP), nitrobenzene (NB), phenol (BP), and toluene (BT). Compared with previous studies, this method does not need complex DNA sequence design, fluorescent dye labeling, or sophisticated organic reactions, rendering the strategy with additional advantages of simplicity and cost-effectiveness. In addition, the as-proposed strategy has been adopted for the detection of TNP in natural water samples, indicating its great potential to be applied in the fields of public safety and environmental monitoring. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Measurement of the Nuclear Dependence of Direct Photon and Neutral Meson Production at High Transverse Momentum by Negative 515-GeV/c Pions Incident on Beryllium and Copper Targets

    Energy Technology Data Exchange (ETDEWEB)

    Sorrell, Lee Ronald [Michigan State Univ., East Lansing, MI (United States)

    1995-01-01

    The nuclear dependence of inclusive direct photon production and inclusive neutral meson production by a 515 GeV/c $\\pi^-$ beam has been measured using data collected by the E706 experiment during the 19.90 fixed, target run at the Fermi National Accelerator Laboratory. The experiment utilized a finely segmented liquid argon calorimeter and a high precision charged particle spectrometer to make precision measurements of inclusive direct photon, neutral pion, and $\\eta$ production in the rapidity interval from -0.75 < $y$ < 0.75. The $\\pi^0$ data is reported for the $P_T$ range from 0.6 GeV /c to 12 GeV /c, while the $\\eta$ data is reported for the range from 3.5 GeV /c to 7.0 GeV /c. The direct photon nuclear dependence results are reported for the range from approxlmately 4.0 GeV/c to 8.5 GeV/c. The data from the beryllium and copper targets have been fit using the parameterization $\\sigma_A$ = $\\sigma_0$ x $A^{\\alpha}$. The neutral meson results are in good agreement with previous charged meson results. The direct photon results are consistent with no anomalous enhancement.

  3. Copper exposure effects on yeast mitochondrial proteome.

    Science.gov (United States)

    Banci, Lucia; Bertini, Ivano; Ciofi-Baffoni, Simone; D'Alessandro, Annamaria; Jaiswal, Deepa; Marzano, Valeria; Neri, Sara; Ronci, Maurizio; Urbani, Andrea

    2011-10-19

    Mitochondria play an important role on the entire cellular copper homeostatic mechanisms. Alteration of cellular copper levels may thus influence mitochondrial proteome and its investigation represents an important contribution to the general understanding of copper-related cellular effects. In these study we have performed an organelle targeted proteomic investigation focusing our attention on the effect of non-lethal 1mM copper concentration on Saccharomyces cerevisiae mitochondrial proteome. Functional copper effects on yeast mitochondrial proteome were evaluated by using both 2D electrophoresis (2-DE) and liquid chromatography coupled with tandem mass spectrometry. Proteomic data have been then analyzed by different unsupervised meta-analysis approaches that highlight the impairment of mitochondrial functions and the activation of oxidative stress response. Interestingly, our data have shown that stress response generated by 1mM copper treatment determines the activation of S. cerevisiae survival pathway. To investigate these findings we have treated yeast cells responsiveness to copper with hydrogen peroxide and observed a protective role of this metal. These results are suggestive of a copper role in the protection from oxidative stress possibly due to the activation of mechanisms involved in cellular survival and growth. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Copper Resistance of the Emerging Pathogen Acinetobacter baumannii.

    Science.gov (United States)

    Williams, Caitlin L; Neu, Heather M; Gilbreath, Jeremy J; Michel, Sarah L J; Zurawski, Daniel V; Merrell, D Scott

    2016-10-15

    are incredibly limited. Copper is an essential nutrient but becomes toxic at high concentrations. The inherent antimicrobial properties of copper give it potential for use in novel therapeutics against drug-resistant pathogens. We show that A. baumannii clinical isolates are sensitive to copper in vitro, both in liquid and on solid metal surfaces. Since bacterial resistance to copper is mediated though mechanisms of efflux and detoxification, we identified genes encoding putative copper-related proteins in A. baumannii and showed that expression of some of these genes is regulated by the copper concentration. We propose that the antimicrobial effects of copper may be beneficial in the development of future therapeutics that target multidrug-resistant bacteria. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  5. Ion Effects in the DARHT-II Downstream Transport

    CERN Document Server

    Chan, Kwok-Chi D; Ekdahl, Carl; Genoni, Thomas C; Hughes, Thomas P; Schulze, Martin E

    2005-01-01

    The DARHT-II accelerator produces an 18-MeV, 2-kA, 2-μs electron beam pulse. After the accelerator, the pulse is delivered to the final focus on an x-ray producing target via a beam transport section called the Downstream Transport. Ions produced due to beam ionization of residual gases in the Downstream Transport can affect the beam dynamics. Ions generated by the head of the pulse will cause modification of space-charge forces at the tail of the pulse so that the beam head and tail will have different beam envelopes. They may also induce ion-hose instability at the tail of the pulse. If these effects are significant, the focusing requirements of beam head and tail at the final focus will become very different. The focusing of the complete beam pulse will be time dependent and difficult to achieve, leading to less efficient x-ray production. In this paper, we will describe the results of our calculations of these ion effects at different residual-gas pressure levels. Our goal is to determine the ma...

  6. Upstream and Downstream Influence in STBLI Instability

    Science.gov (United States)

    Martin, Pino; Priebe, Stephan; Helm, Clara

    2016-11-01

    Priebe and Martín (JFM, 2012) show that the low-frequency unsteadiness in shockwave and turbulent boundary layer interactions (STBLI) is governed by an inviscid instability. Priebe, Tu, Martín and Rowley (JFM, 2016) show that the instability is an inviscid centrifugal one, i.e Görtlerlike vortices. Previous works had given differing conclusions as to whether the low-frequency unsteadiness in STBLI is caused by an upstream or downstream mechanism. In this paper, we reconcile these opposite views and show that upstream and downstream correlations co-exist in the context of the nature of Görtler vortices. We find that the instability is similar to that in separated subsonic and laminar flows. Since the turbulence is modulated but passive to the global mode, the turbulent separated flows are amenable to linear global analysis. As such, the characteristic length and time scales, and the receptivity of the global mode might be determined, and low-order models that represent the low-frequency dynamics in STBLI might be developed. The centrifugal instability persists even under hypersonic conditions. This work is funded by the AFOSR Grant Number AF9550-15-1-0284 with Dr. Ivett Leyva.

  7. Comparative proteomic analysis of the molecular responses of mouse macrophages to titanium dioxide and copper oxide nanoparticles unravels some toxic mechanisms for copper oxide nanoparticles in macrophages.

    Science.gov (United States)

    Triboulet, Sarah; Aude-Garcia, Catherine; Armand, Lucie; Collin-Faure, Véronique; Chevallet, Mireille; Diemer, Hélène; Gerdil, Adèle; Proamer, Fabienne; Strub, Jean-Marc; Habert, Aurélie; Herlin, Nathalie; Van Dorsselaer, Alain; Carrière, Marie; Rabilloud, Thierry

    2015-01-01

    Titanium dioxide and copper oxide nanoparticles are more and more widely used because of their catalytic properties, of their light absorbing properties (titanium dioxide) or of their biocidal properties (copper oxide), increasing the risk of adverse health effects. In this frame, the responses of mouse macrophages were studied. Both proteomic and targeted analyses were performed to investigate several parameters, such as phagocytic capacity, cytokine release, copper release, and response at sub toxic doses. Besides titanium dioxide and copper oxide nanoparticles, copper ions were used as controls. We also showed that the overall copper release in the cell does not explain per se the toxicity observed with copper oxide nanoparticles. In addition, both copper ion and copper oxide nanoparticles, but not titanium oxide, induced DNA strands breaks in macrophages. As to functional responses, the phagocytic capacity was not hampered by any of the treatments at non-toxic doses, while copper ion decreased the lipopolysaccharide-induced cytokine and nitric oxide productions. The proteomic analyses highlighted very few changes induced by titanium dioxide nanoparticles, but an induction of heme oxygenase, an increase of glutathione synthesis and a decrease of tetrahydrobiopterin in response to copper oxide nanoparticles. Subsequent targeted analyses demonstrated that the increase in glutathione biosynthesis and the induction of heme oxygenase (e.g. by lovastatin/monacolin K) are critical for macrophages to survive a copper challenge, and that the intermediates of the catecholamine pathway induce a strong cross toxicity with copper oxide nanoparticles and copper ions.

  8. Comparative Proteomic Analysis of the Molecular Responses of Mouse Macrophages to Titanium Dioxide and Copper Oxide Nanoparticles Unravels Some Toxic Mechanisms for Copper Oxide Nanoparticles in Macrophages

    Science.gov (United States)

    Triboulet, Sarah; Aude-Garcia, Catherine; Armand, Lucie; Collin-Faure, Véronique; Chevallet, Mireille; Diemer, Hélène; Gerdil, Adèle; Proamer, Fabienne; Strub, Jean-Marc; Habert, Aurélie; Herlin, Nathalie; Van Dorsselaer, Alain; Carrière, Marie; Rabilloud, Thierry

    2015-01-01

    Titanium dioxide and copper oxide nanoparticles are more and more widely used because of their catalytic properties, of their light absorbing properties (titanium dioxide) or of their biocidal properties (copper oxide), increasing the risk of adverse health effects. In this frame, the responses of mouse macrophages were studied. Both proteomic and targeted analyses were performed to investigate several parameters, such as phagocytic capacity, cytokine release, copper release, and response at sub toxic doses. Besides titanium dioxide and copper oxide nanoparticles, copper ions were used as controls. We also showed that the overall copper release in the cell does not explain per se the toxicity observed with copper oxide nanoparticles. In addition, both copper ion and copper oxide nanoparticles, but not titanium oxide, induced DNA strands breaks in macrophages. As to functional responses, the phagocytic capacity was not hampered by any of the treatments at non-toxic doses, while copper ion decreased the lipopolysaccharide-induced cytokine and nitric oxide productions. The proteomic analyses highlighted very few changes induced by titanium dioxide nanoparticles, but an induction of heme oxygenase, an increase of glutathione synthesis and a decrease of tetrahydrobiopterin in response to copper oxide nanoparticles. Subsequent targeted analyses demonstrated that the increase in glutathione biosynthesis and the induction of heme oxygenase (e.g. by lovastatin/monacolin K) are critical for macrophages to survive a copper challenge, and that the intermediates of the catecholamine pathway induce a strong cross toxicity with copper oxide nanoparticles and copper ions. PMID:25902355

  9. Comparative proteomic analysis of the molecular responses of mouse macrophages to titanium dioxide and copper oxide nanoparticles unravels some toxic mechanisms for copper oxide nanoparticles in macrophages.

    Directory of Open Access Journals (Sweden)

    Sarah Triboulet

    Full Text Available Titanium dioxide and copper oxide nanoparticles are more and more widely used because of their catalytic properties, of their light absorbing properties (titanium dioxide or of their biocidal properties (copper oxide, increasing the risk of adverse health effects. In this frame, the responses of mouse macrophages were studied. Both proteomic and targeted analyses were performed to investigate several parameters, such as phagocytic capacity, cytokine release, copper release, and response at sub toxic doses. Besides titanium dioxide and copper oxide nanoparticles, copper ions were used as controls. We also showed that the overall copper release in the cell does not explain per se the toxicity observed with copper oxide nanoparticles. In addition, both copper ion and copper oxide nanoparticles, but not titanium oxide, induced DNA strands breaks in macrophages. As to functional responses, the phagocytic capacity was not hampered by any of the treatments at non-toxic doses, while copper ion decreased the lipopolysaccharide-induced cytokine and nitric oxide productions. The proteomic analyses highlighted very few changes induced by titanium dioxide nanoparticles, but an induction of heme oxygenase, an increase of glutathione synthesis and a decrease of tetrahydrobiopterin in response to copper oxide nanoparticles. Subsequent targeted analyses demonstrated that the increase in glutathione biosynthesis and the induction of heme oxygenase (e.g. by lovastatin/monacolin K are critical for macrophages to survive a copper challenge, and that the intermediates of the catecholamine pathway induce a strong cross toxicity with copper oxide nanoparticles and copper ions.

  10. [Newly leaching method of copper from waste print circuit board using hydrochloric acid/n-butylamine/copper sulfate].

    Science.gov (United States)

    Wang, Hong-Yan; Cui, Zhao-Jie; Yao, Ya-Wei

    2010-12-01

    A newly leaching method of copper from waste print circuit board was established by using hydrochloric acid-n-butylamine-copper sulfate mixed solution. The conditions of leaching were optimized by changing the hydrochloric acid, n-butylamine, copper sulfate,temperature and other conditions using copper as target mimics. The results indicated that copper could be leached completely after 8 h at 50 degrees C, hydrochloric acid concentration of 1.75 mol/L, n-butylamine concentration of 0.25 mol/L, and copper sulfate mass of 0.96 g. Under the conditions, copper leaching rates in waste print circuit board samples was up to 95.31% after 9 h. It has many advantages such as better effects, low cost, mild reaction conditions, leaching solution recycling.

  11. Aquatic Life Criteria - Copper

    Science.gov (United States)

    Documents pertain to Aquatic Life Ambient Water Quality criteria for Copper (2007 Freshwater, 2016 Estuarine/marine). These documents contain the safe levels of Copper in water that should protect to the majority of species.

  12. Hes repressors are essential regulators of hematopoietic stem cell development downstream of notch signaling

    NARCIS (Netherlands)

    J. Guiu (Jordi); R. Shimizu (Ritsuko); C. D'Altri; S.T. Fraser (Stuart); S. Hatakeyama (Shingo); E.H. Bresnick (Emery); T. Kageyama (Tsutomu); E.A. Dzierzak (Elaine); M. Yamamoto (Masayuki); L. Espinosa (Lluis); A. Bigas (Anna)

    2013-01-01

    textabstractPrevious studies have identified Notch as a key regulator of hematopoietic stem cell (HSC) development, but the underlying downstream mechanisms remain unknown. The Notch target Hes1 is widely expressed in the aortic endothelium and hematopoietic clusters, though Hes1-deficient mice show

  13. Downstream Thermal Evolution of Vortex Cores

    Science.gov (United States)

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

    1999-11-01

    The downstream evolution of the total temperature field in a quasi-incompressible axisymmetric vortex core has been computed. Starting at an initial station (z=0) with velocity profiles of the Burgers type and given temperature distributions, the numerical results of the evolution show that, according to experimental results, the total temperature in the near-axis region decreases substantially due to the work done by pressure and viscous forces together with the effect of both convection and conduction of heat. Depending on the values of the parameters characterizing the initial profiles and on the value of the Prandtl number, the vortex either breaks down or eventually reaches a self-similar regime. The results obtained shed light on the basic physics involved in the thermal separation phenomenon which appears inside Ranque-Hilsch vortex tubes.

  14. 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.

  15. Ammonia downstream from HH 80 North

    Science.gov (United States)

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

    1994-01-01

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

  16. Copper-tantalum alloy

    Science.gov (United States)

    Schmidt, Frederick A.; Verhoeven, John D.; Gibson, Edwin D.

    1986-07-15

    A tantalum-copper alloy can be made by preparing a consumable electrode consisting of an elongated copper billet containing at least two spaced apart tantalum rods extending longitudinally the length of the billet. The electrode is placed in a dc arc furnace and melted under conditions which co-melt the copper and tantalum to form the alloy.

  17. Metallothionein, Copper and Alpha-Synuclein in Alpha-Synucleinopathies.

    Science.gov (United States)

    Okita, Yuho; Rcom-H'cheo-Gauthier, Alexandre N; Goulding, Michael; Chung, Roger S; Faller, Peter; Pountney, Dean L

    2017-01-01

    Metallothioneins (MTs) are proteins that function by metal exchange to regulate the bioavailability of metals, such as zinc and copper. Copper functions in the brain to regulate mitochondria, neurotransmitter production, and cell signaling. Inappropriate copper binding can result in loss of protein function and Cu(I)/(II) redox cycling can generate reactive oxygen species. Copper accumulates in the brain with aging and has been shown to bind alpha-synuclein and initiate its aggregation, the primary aetiological factor in Parkinson's disease (PD), and other alpha-synucleinopathies. In PD, total tissue copper is decreased, including neuromelanin-bound copper and there is a reduction in copper transporter CTR-1. Conversely cerebrospinal fluid (CSF) copper is increased. MT-1/2 expression is increased in activated astrocytes in alpha-synucleinopathies, yet expression of the neuronal MT-3 isoform may be reduced. MTs have been implicated in inflammatory states to perform one-way exchange of copper, releasing free zinc and recent studies have found copper bound to alpha-synuclein is transferred to the MT-3 isoform in vitro and MT-3 is found bound to pathological alpha-synuclein aggregates in the alpha-synucleinopathy, multiple systems atrophy. Moreover, both MT and alpha-synuclein can be released and taken up by neural cells via specific receptors and so may interact both intra- and extra-cellularly. Here, we critically review the role of MTs in copper dyshomeostasis and alpha-synuclein aggregation, and their potential as biomarkers and therapeutic targets.

  18. Roles of Copper-Binding Proteins in Breast Cancer.

    Science.gov (United States)

    Blockhuys, Stéphanie; Wittung-Stafshede, Pernilla

    2017-04-20

    Copper ions are needed in several steps of cancer progression. However, the underlying mechanisms, and involved copper-binding proteins, are mainly elusive. Since most copper ions in the body (in and outside cells) are protein-bound, it is important to investigate what copper-binding proteins participate and, for these, how they are loaded with copper by copper transport proteins. Mechanistic information for how some copper-binding proteins, such as extracellular lysyl oxidase (LOX), play roles in cancer have been elucidated but there is still much to learn from a biophysical molecular viewpoint. Here we provide a summary of copper-binding proteins and discuss ones reported to have roles in cancer. We specifically focus on how copper-binding proteins such as mediator of cell motility 1 (MEMO1), LOX, LOX-like proteins, and secreted protein acidic and rich in cysteine (SPARC) modulate breast cancer from molecular and clinical aspects. Because of the importance of copper for invasion/migration processes, which are key components of cancer metastasis, further insights into the actions of copper-binding proteins may provide new targets to combat cancer.

  19. 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

  20. Surface films and corrosion of copper

    Energy Technology Data Exchange (ETDEWEB)

    Hilden, J.; Laitinen, T.; Maekelae, K.; Saario, T.; Bojinov, M. [VTT Manufacturing Technology, Espoo (Finland)

    1999-03-01

    In Sweden and Finland the spent nuclear fuel is planned to be encapsulated in cast iron canisters that have an outer shield made of copper. The copper shield is responsible for the corrosion protection of the canister construction. General corrosion of the copper is not expected to be the limiting factor in the waste repository environment when estimating the life-time of the canister construction. However, different forms of localised corrosion, i.e. pitting, stress corrosion cracking, or environmentally assisted creep fracture may cause premature failure of the copper shield. Of the probable constituents in the groundwater, nitrites, chlorides, sulphides and carbonates have been suggested to promote localised corrosion of copper. The main assumption made in planning this research program is that the surface films forming on copper in the repository environment largely determine the susceptibility of copper to the different forms of localised corrosion. The availability of reactants, which also may become corrosion rate limiting, is investigated in several other research programs. This research program consists of a set of successive projects targeted at characterising the properties of surface films on copper in repository environment containing different detrimental anions. A further aim was to assess the significance of the anion-induced changes in the stability of the oxide films with regard to localised corrosion of copper. This report summarises the results from a series of investigations on properties of surface films forming on copper in water of pH = 8.9 at temperature of 80 deg C and pressure of 2 MPa. The main results gained so far in this research program are as follows: The surface films forming on copper in the thermodynamic stability region of monovalent copper at 80 deg C consist of a bulk part (about 1 mm thick) which is a good ionic and electronic conductor, and an outer, interfacial layer (0.001 - 0.005 mm thick) which shows p-type semiconductor

  1. 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.

  2. Handling of Copper and Copper Oxide Nanoparticles by Astrocytes.

    Science.gov (United States)

    Bulcke, Felix; Dringen, Ralf

    2016-02-01

    Copper is an essential trace element for many important cellular functions. However, excess of copper can impair cellular functions by copper-induced oxidative stress. In brain, astrocytes are considered to play a prominent role in the copper homeostasis. In this short review we summarise the current knowledge on the molecular mechanisms which are involved in the handling of copper by astrocytes. Cultured astrocytes efficiently take up copper ions predominantly by the copper transporter Ctr1 and the divalent metal transporter DMT1. In addition, copper oxide nanoparticles are rapidly accumulated by astrocytes via endocytosis. Cultured astrocytes tolerate moderate increases in intracellular copper contents very well. However, if a given threshold of cellular copper content is exceeded after exposure to copper, accelerated production of reactive oxygen species and compromised cell viability are observed. Upon exposure to sub-toxic concentrations of copper ions or copper oxide nanoparticles, astrocytes increase their copper storage capacity by upregulating the cellular contents of glutathione and metallothioneins. In addition, cultured astrocytes have the capacity to export copper ions which is likely to involve the copper ATPase 7A. The ability of astrocytes to efficiently accumulate, store and export copper ions suggests that astrocytes have a key role in the distribution of copper in brain. Impairment of this astrocytic function may be involved in diseases which are connected with disturbances in brain copper metabolism.

  3. 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...

  4. Biogenic nanoparticles: copper, copper oxides, copper sulphides, complex copper nanostructures and their applications.

    Science.gov (United States)

    Rubilar, Olga; Rai, Mahendra; Tortella, Gonzalo; Diez, Maria Cristina; Seabra, Amedea B; Durán, Nelson

    2013-09-01

    Copper nanoparticles have been the focus of intensive study due to their potential applications in diverse fields including biomedicine, electronics, and optics. Copper-based nanostructured materials have been used in conductive films, lubrification, nanofluids, catalysis, and also as potent antimicrobial agent. The biogenic synthesis of metallic nanostructured nanoparticles is considered to be a green and eco-friendly technology since neither harmful chemicals nor high temperatures are involved in the process. The present review discusses the synthesis of copper nanostructured nanoparticles by bacteria, fungi, and plant extracts, showing that biogenic synthesis is an economically feasible, simple and non-polluting process. Applications for biogenic copper nanoparticles are also discussed.

  5. Electron impact single ionization of copper

    Indian Academy of Sciences (India)

    Electron impact single ionization cross sections of copper have been calculated in the binary encounter approximation using accurate expression for as given by Vriens and Hartree–Fock momentum distribution for the target electron. The BEA calculation based on the usual procedure does not show satisfactory ...

  6. Copper-containing zeolite catalysts

    Science.gov (United States)

    Price, Geoffrey L.; Kanazirev, Vladislav

    1996-01-01

    A catalyst useful in the conversion of nitrogen oxides or in the synthesis of nitriles or imines from amines, formed by preparing an intimate mechanical mixture of a copper (II)-containing species, such as CuO or CuCl.sub.2, or elemental copper, with a zeolite having a pore mouth comprising 10 oxygen atoms, such as ZSM-5, converting the elemental copper or copper (II) to copper (I), and driving the copper (I) into the zeolite.

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

    Science.gov (United States)

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

    2015-10-01

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

  8. Improved Electroformed Structural Copper and Copper Alloys

    Science.gov (United States)

    Malone, G. A.; Hudson, W.; Babcock, B.; Edwards, R.

    1998-01-01

    Electroforming offers a superior means for fabricating internally cooled heat exchangers and structures subjected to thermal environments. Copper is deposited from many such applications because of the good thermal conductivity. It suffers from mediocre yield strength as a structural material and loses mechanical strength at intermediate temperatures. Mechanical properties similar to those of electroformed nickel are desired. Phase 1 examined innovative means to improve deposited copper structural performance. Yield strengths as high as 483 MPa (70 ksi) were obtained with useful ductility while retaining a high level of purity essential to good thermal conductivity. Phase 2 represents a program to explore new additive combinations in copper electrolytes to produce a more fine, equiaxed grain which can be thermally stabilized by other techniques such as alloying in modest degrees and dispersion strengthening. Evaluation of new technology - such as the codeposition of fullerness (diamond-like) particles were made to enhance thermal conductivity in low alloys. A test fire quality tube-bundle engine was fabricated using these copper property improvement concepts to show the superiority of the new coppers and fabrications methods over competitive technologies such as brazing and plasma deposition.

  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. Copper (II) Complex

    African Journals Online (AJOL)

    CLEMENT O BEWAJI

    ABSTRACT: N – histidyl – 2, 4 – pentanedione Schiff base was prepared from the reaction of histidine and 2, 4 - pentandione. The reaction of methanolic solution of N – histidyl – 2, 4 – pentanedione Schiff base with ethanolic solution of copper (II) chloride gave diaquo bis( N – histidyl - 2, 4 - pentanedionato) copper (II) ...

  11. Copper Pyrimidine based MOFs

    Indian Academy of Sciences (India)

    Figure S17. Self assembly of the tecton [CuI(pdz)Cl] can occur through two paths that causes the occurrence of supramolecular isomers. .... The pdz ligands bridge a pair of copper atoms in a chain through coordinate bonds. In addition ...... The weight loss thereafter corresponds to degradation of copper halide framework.

  12. Copper and silver halates

    CERN Document Server

    Woolley, EM; Salomon, M

    2013-01-01

    Copper and Silver Halates is the third in a series of four volumes on inorganic metal halates. This volume presents critical evaluations and compilations for halate solubilities of the Group II metals. The solubility data included in this volume are those for the five compounds, copper chlorate and iodate, and silver chlorate, bromate and iodate.

  13. Paralytic shellfish toxins inhibit copper uptake in Chlamydomonas reinhardtii.

    Science.gov (United States)

    Cusick, Kathleen D; Wetzel, Randall K; Minkin, Steven C; Dodani, Sheel C; Wilhelm, Steven W; Sayler, Gary S

    2013-06-01

    Paralytic shellfish toxins are secondary metabolites produced by several species of dinoflagellates and cyanobacteria. Known targets of these toxins, which typically occur at detrimental concentrations during harmful algal blooms, include voltage-gated ion channels in humans and other mammals. However, the effects of the toxins on the co-occurring phytoplankton community remain unknown. The present study examined the molecular mechanisms of the model photosynthetic alga Chlamydomonas reinhardtii in response to saxitoxin exposure as a means of gaining insight into the phytoplankton community response to a bloom. Previous work with yeast indicated that saxitoxin inhibited copper uptake, so experiments were designed to examine whether saxitoxin exhibited a similar mode of action in algae. Expression profiling following exposure to saxitoxin or a copper chelator produced similar profiles in copper homeostasis genes, notably induction of the cytochrome c6 (CYC6) and copper transporter (COPT1, CTR1) genes. Cytochrome c6 is used as an alternative to plastocyanin under conditions of copper deficiency, and immunofluorescence data showed this protein to be present in a significantly greater proportion of saxitoxin-exposed cells compared to controls. Live-cell imaging with a copper-sensor probe for intracellular labile Cu(I) confirmed that saxitoxin blocked copper uptake. Extrapolations of these data to phytoplankton metabolic processes along with the copper transporter as a molecular target of saxitoxin based on existing structural models are discussed. Copyright © 2013 SETAC.

  14. Bioaccessibility and Solubility of Copper in Copper-Treated Lumber

    Science.gov (United States)

    Micronized copper (MC)-treated lumber is a recent replacement for Chromated Copper Arsenate (CCA) and Ammonium Copper (AC)-treated lumbers; though little is known about the potential risk of copper (Cu) exposure from incidental ingestion of MC-treated wood. The bioaccessibility o...

  15. Posttranslational regulation of copper transporters

    NARCIS (Netherlands)

    van den Berghe, P.V.E.

    2009-01-01

    The transition metal copper is an essential cofactor for many redox-active enzymes, but excessive copper can generate toxic reactive oxygen species. Copper homeostasis is maintained by highly conserved proteins, to balance copper uptake, distribution and export on the systemic and cellular level.

  16. Fabricating Copper Nanotubes by Electrodeposition

    Science.gov (United States)

    Yang, E. H.; Ramsey, Christopher; Bae, Youngsam; Choi, Daniel

    2009-01-01

    Copper tubes having diameters between about 100 and about 200 nm have been fabricated by electrodeposition of copper into the pores of alumina nanopore membranes. Copper nanotubes are under consideration as alternatives to copper nanorods and nanowires for applications involving thermal and/or electrical contacts, wherein the greater specific areas of nanotubes could afford lower effective thermal and/or electrical resistivities. Heretofore, copper nanorods and nanowires have been fabricated by a combination of electrodeposition and a conventional expensive lithographic process. The present electrodeposition-based process for fabricating copper nanotubes costs less and enables production of copper nanotubes at greater rate.

  17. Drowning in muddied waters or swimming downstream? A critical ...

    African Journals Online (AJOL)

    Drowning in muddied waters or swimming downstream? A critical analysis of literature reviewing in a phenomenological study through an exploration of the lifeworld, reflexivity and role of the researcher.

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

    Science.gov (United States)

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

    2015-11-01

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

  19. Use of Copper to Selectively Inhibit Brachionus calyciflorus (Predator) Growth in Chlorella kessleri (Prey) Mass Cultures for Algae Biodiesel Production.

    Science.gov (United States)

    Pradeep, Vishnupriya; Van Ginkel, Steven W; Park, Sichoon; Igou, Thomas; Yi, Christine; Fu, Hao; Johnston, Rachel; Snell, Terry; Chen, Yongsheng

    2015-08-31

    A single Brachionus rotifer can consume thousands of algae cells per hour causing an algae pond to crash within days of infection. Thus, there is a great need to reduce rotifers in order for algal biofuel production to become reality. Copper can selectively inhibit rotifers in algae ponds, thereby protecting the algae crop. Differential toxicity tests were conducted to compare the copper sensitivity of a model rotifer-B. calyciflorus and an alga, C. kessleri. The rotifer LC50 was <0.1 ppm while the alga was not affected up to 5 ppm Cu(II). The low pH of the rotifer stomach may make it more sensitive to copper. However, when these cultures were combined, a copper concentration of 1.5 ppm was needed to inhibit the rotifer as the alga bound the copper, decreasing its bioavailability. Copper (X ppm) had no effect on downstream fatty acid methyl ester extraction.

  20. Use of Copper to Selectively Inhibit Brachionus calyciflorus (Predator Growth in Chlorella kessleri (Prey Mass Cultures for Algae Biodiesel Production

    Directory of Open Access Journals (Sweden)

    Vishnupriya Pradeep

    2015-08-01

    Full Text Available A single Brachionus rotifer can consume thousands of algae cells per hour causing an algae pond to crash within days of infection. Thus, there is a great need to reduce rotifers in order for algal biofuel production to become reality. Copper can selectively inhibit rotifers in algae ponds, thereby protecting the algae crop. Differential toxicity tests were conducted to compare the copper sensitivity of a model rotifer—B. calyciflorus and an alga, C. kessleri. The rotifer LC50 was <0.1 ppm while the alga was not affected up to 5 ppm Cu(II. The low pH of the rotifer stomach may make it more sensitive to copper. However, when these cultures were combined, a copper concentration of 1.5 ppm was needed to inhibit the rotifer as the alga bound the copper, decreasing its bioavailability. Copper (X ppm had no effect on downstream fatty acid methyl ester extraction.

  1. Upstream trophic structure modulates downstream community dynamics via resource subsidies.

    Science.gov (United States)

    Harvey, Eric; Gounand, Isabelle; Little, Chelsea J; Fronhofer, Emanuel A; Altermatt, Florian

    2017-08-01

    In many natural systems, the physical structure of the landscape dictates the flow of resources. Despite mounting evidence that communities' dynamics can be indirectly coupled by reciprocal among ecosystem resource flows, our understanding of how directional resource flows might indirectly link biological communities is limited. We here propose that differences in community structure upstream should lead to different downstream dynamics, even in the absence of dispersal of organisms. We report an experimental test of the effect of upstream community structure on downstream community dynamics in a simplified but highly controlled setting, using protist microcosms. We implemented directional flows of resources, without dispersal, from a standard resource pool into upstream communities of contrasting interaction structure and then to further downstream communities of either one or two trophic levels. Our results demonstrate that different types of species interactions in upstream habitats may lead to different population sizes and levels of biomass in these upstream habitats. This, in turn, leads to varying levels of detritus transfer (dead biomass) to the downstream communities, thus influencing their population densities and trophic interactions in predictable ways. Our results suggest that the structure of species interactions in directionally structured ecosystems can be a key mediator of alterations to downstream habitats. Alterations to upstream habitats can thus cascade down to downstream communities, even without dispersal.

  2. 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.

  3. Sliding Friction of Copper

    National Research Council Canada - National Science Library

    Liu, Tung

    1963-01-01

    .... With less clean surfaces, the coefficient of friction obtained was about 0.4. Since the degree of cleanliness cannot be controlled quantitatively, the friction - load curve of sliding copper pairs in air exhibits a bifurcation characteristic...

  4. Copper Phenoxyl Complexes

    OpenAIRE

    Butsch, Katharina

    2010-01-01

    The work described in the following was inspired by radical copper enzymes such as Galactose Oxidase (GO). GO catalyses the two-electron oxidation of terminal alcohols to the corresponding aldehydes using air oxygen. Transfer of two electrons is possible, since GO contains two magnetically coupled one-electron redox centres: a tyrosylate ligand from the apo-protein, which exists either in the tyrosylate or the tyrosyl radical form and is bound to a copper ion possessing two stable oxidation s...

  5. Comparative Proteomic Analysis of the Molecular Responses of Mouse Macrophages to Titanium Dioxide and Copper Oxide Nanoparticles Unravels Some Toxic Mechanisms for Copper Oxide Nanoparticles in Macrophages

    OpenAIRE

    Triboulet, Sarah; Aude-Garcia, Catherine; Armand, Lucie; Collin-Faure, V?ronique; Chevallet, Mireille; Diemer, H?l?ne; Gerdil, Ad?le; Proamer, Fabienne; Strub, Jean-Marc; Habert, Aur?lie; Herlin, Nathalie; Van Dorsselaer, Alain; Carri?re, Marie; Rabilloud, Thierry

    2015-01-01

    Titanium dioxide and copper oxide nanoparticles are more and more widely used because of their catalytic properties, of their light absorbing properties (titanium dioxide) or of their biocidal properties (copper oxide), increasing the risk of adverse health effects. In this frame, the responses of mouse macrophages were studied. Both proteomic and targeted analyses were performed to investigate several parameters, such as phagocytic capacity, cytokine release, copper release, and response at ...

  6. Assessment of the Secondary Copper Reserves of Nations.

    Science.gov (United States)

    Maung, Kyaw Nyunt; Hashimoto, Seiji; Mizukami, Mizuki; Morozumi, Masataka; Lwin, Cherry Myo

    2017-04-04

    The sustainable use of metals demands consideration not only of primary metals in the natural environment but also of secondary metals in society as alternative resources. This study applied our proposed classification framework of secondary resources to copper (1) to investigate the applicability of the framework and (2) to assess the secondary copper reserves and resources of selected countries. To estimate secondary copper reserves, we introduced the variable "secondary reserve ratio": the fraction of in-use copper stocks that is technically and economically recoverable. Our estimates showed that the United States and China have secondary copper reserves of 44 and 33 Mt, respectively, and showed that global secondary copper reserves are about 30% of global primary reserves. The application of the classification framework showed that considerable amounts of secondary copper resources are in landfills, which are potential targets of future extraction of secondary copper through landfill mining. Overall, the classification framework provides a better understanding of the current size of available secondary resources and waste deposits. It also highlights the need for integrated management of primary and secondary resources.

  7. Elevated copper impairs hepatic nuclear receptor function in Wilson's disease.

    Science.gov (United States)

    Wooton-Kee, Clavia Ruth; Jain, Ajay K; Wagner, Martin; Grusak, Michael A; Finegold, Milton J; Lutsenko, Svetlana; Moore, David D

    2015-09-01

    Wilson's disease (WD) is an autosomal recessive disorder that results in accumulation of copper in the liver as a consequence of mutations in the gene encoding the copper-transporting P-type ATPase (ATP7B). WD is a chronic liver disorder, and individuals with the disease present with a variety of complications, including steatosis, cholestasis, cirrhosis, and liver failure. Similar to patients with WD, Atp7b⁻/⁻ mice have markedly elevated levels of hepatic copper and liver pathology. Previous studies have demonstrated that replacement of zinc in the DNA-binding domain of the estrogen receptor (ER) with copper disrupts specific binding to DNA response elements. Here, we found decreased binding of the nuclear receptors FXR, RXR, HNF4α, and LRH-1 to promoter response elements and decreased mRNA expression of nuclear receptor target genes in Atp7b⁻/⁻ mice, as well as in adult and pediatric WD patients. Excessive hepatic copper has been described in progressive familial cholestasis (PFIC), and we found that similar to individuals with WD, patients with PFIC2 or PFIC3 who have clinically elevated hepatic copper levels exhibit impaired nuclear receptor activity. Together, these data demonstrate that copper-mediated nuclear receptor dysfunction disrupts liver function in WD and potentially in other disorders associated with increased hepatic copper levels.

  8. Copper wire bonding

    CERN Document Server

    Chauhan, Preeti S; Zhong, ZhaoWei; Pecht, Michael G

    2014-01-01

    This critical volume provides an in-depth presentation of copper wire bonding technologies, processes and equipment, along with the economic benefits and risks.  Due to the increasing cost of materials used to make electronic components, the electronics industry has been rapidly moving from high cost gold to significantly lower cost copper as a wire bonding material.  However, copper wire bonding has several process and reliability concerns due to its material properties.  Copper Wire Bonding book lays out the challenges involved in replacing gold with copper as a wire bond material, and includes the bonding process changes—bond force, electric flame off, current and ultrasonic energy optimization, and bonding tools and equipment changes for first and second bond formation.  In addition, the bond–pad metallurgies and the use of bare and palladium-coated copper wires on aluminum are presented, and gold, nickel and palladium surface finishes are discussed.  The book also discusses best practices and re...

  9. 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.

  10. Gene expression patterns in the progression of canine copper-associated chronic hepatitis.

    Science.gov (United States)

    Dirksen, Karen; Spee, Bart; Penning, Louis C; van den Ingh, Ted S G A M; Burgener, Iwan A; Watson, Adrian L; Groot Koerkamp, Marian; Rothuizen, Jan; van Steenbeek, Frank G; Fieten, Hille

    2017-01-01

    Copper is an essential trace element, but can become toxic when present in abundance. The severe effects of copper-metabolism imbalance are illustrated by the inherited disorders Wilson disease and Menkes disease. The Labrador retriever dog breed is a novel non-rodent model for copper-storage disorders carrying mutations in genes known to be involved in copper transport. Besides disease initiation and progression of copper accumulation, the molecular mechanisms and pathways involved in progression towards copper-associated chronic hepatitis still remain unclear. Using expression levels of targeted candidate genes as well as transcriptome micro-arrays in liver tissue of Labrador retrievers in different stages of copper-associated hepatitis, pathways involved in progression of the disease were studied. At the initial phase of increased hepatic copper levels, transcriptomic alterations in livers mainly revealed enrichment for cell adhesion, developmental, inflammatory, and cytoskeleton pathways. Upregulation of targeted MT1A and COMMD1 mRNA shows the liver's first response to rising intrahepatic copper concentrations. In livers with copper-associated hepatitis mainly an activation of inflammatory pathways is detected. Once the hepatitis is in the chronic stage, transcriptional differences are found in cell adhesion adaptations and cytoskeleton remodelling. In view of the high similarities in copper-associated hepatopathies between men and dog extrapolation of these dog data into human biomedicine seems feasible.

  11. Gene expression patterns in the progression of canine copper-associated chronic hepatitis.

    Directory of Open Access Journals (Sweden)

    Karen Dirksen

    Full Text Available Copper is an essential trace element, but can become toxic when present in abundance. The severe effects of copper-metabolism imbalance are illustrated by the inherited disorders Wilson disease and Menkes disease. The Labrador retriever dog breed is a novel non-rodent model for copper-storage disorders carrying mutations in genes known to be involved in copper transport. Besides disease initiation and progression of copper accumulation, the molecular mechanisms and pathways involved in progression towards copper-associated chronic hepatitis still remain unclear. Using expression levels of targeted candidate genes as well as transcriptome micro-arrays in liver tissue of Labrador retrievers in different stages of copper-associated hepatitis, pathways involved in progression of the disease were studied. At the initial phase of increased hepatic copper levels, transcriptomic alterations in livers mainly revealed enrichment for cell adhesion, developmental, inflammatory, and cytoskeleton pathways. Upregulation of targeted MT1A and COMMD1 mRNA shows the liver's first response to rising intrahepatic copper concentrations. In livers with copper-associated hepatitis mainly an activation of inflammatory pathways is detected. Once the hepatitis is in the chronic stage, transcriptional differences are found in cell adhesion adaptations and cytoskeleton remodelling. In view of the high similarities in copper-associated hepatopathies between men and dog extrapolation of these dog data into human biomedicine seems feasible.

  12. Copper complexation screen reveals compounds with potent antibiotic properties against methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Haeili, Mehri; Moore, Casey; Davis, Christopher J C; Cochran, James B; Shah, Santosh; Shrestha, Tej B; Zhang, Yaofang; Bossmann, Stefan H; Benjamin, William H; Kutsch, Olaf; Wolschendorf, Frank

    2014-07-01

    Macrophages take advantage of the antibacterial properties of copper ions in the killing of bacterial intruders. However, despite the importance of copper for innate immune functions, coordinated efforts to exploit copper ions for therapeutic interventions against bacterial infections are not yet in place. Here we report a novel high-throughput screening platform specifically developed for the discovery and characterization of compounds with copper-dependent antibacterial properties toward methicillin-resistant Staphylococcus aureus (MRSA). We detail how one of the identified compounds, glyoxal-bis(N4-methylthiosemicarbazone) (GTSM), exerts its potent strictly copper-dependent antibacterial properties on MRSA. Our data indicate that the activity of the GTSM-copper complex goes beyond the general antibacterial effects of accumulated copper ions and suggest that, in contrast to prevailing opinion, copper complexes can indeed exhibit species- and target-specific activities. Based on experimental evidence, we propose that copper ions impose structural changes upon binding to the otherwise inactive GTSM ligand and transfer antibacterial properties to the chelate. In turn, GTSM determines target specificity and utilizes a redox-sensitive release mechanism through which copper ions are deployed at or in close proximity to a putative target. According to our proof-of-concept screen, copper activation is not a rare event and even extends to already established drugs. Thus, copper-activated compounds could define a novel class of anti-MRSA agents that amplify copper-dependent innate immune functions of the host. To this end, we provide a blueprint for a high-throughput drug screening campaign which considers the antibacterial properties of copper ions at the host-pathogen interface. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  13. Copper Complexation Screen Reveals Compounds with Potent Antibiotic Properties against Methicillin-Resistant Staphylococcus aureus

    Science.gov (United States)

    Haeili, Mehri; Moore, Casey; Davis, Christopher J. C.; Cochran, James B.; Shah, Santosh; Shrestha, Tej B.; Zhang, Yaofang; Bossmann, Stefan H.; Benjamin, William H.

    2014-01-01

    Macrophages take advantage of the antibacterial properties of copper ions in the killing of bacterial intruders. However, despite the importance of copper for innate immune functions, coordinated efforts to exploit copper ions for therapeutic interventions against bacterial infections are not yet in place. Here we report a novel high-throughput screening platform specifically developed for the discovery and characterization of compounds with copper-dependent antibacterial properties toward methicillin-resistant Staphylococcus aureus (MRSA). We detail how one of the identified compounds, glyoxal-bis(N4-methylthiosemicarbazone) (GTSM), exerts its potent strictly copper-dependent antibacterial properties on MRSA. Our data indicate that the activity of the GTSM-copper complex goes beyond the general antibacterial effects of accumulated copper ions and suggest that, in contrast to prevailing opinion, copper complexes can indeed exhibit species- and target-specific activities. Based on experimental evidence, we propose that copper ions impose structural changes upon binding to the otherwise inactive GTSM ligand and transfer antibacterial properties to the chelate. In turn, GTSM determines target specificity and utilizes a redox-sensitive release mechanism through which copper ions are deployed at or in close proximity to a putative target. According to our proof-of-concept screen, copper activation is not a rare event and even extends to already established drugs. Thus, copper-activated compounds could define a novel class of anti-MRSA agents that amplify copper-dependent innate immune functions of the host. To this end, we provide a blueprint for a high-throughput drug screening campaign which considers the antibacterial properties of copper ions at the host-pathogen interface. PMID:24752262

  14. Copper-zinc superoxide dismutase is activated through a sulfenic acid intermediate at a copper ion entry site.

    Science.gov (United States)

    Fetherolf, Morgan M; Boyd, Stefanie D; Taylor, Alexander B; Kim, Hee Jong; Wohlschlegel, James A; Blackburn, Ninian J; Hart, P John; Winge, Dennis R; Winkler, Duane D

    2017-07-21

    Metallochaperones are a diverse family of trafficking molecules that provide metal ions to protein targets for use as cofactors. The copper chaperone for superoxide dismutase (Ccs1) activates immature copper-zinc superoxide dismutase (Sod1) by delivering copper and facilitating the oxidation of the Sod1 intramolecular disulfide bond. Here, we present structural, spectroscopic, and cell-based data supporting a novel copper-induced mechanism for Sod1 activation. Ccs1 binding exposes an electropositive cavity and proposed "entry site" for copper ion delivery on immature Sod1. Copper-mediated sulfenylation leads to a sulfenic acid intermediate that eventually resolves to form the Sod1 disulfide bond with concomitant release of copper into the Sod1 active site. Sod1 is the predominant disulfide bond-requiring enzyme in the cytoplasm, and this copper-induced mechanism of disulfide bond formation obviates the need for a thiol/disulfide oxidoreductase in that compartment. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. The effect of carbon nanotube chirality on the spiral flow of copper atoms in their cores

    Energy Technology Data Exchange (ETDEWEB)

    Lim, M.C.G., E-mail: M070041@e.ntu.edu.sg [Nanyang Technological University, School of Mechanical and Aerospace Engineering, 50 Nanyang Avenue, Singapore 639798 (Singapore); Zhong, Z.W. [Nanyang Technological University, School of Mechanical and Aerospace Engineering, 50 Nanyang Avenue, Singapore 639798 (Singapore)

    2012-12-14

    The effect of carbon nanotube (CNT) chirality on the flow of copper atoms along its core has been investigated using molecular dynamics simulations. The investigation is conducted using CNTs of different chirality, and different flow conditions such as temperatures, bias voltages and the initial positions of the copper atoms. The results show that the atoms flow in a spiral fashion along the CNT channels. The effect is most evident in the CNT channel with zigzag CNTs. The movement of the copper atoms is more erratic when the temperature is increased at a low biased voltage, regardless of the types of channel used. The initial positions of the copper atoms affect the way they converge as they move downstream along the channel. A bias voltage of 4 V favours the initiation of a spiral flow, especially when the position of the copper atoms is far from the central axis of the channel. -- Highlights: Black-Right-Pointing-Pointer We model the transportation of copper atoms in armchair and zigzag CNT channels. Black-Right-Pointing-Pointer The spiral flow of copper atoms occurs in a semiconductor-semiconductor CNT. Black-Right-Pointing-Pointer The compact copper mass is predicted to occur at 673 K with a 4 V bias voltage.

  16. Electrical conduction in composites containing copper core-copper ...

    Indian Academy of Sciences (India)

    Composites of nanometre-sized copper core-copper oxide shell with diameters in the range 6.1 to 7.3 nm dispersed in a silica gel were synthesised by a technique comprising reduction followed by oxidation of a suitably chosen precursor gel. The hot pressed gel powders mixed with nanometre-sized copper particles ...

  17. Responses of Lyngbya wollei to exposures of copper-based algaecides: the critical burden concept.

    Science.gov (United States)

    Bishop, W M; Rodgers, J H

    2012-04-01

    The formulation of a specific algaecide can greatly influence the bioavailability, uptake, and consequent control of the targeted alga. In this research, three copper-based algaecide formulations were evaluated in terms of copper sorption to a specific problematic alga and amount of copper required to achieve control. The objectives of this study were (1) to compare the masses of copper required to achieve control of Lyngbya wollei using the algaecide formulations Algimycin-PWF, Clearigate, and copper sulfate pentahydrate in laboratory toxicity experiments; (2) to relate the responses of L. wollei to the masses of copper adsorbed and absorbed (i.e., dose) as well as the concentrations of copper in the exposure water; and (3) to discern the relation between the mass of copper required to achieve control of a certain mass of L. wollei among different algaecide formulations. The critical burden of copper (i.e., threshold algaecide concentration that must be absorbed or adsorbed to achieve control) for L. wollei averaged 3.3 and 1.9 mg Cu/g algae for Algimycin-PWF and Clearigate, respectively, in experiments with a series of aqueous copper concentrations, water volumes, and masses of algae. With reasonable exposures in these experiments, control was not achieved with single applications of copper sulfate despite copper sorption >13 mg Cu/g algae in one experiment. Factors governing the critical burden of copper required for control of problematic cyanobacteria include algaecide formulation and concentration, volume of water, and mass of algae. By measuring the critical burden of copper from an algaecide formulation necessary to achieve control of the targeted algae, selection of an effective product and treatment rate can be calculated at a given field site.

  18. 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.

  19. Epigenetic silencing of downstream genes mediated by tandem orientation in lung cancer.

    Science.gov (United States)

    Kiehl, Steffen; Zimmermann, Tobias; Savai, Rajkumar; Pullamsetti, Soni S; Seeger, Werner; Bartkuhn, Marek; Dammann, Reinhard H

    2017-06-20

    Epigenetic deregulation is of importance in tumorigenesis. In particular CpG islands (CGI), are frequently hypermethylated. Here, genome-wide DNA-methylation profiles of 480,000 CpGs in lung cancer cells were generated. It was observed that intra- and intergenic CGI exhibited higher methylation compared to normal cells. The functional annotation of hypermethylated CGI revealed that the hypermethylation was associated with homeobox domain genes and targets marked by repressive histone modifications. The strongest methylation variation was observed in transitional areas of CGI, termed shores. 5'-shores of promoter-associated CGI in lung cancer cell lines were higher methylated than 3'-shores. Within two tandem-oriented genes, a significant hypermethylation of the downstream-located CGI promoters was revealed. Hypermethylation correlates with the length of the intergenic region between such tandem genes. As the RASSF1A tumor suppressor gene represents such a downstream tandem gene, its silencing was analyzed using an inducible system. It was determined that the induction of an upstream gene led to a repression of RASSF1A through a process involving histone deacetylases and CPSF1. A tumor-specific increase in expression of histone deacetylases and CPSF1 was detected in lung cancer. Our results suggest that the downstream gene could be susceptible to epigenetic silencing when organized in a tandem orientation.

  20. Copper complexes as chemical nucleases

    Indian Academy of Sciences (India)

    Keywords. Copper(II) complexes; nuclease activity; catalytic properties; DNA binding. Abstract. Redox active mononuclear and binuclear copper(II) complexes have been prepared and structurally characterized. ... The cleavage activity of the bis-dpq complex is significantly higher than the bis-phen complex of copper(II).

  1. Concentrations of heavy metals in effluent discharges downstream ...

    African Journals Online (AJOL)

    ONOS

    2010-01-18

    Jan 18, 2010 ... Various effluent samples were collected from their sources of discharge to the Ikpoba river in Benin. City, Edo State between September and October, 2008. Six heavy metals (cadmium, chromium, copper, nickel, lead and zinc) in the effluents and receiving water were analyzed by atomic absorption.

  2. The Nigerian petroleum downstream sector and product pricing ...

    African Journals Online (AJOL)

    This research has been designed to explore critically the history of the downstream petroleum sector and the trend of pricing of Nigeria's petroleum products - looking closely at the contentious issue of subsidy and formulate a statistical model for the appropriate pricing of locally produced petroleum products.

  3. 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 ...

  4. 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...

  5. Downstream and upstream extension of the House of Quality

    DEFF Research Database (Denmark)

    Holmen, Elsebeth; Kristensen, Preben Sander

    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...

  6. 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

  7. Doublesex: a conserved downstream gene controlled by diverse ...

    Indian Academy of Sciences (India)

    2010-09-06

    Sep 6, 2010 ... The Drosophila doublesex (dsx) gene at the bottom of the sex-determination cascade is the best charac- terized candidate so far, and is .... down of tra-2 in these insects results in complete reversal of genotypically female .... tributing the antagonistic effect of sex-specific Dsx proteins on their downstream ...

  8. 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

  9. Constraints on Conceptual and Quantitative Modeling of Early Diagenetic Sediment-Hosted Stratiform Copper Mineralization

    Directory of Open Access Journals (Sweden)

    Alex C. Brown

    2017-10-01

    Full Text Available Early diagenetic sediment-hosted stratiform copper (eSSC mineralization results from low-temperature cuprous chloride complexes carried by saline aqueous solution circulating through footwall aquifers. Favorable copper solubilities are attained in moderately oxidizing, near-neutral pH solutions. That specific oxidation level is not determined by co-existence with hematite, with its near-indiscriminant control over Eh. Instead, redbed footwall aquifers are signatures of diagenetic oxidation. Relentless in-situ oxidation of ferrous minerals in redbeds produces pore waters too reduced to transport copper, thus eliminating compaction waters as ore solutions. Continuous early influxes of descending oxygen-rich meteoric waters which have assimilated evaporitic salts may redden aquifers and still retain oxidation levels capable of carrying copper to form downstream eSSCs.

  10. Copper and Copper Proteins in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Sergio Montes

    2014-01-01

    Full Text Available Copper is a transition metal that has been linked to pathological and beneficial effects in neurodegenerative diseases. In Parkinson’s disease, free copper is related to increased oxidative stress, alpha-synuclein oligomerization, and Lewy body formation. Decreased copper along with increased iron has been found in substantia nigra and caudate nucleus of Parkinson’s disease patients. Copper influences iron content in the brain through ferroxidase ceruloplasmin activity; therefore decreased protein-bound copper in brain may enhance iron accumulation and the associated oxidative stress. The function of other copper-binding proteins such as Cu/Zn-SOD and metallothioneins is also beneficial to prevent neurodegeneration. Copper may regulate neurotransmission since it is released after neuronal stimulus and the metal is able to modulate the function of NMDA and GABA A receptors. Some of the proteins involved in copper transport are the transporters CTR1, ATP7A, and ATP7B and the chaperone ATOX1. There is limited information about the role of those biomolecules in the pathophysiology of Parkinson’s disease; for instance, it is known that CTR1 is decreased in substantia nigra pars compacta in Parkinson’s disease and that a mutation in ATP7B could be associated with Parkinson’s disease. Regarding copper-related therapies, copper supplementation can represent a plausible alternative, while copper chelation may even aggravate the pathology.

  11. Vector averaging occurs downstream from learning in smooth pursuit eye movements of monkeys.

    Science.gov (United States)

    Kahlon, M; Lisberger, S G

    1999-10-15

    How are sensory-motor transformations organized in a cortical motor system? In general, sensory information is transformed through a variety of signal processing operations in the context of distinct coordinate frameworks. We studied the interaction of two distinct operations in pursuit eye movements, learning and vector-averaging, to gain insight into their underlying coordinate frameworks and their sequence in sensory-motor processing. Learning was induced in the initiation of pursuit eye movements by targets that moved initially at one speed for 100 msec and then increased or decreased to a sustained final speed. Vector averaging was studied by comparing the initial eye acceleration evoked by the simultaneous motion of two targets with that evoked by each target singly. Learning caused specific effects on the direction of the vector-averaged responses to two-target stimuli that included one target moving in the direction used to induce learning. Learned increases or decreases in eye acceleration caused the direction of the responses to two-targets to rotate toward or away from the learning direction. Learning also caused nonspecific changes in the responses to two-target stimuli. After any learning protocol, two-target responses usually became smaller, and their directions rotated away from the axis of the target motion used for learning. Quantitative analysis showed that the specific effects of learning were predicted most closely by a model in which vector averaging occurs downstream from the site(s) of learning. We suggest that the pursuit system creates parallel commands for potential movements to each of the targets in two-target stimuli, and that learning occurs in the coordinates of the potential movements.

  12. Precursors for formation of copper selenide, indium selenide, copper indium diselenide, and/or copper indium gallium diselenide films

    Science.gov (United States)

    Curtis, Calvin J; Miedaner, Alexander; Van Hest, Maikel; Ginley, David S

    2014-11-04

    Liquid-based precursors for formation of Copper Selenide, Indium Selenide, Copper Indium Diselenide, and/or copper Indium Galium Diselenide include copper-organoselenides, particulate copper selenide suspensions, copper selenide ethylene diamine in liquid solvent, nanoparticulate indium selenide suspensions, and indium selenide ethylene diamine coordination compounds in solvent. These liquid-based precursors can be deposited in liquid form onto substrates and treated by rapid thermal processing to form crystalline copper selenide and indium selenide films.

  13. Creative Copper Crests

    Science.gov (United States)

    Knab, Thomas

    2011-01-01

    In this article, the author discusses how to create an art activity that would link the computer-created business cards of fourth-grade students with an upcoming school-wide medieval event. Creating family crests from copper foil would be a great connection, since they, like business cards, are an individual's way to identify themselves to others.…

  14. Coping with copper

    DEFF Research Database (Denmark)

    Nunes, Ines; Jacquiod, Samuel; Brejnrod, Asker

    2016-01-01

    Copper has been intensively used in industry and agriculture since mid-18(th) century and is currently accumulating in soils. We investigated the diversity of potential active bacteria by 16S rRNA gene transcript amplicon sequencing in a temperate grassland soil subjected to century-long exposure...

  15. The Effect of Copper

    African Journals Online (AJOL)

    Haematological studies were carried out on the blood of Clarias gariepinus broodstock fed different diets. Five isonitrogenous diets ... (7.5 mg CuSO4/g) while the control diet, CSD0 contained no copper sulphate. The haematological ..... Apis Mellifera Adansonii (Hymenoptera: Apidae) In A. Mangrove Area of Lagos, Nigeria ...

  16. Presenilin promotes dietary copper uptake.

    Directory of Open Access Journals (Sweden)

    Adam Southon

    Full Text Available Dietary copper is essential for multicellular organisms. Copper is redox active and required as a cofactor for enzymes such as the antioxidant Superoxide Dismutase 1 (SOD1. Copper dyshomeostasis has been implicated in Alzheimer's disease. Mutations in the presenilin genes encoding PS1 and PS2 are major causes of early-onset familial Alzheimer's disease. PS1 and PS2 are required for efficient copper uptake in mammalian systems. Here we demonstrate a conserved role for presenilin in dietary copper uptake in the fly Drosophila melanogaster. Ubiquitous RNA interference-mediated knockdown of the single Drosophila presenilin (PSN gene is lethal. However, PSN knockdown in the midgut produces viable flies. These flies have reduced copper levels and are more tolerant to excess dietary copper. Expression of a copper-responsive EYFP construct was also lower in the midgut of these larvae, indicative of reduced dietary copper uptake. SOD activity was reduced by midgut PSN knockdown, and these flies were sensitive to the superoxide-inducing chemical paraquat. These data support presenilin being needed for dietary copper uptake in the gut and so impacting on SOD activity and tolerance to oxidative stress. These results are consistent with previous studies of mammalian presenilins, supporting a conserved role for these proteins in mediating copper uptake.

  17. Copper uptake across rainbow trout gills: mechanisms of apical entry

    DEFF Research Database (Denmark)

    Grosell, Martin Hautopp; Wood, C. M.

    2002-01-01

    Copper, Homeostasis, sodium uptake, copper/sodium interactions, gill, rainbow trout, Oncorhynchus mykiss......Copper, Homeostasis, sodium uptake, copper/sodium interactions, gill, rainbow trout, Oncorhynchus mykiss...

  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

    2015-01-01

    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

  19. 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.

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

    DEFF Research Database (Denmark)

    Howells, John

    of that empirical evidence. They present alleged historical examples of downstream innovation suppression in such important technologies as: Edison's carbon filament light bulb; the automobile; radio; aircraft; the transistor; the computer. This paper presents a contrary interpretation of the role of patents......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...... in any of the examples. I therefore draw the strong conclusion that their general thesis is unsupported by their selection of empirical evidence. The article then argues that although a subset of their cases illustrates patents acting to hinder developers (but not development of the relevant technology...

  1. Minimizing downstream scour due to submerged hydraulic jump using corrugated

    Directory of Open Access Journals (Sweden)

    Hossam Mohamed Ali

    2014-12-01

    Full Text Available Local scour downstream of hydraulic structures due to hydraulic jump is considered one of the tedious and complicated problems facing their stability. Throughout this paper, an experimental study was conducted to study the effect of using different spaced corrugated aprons on the downstream local scour due to submerged jump. Sixty runs were carried out in a horizontal rectangular flume to determine the optimal corrugation wavelength which minimizing the scour. A case of flat apron included to estimate the influence of corrugated aprons on scour holes dimensions. Two types of non-cohesive soil were used. Experiments were performed for a range of Froude numbers between 1.68 and 9.29. The results showed that using spaced triangular corrugated aprons minimize the scour depth and length of fine sand by average percentage of 63.4% and 30.2%, respectively and for coarse sand by 44.2% and 20.6% in comparing with classical jump.

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

    DEFF Research Database (Denmark)

    Howells, John

    Merges and Nelson have proposed that pioneer patents have enabled their owners to 'block' or 'hold-up' downstream innovation in cases as important as the car, radio, aircraft and electric lighting (Merges and Nelson 1990, ; Merges and Nelson 1994). Merges and Nelson use their work to question...... 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...... innovation suppression as claimed.  I argue instead that these cases illustrate problems in the coordination of development caused by various faults in the administration of patents by US Congress, the US Patent Office or the courts....

  3. 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.

  4. 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%

  5. Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation

    Science.gov (United States)

    Wang, Jing; Luo, Cheng; Shan, Changliang; You, Qiancheng; Lu, Junyan; Elf, Shannon; Zhou, Yu; Wen, Yi; Vinkenborg, Jan L.; Fan, Jun; Kang, Heebum; Lin, Ruiting; Han, Dali; Xie, Yuxin; Karpus, Jason; Chen, Shijie; Ouyang, Shisheng; Luan, Chihao; Zhang, Naixia; Ding, Hong; Merkx, Maarten; Liu, Hong; Chen, Jing; Jiang, Hualiang; He, Chuan

    2015-12-01

    Copper is a transition metal that plays critical roles in many life processes. Controlling the cellular concentration and trafficking of copper offers a route to disrupt these processes. Here we report small molecules that inhibit the human copper-trafficking proteins Atox1 and CCS, and so provide a selective approach to disrupt cellular copper transport. The knockdown of Atox1 and CCS or their inhibition leads to a significantly reduced proliferation of cancer cells, but not of normal cells, as well as to attenuated tumour growth in mouse models. We show that blocking copper trafficking induces cellular oxidative stress and reduces levels of cellular ATP. The reduced level of ATP results in activation of the AMP-activated protein kinase that leads to reduced lipogenesis. Both effects contribute to the inhibition of cancer cell proliferation. Our results establish copper chaperones as new targets for future developments in anticancer therapies.

  6. 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.

  7. Pathological mitochondrial copper overload in livers of Wilson's disease patients and related animal models.

    Science.gov (United States)

    Zischka, Hans; Lichtmannegger, Josef

    2014-05-01

    In Wilson's disease (WD) and related animal models, liver mitochondria are confronted with an increasing copper burden. Physiologically, the mitochondrial matrix may act as a dynamic copper buffer that efficiently distributes the metal to its copper-dependent enzymes. Mitochondria are the first responders in the event of an imbalanced copper homeostasis, as typical changes of their structure are among the earliest observable pathological features in WD. These changes are due to accumulating copper in the mitochondrial membranes and can be reversed by copper-chelating therapies. At the early stage, copper-dependent oxidative stress does not seem to occur. On the contrary, however, when copper is massively deposited in mitochondria, severe structural and respiratory impairments are observed upon disease progression. This provokes reactive oxygen species and consequently causes the mitochondrial membranes to disintegrate, which triggers hepatocyte death. Thus, in WD mitochondria are prime targets for copper, and the excessive copper burden causes their destruction, subsequently provoking tissue failure and death. © 2014 New York Academy of Sciences.

  8. 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)

  9. Cholinergic modulation of dopaminergic reward areas: upstream and downstream targets of nicotine addiction

    NARCIS (Netherlands)

    Mansvelder, H.D.; de Rover, M.; McGehee, D.S.; Brussaard, A.B.

    2003-01-01

    Nicotine reinforces smoking behaviour by activating nicotinic acetylcholine receptors in the midbrain dopaminergic reward centres. Upstream of the dopaminergic neurons nicotine induces long-term potentiation of the excitatory input to dopamine cells in the ventral tegmental area, and depresses

  10. The E1 copper binding domain of full-length amyloid precursor protein mitigates copper-induced growth inhibition in brain metastatic prostate cancer DU145 cells

    Energy Technology Data Exchange (ETDEWEB)

    Gough, Mallory, E-mail: m.gough1@lancaster.ac.uk; Blanthorn-Hazell, Sophee, E-mail: s.blanthorn-hazell@lancaster.ac.uk; Delury, Craig, E-mail: c.delury@lancaster.ac.uk; Parkin, Edward, E-mail: e.parkin@lancaster.ac.uk

    2014-10-31

    Highlights: • Copper levels are elevated in the tumour microenvironment. • APP mitigates copper-induced growth inhibition of DU145 prostate cancer (PCa) cells. • The APP intracellular domain is a prerequisite; soluble forms have no effect. • The E1 CuBD of APP is also a prerequisite. • APP copper binding potentially mitigates copper-induced PCa cell growth inhibition. - Abstract: Copper plays an important role in the aetiology and growth of tumours and levels of the metal are increased in the serum and tumour tissue of patients affected by a range of cancers including prostate cancer (PCa). The molecular mechanisms that enable cancer cells to proliferate in the presence of elevated copper levels are, therefore, of key importance in our understanding of tumour growth progression. In the current study, we have examined the role played by the amyloid precursor protein (APP) in mitigating copper-induced growth inhibition of the PCa cell line, DU145. A range of APP molecular constructs were stably over-expressed in DU145 cells and their effects on cell proliferation in the presence of copper were monitored. Our results show that endogenous APP expression was induced by sub-toxic copper concentrations in DU145 cells and over-expression of the wild-type protein was able to mitigate copper-induced growth inhibition via a mechanism involving the cytosolic and E1 copper binding domains of the full-length protein. APP likely represents one of a range of copper binding proteins that PCa cells employ in order to ensure efficient proliferation despite elevated concentrations of the metal within the tumour microenvironment. Targeting the expression of such proteins may contribute to therapeutic strategies for the treatment of cancers.

  11. Chemical Synthesis of Copper Nanoparticles

    OpenAIRE

    Hamid Reza Ghorbani

    2014-01-01

    Metal nanoparticles have attracted considerable interest particularly because of the size dependence of physical and chemical properties and its enormous technological potential. Among different metal nanoparticles, copper nanoparticles have attracted great attention because copper is one of the most key metals in new technology. Chemical methods are used to synthesize copper nanoparticles and among them chemical reduction is the most frequently applied method for the preparation of stable, c...

  12. LIGNOCELLULOSE NANOCOMPOSITE CONTAINING COPPER SULFIDE

    OpenAIRE

    Sanchi Nenkova; Peter Velev; Mirela Dragnevska; Diyana Nikolova; Kiril Dimitrov

    2011-01-01

    Copper sulfide-containing lignocellulose nanocomposites with improved electroconductivity were obtained. Two methods for preparing the copper sulfide lignocellulose nanocomposites were developed. An optimization of the parameters for obtaining of the nanocomposites with respect to obtaining improved electroconductivity, economy, and lower quantities and concentration of copper and sulfur ions in waste waters was conducted. The mechanisms and schemes of delaying and subsequent connection of co...

  13. Inhibitory effect of Disulfiram/copper complex on non-small cell lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Lincan [Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Shen, Hongmei [Cancer Center of Integrative Medicine, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Zhao, Guangqiang [Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Yang, Runxiang [Cancer Chemotherapy Center, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Cai, Xinyi [Colorectal Cancer Center, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Zhang, Lijuan [Department of Pathology, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Jin, Congguo [Cancer Institute, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Huang, Yunchao, E-mail: daliduanlincan@163.com [Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming (China)

    2014-04-18

    Highlights: • Disulfiram and copper synergistically inhibit lung cancer cell proliferation. • Lung cancer cell colony formation ability is inhibited by Disulfiram/copper. • Disulfiram/copper increases the sensitivity of cisplatin to lung cancer cells. • Lung cancer stem cells are specifically targeted by Disulfiram/copper complex. - Abstract: Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related death in both men and women worldwide. Recently, Disulfiram has been reported to be able to inhibit glioblastoma, prostate, or breast cancer cell proliferation. In this study, the synergistic effect of Disulfiram and copper on NSCLC cell growth was investigated. Inhibition of cancer cell proliferation was detected by 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) assay and cell cycle analysis. Liquid colony formation and tumor spheroid formation assays were used to evaluate their effect on cancer cell clonogenicity. Real-time PCR was performed to test the mRNA level of cancer stem cell related genes. We found that Disulfiram or copper alone did not potently inhibit NSCLC cell proliferation in vitro. However, the presence of copper significantly enhanced inhibitory effect of Disulfiram on NSCLC cell growth, indicating a synergistic effect between Disulfiram and copper. Cell cycle analysis showed that Disulfiram/copper complex caused NSCLC cell cycle arrest in G2/M phase. Furthermore, Disulfiram/copper significantly increased the sensitivity of cisplatin in NSCLC cells tested by MTT assay. Liquid colony formation assay revealed that copper dramatically increased the inhibitory effect of Disulfiram on NSCLC cell colony forming ability. Disulfiram combined with copper significantly attenuated NSCLC cell spheroid formation and recuded the mRNA expression of lung cancer stem cell related genes. Our data suggest that Disulfiram/copper complex alone or combined with other chemotherapy is a potential therapeutic strategy for NSCLC patients.

  14. Aspergillus fumigatus Copper Export Machinery and Reactive Oxygen Intermediate Defense Counter Host Copper-Mediated Oxidative Antimicrobial Offense

    Directory of Open Access Journals (Sweden)

    Philipp Wiemann

    2017-05-01

    Full Text Available The Fenton-chemistry-generating properties of copper ions are considered a potent phagolysosome defense against pathogenic microbes, yet our understanding of underlying host/microbe dynamics remains unclear. We address this issue in invasive aspergillosis and demonstrate that host and fungal responses inextricably connect copper and reactive oxygen intermediate (ROI mechanisms. Loss of the copper-binding transcription factor AceA yields an Aspergillus fumigatus strain displaying increased sensitivity to copper and ROI in vitro, increased intracellular copper concentrations, decreased survival in challenge with murine alveolar macrophages (AMΦs, and reduced virulence in a non-neutropenic murine model. ΔaceA survival is remediated by dampening of host ROI (chemically or genetically or enhancement of copper-exporting activity (CrpA in A. fumigatus. Our study exposes a complex host/microbe multifactorial interplay that highlights the importance of host immune status and reveals key targetable A. fumigatus counter-defenses.

  15. Variations of serum copper values in pregnancy

    OpenAIRE

    Vukelić Jelka; Kapamadžija Aleksandra; Petrović Đorđe; Grujić Zorica; Novakov-Mikić Aleksandra; Kopitović Vesna; Bjelica Artur

    2012-01-01

    Introduction. Copper is essential micronutrient and has an important role in the human body. The serum copper increases during pregnancy and is doubled at full term. Lower levels of serum copper in pregnancy are connected with some pathological conditions. Objective. The aim of this study was to estimate the levels of serum copper in normal and pathological pregnancies, comparing them with values of serum copper in non-pregnant women, to determine if serum copper is lower in some pathol...

  16. Flame holding downstream from a co-flow injector

    Science.gov (United States)

    Nicoli, Colette; Haldenwang, Pierre; Denet, Bruno

    2006-07-01

    We present numerical results on the flame attachment in the downstream vicinity of the co-flow injector lip that separates the reactive fluids at injection. Two stability diagrams show the domains where the flame is anchored, blown off, or extinguished, in terms of separating plate thickness and injection velocities of both fluids. Different anchoring modes—stagnation point counter-flow holding or edge flame anchorage—are described, depending particularly on the plate rim thickness. To cite this article: C. Nicoli et al., C. R. Mecanique 334 (2006).

  17. 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.

  18. Nickel, copper and cobalt coalescence in copper cliff converter slag

    Directory of Open Access Journals (Sweden)

    Wolf A.

    2016-01-01

    Full Text Available The aim of this investigation is to assess the effect of various additives on coalescence of nickel, copper and cobalt from slags generated during nickel extraction. The analyzed fluxes were silica and lime while examined reductants were pig iron, ferrosilicon and copper-silicon compound. Slag was settled at the different holding temperatures for various times in conditions that simulated the industrial environment. The newly formed matte and slag were characterized by their chemical composition and morphology. Silica flux generated higher partition coefficients for nickel and copper than the addition of lime. Additives used as reducing agents had higher valuable metal recovery rates and corresponding partition coefficients than fluxes. Microstructural studies showed that slag formed after adding reductants consisted of primarily fayalite, with some minute traces of magnetite as the secondary phase. Addition of 5 wt% of pig iron, ferrosilicon and copper-silicon alloys favored the formation of a metallized matte which increased Cu, Ni and Co recoveries. Addition of copper-silicon alloys with low silicon content was efficient in copper recovery but coalescence of the other metals was low. Slag treated with the ferrosilicon facilitated the highest cobalt recovery while copper-silicon alloys with silicon content above 10 wt% resulted in high coalescence of nickel and copper, 87 % and 72 % respectively.

  19. Structure transitions between copper-sulphate and copper-chloride ...

    Indian Academy of Sciences (India)

    Administrator

    Structure transitions between copper-sulphate and copper-chloride UPD phases on Au(111). 755. Acknowledgements. This work was supported by Research Center Jülich and the University of Bern. I V P also acknowledges support of Deutscher Akademischer Austausch. Dienst (DAAD) for a Ph D Fellowship. References.

  20. Essential roles of the Kar2/BiP molecular chaperone downstream of the UPR pathway in Cryptococcus neoformans.

    Directory of Open Access Journals (Sweden)

    Kwang-Woo Jung

    Full Text Available The endoplasmic reticulum (ER is a central hub where secreted or membrane-bound proteins are maturated and folded properly in eukaryotes. Maintenance of ER homeostasis is particularly important for human fungal pathogens, such as Cryptococcus neoformans, which encounter a plethora of host-mediated stresses during infection. Our previous study demonstrated that the unfolded protein response (UPR pathway, composed of the evolutionarily conserved Ire1 kinase and the unique Hxl1 transcription factor, has pleiotropic roles in ER stress response, thermotolerance, antifungal drug resistance, and virulence in C. neoformans. Here, we functionally characterized an ER-resident molecular chaperone, Kar2/BiP, in C. neoformans. Conditional expression of KAR2 by the copper-regulated promoter revealed that Kar2 is essential for the viability of C. neoformans. Constitutive expression of KAR2 by the strong histone H3 promoter partially restores resistance to ER stress, cell wall stress, thermotolerance, and genotoxic stress in ire1Δ and hxl1Δ mutants, suggesting that Kar2 mainly functions downstream of the UPR pathway. Furthermore, Kar2 appears to control azole resistance in C. neoformans downstream of the UPR pathway without regulation of ERG11 or ERG3. Interestingly, we discovered that azole treatment is sensed as ER-stress and subsequently activates the Ire1-dependent Hxl1 splicing event and induction of KAR2 by the UPR pathway. In contrast, the constitutive expression of Kar2 is not sufficient to restore the Ire1-mediated regulation of capsule production in C. neoformans UPR mutants. In conclusion, this study demonstrates that Kar2 is not only essential for vegetative growth but also required for response and adaptation to the environmental stresses and antifungal drugs downstream of the UPR pathway in C. neoformans.

  1. Impact of drinking water conditions and copper materials on downstream biofilm microbial communities and legionella pneumophila colonization

    Science.gov (United States)

    Legionella pneumophila, the medically important species within the genus Legionella, is a concern in engineered water systems. Its ability to amplify within free-living amoebae is well documented, but its interactions/ecology within the microbial community of drinking water biofi...

  2. Electroleaching of Copper Waste with Recovery of Copper by Electrodialysis

    Directory of Open Access Journals (Sweden)

    Nuñez P.

    2013-04-01

    Full Text Available A new process to leach and recover copper from solid waste using electric fields was designed. The leaching with electro migration is presented as an alternative to traditional leaching. Preliminary data indicate that the copper ion migration is facilitated by using the electrical potential difference; therefore applying a potential difference in the processes of leaching facilitates the removal of copper. This is especially useful when mineral concentrations are very low. Different phenomena associated with transport of copper in solution are studied to generate a model able predict the state of the copper ion concentration in time. A kinetic model for the process was developed and fitted very well the experimental data.

  3. Tryptophan Metabolism Along the Kynurenine Pathway Downstream of Toll-like Receptor Stimulation in Peripheral Monocytes.

    Science.gov (United States)

    Orhan, F; Bhat, M; Sandberg, K; Ståhl, S; Piehl, F; Svensson, C; Erhardt, S; Schwieler, L

    2016-11-01

    Tryptophan degradation along the kynurenine pathway is of central importance for the immune function. Toll-like receptors (TLRs), representing the first line of immune defence against pathogens, are expressed in various cell types. The most abundant expression is found on monocytes, macrophages and dendritic cells. The aim of this study was to investigate whether stimulation with different TLR ligands induces the kynurenine pathway in human peripheral monocytes. Cell supernatants were analysed using a liquid chromatography/mass spectrometry to measure kynurenine, kynurenic acid (KYNA), quinolinic acid (QUIN) and tryptophan. Stimulation of TLR-2, TLR-3, TLR-4, TLR-7/8 and TLR-9 was found to induce the production of kynurenine, but only stimulation of TLR-3 increased levels of further downstream metabolites, such as KYNA and QUIN. Stimulation of TLR-1, TLR-5 and TLR-6 did not induce the kynurenine pathway. Taken together, this study provides novel evidence demonstrating that TLR activation induces a pattern of downstream tryptophan degradation along the kynurenine pathway in monocytes. The results of this study may implicate that TLRs can be used as new drug targets for the regulation of aberrant tryptophan metabolism along this pathway, a potential therapeutic strategy that may be of importance in several disorders. © 2016 The Foundation for the Scandinavian Journal of Immunology.

  4. 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.

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

    Science.gov (United States)

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

    2015-04-01

    In this study, ferric chloride (FeCl3) was used to integrate downstream processes (harvesting, lipid extraction, and esterification). At concentration of 200 mg/L and at pH 3, FeCl3 exhibited an expected degree of coagulation and an increase in cell density of ten times (170 mg/10 mL). An iron-mediated oxidation reaction, Fenton-like reaction, was used to extract lipid from the harvested biomass, and efficiency of 80% was obtained with 0.5% H2O2 at 90 °C. The iron compound was also employed in the esterification step, and converted free fatty acids to fatty acid methyl esters under acidic conditions; thus, the fatal problem of saponification during esterification with alkaline catalysts was avoided, and esterification efficiency over 90% was obtained. This study clearly showed that FeCl3 in the harvesting process is beneficial in all downstream steps and have a potential to greatly reduce the production cost of microalgae-originated biodiesel. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Investigation on local scour downstream of adverse st

    Directory of Open Access Journals (Sweden)

    Javad Farhoudi

    2014-06-01

    Full Text Available This paper is focused on local scour downstream of adverse stilling basins where a submerged wall jet issued from a sluice gate. Experiments were conducted in a wide range of Froude numbers, grain sizes, tailwater depths, and stilling basin slopes. The results showed that the scour profiles at any bed slope follow shape similarity. However, the longitude evolution of scour profiles and the volume of eroded materials were increasing in accordance with slope of basin. A polynomial equation was derived to define the non-dimensional profiles under different slopes. The time evolution of scour hole dimensions and the equilibrium state were defined. It was found that under a specific condition of sediment grain size, approaching Froude number, the length and slope of adverse basin, the scour depth at the downstream of adverse basin, initially increases with tailwater depth, and after reaching its maximum value decreases to a constant value. It was also observed that the maximum depth of scour hole was decreased as the length and slope of stilling basin increased, whereas the longitudinal dimensions of the hole were increased. It was found that the maximum depth of scour hole occurs at the vicinity of side walls with slight decrease in the centerline. Finally, a power equation was expressed to fully define the dimensions of scour hole, time scale and geometry of sluice gate.

  7. Copper (II) complexes with aroylhydrazones

    Indian Academy of Sciences (India)

    Copper(II) complexes with aroylhydrazones ... The coordination chemistry of copper(II) with tridentate aroylhydrazones is briefly discussed in this article. ... EPR spectroscopy and variable temperature magnetic susceptibility measurements have been used to reveal the nature of the coordination geometry and magnetic ...

  8. The Bauschinger Effect in Copper

    DEFF Research Database (Denmark)

    Pedersen, Ole Bøcker; Brown, L .M.; Stobbs, W. M.

    1981-01-01

    A study of the Bauschinger effect in pure copper shows that by comparison with dispersion hardened copper the effect is very small and independent of temperature. This suggests that the obstacles to flow are deformable. A simple composite model based on this principle accounts for the data semi...

  9. Medical CT image reconstruction accuracy in the presence of metal objects using x-rays up to 1 MeV with x-ray targets of beryllium, carbon, aluminum, copper, and tungsten

    Science.gov (United States)

    Clayton, James; Ganguly, Arundhuti; Virshup, Gary

    2012-04-01

    Flat panels imagers based on amorphous silicon technology (a-Si) for digital radiography have been accepted by the medical community as having several advantages over film-based systems. Radiotherapy treatment planning systems employ computed tomographic (CT) data sets and projection images to delineate tumor targets and normal structures that are to be spared from radiation treatment. The accuracy of CT numbers is crucial for radiotherapy dose calculations. Conventional CT scanners operating at kilovoltage X-ray energies typically exhibit significant image reconstruction artifacts in the presence of metal implants in human body. Megavoltage X-ray energies have problems maintaining contrast sensitivity for the same dose as kV X-ray systems. We intend to demonstrate significant improvement in metal artifact reductions and electron density measurements using an amorphous silicon a-Si imager obtained with an X-ray source that can operate at energies up to 1 MeV. We will investigate the ability to maintain contrast sensitivity at this higher X-ray energy by using targets with lower atomic numbers and appropriate amounts of Xray filtration than are typically used as X-ray production targets and filters.

  10. Investigation of Industrial Polyurethane Foams Modified with Antimicrobial Copper Nanoparticles

    Directory of Open Access Journals (Sweden)

    Maria Chiara Sportelli

    2016-07-01

    Full Text Available Antimicrobial copper nanoparticles (CuNPs were electrosynthetized and applied to the controlled impregnation of industrial polyurethane foams used as padding in the textile production or as filters for air conditioning systems. CuNP-modified materials were investigated and characterized morphologically and spectroscopically, by means of Transmission Electron Microscopy (TEM, and X-ray Photoelectron Spectroscopy (XPS. The release of copper ions in solution was studied by Electro-Thermal Atomic Absorption Spectroscopy (ETAAS. Finally, the antimicrobial activity of freshly prepared, as well as aged samples—stored for two months—was demonstrated towards different target microorganisms.

  11. Combining -Omics to Unravel the Impact of Copper Nutrition on Alfalfa (Medicago sativa) Stem Metabolism.

    Science.gov (United States)

    Printz, Bruno; Guerriero, Gea; Sergeant, Kjell; Audinot, Jean-Nicolas; Guignard, Cédric; Renaut, Jenny; Lutts, Stanley; Hausman, Jean-Francois

    2016-02-01

    Copper can be found in the environment at concentrations ranging from a shortage up to the threshold of toxicity for plants, with optimal growth conditions situated in between. The plant stem plays a central role in transferring and distributing minerals, water and other solutes throughout the plant. In this study, alfalfa is exposed to different levels of copper availability, from deficiency to slight excess, and the impact on the metabolism of the stem is assessed by a non-targeted proteomics study and by the expression analysis of key genes controlling plant stem development. Under copper deficiency, the plant stem accumulates specific copper chaperones, the expression of genes involved in stem development is decreased and the concentrations of zinc and molybdenum are increased in comparison with the optimum copper level. At the optimal copper level, the expression of cell wall-related genes increases and proteins playing a role in cell wall deposition and in methionine metabolism accumulate, whereas copper excess imposes a reduction in the concentration of iron in the stem and a reduced abundance of ferritins. Secondary ion mass spectrometry (SIMS) analysis suggests a role for the apoplasm as a copper storage site in the case of copper toxicity. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists.

  12. Copper: From neurotransmission to neuroproteostasis

    Directory of Open Access Journals (Sweden)

    Carlos M Opazo

    2014-07-01

    Full Text Available Copper is critical for the Central Nervous System (CNS development and function. In particular, different studies have shown the effect of copper at brain synapses, where it inhibits Long Term Potentation (LTP and receptor pharmacology. Paradoxically, according to recent studies copper is required for a normal LTP response. Copper is released at the synaptic cleft, where it blocks glutamate receptors, which explain its blocking effects on excitatory neurotransmission. Our results indicate that copper also enhances neurotransmission through the accumulation of PSD95 protein, which increase the levels of AMPA receptors located at the plasma membrane of the post-synaptic density. Thus, our findings represent a novel mechanism for the action of copper, which may have implications for the neurophysiology and neuropathology of the CNS. These data indicate that synaptic configuration is sensitive to transient changes in transition metal homeostasis. Our results suggest that copper increases GluA1 subunit levels of the AMPA receptor through the anchorage of AMPA receptors to the plasma membrane as a result of PSD-95 accumulation. Here, we will review the role of copper on neurotransmission of CNS neurons. In addition, we will discuss the potential mechanisms by which copper could modulate neuronal proteostasis (neuroproteostasis in the CNS with focus in the Ubiquitin Proteasome System, which is particularly relevant to neurological disorders such Alzheimer’s disease (AD where copper and protein dyshomeostasis may contribute to neurodegeneration. An understanding of these mechanisms may ultimately lead to the development of novel therapeutic approaches to control metal and synaptic alterations observed in AD patients.

  13. Spectral analysis of x-ray emission created by intense laser irradiation of copper materials

    Energy Technology Data Exchange (ETDEWEB)

    Huntington, C. M.; Kuranz, C. C.; Drake, R. P. [Atmospheric, Oceanic, Space Science, University of Michigan, Ann Arbor, Michigan 48103 (United States); Malamud, G. [Atmospheric, Oceanic, Space Science, University of Michigan, Ann Arbor, Michigan 48103 (United States); Department of Physics, Nuclear Research Center - Negev, 84190 Beer-Sheva (Israel); Park, H.-S.; Maddox, B. R. [Lawrence Livermore National Laboratory, Livermore, California 94551 (United States)

    2012-10-15

    We have measured the x-ray emission, primarily from K{sub {alpha}},K{sub {beta}}, and He{sub {alpha}} lines, of elemental copper foil and 'foam' targets irradiated with a mid-10{sup 16} W/cm{sup 2} laser pulse. The copper foam at 0.1 times solid density is observed to produce 50% greater He{sub {alpha}} line emission than copper foil, and the measured signal is well-fit by a sum of three synthetic spectra generated by the atomic physics code FLYCHK. Additionally, spectra from both targets reveal characteristic inner shell K{sub {alpha}} transitions from hot electron interaction with the bulk copper. However, only the larger-volume foam target produced significant K{sub {beta}} radiation, confirming a lower bulk temperature in the higher volume sample.

  14. The NCA-1 and NCA-2 Ion Channels Function Downstream of Gq and Rho To Regulate Locomotion in Caenorhabditis elegans.

    Science.gov (United States)

    Topalidou, Irini; Chen, Pin-An; Cooper, Kirsten; Watanabe, Shigeki; Jorgensen, Erik M; Ailion, Michael

    2017-05-01

    The heterotrimeric G protein Gq positively regulates neuronal activity and synaptic transmission. Previously, the Rho guanine nucleotide exchange factor Trio was identified as a direct effector of Gq that acts in parallel to the canonical Gq effector phospholipase C. Here, we examine how Trio and Rho act to stimulate neuronal activity downstream of Gq in the nematode Caenorhabditis elegans Through two forward genetic screens, we identify the cation channels NCA-1 and NCA-2, orthologs of mammalian NALCN, as downstream targets of the Gq-Rho pathway. By performing genetic epistasis analysis using dominant activating mutations and recessive loss-of-function mutations in the members of this pathway, we show that NCA-1 and NCA-2 act downstream of Gq in a linear pathway. Through cell-specific rescue experiments, we show that function of these channels in head acetylcholine neurons is sufficient for normal locomotion in C. elegans Our results suggest that NCA-1 and NCA-2 are physiologically relevant targets of neuronal Gq-Rho signaling in C. elegans. Copyright © 2017 by the Genetics Society of America.

  15. Copper Tolerance and Characterization of a Copper-Responsive Operon, copYAZ, in an M1T1 Clinical Strain of Streptococcus pyogenes.

    Science.gov (United States)

    Young, Christie A; Gordon, Lily D; Fang, Zhong; Holder, Robert C; Reid, Sean D

    2015-08-01

    Infection with Streptococcus pyogenes is associated with a breadth of clinical manifestations ranging from mild pharyngitis to severe necrotizing fasciitis. Elevated levels of intracellular copper are highly toxic to this bacterium, and thus, the microbe must tightly regulate the level of this metal ion by one or more mechanisms, which have, to date, not been clearly defined. In this study, we have identified two virulence mechanisms by which S. pyogenes protects itself against copper toxicity. We defined a set of putative genes, copY (for a regulator), copA (for a P1-type ATPase), and copZ (for a copper chaperone), whose expression is regulated by copper. Our results indicate that these genes are highly conserved among a range of clinical S. pyogenes isolates. The copY, copA, and copZ genes are induced by copper and are transcribed as a single unit. Heterologous expression assays revealed that S. pyogenes CopA can confer copper tolerance in a copper-sensitive Escherichia coli mutant by preventing the accumulation of toxic levels of copper, a finding that is consistent with a role for CopA in copper export. Evaluation of the effect of copper stress on S. pyogenes in a planktonic or biofilm state revealed that biofilms may aid in protection during initial exposure to copper. However, copper stress appears to prevent the shift from the planktonic to the biofilm state. Therefore, our results indicate that S. pyogenes may use several virulence mechanisms, including altered gene expression and a transition to and from planktonic and biofilm states, to promote survival during copper stress. Bacterial pathogens encounter multiple stressors at the host-pathogen interface. This study evaluates a virulence mechanism(s) utilized by S. pyogenes to combat copper at sites of infection. A better understanding of pathogen tolerance to stressors such as copper is necessary to determine how host-pathogen interactions impact bacterial survival during infections. These insights may

  16. Diffusion coefficient of copper, tin and copper tin alloy

    Directory of Open Access Journals (Sweden)

    Makradi A.

    2011-05-01

    Full Text Available Pseudopotential formalism is used to construct an ionic effective potential (ion-ion potential screened by electrons. Molecular Dynamics is used in conjunction with the constructed effective potential to get the atomic structure factor of the pure components copper and tin which are compared to the experimental ones. We selected the Shaw Optimized Model Potential having proved that it adequately describes the atomic structure, we used it to calculate the velocity autocorrelation function and to deduce the self diffusion of pure metals: copper, tin and the diffusion coefficient of copper in the Sn95,6%Cu4,4% .

  17. Interactive Learning-driven Innovation in Upstream-Downstream Relations

    DEFF Research Database (Denmark)

    Machikita, Tomohiro; Ueki, Yasushi

    2012-01-01

    with new technologies and new markets. However, this is not true for simple improvement of products or process innovation. Mutual exchanges with engineers between producers and suppliers within a chain can be expected to play an important role in the case of costly innovation and in situations unknown......This paper presents a simple framework of the innovations that result from interfirm learning through exchanges of engineers in upstream-downstream relations within a production chain. To examine the framework, we empirically investigate the impact of mutual knowledge exchanges on product...... and process innovation using a survey of firm's self-reporting customer and supplier data in Indonesia, the Philippines, Thailand and Vietnam. Evidence from interconnected firms within a production chain suggests that firms with mutual exchanges between engineers and customers achieved product innovations...

  18. Efficient industry configurations in downstream gas markets. An empirical assessment

    Energy Technology Data Exchange (ETDEWEB)

    Casarin, Ariel A. [IAE Escuela de Direccion y Negocios, Universidad Austral, Buenos Aires (Argentina)

    2007-03-15

    This paper examines the production technology of the downstream gas industry in order to provide some useful insights into its efficient structure by looking at the optimal size of firms and the productive efficiency reasons for and against their vertical integration. The analysis is based on a restricted cost function model estimated using firm level data for Argentina and Great Britain. The findings provide evidence for the presence of vertical diseconomies between stages. Results indicate that a single transmitter is able to produce the industry's output at lower costs for large market sizes and that several regional firms are able to operate without sacrificing scale economies if gas distribution is integrated with supply. The findings also indicate that a gas retailer experiences constant returns to scale when it supplies a large customer base. Liberalisation could thus result in oligopolistic industry configurations. (Author)

  19. 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.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    of six representative crystal habits of 5-ASA (needles, plates, rectangular bars, rhombohedrals, elongated hexagons, and spheroids) in the context of direct compression using ring shear tester, flow rate analyzer, and instrumented tablet press. As expected, needles were very cohesive, had low flow rate...... and tabletability, creating significant processability difficulties on a production scale. However, such a habit can be adapted to the needs of downstream processing. To this end, we modified the needle-like crystal habit of the model API 5-aminosalicylic acid (5-ASA). This study reports processability assessment...... (1.0 ± 0.08 mg/s), and low bulk density (0.14 ± 0.01 g/mL) but showed better tabletability, whereas the opposite was observed with more isotropic crystal habits. For instance, spheroids, elongated hexagons, and rhombohedrals were easy/free-flowing and had high bulk densities (≥0.5 g/mL), but final...

  1. Allogeneic cell therapy bioprocess economics and optimization: downstream processing decisions.

    Science.gov (United States)

    Hassan, Sally; Simaria, Ana S; Varadaraju, Hemanthram; Gupta, Siddharth; Warren, Kim; Farid, Suzanne S

    2015-01-01

    To develop a decisional tool to identify the most cost effective process flowsheets for allogeneic cell therapies across a range of production scales. A bioprocess economics and optimization tool was built to assess competing cell expansion and downstream processing (DSP) technologies. Tangential flow filtration was generally more cost-effective for the lower cells/lot achieved in planar technologies and fluidized bed centrifugation became the only feasible option for handling large bioreactor outputs. DSP bottlenecks were observed at large commercial lot sizes requiring multiple large bioreactors. The DSP contribution to the cost of goods/dose ranged between 20-55%, and 50-80% for planar and bioreactor flowsheets, respectively. This analysis can facilitate early decision-making during process development.

  2. Receptor-targeted metalloradiopharmaceuticals. Final technical report

    Energy Technology Data Exchange (ETDEWEB)

    Green, Mark A.

    2000-03-22

    Copper (II) and platinum (II) coordination complexes were prepared and characterized. These complexes were designed to afford structural homology with steroidal and non-steroidal estrogens for possible use as receptor-targeted radiopharmaceuticals. While weak affinity for the estrogen receptor was detectable, none would appear to have sufficient receptor-affinity for estrogen-receptor-targeted imaging or therapy.

  3. 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

  4. 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

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

    Science.gov (United States)

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

    2002-11-01

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

  6. A Copernicus downstream service for surface displacement monitoring in Germany

    Science.gov (United States)

    Cahyadi Kalia, Andre; Frei, Michaela; Lege, Thomas

    2016-04-01

    SAR Interferometry is a powerful technique able to detect and monitor various surface displacements caused by e.g. gravitative mass movement, subrosion, groundwater extraction, fluid injection, natural gas extraction. These processes can e.g. cause damage to buildings, infrastructure, affect ecosystems, agriculture and the economic use of the geological underground by influencing the hydro(geo)logical setting. Advanced techniques of interferometric processing (Persistent Scatterer Interferometry, PSI) allow highly precise displacement measurements (mm precision) by analyzing stacks of SAR imagery. The PSI mapping coverage can be increased to entire nations by using several adjacent satellite tracks. In order to assist the operational use of this technique a German-wide, officially approved, PSI dataset is under development. The intention of this presentation is to show i) the concept of the Copernicus downstream service for surface displacement monitoring in Germany and ii) a pilot study to exemplarily demonstrate the workflow and potential products from the Copernicus downstream service. The pilot study is focusing on the built up of an officially approved wide-area PSI dataset. The study area covers an area of more than 30.000 km² and is located in the Northwest German Basin. Several natural processes (e.g. compaction of marine sediments, peat loss) and anthropogenic activities (e.g. natural gas extraction, rock salt mining) are causing surface displacements in the study area. The PSI analysis is based on six ERS-1/-2 data stacks covering the timespan from 1992 until 2001. Each data stack consists of 49 to 73 ERS-1/-2 SAR images. A comparison of the PSI results with thematic data (e.g. volume and location of extracted natural gas) strongly indicates that a part of the detected land subsidence is caused by natural gas extraction. Furthermore, land subsidence caused by e.g. fluid injection and rock salt mining were successfully detected by the PSI analysis.

  7. Inactivation of norovirus on dry copper alloy surfaces.

    Science.gov (United States)

    Warnes, Sarah L; Keevil, C William

    2013-01-01

    Noroviruses (family Caliciviridae) are the primary cause of viral gastroenteritis worldwide. The virus is highly infectious and touching contaminated surfaces can contribute to infection spread. Although the virus was identified over 40 years ago the lack of methods to assess infectivity has hampered the study of the human pathogen. Recently the murine virus, MNV-1, has successfully been used as a close surrogate. Copper alloys have previously been shown to be effective antimicrobial surfaces against a range of bacteria and fungi. We now report rapid inactivation of murine norovirus on alloys, containing over 60% copper, at room temperature but no reduction of infectivity on stainless steel dry surfaces in simulated wet fomite and dry touch contamination. The rate of inactivation was initially very rapid and proportional to copper content of alloy tested. Viral inactivation was not as rapid on brass as previously observed for bacteria but copper-nickel alloy was very effective. The use of chelators and quenchers of reactive oxygen species (ROS) determined that Cu(II) and especially Cu(I) ions are still the primary effectors of toxicity but quenching superoxide and hydroxyl radicals did not confer protection. This suggests Fenton generation of ROS is not important for the inactivation mechanism. One of the targets of copper toxicity was the viral genome and a reduced copy number of the gene for a viral encoded protein, VPg (viral-protein-genome-linked), which is essential for infectivity, was observed following contact with copper and brass dry surfaces. The use of antimicrobial surfaces containing copper in high risk closed environments such as cruise ships and care facilities could help to reduce the spread of this highly infectious and costly pathogen.

  8. Inactivation of norovirus on dry copper alloy surfaces.

    Directory of Open Access Journals (Sweden)

    Sarah L Warnes

    Full Text Available Noroviruses (family Caliciviridae are the primary cause of viral gastroenteritis worldwide. The virus is highly infectious and touching contaminated surfaces can contribute to infection spread. Although the virus was identified over 40 years ago the lack of methods to assess infectivity has hampered the study of the human pathogen. Recently the murine virus, MNV-1, has successfully been used as a close surrogate. Copper alloys have previously been shown to be effective antimicrobial surfaces against a range of bacteria and fungi. We now report rapid inactivation of murine norovirus on alloys, containing over 60% copper, at room temperature but no reduction of infectivity on stainless steel dry surfaces in simulated wet fomite and dry touch contamination. The rate of inactivation was initially very rapid and proportional to copper content of alloy tested. Viral inactivation was not as rapid on brass as previously observed for bacteria but copper-nickel alloy was very effective. The use of chelators and quenchers of reactive oxygen species (ROS determined that Cu(II and especially Cu(I ions are still the primary effectors of toxicity but quenching superoxide and hydroxyl radicals did not confer protection. This suggests Fenton generation of ROS is not important for the inactivation mechanism. One of the targets of copper toxicity was the viral genome and a reduced copy number of the gene for a viral encoded protein, VPg (viral-protein-genome-linked, which is essential for infectivity, was observed following contact with copper and brass dry surfaces. The use of antimicrobial surfaces containing copper in high risk closed environments such as cruise ships and care facilities could help to reduce the spread of this highly infectious and costly pathogen.

  9. Copper uptake and retention in liver parenchymal cells isolated from nutritionally copper-deficient rats

    NARCIS (Netherlands)

    van den Berg, G. J.; de Goeij, J. J.; Bock, I.; Gijbels, M. J.; Brouwer, A.; Lei, K. Y.; Hendriks, H. F.

    1991-01-01

    Copper uptake and retention were studied in primary cultures of liver parenchymal cells isolated from copper-deficient rats. Male Sprague-Dawley rats were fed a copper-deficient diet (less than 1 mg Cu/kg) for 10 wk. Copper-deficient rats were characterized by low copper concentrations in plasma and

  10. Copper uptake and retention in liver parenchymal cells isolated from nutritionally copper-deficient rats

    NARCIS (Netherlands)

    Berg, G.J. van den; Goeij, J.J.M. de; Bock, I.; Gijbels, M.J.J.; Brouwer, A.; Lei, K.Y.; Hendruiks, H.F.J.

    1991-01-01

    Copper uptake and retention were studied in primary cultures of liver parenchymal cells isolated from copper-deficient rats. Male Sprague-Dawley rats were fed a copper-deficient diet (< 1 mg Cu/kg) for 10 wk. Copper-deficient rats were characterized by low copper concentrations in plasma and liver,

  11. Additive and Photochemical Manufacturing of Copper

    Science.gov (United States)

    Yung, Winco K. C.; Sun, Bo; Meng, Zhengong; Huang, Junfeng; Jin, Yingdi; Choy, Hang Shan; Cai, Zhixiang; Li, Guijun; Ho, Cheuk Lam; Yang, Jinlong; Wong, Wai Yeung

    2016-12-01

    In recent years, 3D printing technologies have been extensively developed, enabling rapid prototyping from a conceptual design to an actual product. However, additive manufacturing of metals in the existing technologies is still cost-intensive and time-consuming. Herein a novel platform for low-cost additive manufacturing is introduced by simultaneously combining the laser-induced forward transfer (LIFT) method with photochemical reaction. Using acrylonitrile butadiene styrene (ABS) polymer as the sacrificial layer, sufficient ejection momentum can be generated in the LIFT method. A low-cost continuous wave (CW) laser diode at 405 nm was utilized and proved to be able to transfer the photochemically synthesized copper onto the target substrate. The wavelength-dependent photochemical behaviour in the LIFT method was verified and characterized by both theoretical and experimental studies compared to 1064 nm fiber laser. The conductivity of the synthesized copper patterns could be enhanced using post electroless plating while retaining the designed pattern shapes. Prototypes of electronic circuits were accordingly built and demonstrated for powering up LEDs. Apart from pristine PDMS materials with low surface energies, the proposed method can simultaneously perform laser-induced forward transfer and photochemical synthesis of metals, starting from their metal oxide forms, onto various target substrates such as polyimide, glass and thermoplastics.

  12. 49 CFR 192.279 - Copper pipe.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Copper pipe. 192.279 Section 192.279 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... Copper pipe. Copper pipe may not be threaded except that copper pipe used for joining screw fittings or...

  13. Copper transporters and chaperones: Their function on ...

    Indian Academy of Sciences (India)

    Copper, although known as a micronutrient, has a pivotal role in modulating the cellular metabolism. Many studieshave reported the role of copper in angiogenesis. Copper chaperones are intracellular proteins that mediate coppertrafficking to various cell organelles. However, the role and function of copper chaperones in ...

  14. Metabolism and functions of copper in brain.

    Science.gov (United States)

    Scheiber, Ivo F; Mercer, Julian F B; Dringen, Ralf

    2014-05-01

    Copper is an important trace element that is required for essential enzymes. However, due to its redox activity, copper can also lead to the generation of toxic reactive oxygen species. Therefore, cellular uptake, storage as well as export of copper have to be tightly regulated in order to guarantee sufficient copper supply for the synthesis of copper-containing enzymes but also to prevent copper-induced oxidative stress. In brain, copper is of importance for normal development. In addition, both copper deficiency as well as excess of copper can seriously affect brain functions. Therefore, this organ possesses ample mechanisms to regulate its copper metabolism. In brain, astrocytes are considered as important regulators of copper homeostasis. Impairments of homeostatic mechanisms in brain copper metabolism have been associated with neurodegeneration in human disorders such as Menkes disease, Wilson's disease and Alzheimer's disease. This review article will summarize the biological functions of copper in the brain and will describe the current knowledge on the mechanisms involved in copper transport, storage and export of brain cells. The role of copper in diseases that have been connected with disturbances in brain copper homeostasis will also be discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. A conditional mutation affecting localization of the Menkes disease copper ATPase. Suppression by copper supplementation

    National Research Council Canada - National Science Library

    Kim, Byung-Eun; Smith, Kathryn; Meagher, Carisa K; Petris, Michael J

    2002-01-01

    Copper is an essential co-factor for several key metabolic processes. This requirement in humans is underscored by Menkes disease, an X-linked copper deficiency disorder caused by mutations in the copper transporting P-type ATPase, MNK...

  16. Majorana Electroformed Copper Mechanical Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Overman, Nicole R.; Overman, Cory T.; Kafentzis, Tyler A.; Edwards, Danny J.; Hoppe, Eric W.

    2012-04-30

    The MAJORANA DEMONSTRATOR is a large array of ultra-low background high-purity germanium detectors, enriched in 76Ge, designed to search for zero-neutrino double-beta decay. The DEMONSTRATOR will utilize ultra high purity electroformed copper for a variety of detector components and shielding. A preliminary mechanical evaluation was performed on the Majorana prototype electroformed copper material. Several samples were removed from a variety of positions on the mandrel. Tensile testing, optical metallography, scanning electron microscopy, and hardness testing were conducted to evaluate mechanical response. Analyses carried out on the Majorana prototype copper to this point show consistent mechanical response from a variety of test locations. Evaluation shows the copper meets or exceeds the design specifications.

  17. Hereditary iron and copper deposition

    DEFF Research Database (Denmark)

    Aaseth, Jan; Flaten, Trond Peder; Andersen, Ole

    2007-01-01

    Hereditary deposition of iron (primary haemochromatosis) or copper (Wilson's disease) are autosomal recessive metabolic disease characterized by progressive liver pathology and subsequent involvement of various other organs. The prevalence of primary haemochromatosis is approximately 0.5%, about...

  18. Electron acceleration at nearly perpendicular collisionless shocks. 3: Downstream distributions

    Science.gov (United States)

    Krauss-Varban, D.

    1994-01-01

    Spacecraft observations at the Earth's bow shock and at interplanetary shocks have established that the largest fluxes of accelerated suprathermal electrons occur in so-called shock spike events immediately downstream of the shock ramp. Previous theoretical efforts have mainly focused on explaining upstream energetic electron beams. Here we investigate the general motion and acceleration of energetic electrons in a curved, nearly perpendicular shock by numerically integrating the orbits of solar wind halo electrons in shock fields generated by a hybrid simulation (core electron fluid and kinetic ions). Close to the angle Theta(sub Bn) = 90 degs between the upstream magnetic field and shock normal, the calculations result in a (perpendicular) temperature increase proportional to the magnetic field ratio and give the highest phase space densities in the overshoot. For a steep distribution, the temperature change can correspond to an enhancement of the distribution by several orders of magnitude. These results are in agreement with predictions from adiabatic mapping. With smaller angles Theta(sub Bn), the overshoot and downstream densities fall off quickly, because the adiabatic energy gain is less and fewer electrons transmit. The shock curvature also leads to an accumulation of electrons close to 90 degs. Without pitch angle scattering, energization is only significant within a few (approximately 5 to 10 degs) degrees of the point of tangency. However, shock spike events appear to be observed more easily and farther away from 90 degs. Given that over a region of several degrees around 90 degs the theory gives enhancements of up to approximately 4 orders of magnitude, such electrons could in principle account for the typically observed enhancements of 1 to 2 orders of magnitude, if they were distributed over Theta(sub Bn). To test the idea that scattering could efficiently redistribute the energetic electrons, we have conducted test particle simulations in which

  19. 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

  20. Copper atomic-scale transistors

    Directory of Open Access Journals (Sweden)

    Fangqing Xie

    2017-03-01

    Full Text Available We investigated copper as a working material for metallic atomic-scale transistors and confirmed that copper atomic-scale transistors can be fabricated and operated electrochemically in a copper electrolyte (CuSO4 + H2SO4 in bi-distilled water under ambient conditions with three microelectrodes (source, drain and gate. The electrochemical switching-on potential of the atomic-scale transistor is below 350 mV, and the switching-off potential is between 0 and −170 mV. The switching-on current is above 1 μA, which is compatible with semiconductor transistor devices. Both sign and amplitude of the voltage applied across the source and drain electrodes (Ubias influence the switching rate of the transistor and the copper deposition on the electrodes, and correspondingly shift the electrochemical operation potential. The copper atomic-scale transistors can be switched using a function generator without a computer-controlled feedback switching mechanism. The copper atomic-scale transistors, with only one or two atoms at the narrowest constriction, were realized to switch between 0 and 1G0 (G0 = 2e2/h; with e being the electron charge, and h being Planck’s constant or 2G0 by the function generator. The switching rate can reach up to 10 Hz. The copper atomic-scale transistor demonstrates volatile/non-volatile dual functionalities. Such an optimal merging of the logic with memory may open a perspective for processor-in-memory and logic-in-memory architectures, using copper as an alternative working material besides silver for fully metallic atomic-scale transistors.

  1. Formation of copper-indium-selenide and/or copper-indium-gallium-selenide films from indium selenide and copper selenide precursors

    Science.gov (United States)

    Curtis, Calvin J [Lakewood, CO; Miedaner, Alexander [Boulder, CO; Van Hest, Maikel [Lakewood, CO; Ginley, David S [Evergreen, CO; Nekuda, Jennifer A [Lakewood, CO

    2011-11-15

    Liquid-based indium selenide and copper selenide precursors, including copper-organoselenides, particulate copper selenide suspensions, copper selenide ethylene diamine in liquid solvent, nanoparticulate indium selenide suspensions, and indium selenide ethylene diamine coordination compounds in solvent, are used to form crystalline copper-indium-selenide, and/or copper indium gallium selenide films (66) on substrates (52).

  2. Elevated copper impairs hepatic nuclear receptor function in Wilson’s disease

    Science.gov (United States)

    Wooton-Kee, Clavia Ruth; Jain, Ajay K.; Wagner, Martin; Grusak, Michael A.; Finegold, Milton J.; Lutsenko, Svetlana; Moore, David D.

    2015-01-01

    Wilson’s disease (WD) is an autosomal recessive disorder that results in accumulation of copper in the liver as a consequence of mutations in the gene encoding the copper-transporting P-type ATPase (ATP7B). WD is a chronic liver disorder, and individuals with the disease present with a variety of complications, including steatosis, cholestasis, cirrhosis, and liver failure. Similar to patients with WD, Atp7b–/– mice have markedly elevated levels of hepatic copper and liver pathology. Previous studies have demonstrated that replacement of zinc in the DNA-binding domain of the estrogen receptor (ER) with copper disrupts specific binding to DNA response elements. Here, we found decreased binding of the nuclear receptors FXR, RXR, HNF4α, and LRH-1 to promoter response elements and decreased mRNA expression of nuclear receptor target genes in Atp7b–/– mice, as well as in adult and pediatric WD patients. Excessive hepatic copper has been described in progressive familial cholestasis (PFIC), and we found that similar to individuals with WD, patients with PFIC2 or PFIC3 who have clinically elevated hepatic copper levels exhibit impaired nuclear receptor activity. Together, these data demonstrate that copper-mediated nuclear receptor dysfunction disrupts liver function in WD and potentially in other disorders associated with increased hepatic copper levels. PMID:26241054

  3. Host Cell Copper Transporters CTR1 and ATP7A are important for Influenza A virus replication.

    Science.gov (United States)

    Rupp, Jonathan C; Locatelli, Manon; Grieser, Alexis; Ramos, Andrea; Campbell, Patricia J; Yi, Hong; Steel, John; Burkhead, Jason L; Bortz, Eric

    2017-01-23

    The essential role of copper in eukaryotic cellular physiology is known, but has not been recognized as important in the context of influenza A virus infection. In this study, we investigated the effect of cellular copper on influenza A virus replication. Influenza A/WSN/33 (H1N1) virus growth and macromolecule syntheses were assessed in cultured human lung cells (A549) where the copper concentration of the growth medium was modified, or expression of host genes involved in copper homeostasis was targeted by RNA interference. Exogenously increasing copper concentration, or chelating copper, resulted in moderate defects in viral growth. Nucleoprotein (NP) localization, neuraminidase activity assays and transmission electron microscopy did not reveal significant defects in virion assembly, morphology or release under these conditions. However, RNAi knockdown of the high-affinity copper importer CTR1 resulted in significant viral growth defects (7.3-fold reduced titer at 24 hours post-infection, p = 0.04). Knockdown of CTR1 or the trans-Golgi copper transporter ATP7A significantly reduced polymerase activity in a minigenome assay. Both copper transporters were required for authentic viral RNA synthesis and NP and matrix (M1) protein accumulation in the infected cell. These results demonstrate that intracellular copper regulates the influenza virus life cycle, with potentially distinct mechanisms in specific cellular compartments. These observations provide a new avenue for drug development and studies of influenza virus pathogenesis.

  4. 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.

  5. Oxidative stress and its downstream signaling in aging eyes.

    Science.gov (United States)

    Pinazo-Durán, María Dolores; Gallego-Pinazo, Roberto; García-Medina, Jose Javier; Zanón-Moreno, Vicente; Nucci, Carlo; Dolz-Marco, Rosa; Martínez-Castillo, Sebastián; Galbis-Estrada, Carmen; Marco-Ramírez, Carla; López-Gálvez, Maria Isabel; Galarreta, David J; Díaz-Llópis, Manuel

    2014-01-01

    Oxidative stress (OS) and its biomarkers are the biochemical end point of the imbalance between reactive oxygen species (ROS) production and the ability of the antioxidant (AOX) biological systems to fight against oxidative injury. We reviewed the role of OS and its downstream signaling in aging eyes. A search of the literature and current knowledge on the physiological and pathological mechanisms of OS were revisited in relation to the eyes and the aging process. Most prevalent ocular diseases have been analyzed herein in relation to OS and nutraceutic supplements, such as dry-eye disorders, glaucoma, age-related macular degeneration, and diabetic retinopathy. Clinical, biochemical, and molecular data from anterior and posterior eye segment diseases point to OS as the common pathogenic mechanism in the majority of these ocular disorders, many of which are pathologies causing visual impairment, blindness, and subsequent loss of life quality. Studies with nutraceutic supplements in aging eye-related pathologies have also been reviewed. OS, nutritional status, and nutraceutic supplements have to be considered within the standards of care of older ophthalmologic patients. OS biomarkers and surrogate end points may help in managing the aging population with ocular diseases.

  6. 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.

  7. 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.

  8. Downstream migration and multiple dam passage by Atlantic Salmon smolts

    Science.gov (United States)

    Nyqvist, D.; McCormick, Stephen; Greenberg, L.; Ardren, W.R.; Bergman, E.; Calles, O.; Castro-Santos, Theodore R.

    2017-01-01

    The purpose of this study was to investigate behavior and survival of radio-tagged wild and hatchery-reared landlocked Atlantic Salmon Salmo salar smolts as they migrated past three hydropower dams equipped with fish bypass solutions in the Winooski River, Vermont. Among hatchery-reared smolts, those released early were more likely to initiate migration and did so after less delay than those released late. Once migration was initiated, however, the late-released hatchery smolts migrated at greater speeds. Throughout the river system, hatchery-reared fish performed similarly to wild fish. Dam passage rates varied between the three dams and was highest at the dam where unusually high spill levels occurred throughout the study period. Of the 50 fish that did migrate downstream, only 10% managed to reach the lake. Migration success was low despite the presence of bypass solutions, underscoring the need for evaluations of remedial measures; simply constructing a fishway is not synonymous with providing fish passage.

  9. Synthetic Routes to Methylerythritol Phosphate Pathway Intermediates and Downstream Isoprenoids.

    Science.gov (United States)

    Jarchow-Choy, Sarah K; Koppisch, Andrew T; Fox, David T

    2014-04-01

    Isoprenoids constitute the largest class of natural products with greater than 55,000 identified members. They play essential roles in maintaining proper cellular function leading to maintenance of human health, plant defense mechanisms against predators, and are often exploited for their beneficial properties in the pharmaceutical and nutraceutical industries. Most impressively, all known isoprenoids are derived from one of two C5-precursors, isopentenyl diphosphate (IPP) or dimethylallyl diphosphate (DMAPP). In order to study the enzyme transformations leading to the extensive structural diversity found within this class of compounds there must be access to the substrates. Sometimes, intermediates within a biological pathway can be isolated and used directly to study enzyme/pathway function. However, the primary route to most of the isoprenoid intermediates is through chemical catalysis. As such, this review provides the first exhaustive examination of synthetic routes to isoprenoid and isoprenoid precursors with particular emphasis on the syntheses of intermediates found as part of the 2C-methylerythritol 4-phosphate (MEP) pathway. In addition, representative syntheses are presented for the monoterpenes (C10), sesquiterpenes (C15), diterpenes (C20), triterpenes (C30) and tetraterpenes (C40). Finally, in some instances, the synthetic routes to substrate analogs found both within the MEP pathway and downstream isoprenoids are examined.

  10. The Maternal Obesity Management (MOM) Trial Protocol: a lifestyle intervention during pregnancy to minimize downstream obesity.

    Science.gov (United States)

    Adamo, Kristi B; Ferraro, Zachary M; Goldfield, Gary; Keely, Erin; Stacey, Dawn; Hadjiyannakis, Stasia; Jean-Philippe, Sonia; Walker, Mark; Barrowman, Nicholas J

    2013-05-01

    Maternal obesity and/or high gestational weight gain (GWG) are associated with downstream child obesity. Pregnancy represents a critical period for prevention as women are highly motivated and more receptive to behavior change. This pilot study was developed to test the feasibility of intervening with the mother, specifically keeping her GWG within the Institute of Medicine (IOM) limits, with the intended target of preventing obesity in her child downstream. We are testing the practicality of delivering a structured physical activity and nutrition intervention to pregnant women during gestation and then following mom and baby to 24 months of age. This study is a two-arm, parallel group, randomized controlled trial being conducted in Ottawa. Pregnant women, with pregravid BMI >18.5, between 12 and 20 weeks gestation are randomized to one of two groups: intervention (n=30) who receive the MOM trial Handbook (guide to healthy gestation) plus a structured physical activity and nutrition program, or a standard clinical care control group (n=30). The intervention lasts 25-28 weeks (6 months) depending on anticipated delivery date, with follow-up assessment on mother and child at 3, 6, 12 and 24 months post-delivery. Pregnancy, a critical time of growth, development and physiological change, provides an opportunity for early lifestyle intervention. The goal of identifying an effective lifestyle program for the gestational period that leads to healthy fetal development and subsequently normal weight offspring, less likely to develop obesity and its co-morbidities, is unique and could possibly attenuate the inter-generational cycle of obesity. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Subpicosecond laser ablation of copper and fused silica: Initiation threshold and plasma expansion

    Energy Technology Data Exchange (ETDEWEB)

    Axente, E., E-mail: emanuel.axente@inflpr.ro [Lasers Department, National Institute for Lasers, Plasma, and Radiation Physics, P.O. Box MG 36, RO-77125, Bucharest-Magurele (Romania); Laboratoire LP3, CNRS - Universite Aix-Marseille II, Luminy, 13288 Marseille (France); Noel, S.; Hermann, J.; Sentis, M. [Laboratoire LP3, CNRS - Universite Aix-Marseille II, Luminy, 13288 Marseille (France); Mihailescu, I.N. [Lasers Department, National Institute for Lasers, Plasma, and Radiation Physics, P.O. Box MG 36, RO-77125, Bucharest-Magurele (Romania)

    2009-09-30

    We investigated the subpicosecond laser ablation of copper and fused silica under 100 fs laser irradiation at 800 nm in vacuum by means of fast plume imaging and time- and space-resolved optical emission spectroscopy. We found that, to the difference of copper ablation, the laser-generated plasma from a fused silica target exhibited one 'main' component only. The 'slow' plasma component, observed during copper ablation and usually assigned to optical emission from nanoparticles was not detected by either plasma fast imaging or optical emission spectroscopy even when fused silica targets were submitted to the highest incident fluences used in our experiments. The characteristic expansion velocity of this unique component was about three times larger than the velocity of the fast plume component observed during copper ablation. The dependence of laser fluence on both plasma expansion and ablation rate was investigated and discussed in terms of ablation efficiency and initiation mechanisms.

  12. 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.

  13. The essential and downstream common proteins of amyotrophic lateral sclerosis: A protein-protein interaction network analysis.

    Science.gov (United States)

    Mao, Yimin; Kuo, Su-Wei; Chen, Le; Heckman, C J; Jiang, M C

    2017-01-01

    Amyotrophic Lateral Sclerosis (ALS) is a devastative neurodegenerative disease characterized by selective loss of motoneurons. While several breakthroughs have been made in identifying ALS genetic defects, the detailed molecular mechanisms are still unclear. These genetic defects involve in numerous biological processes, which converge to a common destiny: motoneuron degeneration. In addition, the common comorbid Frontotemporal Dementia (FTD) further complicates the investigation of ALS etiology. In this study, we aimed to explore the protein-protein interaction network built on known ALS-causative genes to identify essential proteins and common downstream proteins between classical ALS and ALS+FTD (classical ALS + ALS/FTD) groups. The results suggest that classical ALS and ALS+FTD share similar essential protein set (VCP, FUS, TDP-43 and hnRNPA1) but have distinctive functional enrichment profiles. Thus, disruptions to these essential proteins might cause motoneuron susceptible to cellular stresses and eventually vulnerable to proteinopathies. Moreover, we identified a common downstream protein, ubiquitin-C, extensively interconnected with ALS-causative proteins (22 out of 24) which was not linked to ALS previously. Our in silico approach provides the computational background for identifying ALS therapeutic targets, and points out the potential downstream common ground of ALS-causative mutations.

  14. The essential and downstream common proteins of amyotrophic lateral sclerosis: A protein-protein interaction network analysis.

    Directory of Open Access Journals (Sweden)

    Yimin Mao

    Full Text Available Amyotrophic Lateral Sclerosis (ALS is a devastative neurodegenerative disease characterized by selective loss of motoneurons. While several breakthroughs have been made in identifying ALS genetic defects, the detailed molecular mechanisms are still unclear. These genetic defects involve in numerous biological processes, which converge to a common destiny: motoneuron degeneration. In addition, the common comorbid Frontotemporal Dementia (FTD further complicates the investigation of ALS etiology. In this study, we aimed to explore the protein-protein interaction network built on known ALS-causative genes to identify essential proteins and common downstream proteins between classical ALS and ALS+FTD (classical ALS + ALS/FTD groups. The results suggest that classical ALS and ALS+FTD share similar essential protein set (VCP, FUS, TDP-43 and hnRNPA1 but have distinctive functional enrichment profiles. Thus, disruptions to these essential proteins might cause motoneuron susceptible to cellular stresses and eventually vulnerable to proteinopathies. Moreover, we identified a common downstream protein, ubiquitin-C, extensively interconnected with ALS-causative proteins (22 out of 24 which was not linked to ALS previously. Our in silico approach provides the computational background for identifying ALS therapeutic targets, and points out the potential downstream common ground of ALS-causative mutations.

  15. Use of copper radioisotopes in investigating disorders of copper metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Camakaris, J.; Voskoboinik, I.; Brooks, H.; Greenough, M. [University of Melbourne, Parkville, VIC (Australia). Department of Genetics; Smith, S. [Australian Nuclear Science and Technology Organisation (ANSTO), Lucas Heights, NSW (Australia). Radiopharmaceuticals Division; Mercer, J. [Deakin University, Rusden Campus, Clayton, VIC (Australia). Centre of Cellular and Molecular Biology

    1998-12-31

    Full text: Copper is an essential trace element for life as a number of vital enzymes require it. Copper deficiency can lead to neurological disorders, osteoporosis and weakening of arteries. However Cu is also highly toxic and homeostatic mechanisms have evolved to maintain Cu at levels which satisfy requirements but do not cause toxicity. Toxicity is mediated by the oxidative capacity of Cu and its ability to generate toxic free radicals. There are several acquired and inherited diseases due to either Cu toxicity or Cu deficiency. The study of these diseases facilitates identification of genes and proteins involved in copper homeostasis, and this in turn will provide rational therapeutic approaches. Our studies have focused on Menkes disease in humans which is an inherited and usually lethal copper deficiency. Using copper radioisotopes {sup 64}Cu (t 1/2 = 12.8 hr) and {sup 67}Cu (t 1/2 = 61 hr) we have studied the protein which is mutated in Menkes disease. This is a transmembrane copper pump which is responsible for absorption of copper into the body and also functions to pump out excess Cu from cells when Cu is elevated. It is therefore a vital component of normal Cu homeostasis. We have provided the first biochemical evidence that the Menkes protein functions as a P-type ATPase Cu pump (Voskoboinik et al., FEBS Letters, in press) and these data will be discussed. The assay involved pumping of radiocopper into purified membrane vesicles. Furthermore we have transfected normal and mutant Menkes genes into cells and are carrying out structure-function studies. We are also studying the role of amyloid precursor protein (APP) as a Cu transport protein in order to determine how Cu regulates this protein and its cleavage products. These studies will provide vital information on the relationship between Cu and APP and processes which lead to Alzheimers disease

  16. 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

  17. Improving Beneficiation of Copper and Iron from Copper Slag by Modifying the Molten Copper Slag

    Directory of Open Access Journals (Sweden)

    Zhengqi Guo

    2016-04-01

    Full Text Available In the paper, a new technology was developed to improve the beneficiation of copper and iron components from copper slag, by modifying the molten slag to promote the mineralization of valuable minerals and to induce the growth of mineral grains. Various parameters, including binary basicity, dosage of compound additive, modification temperature, cooling rate and the end point temperature of slow cooling were investigated. Meanwhile, optical microscope, scanning electron microscope and energy dispersive spectrometer (SEM-EDS was employed to determine the mineralogy of the modified and unmodified slag, as well as to reveal the mechanisms of enhancing beneficiation. The results show that under the proper conditions, the copper grade of rougher copper concentrate was increased from 6.43% to 11.04%, iron recovery of magnetic separation was increased significantly from 32.40% to 63.26%, and other evaluation indexes were changed slightly, in comparison with unmodified copper slag. Moreover, matte and magnetite grains in the modified slag aggregated together and grew obviously to the mean size of over 50 μm, resulting in an improvement of beneficiation of copper and iron.

  18. Thiol-based copper handling by the copper chaperone Atox1.

    Science.gov (United States)

    Hatori, Yuta; Inouye, Sachiye; Akagi, Reiko

    2017-04-01

    Human antioxidant protein 1 (Atox1) plays a crucial role in cellular copper homeostasis. Atox1 captures cytosolic copper for subsequent transfer to copper pumps in trans Golgi network, thereby facilitating copper supply to various copper-dependent oxidereductases matured within the secretory vesicles. Atox1 and other copper chaperones handle cytosolic copper using Cys thiols which are ideal ligands for coordinating Cu(I). Recent studies demonstrated reversible oxidation of these Cys residues in copper chaperones, linking cellular redox state to copper homeostasis. Highlighted in this review are unique redox properties of Atox1 and other copper chaperones. Also, summarized are the redox nodes in the cytosol which potentially play dominant roles in the redox regulation of copper chaperones. © 2016 IUBMB Life, 69(4):246-254, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

  19. Spall response of annealed copper to direct explosive loading

    Science.gov (United States)

    Finnegan, S. G.; Burns, M. J.; Markland, L.; Goff, M.; Ferguson, J. W.

    2017-01-01

    Taylor wave spall experiments were conducted on annealed copper targets using direct explosive loading. The targets were mounted on the back of an explosive disc which was being used for a shock to detonation transition (SDT) test in a gas gun. This technique allows two experiments to be conducted with one piece of explosive. Explosive loading creates a high stress state within the target with a lower strain rate than an equivalent plate impact experiment, although the shock front will also have some curvature. Three shots were performed on two differently annealed batches of copper to investigate the viability of the technique and the effect of annealing on the spall response. One pair of targets was annealed at 850°C for four hours and the other target was annealed at 600°C for one hour. The free surface velocity (FSV) profiles were recorded using a Photonic Doppler Velocimetry (PDV) probe focused on the center of the target. The profiles were compared to predictions from the CREST reactive burn model. One profile recorded a significantly lower peak velocity which was attributed to the probe being located off center. Despite this, all three calculated spall strengths closely agreed and it was concluded that the technique is a viable one for loading an inert target.

  20. Catecholase activity associated with copper-S100B.

    Science.gov (United States)

    Senior, SueAnn Z; Mans, Laura L; VanGuilder, Heather D; Kelly, Kimberly A; Hendrich, Michael P; Elgren, Timothy E

    2003-04-22

    This study addresses the spectroscopic properties and reactivity associated with the copper-loaded form of S100B isolated from bovine brain. Copper(II)-S100B displays EPR features typical of a type II copper center and is shown here to exhibit catecholase activity, the two-electron oxidation of catechols. The steady-state kinetics associated with the oxidation of several catecholamines has been probed in order to further characterize this activity. The evidence provided indicates that the catecholase chemistry is copper initiated. Superoxide dismutase has no effect on the rates of catecholamine oxidation catalyzed by Cu-S100B, establishing that superoxide is not produced during this reaction, ruling out an autoxidative mechanism. Addition of catalase to the Cu-S100B reaction with catechols reduces the amount of oxygen consumed by 50%, demonstrating that peroxide is released during this reaction. The release of peroxide is mechanistically distinct from the type III dinuclear copper proteins, catechol oxidase and tyrosinase.

  1. 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

  2. Copper metallurgy at the crossroads

    Directory of Open Access Journals (Sweden)

    Habashi F.

    2007-01-01

    Full Text Available Copper technology changed from the vertical to the horizontal furnace and from the roast reaction to converting towards the end of the last century. However, the horizontal furnace proved to be an inefficient and polluting reactor. As a result many attempts were made to replace it. In the past 50 years new successful melting processes were introduced on an industrial scale that were more energy efficient and less polluting. In addition, smelting and converting were conducted in a single reactor in which the concentrate was fed and the raw copper was produced. The standing problem in many countries, however, is marketing 3 tonnes of sulfuric acid per tonne of copper produced as well as emitting large amounts of excess SO2 in the atmosphere. Pressure hydrometallurgy offers the possibility of liberating the copper industry from SO2 problem. Heap leaching technology has become a gigantic operation. Combined with solvent extraction and electrowinning it contributes today to about 20% of copper production and is expected to grow. Pressure leaching offers the possibility of liberating the copper industry from SO2 problem. The technology is over hundred years old. It is applied for leaching a variety of ores and concentrates. Hydrothermal oxidation of sulfide concentrates has the enormous advantage of producing elemental sulfur, hence solving the SO2 and sulfuric acid problems found in smelters. Precipitation of metals such as nickel and cobalt under hydrothermal conditions has been used for over 50 years. It has the advantage of a compact plant but the disadvantage of producing ammonium sulfate as a co-product. In case of copper, however, precipitation takes place without the need of neutralizing the acid, which is a great advantage and could be an excellent substitute for electrowinning which is energy intensive and occupies extensive space. Recent advances in the engineering aspects of pressure equipment design open the door widely for increased

  3. [Copper - a major contraceptive agent?].

    Science.gov (United States)

    Leroy-martin, B; Saint-pol, P; Hermand, E

    1987-06-01

    The effect of copper ions on the motility of human sperm was studied in vitro to determine whether copper is toxic to sperm. Sperm samples from 30 men of proven fertility who had high quality sperm were collected, separated from the seminal fluid, and resuspended in Menezzo, a chemical medium designed to resemble the secretions of the Fallopian tubes. Menezzo contains all the known constituents which aid sperm capacitation, including mineral salts, organic compounds, free amino acids, and enzymes. Its pH is between 7.4 and 7.6. After 1 hour of incubation the dead and weak sperm were separated out and only mobile sperm were tested. Crystallized copper sulfate was added to 4 of the 5 sperm-Menezzo mixtures. The final concentrations were of 1 millimolar, .1 millimolar, .01 millimolar, and .001 millimolar. Sperm motility showed a statistically significant decrease in the concentration of 1 millimolar but only after a latency period of at least 5 hours. At lesser concentrations and in shorter time periods no significant difference was observed compared to the control. The copper released from a copper IUD into the uterine fluid does not exceed a concentration of .1 millimolar. The lower concentration and the long latency period before the toxic effect manifests itself, seem to indicate that copper has no direct contraceptive effect. Copper is however known to promote inflammatory reactions, and it may work in vivo through the intermediacy of the leukocytes in the uterine cavity, either by directly stimulating phagocytosis or by release of substances toxic to sperm.

  4. Which tributaries disrupt downstream fining along gravel-bed rivers?

    Science.gov (United States)

    Rice, Stephen

    1998-02-01

    Tributaries and other lateral sediment sources can have a significant impact on river bed sediment texture and, in turn, on channel form. Sufficiently voluminous or distinct sediment inputs redefine the mainstem grain-size distribution, punctuating downstream maturation and isolating a sequence of discrete sedimentary links. Within these links fining processes usually dominate, such that models of sorting and abrasion, when applied to individual links, provide reasonable predictions of grain-size change. Links represent the fundamental natural unit within which fining models can be tested, developed and applied. Identification of significant lateral sources is therefore important, yet, beyond vague references to relative tributary size, sediment load, and sediment calibre, no criteria exist for the a priori discrimination of such sources. In this paper a procedure for identifying significant lateral (tributary) sources, without the benefit of grain-size information, is outlined. A high-resolution characterisation of bed material texture along two Canadian gravel-bed rivers facilitated classification of all their perennial tributaries as either significant or insignificant. Three absolute tributary basin parameters and their relative counterparts, chosen to reflect the likely controls on tributary significance, are then used to develop a discriminant function which isolates a large proportion of significant tributaries while minimising incorrect classifications. Examination of consistently misclassified (anomalous) tributaries reveals the importance of lateral source spacing and of inconsistencies in the geomorphic history of the contributing basins. In turn, a general tributary categorisation procedure is suggested which includes a logistic regression model for attaching probability statements to individual classifications. The generality of the discriminant and logistic functions cannot be assessed because of the lack of other suitable data sets.

  5. Downstream Propagation of Thermal Pollution in Urban Streams

    Science.gov (United States)

    Somers, K. A.; Urban, D. L.; Bernhardt, E. S.; Losordo, M.

    2011-12-01

    Cities create "heat islands" with air temperatures up to 12 degrees C greater than surrounding areas and impervious surface temperatures reaching 50 degrees C greater than the air. Streams that drain urban areas tend to be hotter at baseflow due to warmer air temperatures and decreased riparian canopy cover. Further, urban stormflow routes precipitation over hot impervious surfaces and through storm drains directly into streams, creating rapid changes in stream temperatures. The resulting alterations in stream thermal regimes directly stress aquatic organisms and indirectly lead to changes in stream microbial activity and dissolved oxygen concentrations. To date, there has been little work done to understand how urban heating of streams propagates downstream from thermal pollution sources. In response to this lack, we used a fiber optic distributed temperature sensor as well as multiple individual temperature loggers to measure high spatiotemporal resolution patterns of stream temperature along 1.5 km of Mud Creek in Durham, NC. Mud Creek originates in the storm drains of a suburban neighborhood, where high-density residential complexes with large amounts of impervious surface are connected directly to the stream. The stream flows in a confined channel alongside apartment complexes for 0.5 km before entering a protected forest area. At baseflow, we found temperature was heterogeneous and explained primarily by canopy openness, rather than the amount of development upstream of the location. During summer stormflows, stream temperatures became more homogeneous and increased by up to 4 degrees C due to runoff at the top of the reach. These peak temperatures were dampened to only 2 degrees C increases after 1 km of travel through mature forest. In contrast, a fully forested tributary to Mud Creek decreased in temperature for the same storm events. This spatial propagation of stormflow heat pulses will substantially limit our ability to protect urban stream ecosystems.

  6. 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

  7. 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

  8. Membrane lipid peroxidation in copper alloy-mediated contact killing of Escherichia coli.

    Science.gov (United States)

    Hong, Robert; Kang, Tae Y; Michels, Corinne A; Gadura, Nidhi

    2012-03-01

    Copper alloy surfaces are passive antimicrobial sanitizing agents that kill bacteria, fungi, and some viruses. Studies of the mechanism of contact killing in Escherichia coli implicate the membrane as the target, yet the specific component and underlying biochemistry remain unknown. This study explores the hypothesis that nonenzymatic peroxidation of membrane phospholipids is responsible for copper alloy-mediated surface killing. Lipid peroxidation was monitored with the thiobarbituric acid-reactive substances (TBARS) assay. Survival, TBARS levels, and DNA degradation were followed in cells exposed to copper alloy surfaces containing 60 to 99.90% copper or in medium containing CuSO(4). In all cases, TBARS levels increased with copper exposure levels. Cells exposed to the highest copper content alloys, C11000 and C24000, exhibited novel characteristics. TBARS increased immediately at a very rapid rate but peaked at about 30 min. This peak was associated with the period of most rapid killing, loss in membrane integrity, and DNA degradation. DNA degradation is not the primary cause of copper-mediated surface killing. Cells exposed to the 60% copper alloy for 60 min had fully intact genomic DNA but no viable cells. In a fabR mutant strain with increased levels of unsaturated fatty acids, sensitivity to copper alloy surface-mediated killing increased, TBARS levels peaked earlier, and genomic DNA degradation occurred sooner than in the isogenic parental strain. Taken together, these results suggest that copper alloy surface-mediated killing of E. coli is triggered by nonenzymatic oxidative damage of membrane phospholipids that ultimately results in the loss of membrane integrity and cell death.

  9. Assessing downstream flood impacts due to a potential GLOF from Imja Tsho in Nepal

    National Research Council Canada - National Science Library

    Somos-Valenzuela, M. A; McKinney, D. C; Byers, A. C; Rounce, D. R; Portocarrero, C; Lamsal, D

    2015-01-01

    Glacial-dominated areas pose unique challenges to downstream communities in adapting to recent and continuing global climate change, including increased threats of glacial lake outburst floods (GLOFs...

  10. Regulation of copper and iron homeostasis by metal chelators: a possible chemotherapy for Alzheimer's disease.

    Science.gov (United States)

    Robert, Anne; Liu, Yan; Nguyen, Michel; Meunier, Bernard

    2015-05-19

    With the increase of life expectancy of humans in more than two-thirds of the countries in the World, aging diseases are becoming the frontline health problems. Alzheimer's disease (AD) is now one of the major challenges in drug discovery, since, with the exception of memantine in 2003, all clinical trials with drug candidates failed over the past decade. If we consider that the loss of neurons is due to a high level of oxidative stress produced by nonregulated redox active metal ions like copper linked to amyloids of different sizes, regulation of metal homeostasis is a key target. The difficulty for large copper-carrier proteins to directly extract copper ions from metalated amyloids might be considered as being at the origin of the rupture of the copper homeostasis regulation in AD brains. So, there is an urgent need for new specific metal chelators that should be able to regulate the homeostasis of metal ions, specially copper and iron, in AD brains. As a consequence of that concept, chelators promoting metal excretion from brain are not desired. One should favor ligands able to extract copper ions from sinks (amyloids being the major one) and to transfer these redox-active metal ions to copper-carrier proteins or copper-containing enzymes. Obviously, the affinity of these chelators for the metal ion should not be a sufficient criterion, but the metal specificity and the ability of the chelators to release the metal under specific biological conditions should be considered. Such an approach is still largely unexplored. The requirements for the chelators are very high (ability to cross the brain-blood barrier, lack of toxicity, etc.), few chemical series were proposed, and, among them, biochemical or biological data are scarce. As a matter of fact, the bioinorganic pharmacology of AD represents less than 1% of all articles dedicated to AD drug research. The major part of these articles deals with an old and rather toxic drug, clioquinol and related analogs, that

  11. A copper complex (2,2¢-bipyridine)(salicyclideneglycinato) copper(II ...

    Indian Academy of Sciences (India)

    Administrator

    In aqueous–methanol, ascorbic acid reduces the copper(II) complex to form a brown copper(I) species which readily converts to the green precursor copper(II) complex in the presense of dioxygen. The proposed catalytic cycle for this conversion in air is shown below. The copper(II) complex is also catalytically active in.

  12. Copper nitrate redispersion to arrive at highly active silica-supported copper catalysts

    NARCIS (Netherlands)

    Munnik, P.|info:eu-repo/dai/nl/328228524; Wolters, M.|info:eu-repo/dai/nl/304829560; Gabrielsson, A.; Pollington, S.D.; Headdock, G.; Bitter, J.H.|info:eu-repo/dai/nl/160581435; de Jongh, P.E.|info:eu-repo/dai/nl/186125372; de Jong, K.P.|info:eu-repo/dai/nl/06885580X

    2011-01-01

    In order to obtain copper catalysts with high dispersions at high copper loadings, the gas flow rate and gas composition was varied during calcination of silica gel impregnated with copper nitrate to a loading of 18 wt % of copper. Analysis by X-ray diffraction (XRD), N2O chemisorption, and

  13. Freeze-responsive regulation of MEF2 proteins and downstream gene networks in muscles of the wood frog, Rana sylvatica.

    Science.gov (United States)

    Aguilar, Oscar A; Hadj-Moussa, Hanane; Storey, Kenneth B

    2017-07-01

    The wood frog survives frigid North American winters by retreating into a state of suspended animation characterized by the freezing of up to 65% of total body water as extracellular ice and displaying no heartbeat, breathing, brain activity, or movement. Physiological and biochemical adaptations are in place to facilitate global metabolic depression and protect against the consequences of whole body freezing. This study examined the myocyte enhancer factor 2 (MEF2) transcription factor family, proteins responsible for coordinating selective gene expression of a myriad of cellular functions from muscle development and remodelling to various stress responses. Immunoblotting, subcellular localization, and RT-PCR were used to analyze the regulation of MEF2A and MEF2C transcription factors and selected downstream targets under their control at transcriptional, translational, and post-translational levels in skeletal and cardiac muscles from control, frozen and thawed frogs. Both MEF2A/C proteins were freeze-responsive in skeletal muscle, displaying increases of 1.7-2 fold for phosphorylated MEF2A Thr312 and MEF2C Thr300 during freezing with an enrichment of nuclear phosphorylated MEF2 proteins (by 1.7-2.1 fold) observed as early as 4h post-freezing. Despite the reduced response of total and phosphorylated MEF2A/C protein levels observed in cardiac muscle, the MEF2 downstream gene targets (glucose transporter-4, calreticulin, and creatine kinase brain and muscle isozymes) displayed similar increases in transcript levels (1.7-4.8 fold) after 24h freezing in both muscle types. This study describes a novel freeze-responsive function for MEF2 transcription factors and further elaborates our understanding of the molecular mechanisms underlying natural freeze tolerance. This novel freeze-responsive regulation suggests a role for MEF2s and downstream genes in cryoprotectant glucose distribution, calcium homeostasis, and maintenance of energy reserves vital for successful

  14. Thermotransport in liquid aluminum-copper alloys

    Science.gov (United States)

    Bhat, B. N.

    1973-01-01

    A thermotransport study was made on a series of liquid aluminum-copper alloys which contained from trace amounts to 33 weight percent copper. The samples in the form of narrow capillaries were held in known temperature gradient of thermotransport apparatus until the stationary state was reached. The samples were analyzed for the concentration of copper along the length. Copper was observed to migrate to the colder regions in all the samples. The heat of transport, Q*, was determined for each composition from a plot of concentration of copper versus reciprocal absolute temperature. The value of Q* is the highest at trace amounts of copper (4850 cal/gm-atom), but decreases with increasing concentration of copper and levels off to 2550 cal/gm-atom at about 25 weight percent copper. The results are explained on the basis of electron-solute interaction and a gas model of diffusion.

  15. Copper tolerance and virulence in bacteria

    Science.gov (United States)

    Ladomersky, Erik; Petris, Michael J.

    2015-01-01

    Copper (Cu) is an essential trace element for all aerobic organisms. It functions as a cofactor in enzymes that catalyze a wide variety of redox reactions due to its ability to cycle between two oxidation states, Cu(I) and Cu(II). This same redox property of copper has the potential to cause toxicity if copper homeostasis is not maintained. Studies suggest that the toxic properties of copper are harnessed by the innate immune system of the host to kill bacteria. To counter such defenses, bacteria rely on copper tolerance genes for virulence within the host. These discoveries suggest bacterial copper intoxication is a component of host nutritional immunity, thus expanding our knowledge of the roles of copper in biology. This review summarizes our current understanding of copper tolerance in bacteria, and the extent to which these pathways contribute to bacterial virulence within the host. PMID:25652326

  16. Global assessment of undiscovered copper resources

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — Deposits, prospects, and permissive tracts for porphyry and sediment-hosted copper resources worldwide, with estimates of undiscovered copper resources. pCu_tracts...

  17. Mechanochemical reduction of copper sulfide

    DEFF Research Database (Denmark)

    Balaz, P.; Takacs, L.; Jiang, Jianzhong

    2002-01-01

    The mechanochemical reduction of copper sulfide with iron was induced in a Fritsch P-6 planetary mill, using WC vial filled with argon and WC balls. Samples milled for specific intervals were analyzed by XRD and Mossbauer spectroscopy. Most of the reaction takes place during the first 10 min...... of milling and only FeS and Cu are found after 60 min. The main chemical process is accompanied by phase transformations of the sulfide phases as a result of milling. Djurleite partially transformed to chalcocite and a tetragonal copper sulfide phase before reduction. The cubic modification of FeS was formed...... first, transforming to hexagonal during the later stages of the process. The formation of off-stoichiometric phases and the release of some elemental sulfur by copper sulfide are also probable....

  18. Copper tolerance of Trichoderma species

    Directory of Open Access Journals (Sweden)

    Jovičić-Petrović Jelena

    2014-01-01

    Full Text Available Some Trichoderma strains can persist in ecosystems with high concentrations of heavy metals. The aim of this research was to examine the variability of Trichoderma strains isolated from different ecosystems, based on their morphological properties and restriction analysis of ITS fragments. The fungal growth was tested on potato dextrose agar, amended with Cu(II concentrations ranging from 0.25 to 10 mmol/l, in order to identify copper-resistant strains. The results indicate that some isolated strains of Trichoderma sp. show tolerance to higher copper concentrations. Further research to examine the ability of copper bioaccumulation by tolerant Trichoderma strains is needed. [Projekat Ministarstva nauke Republike Srbije, br. TR 31080 i br. III 43010

  19. Copper-mediated DNA damage by the neurotransmitter dopamine and L-DOPA: A pro-oxidant mechanism.

    Science.gov (United States)

    Rehmani, Nida; Zafar, Atif; Arif, Hussain; Hadi, Sheikh Mumtaz; Wani, Altaf A

    2017-04-01

    Oxidative DNA damage has been implicated in the pathogenesis of neurological disorders, cancer and ageing. Owing to the established link between labile copper concentrations and neurological diseases, it is critical to explore the interactions of neurotransmitters and drug supplements with copper. Herein, we investigate the pro-oxidant DNA damage induced by the interaction of L-DOPA and dopamine (DA) with copper. The DNA binding affinity order of the compounds has been determined by in silico molecular docking. Agarose gel electrophoresis reveals that L-DOPA and DA are able to induce strand scission in plasmid pcDNA3.1 (+/-) in a copper dependent reaction. These metabolites also cause cellular DNA breakage in human lymphocytes by mobilizing endogenous copper, as assessed by comet assay. Further, L-DOPA and DA-mediated DNA breaks were detected by the appearance of post-DNA damage sensitive marker γH2AX in cancer cell lines accumulating high copper. Immunofluorescence demonstrated the co-localization of downstream repair factor 53BP1 at the damaged induced γH2AX foci in cancer cells. The present study corroborates and provides a mechanism to the hypothesis that suggests metal-mediated oxidation of catecholamines contributes to the pathogenesis of neurodegenerative diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Copper toxicity in aquaculture: A practical approach

    Science.gov (United States)

    Copper sulfate is used as a therapeutant for various applications in aquaculture. There is a great deal of information on the toxicity of copper, especially in low-alkalinity waters; however, much of this information is fragmented, and a comprehensive guide of copper toxicity and safe concentration...

  1. Canine Models for Copper Homeostasis Disorders

    NARCIS (Netherlands)

    Wu, Xiaoyan; Leegwater, Peter A J; Fieten, Hille

    2016-01-01

    Copper is an essential trace nutrient metal involved in a multitude of cellular processes. Hereditary defects in copper metabolism result in disorders with a severe clinical course such as Wilson disease and Menkes disease. In Wilson disease, copper accumulation leads to liver cirrhosis and

  2. Extra-Hepatic Storage of Copper

    DEFF Research Database (Denmark)

    Heydorn, Kaj; Damsgaard, Else; Horn, N.

    1975-01-01

    The distribution of copper among the organs of an aborted, male foetus, expected to develop Menkes' syndrome, was entirely different from the distribution in 4 normal foetuses. Copper concentrations determined by neutron activation analysis showed a considerably reduced content in the liver......, but increased concentrations in the other organs analysed; total foetal copper was normal....

  3. Plasma Copper Status in Hypercholesterolemic Patients

    African Journals Online (AJOL)

    Dr Femi Olaleye

    1991). Moreover feeding rats a Copper – deficient diet resulted in hypercholesterolemia (Al-Othman et al 1994; Carr et al 1990). Biochemical correlate of copper insufficiency included hyper- cholesterolemia when over 30 men and women were depleted of copper carefully with diets made with conventional foods containing ...

  4. 21 CFR 184.1260 - Copper gluconate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Copper gluconate. 184.1260 Section 184.1260 Food... Specific Substances Affirmed as GRAS § 184.1260 Copper gluconate. (a) Copper gluconate (cupric gluconate... solutions with cupric oxide or basic cupric carbonate. (b) The ingredient meets the specifications of the...

  5. Transfer of sediment-associated metals downstream of abandoned and active mining sites in the Quesnel River catchment, British Columbia

    NARCIS (Netherlands)

    Perk, M. van der; Lipzig, M.L.H.M. van; Karimlou, G.; Owens, P.N.; Petticrew, E.L.

    2011-01-01

    Metal mining may have considerable impact on downstream water and sediment composition. The rate and extent that metals move downstream determine the magnitude and time scale of downstream sediment contamination. Conversely, the downstream metal content of sediments provide important clues of

  6. Molybdenum-copper and tungsten-copper alloys and method of making

    Science.gov (United States)

    Schmidt, Frederick A.; Verhoeven, John D.; Gibson, Edwin D.

    1989-05-23

    Molybdenum-copper and tungsten-copper alloys are prepared by a consumable electrode method in which the electrode consists of a copper matrix with embedded strips of refractory molybdenum or tungsten. The electrode is progressively melted at its lower end with a superatmospheric inert gas pressure maintained around the liquifying electrode. The inert gas pressure is sufficiently above the vapor pressure of copper at the liquidus temperature of the alloy being formed to suppress boiling of liquid copper.

  7. Joining of alumina via copper/niobium/copper interlayers

    Energy Technology Data Exchange (ETDEWEB)

    Marks, Robert A.; Chapman, Daniel R.; Danielson, David T.; Glaeser, Andreas M.

    2000-03-15

    Alumina has been joined at 1150 degrees C and 1400 degrees C using multilayer copper/niobium/copper interlayers. Four-point bend strengths are sensitive to processing temperature, bonding pressure, and furnace environment (ambient oxygen partial pressure). Under optimum conditions, joints with reproducibly high room temperature strengths (approximately equal 240 plus/minus 20 MPa) can be produced; most failures occur within the ceramic. Joints made with sapphire show that during bonding an initially continuous copper film undergoes a morphological instability, resulting in the formation of isolated copper-rich droplets/particles at the sapphire/interlayer interface, and extensive regions of direct bonding between sapphire and niobium. For optimized alumina bonds, bend tests at 800 degrees C-1100 degrees C indicate significant strength is retained; even at the highest test temperature, ceramic failure is observed. Post-bonding anneals at 1000 degrees C in vacuum or in gettered argon were used to assess joint stability and to probe the effect of ambient oxygen partial pressure on joint characteristics. Annealing in vacuum for up to 200 h causes no significant decrease in room temperature bend strength or change in fracture path. With increasing anneal time in a lower oxygen partial pressure environment, the fracture strength decreases only slightly, but the fracture path shifts from the ceramic to the interface.

  8. Non-Alcoholic Fatty Liver Disease and Nutritional Implications: Special Focus on Copper

    Directory of Open Access Journals (Sweden)

    Laura Antonucci

    2017-10-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is characterized by excess lipids in hepatocytes, due to excessive fatty acid influx from adipose tissue, de novo hepatic lipogenesis, in addition to excessive dietary fat and carbohydrate intake. Chronic hepatic lipid overload induces mitochondrial oxidative stress and cellular damage leading the development of NAFLD into a more severe liver disease condition, non-alcoholic steato-hepatitis (NASH. In turn, this can progress to cirrhosis and hepatocellular carcinoma (HCC. Among others, copper is one of the main bio-metals required for the preponderance of the enzymes involved in physiological redox reactions, which primarily occurs during mitochondrial respiration. Thus, copper homeostasis could be considered a target point for counteracting the progression of NAFLD. Accordingly, many diseases are correlated to unbalanced copper levels and, actually, some clinical trials are examining the use of copper chelating agents. Currently, no pharmacological interventions are approved for NAFLD, but nutritional and lifestyle modifications are always recommended. Fittingly, antioxidant food agents recognized to improve NAFLD and its complications have been described in the literature to bind copper. Therefore, this review describes the role of nutrition in the development and progression of NAFLD with a particular focus on copper and copper-binding antioxidant compounds against NAFLD.

  9. Cell density dependence of Microcystis aeruginosa responses to copper algaecide concentrations: Implications for microcystin-LR release.

    Science.gov (United States)

    Kinley, Ciera M; Iwinski, Kyla J; Hendrikse, Maas; Geer, Tyler D; Rodgers, John H

    2017-11-01

    Along with mechanistic models, predictions of exposure-response relationships for copper are often derived from laboratory toxicity experiments with standardized experimental exposures and conditions. For predictions of copper toxicity to algae, cell density is a critical factor often overlooked. For pulse exposures of copper-based algaecides in aquatic systems, cell density can significantly influence copper sorbed by the algal population, and consequent responses. A cyanobacterium, Microcystis aeruginosa, was exposed to a copper-based algaecide over a range of cell densities to model the density-dependence of exposures, and effects on microcystin-LR (MC-LR) release. Copper exposure concentrations were arrayed to result in a gradient of MC-LR release, and masses of copper sorbed to algal populations were measured following exposures. While copper exposure concentrations eliciting comparable MC-LR release ranged an order of magnitude (24-h EC50s 0.03-0.3mg Cu/L) among cell densities of 10 6 through 10 7 cells/mL, copper doses (mg Cu/mg algae) were similar (24-h EC50s 0.005-0.006mg Cu/mg algae). Comparisons of MC-LR release as a function of copper exposure concentrations and doses provided a metric of the density dependence of algal responses in the context of copper-based algaecide applications. Combined with estimates of other site-specific factors (e.g. water characteristics) and fate processes (e.g. dilution and dispersion, sorption to organic matter and sediments), measuring exposure-response relationships for specific cell densities can refine predictions for in situ exposures and algal responses. These measurements can in turn decrease the likelihood of amending unnecessary copper concentrations to aquatic systems, and minimize risks for non-target aquatic organisms. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. 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.

  11. Identification of possible downstream genes required for the extension of peripheral axons in primary sensory neurons.

    Science.gov (United States)

    Aoki, Makoto; Segawa, Hiroshi; Naito, Mayumi; Okamoto, Hitoshi

    2014-03-07

    The LIM-homeodomain transcription factor Islet2a establishes neuronal identity in the developing nervous system. Our previous study showed that Islet2a function is crucial for extending peripheral axons of sensory neurons in zebrafish embryo. Overexpressing a dominant-negative form of Islet2a significantly reduced peripheral axon extension in zebrafish sensory neurons, implicating Islet2a in the gene regulation required for neurite formation or proper axon growth in developing sensory neurons. Based on this, we conducted systematic screening to isolate genes regulated by Islet2a and affecting the development of axon growth in embryonic zebrafish sensory neurons. The 26 genes selected included some encoding factors involved in neuronal differentiation, axon growth, cellular signaling, and structural integrity of neurons, as well as genes whose functions are not fully determined. We chose four representative candidates as possible Islet2a downstream functional targets (simplet, tppp, tusc5 and tmem59l) and analyzed their respective mRNA expressions in dominant-negative Islet2a-expressing embryos. They are not reported the involvement of axonal extension or their functions in neural cells. Finally, knockdown of these genes suggested their direct actual involvement in the extension of peripheral axons in sensory neurons. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Association of dietary copper and zinc levels with hepatic copper and zinc concentration in Labrador Retrievers.

    Science.gov (United States)

    Fieten, H; Hooijer-Nouwens, B D; Biourge, V C; Leegwater, P A J; Watson, A L; van den Ingh, T S G A M; Rothuizen, J

    2012-01-01

    Copper-associated hepatitis is an inherited disease in the Labrador Retriever. Apart from genetic factors, dietary intake of copper and zinc are suspected to play a role in the pathogenesis. To investigate whether dietary copper and zinc levels of commercially available dry diets are associated with hepatic copper and zinc concentrations in Labrador Retrievers. Fifty-five Labrador Retrievers that were fed a single brand and type of commercial dry food for at least 1 year. Of these, 44 dogs were family members of Labrador Retrievers with copper-associated hepatitis. Liver biopsies, blood samples, and diet samples were obtained. Liver specimens were scored histologically and copper and zinc concentrations were quantified. Dietary concentrations of copper and zinc were measured. The association between dietary intake of copper and zinc and hepatic copper and zinc concentrations was investigated by linear regression analysis. High dietary copper and low dietary zinc levels were significantly associated with high hepatic copper levels. No association between dietary intake and hepatic zinc was present. Dietary copper and zinc at current levels in commercially available dry dog food can influence hepatic copper and can be a risk factor for the development of copper-associated hepatitis in Labrador Retrievers with a genetic susceptibility to copper. Copyright © 2012 by the American College of Veterinary Internal Medicine.

  13. Copper mobilization affected by weather conditions in a stormwater detention system receiving runoff waters from vineyard soils (Champagne, France)

    Energy Technology Data Exchange (ETDEWEB)

    Banas, D., E-mail: damien.banas@u-psud.f [Univ. Reims Champagne-Ardenne, Lab. Eco-Toxicologie, BP 1039, F-51687 Reims Cedex 2 (France); Univ. Nancy, UR-AFPA, INRA, 2 Av. Foret Haye, F-54505 Vandoeuvre-les-Nancy (France); Marin, B., E-mail: beatrice.marin@univ-reims.f [Univ. Reims Champagne-Ardenne, EA3795 GEGENA, 2 Esplanade Roland Garros, F-51100 Reims (France); Skraber, S., E-mail: skraber@lippmann.l [Centre de Recherche Public, Gabriel Lippmann, Department of Environment and Agro-biotechnologies (EVA), 41 rue du Brill, L-4422 Belvaux (Luxembourg); Chopin, E.I.B., E-mail: chopin@oakland.ed [Oakland University, Department of Chemistry, Rochester, MI 48309 (United States); Zanella, A., E-mail: augusto.zanella@unipd.i [Univ. Padova, Facolta di Agraria, Viale dell' Universita 16, I-35020 Legnaro (Italy)

    2010-02-15

    Copper, a priority substance on the EU-Water Framework Directive list, is widely used to protect grapevines against fungus diseases. Many vineyards being located on steep slopes, large amounts of Cu could be discharged in downstream systems by runoff water. The efficiency of stormwater detention basins to retain copper in a vineyard catchment was estimated. Suspended solids, dissolved (Cu{sub diss}) and total Cu (Cu{sub tot}) concentrations were monitored in runoff water, upstream, into and downstream from a detention pond. Mean Cu{sub tot} concentrations in entering water was 53.6 mug/L whereas it never exceeded 2.4 mug/L in seepage. Cu{sub tot} concentrations in basin water (>100 mug/L in 24% of the samples) exceeded LC{sub 50} values for several aquatic animals. Copper was principally sequestered by reduced compounds in the basin sediments (2/3 of Cu{sub tot}). Metal sequestration was reversible since sediment resuspension resulted in Cu remobilization. Wind velocity controlled resuspension, explained 70% of Cu{sub diss} variability and could help predicting Cu mobilization. - Copper in stormwater basin is efficiently retained but can be released during windy events or after dredging.

  14. A Study of the Ion Hose Instability in the DARHT-II Downstream Transport Region

    Energy Technology Data Exchange (ETDEWEB)

    McCarrick, J F

    2004-11-11

    The second axis of the DARHT flash X-ray facility at Los Alamos National Laboratory (''DARHT-II'') is a multiple-pulse, 18.4 MeV, 2 kA induction electron linear accelerator [1]. A train of short ({approx}50 ns) pulses are converted via bremsstrahlung to X-rays, which are then used to make radiographic images at various times (nominally four) during a ''hydrotest'' experiment. The train of pulses is created by carving them out of a two microsecond long macropulse, using a fast switching element called a kicker [2]. The unused portion of the macropulse is absorbed in a beam dump. Thus, upstream of the kicker, two microseconds of beam are transported through a vacuum system roughly sixty meters long. These conditions involve length and, specifically, time scales which are new to the transport of high-current beams. A concern under such conditions are the macroscopic interactions between the electron beam and positive ions created by impact ionization of the residual gas in the vacuum system. Over two microseconds, the ion density can develop to a hundredth or even a tenth of a percent of the beam density--small, to be sure, but large enough to have cumulative effects over such a long transport distance. Two such effects will be considered here: the ion hose instability, where transverse forces conspire to pull the electron beam farther and farther off axis, and background gas focusing, where radial forces (with respect to the beam) change the beam envelope during the course of the macropulse. The former effect can cause beam emittance growth (affecting the ability to focus the beam on the target) and eventually catastrophic beam loss; the latter can cause either serious degradation of the statically tuned final focus on the converter target, or a pinching of the beam on the surface of the main dump to the point where the heat flux causes damage. The beam transport upstream of the kicker has two distinct phases. First, the beam

  15. The effect of downstream perforated blanket on the safety against piping in heading-up structures

    Directory of Open Access Journals (Sweden)

    Mona A. Hagras

    2014-03-01

    It was found that piping index (Pe is governed by perforation ration (PR, relative hole diameter (D/Lb, ratio of length of the blanket to length of the apron (Lb/La, head difference between upstream and downstream structure and the depth of downstream cutoff.

  16. 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 ...

  17. PLUTONIUM-CERIUM-COPPER ALLOYS

    Science.gov (United States)

    Coffinberry, A.S.

    1959-05-12

    A low melting point plutonium alloy useful as fuel is a homogeneous liquid metal fueled nuclear reactor is described. Vessels of tungsten or tantalum are useful to contain the alloy which consists essentially of from 10 to 30 atomic per cent copper and the balance plutonium and cerium. with the plutontum not in excess of 50 atomic per cent.

  18. on THICKNESS OF COPPER (|) OXIDE

    African Journals Online (AJOL)

    2006-12-20

    Dec 20, 2006 ... Observed to be an attractive starting material for the production of solar cells for low cost terrestrial conversion of solar energy to electricity. Copper (I) oxide is one Of the earliest known photovoltaic materials and the first in which the photovOltaic effect was successfully explained (Fortin and Sears,. 1981).

  19. binuclear copper(II) complexes

    Indian Academy of Sciences (India)

    Administrator

    403. Synthesis, electrochemical and magnetic properties of new acylic. 'end-off' binuclear copper(II) complexes. T M RAJENDIRAN, R KANNAPPAN, R VENKATESAN and. P SAMBASIVA RAO. Department of Chemistry, Pondicherry University, R.V. Nagar, Kalapet,. Pondicherry 605 014, India. A series of nonbridged nitrito ...

  20. 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

  1. Microstructural and component evolution of self-assembled nanoperiod multilayered carbon-copper films with deposition pressure

    Science.gov (United States)

    Wang, Weiqi; Ji, Li; Li, Hongxuan; Zhao, Yiman; Zhou, Huidi; Chen, Jianmin

    2017-04-01

    Here, we report a facile synthesis method for the fabrication of various nanoperiod multilayers in carbon-copper films only by conveniently changing the deposition pressure from the reactive magnetron sputter process. To obtain the nano-multilayered structure with different number of layers, only one single sputtering target of copper is used at gas pressure varied from 0.4 Pa to 1.2 Pa by flowing gas mixture of argon and methane, while 600W DC input power is applied to a copper target. The influence of deposition pressure on the microstructure and constitution of the films are investigated by X-ray photoelectron spectroscopy (XPS), field emission scanning electron microscopy (FESEM) and high-resolution transmission electron microscopy (HRTEM). The results show that carbon-rich layers and copper-rich layers are alternately arranged to self-organize the multilayered structure in the carbon-copper films, both of the carbon-rich layer and copper-rich layer constitute a period. The amount of layers in the multilayered structure is found to decrease with the deposition pressure, the film deposited with 0.4 Pa has the maximum layers and the highest copper content compared with the other deposition pressure. Effects of the growth condition on the growth rate, the number of the layers and the energy of plasmas during deposition process are discussed. Based on the (a) influence of the effect of carbon absorbed on the copper target leading to target poisoning, (b) influence of deposition pressure on the energy of etching ions and (c) the energetic ions bombardment enhanced inter diffusion of deposition ions, the mechanism of self-organized formation of nano-multilayer in the carbon-copper films with various number of layer is proposed.

  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. Regulation of germline stem cell proliferation downstream of nutrient sensing

    Directory of Open Access Journals (Sweden)

    Roy Richard

    2006-12-01

    Full Text Available Abstract Stem cells have recently attracted significant attention largely due to their potential therapeutic properties, but also because of their role in tumorigenesis and their resemblance, in many aspects, to cancerous cells. Understanding how stem cells are regulated, namely with respect to the control of their proliferation and differentiation within a functional organism, is thus primordial to safely profit from their therapeutic benefits. Here, we review recent advances in the understanding of germline stem cell proliferation control by factors that respond to the nutritional status and/or insulin signaling, through studies performed in C. elegans and Drosophila. Together, these data uncover some shared fundamental features that underlie the central control of cellular proliferation within a target stem cell population in an organism. These features may indeed be conserved in higher organisms and may apply to various other stem cell populations.

  4. Gender Effects on Plasma and Brain Copper

    Directory of Open Access Journals (Sweden)

    Joseph F. Quinn

    2011-01-01

    Full Text Available The effect of gender on systemic and brain levels of copper is relatively understudied. We examined gender effects in mice and human subjects. We observed a trend to higher serum copper levels in female compared to male LaFerla “triple transgenic” (1399±233 versus 804±436 ng/mL, P=0.06 mice, and significantly higher brain copper levels in female- versus male wild-type mice (5.2±0.2 versus 4.18±0.3 ng/mg wet wt, P=0.03. Plasma copper was significantly correlated with brain copper in mice (R2 = 0.218; P=0.038. Among human subjects with AD, both plasma copper (1284±118 versus 853±81 ng/mL, P=0.005 and cerebrospinal fluid copper (12.8±1 versus 10.4±0.7 ng/mL, P=0.01 were elevated in women compared to men. Among healthy control subjects, plasma copper (1008±51 versus 836±41 ng/mL; P=0.01 was higher in women than in men, but there was no difference in cerebrospinal fluid copper. We conclude that gender differences in copper status may influence copper-mediated pathological events in the brain.

  5. Reactivity test between beryllium and copper

    Energy Technology Data Exchange (ETDEWEB)

    Kawamura, H. [Japan Atomic Energy Research Institute, Ibaraki-ken (Japan); Kato, M. [NGK Insulators, Ltd., Aichi-ken (Japan)

    1995-09-01

    Beryllium has been expected for using as plasma facing material on ITER. And, copper alloy has been proposed as heat sink material behind plasma facing components. Therefore, both materials must be joined. However, the elementary process of reaction between beryllium and copper alloy does not clear in detail. For example, other authors reported that beryllium reacted with copper at high temperature, but it was not obvious about the generation of reaction products and increasing of the reaction layer. In the present work, from this point, for clarifying the elementary process of reaction between beryllium and copper, the out-of-pile compatibility tests were conducted with diffusion couples of beryllium and copper which were inserted in the capsule filled with high purity helium gas (6N). Annealing temperatures were 300, 400, 500, 600 and 700{degrees}C, and annealing periods were 100, 300 and 1000h. Beryllium specimens were hot pressed beryllium, and copper specimens were OFC (Oxygen Free Copper).

  6. Controlling Copper Electrochemical Deposition (ECD)

    Science.gov (United States)

    West, Michael; McDonald, Robert; Anderson, Marc; Kingston, Skip; Mui, Rudy

    2003-09-01

    The implementation of copper processing in semiconductor manufacturing has resulted in major process development and manufacturing challenges. A fundamental understanding of the copper plating processes used in manufacturing has been limited by the lack of in-line methods for direct measurement and control of process chemistry. Plating bath chemistry adjustments and change-out frequencies are currently determined using a combination of indirect electrochemical monitoring techniques, off-line analyses of wafer metrology and analytical lab measurements. There have been a number of industry reports of major process startup delays, yield management problems and reliability issues as a result of these difficulties. A new in-process mass spectrometry (IPMS) approach enables automated, real-time measurement of both the inorganic components and organic additives in the copper electroplating chemistry as they change during production. The tool is not only capable of real time direct quantification of the copper, chloride, pH, and organic additives in the plating bath, but can also monitor additive breakdown byproducts as they occur during the production process. These breakdown products, as well as changes in the original bath constituent composition can be expected to have a major impact on process performance. We are now in the process of measuring longer term plating bath stability and chemistry changes in prototype applications in semiconductor fab manufacturing environments. The first results demonstrate improved process understanding and the potential for greatly improved process control. We will discuss the technical challenges that were successfully addressed in developing the IPMS capability for application to the copper plating process and the initial process data subsequently obtained.

  7. Diquat associated with copper sources for algae control: Efficacy and ecotoxicology.

    Science.gov (United States)

    Garlich, Nathalia; Da Cruz, Claudinei; Da Silva, Adilson F; Carraschi, Silvia P; Malaspina, Igor C; Pitelli, Robinson A; Bianco, Silvano

    2016-01-01

    The aims of this research were to evaluate the efficacy of copper oxychloride (CuCl2.3Cu(OH)2), copper hydroxide (Cu(OH)2) and diquat (1.1'-ethylene-2.2'-bipyridyldiylium dibromide), isolated and in association with 0.1% of both copper sources, in the control of the unicellular algae Ankistrodesmus gracilis and the filamentous algae Pithophora kewesis, and to determine the acute toxicity of the tested chemicals in Hyphressobrycon eques, Pomacea canaliculata, Lemna minor and Azolla caroliniana. The efficacy was estimated by the methods of chlorophyll a and pheophytin a readings, changed into growth inhibition percentage. Both algae were exposed to the following concentrations: 0.2; 0.4; 0.8; 1.2 mg L(-1) of diquat and its association with the copper sources; and 0.1; 0.3; 0.5; 0.7; 1.0 and 1.5 mg L(-1) in the isolated applications of copper hydroxide and copper oxychloride. An untreated control was kept. The acute toxicity was estimatedby 50% lethal concentration (LC50). The copper sources were effective for A. gracilis control, at rates as high as 0.1 mg L(-1) (>95% efficacy). Isolated diquat and its association with copper hydroxide were both effective at rates as high as 0.4 mg L(-1), with 95 and 88% control efficacy, respectively. The copper oxychloride was effective at 0.2 mg L(-1), with 93% efficacy. None of the tested chemicals and associations was effective on P. kewesis control. The most sensitive non target organism to the tested chemicals was L. minor; the less sensitive was H. eques.

  8. Copper-gold nanoparticles: Fabrication, characteristic and application as drug carriers

    Energy Technology Data Exchange (ETDEWEB)

    Woźniak-Budych, Marta J., E-mail: marta.budych@amu.edu.pl; Langer, Krzysztof; Peplińska, Barbara; Przysiecka, Łucja; Jarek, Marcin; Jarzębski, Maciej; Jurga, Stefan

    2016-08-15

    In this investigation, the fabrication of porous core/shell nanostructures consisting of copper (core) and copper-gold nanoalloy (shell) for medical applications is presented. As a core triangular-shaped copper nanoparticles were used. The porous bimetallic nanoshell was prepared via galvanic reaction in the presence of oil-in water emulsion. It was proved that porous nanoalloy layer can be prepared at pH 7 and in the presence 0.1% and 0.5% oil-in water emulsion. The porous structure fabrication was mainly determined by volume fraction of hexadecane to acetone in the oil-in water emulsion and Zeta-potential of emulsion droplets (pH of emulsion). The influence of emulsion droplets size before galvanic reaction on porous structure preparation was negligible. It was found that doxorubicin could be easily introduced and released from porous core/shell nanostructures, due to spontaneous adsorption on the copper-gold nanoporous surface. The in vitro test showed that cytotoxic effect was more prominent once the doxorubicin was adsorbed on the porous copper-gold nanocarriers. It was demonstrated, that doxorubicin-loaded copper-gold nanostructures caused inhibition cell proliferation and viability of cancer cells, in a concentration-dependent manner. The results indicates that presented coper-gold nanocarrier have potential to be used in targeted cancer therapy, due to its porous structure and cytotoxic effect in cancer cells. - Highlights: • Porous copper-gold nanostructure as a cytostatic drug carrier was prepared. • Kinetics and thermodynamics of drug adsorption were studied. • DOX-loaded copper-gold nanoparticles showed a pH-controlled release rate. • DOX-loaded copper-gold NPs caused inhibition cell proliferation of cancer cells. • The Cu-Au NPs could serve as a theranostic platform for biomedical applications.

  9. Copper economy in Chlamydomonas: Prioritized allocation and reallocation of copper to respiration vs. photosynthesis

    Science.gov (United States)

    Kropat, Janette; Gallaher, Sean D.; Urzica, Eugen I.; Nakamoto, Stacie S.; Strenkert, Daniela; Tottey, Stephen; Mason, Andrew Z.; Merchant, Sabeeha S.

    2015-01-01

    Inorganic elements, although required only in trace amounts, permit life and primary productivity because of their functions in catalysis. Every organism has a minimal requirement of each metal based on the intracellular abundance of proteins that use inorganic cofactors, but elemental sparing mechanisms can reduce this quota. A well-studied copper-sparing mechanism that operates in microalgae faced with copper deficiency is the replacement of the abundant copper protein plastocyanin with a heme-containing substitute, cytochrome (Cyt) c6. This switch, which is dependent on a copper-sensing transcription factor, copper response regulator 1 (CRR1), dramatically reduces the copper quota. We show here that in a situation of marginal copper availability, copper is preferentially allocated from plastocyanin, whose function is dispensable, to other more critical copper-dependent enzymes like Cyt oxidase and a ferroxidase. In the absence of an extracellular source, copper allocation to Cyt oxidase includes CRR1-dependent proteolysis of plastocyanin and quantitative recycling of the copper cofactor from plastocyanin to Cyt oxidase. Transcriptome profiling identifies a gene encoding a Zn-metalloprotease, as a candidate effecting copper recycling. One reason for the retention of genes encoding both plastocyanin and Cyt c6 in algal and cyanobacterial genomes might be because plastocyanin provides a competitive advantage in copper-depleted environments as a ready source of copper. PMID:25646490

  10. Variations of serum copper values in pregnancy

    Directory of Open Access Journals (Sweden)

    Vukelić Jelka

    2012-01-01

    Full Text Available Introduction. Copper is essential micronutrient and has an important role in the human body. The serum copper increases during pregnancy and is doubled at full term. Lower levels of serum copper in pregnancy are connected with some pathological conditions. Objective. The aim of this study was to estimate the levels of serum copper in normal and pathological pregnancies, comparing them with values of serum copper in non-pregnant women, to determine if serum copper is lower in some pathological pregnancies and if this is of some importance. Methods. A total of 2170 plasma samples for copper analyses were made in the following groups: healthy non-pregnant women; healthy pregnant women from the 5th-40th gestational week, during the first delivery stage and during the first three postpartum weeks, in pregnant women with habitual abortion, imminent abortion, abortion in progress, missed abortion (9th-24th weeks, missed labour and premature rupture of membranes (29th-40th weeks. Levels of serum copper were determined by colorimetric technique of bathocuproin with disulphate as a chromogen. Results. Serum copper values in non-pregnant women range from 11.6-25.8 μmol/L. In healthy pregnant women, there is a constant trend of the increase of serum copper. The mean serum copper values revealed three significant peaks at the 22nd, 27th and 35th gestational week. Serum copper values in the patients with some pathological pregnancies in relation to the serum copper values of the healthy pregnant women were significantly lower. Conclusion. Serum copper values can be used as an indicator of some pathological pregnancies.

  11. Target Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — [Part of the ATLAS user facility.] The Physics Division operates a target development laboratory that produces targets and foils of various thickness and substrates,...

  12. Quantitative proteomic analysis of metabolic regulation by copper ions in Methylococcus capsulatus (Bath).

    Science.gov (United States)

    Kao, Wei-Chun; Chen, Yet-Ran; Yi, Eugene C; Lee, Hookeun; Tian, Qiang; Wu, Keh-Ming; Tsai, Shih-Feng; Yu, Steve S-F; Chen, Yu-Ju; Aebersold, Ruedi; Chan, Sunney I

    2004-12-03

    Copper ions switch the oxidation of methane by soluble methane monooxygenase to particulate methane monooxygenase in Methylococcus capsulatus (Bath). Toward understanding the change in cellular metabolism related to this transcriptional and metabolic switch, we have undertaken genomic sequencing and quantitative comparative analysis of the proteome in M. capsulatus (Bath) grown under different copper-to-biomass ratios by cleavable isotope-coded affinity tag technology. Of the 682 proteins identified, the expressions of 60 proteins were stimulated by at least 2-fold by copper ions; 68 proteins were down-regulated by 2-fold or more. The 60 proteins overexpressed included the methane and carbohydrate metabolic enzymes, while the 68 proteins suppressed were mainly responsible for cellular signaling processes, indicating a role of copper ions in the expression of the genes associated with the metabolism of the organism downstream of methane oxidation. The study has also provided a complete map of the C1 metabolism pathways in this methanotroph and clarified the interrelationships between them.

  13. Aquatic assessment of the Ely Copper Mine Superfund site, Vershire, Vermont

    Science.gov (United States)

    Seal, Robert R.; Kiah, Richard G.; Piatak, Nadine M.; Besser, John M.; Coles, James F.; Hammarstrom, Jane M.; Argue, Denise M.; Levitan, Denise M.; Deacon, Jeffrey R.; Ingersoll, Christopher G.

    2010-01-01

    The Ely Mine, which operated from 1821 to 1905, and its area of downstream impact constitute the Ely Copper Mine Superfund site. The site was placed on the National Priorities List in 2001. The mine comprises underground workings, foundations from historical structures, several waste-rock piles, roast beds associated with the smelting operation, and slag piles resulting from the smelting. The mine site is drained by Ely Brook, which includes several tributaries, one of which drains a series of six ponds. Ely Brook empties into Schoolhouse Brook, which flows 3.3 kilometers and joins the Ompompanoosuc River.

  14. Comparing potential copper chelation mechanisms in Parkinson's disease protein

    Science.gov (United States)

    Rose, Frisco; Hodak, Miroslav; Bernholc, Jerry

    2011-03-01

    We have implemented the nudged elastic band (NEB) as a guided dynamics framework for our real-space multigrid method of DFT-based quantum simulations. This highly parallel approach resolves a minimum energy pathway (MEP) on the energy hypersurface by relaxing intermediates in a chain-of-states. As an initial application we present an investigation of chelating agents acting on copper ion bound to α -synuclein, whose misfolding is implicated in Parkinson's disease (PD). Copper ions are known to act as highly effective misfolding agents in a-synuclein and are thus an important target in understanding PD. Furthermore, chelation therapy has shown promise in the treatment of Alzheimer's and other neuro-degenerative diseases with similar metal-correlated pathologies. At present, our candidate chelating agents include nicotine, curcumin and clioquinol. We examine their MEP activation barriers in the context of a PD onset mechanism to assess the viability of various chelators for PD remediation.

  15. 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.

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

    Science.gov (United States)

    Lavender, Christopher A; Cannady, Kimberly R; Hoffman, Jackson A; Trotter, Kevin W; Gilchrist, Daniel A; Bennett, Brian D; Burkholder, Adam B; Burd, Craig J; Fargo, David C; Archer, Trevor K

    2016-08-01

    Antisense transcription is a prevalent feature at mammalian promoters. Previous studies have primarily focused on antisense transcription initiating upstream of genes. Here, we characterize promoter-proximal antisense transcription downstream of gene transcription starts sites in human breast cancer cells, investigating the genomic context of downstream antisense transcription. We find extensive correlations between antisense transcription and features associated with the chromatin environment at gene promoters. Antisense transcription downstream of promoters is widespread, with antisense transcription initiation observed within 2 kb of 28% of gene transcription start sites. Antisense transcription initiates between nucleosomes regularly positioned downstream of these promoters. The nucleosomes between gene and downstream antisense transcription start sites carry histone modifications associated with active promoters, such as H3K4me3 and H3K27ac. This region is bound by chromatin remodeling and histone modifying complexes including SWI/SNF subunits and HDACs, suggesting that antisense transcription or resulting RNA transcripts contribute to the creation and maintenance of a promoter-associated chromatin environment. Downstream antisense transcription overlays additional regulatory features, such as transcription factor binding, DNA accessibility, and the downstream edge of promoter-associated CpG islands. These features suggest an important role for antisense transcription in the regulation of gene expression and the maintenance of a promoter-associated chromatin environment.

  17. Aquatic assessment of the Pike Hill Copper Mine Superfund site, Corinth, Vermont

    Science.gov (United States)

    Piatak, Nadine M.; Argue, Denise M.; Seal, Robert R.; Kiah, Richard G.; Besser, John M.; Coles, James F.; Hammarstrom, Jane M.; Levitan, Denise M.; Deacon, Jeffrey R.; Ingersoll, Christopher G.

    2013-01-01

    The Pike Hill Copper Mine Superfund site in Corinth, Orange County, Vermont, includes the Eureka, Union, and Smith mines along with areas of downstream aquatic ecosystem impairment. The site was placed on the U.S. Environmental Protection Agency (USEPA) National Priorities List in 2004. The mines, which operated from about 1847 to 1919, contain underground workings, foundations from historical structures, several waste-rock piles, and some flotation tailings. The mine site is drained to the northeast by Pike Hill Brook, which includes several wetland areas, and to the southeast by an unnamed tributary that flows to the south and enters Cookville Brook. Both brooks eventually drain into the Waits River, which flows into the Connecticut River. The aquatic ecosystem at the site was assessed using a variety of approaches that investigated surface-water quality, sediment quality, and various ecological indicators of stream-ecosystem health. The degradation of surface-water quality is caused by elevated concentrations of copper, and to a lesser extent cadmium, with localized effects caused by aluminum, iron, and zinc. Copper concentrations in surface waters reached or exceeded the USEPA national recommended chronic water-quality criteria for the protection of aquatic life in all of the Pike Hill Brook sampling locations except for the location farthest downstream, in half of the locations sampled in the tributary to Cookville Brook, and in about half of the locations in one wetland area located in Pike Hill Brook. Most of these same locations also contained concentrations of cadmium that exceeded the chronic water-quality criteria. In contrast, surface waters at background sampling locations were below these criteria for copper and cadmium. Comparison of hardness-based and Biotic Ligand Model (BLM)-based criteria for copper yields similar results with respect to the extent or number of stations impaired for surface waters in the affected area. However, the BLM

  18. Cascade pathway of filopodia formation downstream of SCAR.

    Science.gov (United States)

    Biyasheva, Assel; Svitkina, Tatyana; Kunda, Patricia; Baum, Buzz; Borisy, Gary

    2004-02-29

    The protrusion of two distinct actin-containing organelles, lamellipodia and filopodia, is thought to be regulated by two parallel pathways: from Rac1 through Scar/WAVEs to lamellipodia, and from Cdc42 through N-WASP to filopodia. We tested this hypothesis in Drosophila, which contains a single gene for each WASP subfamilies, SCAR and WASp. We performed targeted depletion of SCAR or WASp by dsRNA-mediated interference in two Drosophila cultured cell lines expressing lamellipodial and filopodial protrusion. Knockdown was verified by laser capture microdissection and RT-PCR, as well as western blotting. Morphometrical, kinetic and electron microscopy analyses of the SCAR-depleted phenotype in both cell types revealed strong inhibition of lamellipodial formation and cell spreading, as expected. More importantly, filopodia formation was also strongly inhibited, which is not consistent with the parallel pathway hypothesis. By contrast, depletion of WASp did not produce any significant phenotype, except for a slight inhibition of spreading, showing that both lamellipodia and filopodia in Drosophila cells are regulated predominantly by SCAR. We propose a new, cascade pathway model of filopodia regulation in which SCAR signals to lamellipodia and then filopodia arise from lamellipodia in response to additional signal(s).

  19. 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.

  20. Cellular copper levels determine the phenotype of the Arg875 variant of ATP7B/Wilson disease protein

    Science.gov (United States)

    Gupta, Arnab; Bhattacharjee, Ashima; Dmitriev, Oleg Y.; Nokhrin, Sergiy; Braiterman, Lelita; Hubbard, Ann L.; Lutsenko, Svetlana

    2011-01-01

    In human disorders, the genotype-phenotype relationships are often complex and influenced by genetic and/or environmental factors. Wilson disease (WD) is a monogenic disorder caused by mutations in the copper-transporting P-type ATPase ATP7B. WD shows significant phenotypic diversity even in patients carrying identical mutations; the basis for such diverse manifestations is unknown. We demonstrate that the 2623A/G polymorphism (producing the Gly875→Arg substitution in the A-domain of ATP7B) drastically alters the intracellular properties of ATP7B, whereas copper reverses the effects. Under basal conditions, the common Gly875 variant of ATP7B is targeted to the trans-Golgi network (TGN) and transports copper into the TGN lumen. In contrast, the Arg875 variant is located in the endoplasmic reticulum (ER) and does not deliver copper to the TGN. Elevated copper corrects the ATP7B-Arg875 phenotype. Addition of only 0.5–5 μM copper triggers the exit of ATP7B-Arg875 from the ER and restores copper delivery to the TGN. Analysis of the recombinant A-domains by NMR suggests that the ER retention of ATP7B-Arg875 is attributable to increased unfolding of the Arg875-containing A-domain. Copper is not required for the folding of ATP7B-Arg875 during biosynthesis, but it stabilizes protein and stimulates its activity. A chemotherapeutical drug, cisplatin, that mimics a copper-bound state of ATP7B also corrects the “disease-like” phenotype of ATP7B-Arg875 and promotes its TGN targeting and transport function. We conclude that in populations harboring the Arg875 polymorphism, the levels of bioavailable copper may play a vital role in the manifestations of WD. PMID:21406592

  1. Coupling of downstream RNA polymerase-promoter interactions with formation of catalytically competent transcription initiation complex.

    Science.gov (United States)

    Mekler, Vladimir; Minakhin, Leonid; Borukhov, Sergei; Mustaev, Arkady; Severinov, Konstantin

    2014-12-12

    Bacterial RNA polymerase (RNAP) makes extensive contacts with duplex DNA downstream of the transcription bubble in initiation and elongation complexes. We investigated the role of downstream interactions in formation of catalytically competent transcription initiation complex by measuring initiation activity of stable RNAP complexes with model promoter DNA fragments whose downstream ends extend from +3 to +21 relative to the transcription start site at +1. We found that DNA downstream of position +6 does not play a significant role in transcription initiation when RNAP-promoter interactions upstream of the transcription start site are strong and promoter melting region is AT rich. Further shortening of downstream DNA dramatically reduces efficiency of transcription initiation. The boundary of minimal downstream DNA duplex needed for efficient transcription initiation shifted further away from the catalytic center upon increasing the GC content of promoter melting region or in the presence of bacterial stringent response regulators DksA and ppGpp. These results indicate that the strength of RNAP-downstream DNA interactions has to reach a certain threshold to retain the catalytically competent conformation of the initiation complex and that establishment of contacts between RNAP and downstream DNA can be coupled with promoter melting. The data further suggest that RNAP interactions with DNA immediately downstream of the transcription bubble are particularly important for initiation of transcription. We hypothesize that these active center-proximal contacts stabilize the DNA template strand in the active center cleft and/or position the RNAP clamp domain to allow RNA synthesis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Impact of the rainfall pattern on synthetic pesticides and copper runoff from a vineyard catchment

    Science.gov (United States)

    Payraudeau, Sylvain; Meite, Fatima; Wiegert, Charline; Imfeld, Gwenaël

    2017-04-01

    Runoff is a major process of pesticide transport from agricultural land to downstream aquatic ecosystems. The impact of rainfall characteristics on the transport of runoff-related pesticide is rarely evaluated at the catchment scale. Here, we evaluate the influence of rainfall pattern on the mobilization of synthetic pesticides and copper fungicides in runoff from a small vineyard catchment, both at the plot and catchment scales. During two vineyard growing seasons in 2015 and 2016 (from March to October), we monitored rainfall, runoff, and concentrations of copper and 20 fungicides and herbicides applied by winegrowers at the Rouffach vineyard catchment (France, Alsace; 42.5 ha). Rainfall data were recorded within the catchment while runoff measurement and flow-proportional water sampling were carried out at the outlet of the plot (1486 m2; 87.5 × 17 m) and the catchment. In total, discharges of the 14 runoff events were continuously monitored between March and October 2015 using bubbler flow modules combined with Venturi channels. Detailed and distributed dataset on pesticide applications were extracted from survey (copper formulations and type of pesticides, amount and application dates). Pools of copper and synthetic pesticides were quantified weekly in the topsoil (0-3 cm) by systematic sampling across the catchment. The concentrations of copper (10 mg.kg-1 dried soil) and synthetic pesticides (close to the quantification limit, i.e. 0.05 µg.L-1) available in the top soil for off-site transport largely differed over time. Between March and October, an accumulation of copper of 10% was observed in the top-soil while pesticide concentration decreased below the quantification limits after a few days or weeks following application, depending of the compounds. The average runoff generated at the plot scale was very low (0.13% ± 0.30). The maximum runoff reached 1.37% during the storm of July 22, 2015. Synthetic pesticides exported by runoff was less than 1‰ of

  3. Nanoscale Copper and Copper Compounds for Advanced Device Applications

    Science.gov (United States)

    Chen, Lih-Juann

    2016-12-01

    Copper has been in use for at least 10,000 years. Copper alloys, such as bronze and brass, have played important roles in advancing civilization in human history. Bronze artifacts date at least 6500 years. On the other hand, discovery of intriguing properties and new applications in contemporary technology for copper and its compounds, particularly on nanoscale, have continued. In this paper, examples for the applications of Cu and Cu alloys for advanced device applications will be given on Cu metallization in microelectronics devices, Cu nanobats as field emitters, Cu2S nanowire array as high-rate capability and high-capacity cathodes for lithium-ion batteries, Cu-Te nanostructures for field-effect transistor, Cu3Si nanowires as high-performance field emitters and efficient anti-reflective layers, single-crystal Cu(In,Ga)Se2 nanotip arrays for high-efficiency solar cell, multilevel Cu2S resistive memory, superlattice Cu2S-Ag2S heterojunction diodes, and facet-dependent Cu2O diode.

  4. 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.

  5. Systems toxicology used in nanotoxicology: mechanistic insights into the hepatotoxicity of nano-copper particles from toxicogenomics.

    Science.gov (United States)

    Yang, BaoHua; Wang, Quanjun; Lei, RongHui; Wu, ChunQi; Shi, Chang; Wang, QingXiu; Yuan, Ye; Wang, Ying; Luo, YongWei; Hu, ZhongHui; Ma, Huazhi; Liao, MingYang

    2010-12-01

    In some studies, nano-copper particles have been found to be acutely toxic to exposed mice, with the liver and kidney being the target tissues. However, the characteristics of subacute toxicity from repeated nano-copper exposure in rats and the molecular mechanism of its hepatotoxicity at the genomic level remain unclear. We investigated the mechanisms of nano-copper-induced hepatotoxicity, which were identified from hepatic gene expression profiles that were phenotypically anchored to conventional toxicological outcomes, and identified biomarkers of nanotoxicity caused by nano-copper. Male Wistar rats were administered nano-copper or micro-copper at different doses for five days. Subsequently, we examined conventional toxicological parameters including body weight, clinical chemistry, and histopathology, and also used microarrays to identify gene expression changes in rat liver. High dose nano-copper induced increases in alanine aminotransferase, aspartate aminotransferase, triglyceride, total bilirubin, total bile acid levels, and a decrease in body weight. Histopathological studies of the liver indicated scattered, dotted hepatocytic necrosis in all rats in the high dose nano-copper group. Identified genes from the group receiving the high dose were functionally categorized, and results showed that genes related to oxidoreductase activity, metabolism, and signal transduction were involved in the development of the observed phenotypes. The results also suggest that altered gene expression patterns induced by exposure to a low, subtoxic dose of nano-copper may reveal signs of cell stress or subtle cell injury indicative of overt toxicity at higher doses. Results in this study provide new insights into the toxicology of nano-copper particles and illustrate how toxicogenomic approaches are providing an unprecedented amount of mechanistic information on molecular responses to nano-copper, as well as how they are likely to impact hazard and risk assessment. Gene

  6. Canine Models for Copper Homeostasis Disorders.

    Science.gov (United States)

    Wu, Xiaoyan; Leegwater, Peter A J; Fieten, Hille

    2016-02-04

    Copper is an essential trace nutrient metal involved in a multitude of cellular processes. Hereditary defects in copper metabolism result in disorders with a severe clinical course such as Wilson disease and Menkes disease. In Wilson disease, copper accumulation leads to liver cirrhosis and neurological impairments. A lack in genotype-phenotype correlation in Wilson disease points toward the influence of environmental factors or modifying genes. In a number of Non-Wilsonian forms of copper metabolism, the underlying genetic defects remain elusive. Several pure bred dog populations are affected with copper-associated hepatitis showing similarities to human copper metabolism disorders. Gene-mapping studies in these populations offer the opportunity to discover new genes involved in copper metabolism. Furthermore, due to the relatively large body size and long life-span of dogs they are excellent models for development of new treatment strategies. One example is the recent use of canine organoids for disease modeling and gene therapy of copper storage disease. This review addresses the opportunities offered by canine genetics for discovery of genes involved in copper metabolism disorders. Further, possibilities for the use of dogs in development of new treatment modalities for copper storage disorders, including gene repair in patient-derived hepatic organoids, are highlighted.

  7. Canine Models for Copper Homeostasis Disorders

    Directory of Open Access Journals (Sweden)

    Xiaoyan Wu

    2016-02-01

    Full Text Available Copper is an essential trace nutrient metal involved in a multitude of cellular processes. Hereditary defects in copper metabolism result in disorders with a severe clinical course such as Wilson disease and Menkes disease. In Wilson disease, copper accumulation leads to liver cirrhosis and neurological impairments. A lack in genotype-phenotype correlation in Wilson disease points toward the influence of environmental factors or modifying genes. In a number of Non-Wilsonian forms of copper metabolism, the underlying genetic defects remain elusive. Several pure bred dog populations are affected with copper-associated hepatitis showing similarities to human copper metabolism disorders. Gene-mapping studies in these populations offer the opportunity to discover new genes involved in copper metabolism. Furthermore, due to the relatively large body size and long life-span of dogs they are excellent models for development of new treatment strategies. One example is the recent use of canine organoids for disease modeling and gene therapy of copper storage disease. This review addresses the opportunities offered by canine genetics for discovery of genes involved in copper metabolism disorders. Further, possibilities for the use of dogs in development of new treatment modalities for copper storage disorders, including gene repair in patient-derived hepatic organoids, are highlighted.

  8. Metallic Copper as an Antimicrobial Surface▿

    Science.gov (United States)

    Grass, Gregor; Rensing, Christopher; Solioz, Marc

    2011-01-01

    Bacteria, yeasts, and viruses are rapidly killed on metallic copper surfaces, and the term “contact killing” has been coined for this process. While the phenomenon was already known in ancient times, it is currently receiving renewed attention. This is due to the potential use of copper as an antibacterial material in health care settings. Contact killing was observed to take place at a rate of at least 7 to 8 logs per hour, and no live microorganisms were generally recovered from copper surfaces after prolonged incubation. The antimicrobial activity of copper and copper alloys is now well established, and copper has recently been registered at the U.S. Environmental Protection Agency as the first solid antimicrobial material. In several clinical studies, copper has been evaluated for use on touch surfaces, such as door handles, bathroom fixtures, or bed rails, in attempts to curb nosocomial infections. In connection to these new applications of copper, it is important to understand the mechanism of contact killing since it may bear on central issues, such as the possibility of the emergence and spread of resistant organisms, cleaning procedures, and questions of material and object engineering. Recent work has shed light on mechanistic aspects of contact killing. These findings will be reviewed here and juxtaposed with the toxicity mechanisms of ionic copper. The merit of copper as a hygienic material in hospitals and related settings will also be discussed. PMID:21193661

  9. Antimicrobial activity of different copper alloy surfaces against copper resistant and sensitive Salmonella enterica.

    Science.gov (United States)

    Zhu, Libin; Elguindi, Jutta; Rensing, Christopher; Ravishankar, Sadhana

    2012-05-01

    Copper has shown antibacterial effects against foodborne pathogens. The objective of this study was to evaluate the antibacterial activity of copper surfaces on copper resistant and sensitive strains of Salmonella enterica. Six different copper alloy coupons (60-99.9% copper) were tested along with stainless steel as the control. The coupons were surface inoculated with either S. Enteritidis or one of the 3 copper resistant strains, S. Typhimurium S9, S19 and S20; stored under various incubation conditions at room temperature; and sampled at various times up to 2 h. The results showed that under dry incubation conditions, Salmonella only survived 10-15 min on high copper content alloys. Salmonella on low copper content alloys showed 3-4 log reductions. Under moist incubation conditions, no survivors were detected after 30 min-2 h on high copper content alloys, while the cell counts decreased 2-4 logs on low copper content coupons. Although the copper resistant strains survived better than S. Enteritidis, they were either completely inactivated or survival was decreased. Copper coupons showed better antimicrobial efficacy in the absence of organic compounds. These results clearly show the antibacterial effects of copper and its potential as an alternative to stainless steel for selected food contact surfaces. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Synthesis of cytochrome c oxidase 1 (SCO1) inhibits insulin sensitivity by decreasing copper levels in adipocytes.

    Science.gov (United States)

    Wei, Xiang-Bo; Guo, Liang; Liu, Yang; Zhou, Shui-Rong; Liu, Yuan; Dou, Xin; Du, Shao-Yue; Ding, Meng; Peng, Wan-Qiu; Qian, Shu-Wen; Huang, Hai-Yan; Tang, Qi-Qun

    2017-09-23

    Dysregulation of insulin signaling leads to type 2 diabetes mellitus (T2DM) and other metabolic disorders. Obesity is an important contributor to insulin resistance, and although the understanding of this relationship has improved in recent years, the mechanism of obesity-induced insulin resistance is not completely understood. Disorders of copper metabolism tend to accompany the development of obesity, which increases the risk of insulin resistance. Synthesis of cytochrome c oxidase 1 (SCO1) functions in the assembly of cytochrome c oxidase (COX) and cellular copper homeostasis. However, the role of SCO1 in the regulation of metabolism remains unknown. Here, we found that obese mice had higher expression of SCO1 and lower levels of copper in white adipose tissue (WAT) than did the control mice. Overexpression of SCO1 in adipocytes was associated with copper deficiency. Copper increased insulin sensitivity by decreasing the level of phosphatase and tensin homolog (PTEN) protein. Ectopic expression of SCO1 led to insulin resistance and was accompanied by a decrease in intracellular copper level, and addition of copper abolished the inhibitory effect of SCO1 on insulin sensitivity. Our results demonstrated a novel role of SCO1 in modulating insulin sensitivity via the regulation of copper concentration in WAT and suggested a potential therapeutic target for T2DM. Copyright © 2017. Published by Elsevier Inc.

  11. Multilevel Dual Damascene copper interconnections

    Science.gov (United States)

    Lakshminarayanan, S.

    Copper has been acknowledged as the interconnect material for future generations of ICs to overcome the bottlenecks on speed and reliability present with the current Al based wiring. A new set of challenges brought to the forefront when copper replaces aluminum, have to be met and resolved to make it a viable option. Unit step processes related to copper technology have been under development for the last few years. In this work, the application of copper as the interconnect material in multilevel structures with SiO2 as the interlevel dielectric has been explored, with emphasis on integration issues and complete process realization. Interconnect definition was achieved by the Dual Damascene approach using chemical mechanical polishing of oxide and copper. The choice of materials used as adhesion promoter/diffusion barrier included Ti, Ta and CVD TiN. Two different polish chemistries (NH4OH or HNO3 based) were used to form the interconnects. The diffusion barrier was removed during polishing (in the case of TiN) or by a post CMP etch (as with Ti or Ta). Copper surface passivation was performed using boron implantation and PECVD nitride encapsulation. The interlevel dielectric way composed of a multilayer stack of PECVD SiO2 and SixNy. A baseline process sequence which ensured the mechanical and thermal compatibility of the different unit steps was first created. A comprehensive test vehicle was designed and test structures were fabricated using the process flow developed. Suitable modifications were subsequently introduced in the sequence as and when processing problems were encountered. Electrical characterization was performed on the fabricated devices, interconnects, contacts and vias. The structures were subjected to thermal stressing to assess their stability and performance. The measurement of interconnect sheet resistances revealed lower copper loss due to dishing on samples polished using HNO3 based slurry. Interconnect resistances remained stable upto 400o

  12. LEP Radio Frequency Copper Cavity

    CERN Document Server

    The pulse of a particle accelerator. 128 of these radio frequency cavities were positioned around CERN's 27-kilometre LEP ring to accelerate electrons and positrons. The acceleration was produced by microwave electric oscillations at 352 MHz. The electrons and positrons were grouped into bunches, like beads on a string, and the copper sphere at the top stored the microwave energy between the passage of individual bunches. This made for valuable energy savings as it reduced the heat generated in the cavity.

  13. Pulsed laser ablation of copper

    Science.gov (United States)

    Jordan, R.; Cole, D.; Lunney, J. G.; Mackay, K.; Givord, D.

    1995-02-01

    The laser ablation of copper with a 532 nm, 6 ns laser has been investigated in the regime normally used for pulsed laser deposition. The ablation depth per pulse and the flux and energy distribution of the ions in the plume were measured and compared to the deposition rate as measured by a quartz microbalance. These measurements were compared with an analytic model of ablation via a laser sustained plasma. It is shown that self-sputtering of the growing film is significant.

  14. 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...

  15. Modeling of local scour depth downstream hydraulic structures in trapezoidal channel using GEP and ANNs

    Directory of Open Access Journals (Sweden)

    Yasser Abdallah Mohamed Moussa

    2013-12-01

    Full Text Available Local scour downstream stilling basins is so complex that it makes it difficult to establish a general empirical model to provide accurate estimation for scour depth. Lack estimation of local scour can endanger to stability of hydraulic structure and can cause risk of failure. This paper presents Gene expression program (GEP and artificial neural network (ANNs, to simulate local scour depth downstream hydraulic structures. The experimental data is collected from the literature for the scour depth downstream the stilling basin through a trapezoidal channel. Using GEP approach gives satisfactory results compared with artificial neural network (ANN and multiple linear regression (MLR modeling in predicting the scour depth downstream of hydraulic structures.

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

    Science.gov (United States)

    Deb, Nebras; Anis, Hanan

    2011-08-15

    We propose a novel wavelength-division-multiplexed passive optical network (WDM-PON) architecture with enhanced tolerance toward chromatic dispersion where a DPSK-modulated downstream signal with constant intensity is remodulated at the ONU side with a return to zero (RZ-DPSK). Driving the downstream modulator with a 50% RZ data enabled us to employ the pulse carver at the ONU for both removing downstream data and generating the optical RZ signal for upstream. This offers an attractive alternative to earlier proposed schemes as it allows us to use full modulation depth (FMD) and balanced detection for downstream data restoration. We experimentally demonstrate the system with both balanced and single-ended detection at 2.5 Gb/s. Error-free operation has been achieved along a 20 Km single mode fiber without dispersion compensation. © 2011 Optical Society of America

  17. 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

  18. Speciation and leachability of copper in mine tailings from porphyry copper mining

    DEFF Research Database (Denmark)

    Hansen, Henrik K.; Yianatos, Juan B; Ottosen, Lisbeth M.

    2005-01-01

    to evaluate the speciation of copper. It was found that the particles of smallest size contained 50-60% weak acid leachable copper, whereas only 32% of the copper found in largest particles could be leached in weak acid. Copper oxides and carbonates were the dominating species in the smaller particles......Mine tailing from the El Teniente-Codelco copper mine situated in VI Region of Chile was analysed in order to evaluate the mobility and speciation of copper in the solid material. Mine tailing was sampled after the rougher flotation circuits, and the copper content was measured to 1150mgkg^-^1 dry...... matter. This tailing was segmented into fractions of different size intervals: 0-38, 38-45, 45-53, 53-75, 75-106, 106-150, 150-212, and >212@mm, respectively. Copper content determination, sequential chemical extraction, and desorption experiments were carried out for each size interval in order...

  19. ANALYSIS AND DEVELOPMENT OF COPPER RECYCLING OF DEAD COPPER-CONTAINING CATALYSTS

    Directory of Open Access Journals (Sweden)

    O. S. Komarov

    2009-01-01

    Full Text Available The technology of processing of copper-bearing dead catalysts, which includes leaching and deposition of copper by means of electrolysis and also their application in composition of the mixture for alloy doping is offered.

  20. Inspection of copper canisters for spent nuclear fuel by means of ultrasound. Synthetic aperture imaging, evaluation of ultrasonic attenuation in copper

    Energy Technology Data Exchange (ETDEWEB)

    Stepinski, Tadeusz (ed.); Lingvall, Fredrik; Wennerstroem, Erik; Ping Wu [Uppsala Univ. (Sweden). Department of Engineering Sciences

    2006-01-15

    This report contains the research results concerning advanced ultrasound for the inspection of copper canisters for spent nuclear fuel obtained at Signals and Systems, Uppsala University in years 2004/2005. After a short introduction a new super-resolution synthetic aperture imaging (SRSAI) technique is proposed. The proposed SRSAI is characterized by an excellent lateral resolution and much higher signal to noise ratio compared with ESAFT which was proposed in our previous reports. The ESAFT is based on the assumption that probability density of the imaged targets (so called prior) is Gaussian, which is the simplest case for the analysis. The increased performance of SRSAI is due to more realistic assumption concerning probability density function of targets in the region of interest. It is shown, both using simulations and in an experiment that if the target reflectivity is assumed to be positive a substantial increase of resolution and signal to noise ratio in the reconstructed image can be obtained. In the second chapter the result of the evaluation of ultrasonic attenuation in copper blocks with different grain size is presented. A short presentation of basic theory of the buffer-rod and the immersion methods is given in the beginning (the detailed derivation is provided in the appendix). Then the measurement setup and copper specimens are specified and the results of measurements made on copper specimens are presented. Correlation between the attenuation and grain size for the inspected specimens is discussed.

  1. Autophagic-lysosomal dysregulation downstream of cathepsin B inactivation in human skin fibroblasts exposed to UVA.

    Science.gov (United States)

    Lamore, Sarah D; Wondrak, Georg T

    2012-01-01

    Recently, using 2D-DIGE proteomics we have identified cathepsin B as a novel target of UVA in human Hs27 skin fibroblasts. In response to chronic exposure to noncytotoxic doses of UVA (9.9 J cm(-2), twice a week, 3 weeks), photooxidative impairment of cathepsin B enzymatic activity occurred with accumulation of autofluorescent aggregates colocalizing with lysosomes, an effect mimicked by pharmacological antagonism of cathepsin B using the selective inhibitor CA074Me. Here, we have further explored the mechanistic involvement of cathepsin B inactivation in UVA-induced autophagic-lysosomal alterations using autophagy-directed PCR expression array analysis as a discovery tool. Consistent with lysosomal expansion, UVA upregulated cellular protein levels of the lysosomal marker glycoprotein Lamp-1, and increased levels of the lipidated autophagosomal membrane constituent LC3-II were detected. UVA did not alter expression of beclin 1 (BECN1), an essential factor for initiation of autophagy, but upregulation of p62 (sequestosome 1, SQSTM1), a selective autophagy substrate, and α-synuclein (SNCA), an autophagic protein substrate and aggresome component, was observed at the mRNA and protein level. Moreover, UVA downregulated transglutaminase-2 (TGM2), an essential enzyme involved in autophagolysosome maturation. Strikingly, UVA effects on Lamp-1, LC3-II, beclin 1, p62, α-synuclein, and transglutaminase-2 were mimicked by CA074Me treatment. Taken together, our data suggest that UVA-induced autophagic-lysosomal alterations occur as a consequence of impaired autophagic flux downstream of cathepsin B inactivation, a novel molecular mechanism potentially involved in UVA-induced skin photodamage. This journal is © The Royal Society of Chemistry and Owner Societies 2012

  2. Copper: a metal for the ages

    Science.gov (United States)

    Doebrich, Jeff

    2009-01-01

    Copper was one of the first metals ever extracted and used by humans, and it has made vital contributions to sustaining and improving society since the dawn of civilization. Copper was first used in coins and ornaments starting about 8000 B.C., and at about 5500 B.C., copper tools helped civilization emerge from the Stone Age. The discovery that copper alloyed with tin produces bronze marked the beginning of the Bronze Age at about 3000 B.C. Copper is easily stretched, molded, and shaped; is resistant to corrosion; and conducts heat and electricity efficiently. As a result, copper was important to early humans and continues to be a material of choice for a variety of domestic, industrial, and high-technology applications today.

  3. Functional understanding of the versatile protein copper metabolism MURR1 domain 1 (COMMD1) in copper homeostasis

    NARCIS (Netherlands)

    Fedoseienko, Alina; Bartuzi, Paulina; van de Sluis, Bart

    2014-01-01

    Copper is an important cofactor in numerous biological processes in all living organisms. However, excessive copper can be extremely toxic, so it is vital that the copper level within a cell is tightly regulated. The damaging effect of copper is seen in several hereditary forms of copper toxicity in

  4. Copper Isotope Constraints on the Genesis of the Keweenaw Peninsula Native Copper District, Michigan, USA

    Directory of Open Access Journals (Sweden)

    Theodore J. Bornhorst

    2017-09-01

    Full Text Available The Keweenaw Peninsula native copper district of Michigan, USA is the largest concentration of native copper in the world. The copper isotopic composition of native copper was measured from stratabound and vein deposits, hosted by multiple rift-filling basalt-dominated stratigraphic horizons over 110 km of strike length. The δ65Cu of the native copper has an overall mean of +0.28‰ and a range of −0.32‰ to +0.80‰ (excluding one anomalous value. The data appear to be normally distributed and unimodal with no substantial differences between the native copper isotopic composition from the wide spread of deposits studied here. This suggests a common regional and relatively uniform process of derivation and precipitation of the copper in these deposits. Several published studies indicate that the ore-forming hydrothermal fluids carried copper as Cu1+, which is reduced to Cu0 during the precipitation of native copper. The δ65Cu of copper in the ore-forming fluids is thereby constrained to +0.80‰ or higher in order to yield the measured native copper values by reductive precipitation. The currently accepted hypothesis for the genesis of native copper relies on the leaching of copper from the rift-filling basalt-dominated stratigraphic section at a depth below the deposits during burial metamorphism. Oxidative dissolution of copper from magmatic source rocks with magmatic δ65Cu of 0‰ ± 0.3‰ is needed to obtain the copper isotopic composition of the metamorphogenic ore-forming hydrothermal fluids. In order to accommodate oxidative dissolution of copper from the rift-filling basalt source rocks, the copper needs to have been sited in native copper. Magmatic native copper in basalt is likely stable when the magma is low in sulfur. Low sulfur is predicted by the lack of sulfide minerals in the ore deposits and in the rift-filling basalt-dominated section, which are source rocks, the same rocks through which the ore fluids moved upwards, and

  5. 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.

  6. Detection of copper ions from aqueous solutions using layered double hydroxides thin films deposited by PLD

    Energy Technology Data Exchange (ETDEWEB)

    Vlad, A., E-mail: angela.vlad@gmail.com [National Institute for Lasers, Plasma and Radiation Physics, 409 Atomistilor Str., 76900 Bucharest-Magurele (Romania); Birjega, R.; Matei, A.; Luculescu, C.; Nedelcea, A.; Dinescu, M. [National Institute for Lasers, Plasma and Radiation Physics, 409 Atomistilor Str., 76900 Bucharest-Magurele (Romania); Zavoianu, R.; Pavel, O.D. [University of Bucharest, Faculty of Chemistry, Department of Chemical Technology and Catalysis, 4-12 Regina Elisabeta Bd., Bucharest (Romania)

    2015-10-15

    Highlights: • PLD was successfully used to produce Mg2Al thin films from Mg–Al LDH target (Mg/Al = 2). • Well oriented LDH films were obtained for all three wavelengths of a Nd:YAG laser: 266 nm, 352 nm, 1064 nm. • Mg–Al LDH thin films obtained in this work could be suitable as adsorbent material for the detection of copper in aqueous solutions. - Abstract: Layered double hydroxides (LDHs) thin films with Mg–Al were deposited using pulsed laser deposition (PLD) technique. We studied the ability of our films to detect copper ions in aqueous solutions. Copper is known to be a common pollutant in water, originating from urban and industrial waste. Clay minerals, including layered double hydroxides (LDHs), can reduce the toxicity of such wastes by adsorbing copper. We report on the uptake of copper ions from aqueous solution on LDH thin films obtained via PLD. The obtained thin films were characterized using X-ray Diffraction, Atomic Force Microscopy, and Scanning Electron Microscopy with Energy Dispersive X-ray analysis. The results in this study indicate that LDHs thin films obtained by PLD have potential as an efficient adsorbent for removing copper from aqueous solution.

  7. Wilson disease protein ATP7B utilizes lysosomal exocytosis to maintain copper homeostasis.

    Science.gov (United States)

    Polishchuk, Elena V; Concilli, Mafalda; Iacobacci, Simona; Chesi, Giancarlo; Pastore, Nunzia; Piccolo, Pasquale; Paladino, Simona; Baldantoni, Daniela; van IJzendoorn, Sven C D; Chan, Jefferson; Chang, Christopher J; Amoresano, Angela; Pane, Francesca; Pucci, Piero; Tarallo, Antonietta; Parenti, Giancarlo; Brunetti-Pierri, Nicola; Settembre, Carmine; Ballabio, Andrea; Polishchuk, Roman S

    2014-06-23

    Copper is an essential yet toxic metal and its overload causes Wilson disease, a disorder due to mutations in copper transporter ATP7B. To remove excess copper into the bile, ATP7B traffics toward canalicular area of hepatocytes. However, the trafficking mechanisms of ATP7B remain elusive. Here, we show that, in response to elevated copper, ATP7B moves from the Golgi to lysosomes and imports metal into their lumen. ATP7B enables lysosomes to undergo exocytosis through the interaction with p62 subunit of dynactin that allows lysosome translocation toward the canalicular pole of hepatocytes. Activation of lysosomal exocytosis stimulates copper clearance from the hepatocytes and rescues the most frequent Wilson-disease-causing ATP7B mutant to the appropriate functional site. Our findings indicate that lysosomes serve as an important intermediate in ATP7B trafficking, whereas lysosomal exocytosis operates as an integral process in copper excretion and hence can be targeted for therapeutic approaches to combat Wilson disease. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Mitochondrial proteomic alterations caused by long-term low-dose copper exposure in mouse cortex.

    Science.gov (United States)

    Lin, Xuemei; Wei, Gang; Huang, Zhijun; Qu, Zhongsen; Huang, Xinfeng; Xu, Hua; Liu, Jianjun; Zhuang, Zhixiong; Yang, Xifei

    2016-11-30

    Mitochondrial dysfunction is involved in neurotoxicity caused by exposure of various chemicals such as copper. However, the effects of long-term low-dose copper exposure on mitochondrial proteome remain unclear. In this study, we found the treatment of copper (0.13ppm copper sulfate in drinking water) for 12 months caused abnormal expression of a total of 13 mitochondrial proteins (7 up-regulated and 6 down-regulated) as revealed by two-dimensional electrophoresis coupled with mass spectrometry in mouse cortex. Protein functional analysis revealed that these differentially expressed proteins mainly included apoptosis-associated proteins, axon guidance-associated proteins, axonogenesis-associated proteins and mitochondrial respiratory chain complex. Among these differentially expressed mitochondrial proteins, GRP75 (75kDa glucose-regulated protein) and GRP78 (78kDa glucose-regulated protein) were found to be significantly down-regulated as confirmed by Western-blot analysis. The down-regulation of GRP75 was shown to promote apoptosis. The down-regulation of GRP78/BiP could up-regulate endoplasmic reticulum (ER) stress mediators and thus cause apoptosis. Our study suggested that these differentially expressed mitochondrial proteins such as GRP75 and GRP78 could be involved in neurotoxicity caused by long-term low-dose copper exposure and serve as potential molecular targets for the treatment of copper neurotoxicity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Achieving Plant CRISPR Targeting that Limits Off-Target Effects

    Directory of Open Access Journals (Sweden)

    Jeffrey D. Wolt

    2016-11-01

    Full Text Available The CRISPR-Cas9 system (clustered regularly interspaced short palindromic repeats with associated Cas9 protein has been used to generate targeted changes for direct modification of endogenous genes in an increasing number of plant species; but development of plant genome editing has not yet fully considered potential off-target mismatches that may lead to unintended changes within the genome. Assessing the specificity of CRISPR-Cas9 for increasing editing efficiency as well as the potential for unanticipated downstream effects from off-target mutations is an important regulatory consideration for agricultural applications. Increasing genome-editing specificity entails developing improved design methods that better predict the prevalence of off-target mutations as a function of genome composition and design of the engineered ribonucleoprotein (RNP. Early results from CRISPR-Cas9 genome editing in plant systems indicate that the incidence of off-target mutation frequencies is quite low; however, by analyzing CRISPR-edited plant lines and improving both computational tools and reagent design, it may be possible to further decrease unanticipated effects at potential mismatch sites within the genome. This will provide assurance that CRISPR-Cas9 reagents can be designed and targeted with a high degree of specificity. Improved and experimentally validated design tools for discriminating target and potential off-target positions that incorporate consideration of the designed nuclease fidelity and selectivity will help to increase confidence for regulatory decision making for genome-edited plants.

  10. The copper-transporting ATPase pump and its potential role in copper-tolerance

    Science.gov (United States)

    Katie Ohno; C.A. Clausen; Frederick Green; G. Stanosz

    2016-01-01

    Copper-tolerant brown-rot decay fungi exploit intricate mechanisms to neutralize the efficacy of copper-containing preservative formulations. The production and accumulation oxalate is the most widely recognized theory regarding the mechanism of copper-tolerance in these fungi. The role of oxalate, however, may be only one part of a series of necessary components...

  11. Electrochemical in-situ impregnation of wood using a copper nail as source for copper

    DEFF Research Database (Denmark)

    Ottosen, Lisbeth M.; Block, Thomas; Nymark, Morten

    2011-01-01

    A new method for copper impregnation of wood in structures was suggested and tested in laboratory scale with specimen of new pine sapwood. A copper nail and a steel screw were placed in the wood, and an electric direct current field was applied, so the copper nail was anode and the screw...

  12. Copper Smelting and Refining at Kosaka Smelter

    National Research Council Canada - National Science Library

    HOSHIKAWA, Yoshihiko

    2007-01-01

      Kosaka smelter started copper production in 1901 using blast furnace, and diversified into other products and metallurgical technologies that treated complex concentrates produced at black ore mine...

  13. Diets deficient in copper and zinc?

    Science.gov (United States)

    Klevay, L M

    1979-12-01

    Hospital diets, and, perhaps, diets in general may be low in copper and zinc, with the diets being lower in copper than zinc in comparison to requirements. Several human diseases or pathologic conditions of unknown etiology have similarities to findings in deficient animals. Thus nutritional status and metabolism of copper may be important in anemia, ischemic heart disease, rheumatoid arthritis, osteoporosis, multiple sclerosis and seborrheic dermatitis. Zinc may be involved in growth failure, acne, difficulties of labor, congenital abnormalities and wound healing. Whether or not dietary amounts of copper and zinc are involved in the etiology or the pathogenesis of these conditions can be determined by clinical investigation.

  14. Chronic copper poisoning in feeder lambs

    Energy Technology Data Exchange (ETDEWEB)

    Tait, R.M.; Krishnamurti, C.R.; Gilchrist, E.W.; MacDonald, K.

    1971-03-01

    Nineteen of 55 feeder lambs succumbed to chronic copper poisoning after consuming a concentrate ration containing 27 ppm copper for a period of 16 weeks. Liver copper levels averaged 1312 +/- 172 ppm on a dry matter basis, being at least three to four times normal. The use of soybean meal or urea as sources of supplemental nitrogen did not appear to influence the occurrence of this disorder. The fastest growing lambs were not necessarily the first to succumb. The copper content of ingredients and mineral supplements should receive attention when rations for sheep are formulated. 10 references, 3 figures.

  15. Integrative Genomics Implicates EGFR as a Downstream Mediator in NKX2-1 Amplified Non-Small Cell Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Nicole Clarke

    Full Text Available NKX2-1, encoding a homeobox transcription factor, is amplified in approximately 15% of non-small cell lung cancers (NSCLC, where it is thought to drive cancer cell proliferation and survival. However, its mechanism of action remains largely unknown. To identify relevant downstream transcriptional targets, here we carried out a combined NKX2-1 transcriptome (NKX2-1 knockdown followed by RNAseq and cistrome (NKX2-1 binding sites by ChIPseq analysis in four NKX2-1-amplified human NSCLC cell lines. While NKX2-1 regulated genes differed among the four cell lines assayed, cell proliferation emerged as a common theme. Moreover, in 3 of the 4 cell lines, epidermal growth factor receptor (EGFR was among the top NKX2-1 upregulated targets, which we confirmed at the protein level by western blot. Interestingly, EGFR knockdown led to upregulation of NKX2-1, suggesting a negative feedback loop. Consistent with this finding, combined knockdown of NKX2-1 and EGFR in NCI-H1819 lung cancer cells reduced cell proliferation (as well as MAP-kinase and PI3-kinase signaling more than knockdown of either alone. Likewise, NKX2-1 knockdown enhanced the growth-inhibitory effect of the EGFR-inhibitor erlotinib. Taken together, our findings implicate EGFR as a downstream effector of NKX2-1 in NKX2-1 amplified NSCLC, with possible clinical implications, and provide a rich dataset for investigating additional mediators of NKX2-1 driven oncogenesis.

  16. Performance characteristics, plasma lipids and copper residue in ...

    African Journals Online (AJOL)

    Copper proteinate) and inorganic (Copper sulphate) Cu source on growth performance, plasma lipids and copper residue in organs and tissues of cockerel chickens. 240 day-old commercial Black-Harco cockerel chicks were randomly distributed to ...

  17. 77 FR 74985 - Water Quality Standards for the State of Florida's Streams and Downstream Protection Values for...

    Science.gov (United States)

    2012-12-18

    ... Downstream Protection Values for Lakes: Remanded Provisions AGENCY: Environmental Protection Agency (EPA... cannot be performed to derive downstream protection values (DPVs) that will ensure the attainment and... lakes, springs, flowing waters, estuaries, and coastal waters, as well as downstream protection values...

  18. Molecular Characterization of CTR-type Copper Transporters in an Oceanic Diatom, Thalassiosira oceanica 1005

    Science.gov (United States)

    Kong, L.; Price, N. M.

    2016-02-01

    Copper is an essential micronutrient for phytoplankton growth because of its role as a redox cofactor in electron transfer proteins in photosynthesis and respiration, and a potentially limiting resource in parts of the open sea. Thalassiosira oceanica 1005 can grow at inorganic copper concentrations varying from 10 fmol/L to 10 nmol/L by regulating copper uptake across plasma membrane. Four putative CTR-type copper transporter genes (ToCTR1, ToCTR2, ToCTR3.1 and ToCTR3.2) were identified by BLASTP search against the T. oceanica genome. Predicted gene models were revised by assembled mRNA sequencing transcripts and updated gene models contained all conserved features of characterized CTR-type copper transporters. ToCTR3.1 and ToCTR3.2 may arise from one another by gene duplication as they shared a sequence similarity of 97.6% with a peptide insertion of 5 amino acids at N-terminus of ToCTR3.1. The expression of ToCTR1, ToCTR2 and ToCTR3.1/3.2 was upregulated in low copper concentrations, but only ToCTR3.1/3.2 showed a significant increase (2.5 fold) in copper-starved cells. Both ToCTR3.1 and ToCTR3.2 restored growth of a yeast double mutant, Saccharomyces cerevisiae ctr1Δctr3Δ, in copper deficient medium. GFP-fused ToCTR expression showed that some ToCTR3.1 localized to the plasma membrane but a large portion was retained in the endoplasmic reticulum. Inefficient targeting of ToCTR3.1 to the yeast outer membrane may explain poorer growth compared to the Saccharomyces native ScCTR1 transformant. Thus, diatom CTR genes encoding CTR-type copper transporters show high-affinity copper uptake and their regulation may enable diatoms to survive in ocean environments containing a wide range of copper concentrations.

  19. Energy and materials flows in the copper industry

    Energy Technology Data Exchange (ETDEWEB)

    Gaines, L.L.

    1980-12-01

    The copper industry comprises both the primary copper industry, which produces 99.9%-pure copper from copper ore, and the secondary copper industry, which salvages and recycles copper-containing scrap metal to extract pure copper or copper alloys. The United States uses about 2 million tons of copper annually, 60% of it for electrical applications. Demand is expected to increase less than 4% annually for the next 20 years. The primary copper industry is concentrated in the Southwest; Arizona produced 66% of the 1979 total ore output. Primary production uses about 170 x 10/sup 12/ Btu total energy annually (about 100 x 10/sup 6/ Btu/ton pure copper produced from ore). Mining and milling use about 60% of the total consumption, because low-grade ore (0.6% copper) is now being mined. Most copper is extracted by smelting sulfide ores, with concomitant production of sulfur dioxide. Clean air regulations will require smelters to reduce sulfur emissions, necessitating smelting process modifications that could also save 20 x 10/sup 12/ Btu (10 x 10/sup 6/ Btu/ton of copper) in smelting energy. Energy use in secondary copper production averages 20 x 10/sup 6/ Btu/ton of copper. If all copper products were recycled, instead of the 30% now salvaged, the energy conservation potential would be about one-half the total energy consumption of the primary copper industry.

  20. Synthesis of Commercial Products from Copper Wire-Drawing Waste

    Science.gov (United States)

    Ayala, J.; Fernández, B.

    2014-06-01

    Copper powder and copper sulfate pentahydrate were obtained from copper wire-drawing scale. The hydrometallurgical recycling process proposed in this article yields a high-purity copper powder and analytical grade copper sulfate pentahydrate. In the first stage of this process, the copper is dissolved in sulfuric acid media via dismutation of the scale. In the second stage, copper sulfate pentahydrate is precipitated using ethanol. Effects such as pH, reaction times, stirring speed, initial copper concentration, and ethanol/solution volume ratio were studied during the precipitation from solution reaction. The proposed method is technically straightforward and provides efficient recovery of Cu from wire-drawing scale.

  1. 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.

  2. Salicylate-mediated suppression of jasmonate-responsive gene expression in Arabidopsis is targeted downstream of the jasmonate biosynthesis pathway

    NARCIS (Netherlands)

    Leon Reyes, H.A.; Does, D. van der; Lange, E.S. de; Delker, C.; Wasternack, C.; Wees, A.C.M. van; Ritsema, T.; Pieterse, C.M.J.

    2010-01-01

    Jasmonates (JAs) and salicylic acid (SA) are plant hormones that play pivotal roles in the regulation of induced defenses against microbial pathogens and insect herbivores. Their signaling pathways cross-communicate providing the plant with a regulatory potential to finely tune its defense response

  3. Plasminogen activator inhibitor-1 is a critical downstream target of p53 in the induction of replicative senescence

    NARCIS (Netherlands)

    Kortlever, R.M.; Higgins, P.J.; Bernards, R.A.

    2006-01-01

    genesPAI-1PI(3)KPKBGSK3cyclin D1p19ARFp21CIP1uPAp16INK4Acyclin EPCNAp53 limits the proliferation of primary diploid fibroblasts by inducing a state of growth arrest named replicative senescence — a process which protects against oncogenic transformation and requires integrity of the p53 tumour

  4. Annual Copper Mountain Conferences on Multigrid and Iterative Methods, Copper Mountain, Colorado

    Energy Technology Data Exchange (ETDEWEB)

    McCormick, Stephen F. [Front Range Scientific, Inc., Lake City, CO (United States)

    2016-03-25

    This project supported the Copper Mountain Conference on Multigrid and Iterative Methods, held from 2007 to 2015, at Copper Mountain, Colorado. The subject of the Copper Mountain Conference Series alternated between Multigrid Methods in odd-numbered years and Iterative Methods in even-numbered years. Begun in 1983, the Series represents an important forum for the exchange of ideas in these two closely related fields. This report describes the Copper Mountain Conference on Multigrid and Iterative Methods, 2007-2015. Information on the conference series is available at http://grandmaster.colorado.edu/~copper/.

  5. COPPER AND COPPER-CONTAINING PESTICIDES: METABOLISM, TOXICITY AND OXIDATIVE STRESS

    Directory of Open Access Journals (Sweden)

    Viktor Husak

    2015-05-01

    Full Text Available The purpose of this paper is to provide a brief review of the current knowledge regarding metabolism and toxicity of copper and copper-based pesticides in living organisms. Copper is an essential trace element in all living organisms (bacteria, fungi, plants, and animals, because it participates in different metabolic processes and maintain functions of organisms. The transport and metabolism of copper in living organisms is currently the subject of many studies. Copper is absorbed, transported, distributed, stored, and excreted in the body via the complex of homeostatic processes, which provide organisms with a needed constant level of this micronutrient and avoid excessive amounts. Many aspects of copper homeostasis were studied at the molecular level. Copper based-pesticides, in particularly fungicides, bacteriocides and herbicides, are widely used in agricultural practice throughout the world. Copper is an integral part of antioxidant enzymes, particularly copper-zinc superoxide dismutase (Cu,Zn-SOD, and plays prominent roles in iron homeostasis. On the other hand, excess of copper in organism has deleterious effect, because it stimulates free radical production in the cell, induces lipid peroxidation, and disturbs the total antioxidant capacity of the body. The mechanisms of copper toxicity are discussed in this review also.

  6. Copper oxide--copper sulfate water-splitting cycle

    Energy Technology Data Exchange (ETDEWEB)

    Foh, S. E.; Schreiber, J. D.; Dafler, J. R.

    1978-08-01

    A hybrid copper oxide--copper sulfate thermochemical water-splitting cycle, IGT's H-5, has been demonstrated in the laboratory with recycled materials. The optimum configuration and operating conditions for the electrolytic hydrogen-producing step have not yet been defined. With cooperative funding (A.G.A./G.R.I./DOE) a conceptual flowsheet was developed for this cycle and a load-line efficiency of about 37% calculated. This figure is the result of a single iteration on the original base case flow sheet and compares well with the values calculated for other processes at this stage of development. An iterative optimization of process conditions would improve efficiency. The data required to perform an economic analysis are not yet available and the electrolysis step must be more fully defined. An attractive process efficiency, relatively few corrosive materials, and few gas-phase separations are attributes of Cycle H-5 that lead us to believe hydrogen costs (to be developed during future analyses) would be improved significantly over similar processes analyzed to date.

  7. Different pathways for copper sulphate and copper nitrate antioxidation and organic acid excretion in Typha latifolia?

    Directory of Open Access Journals (Sweden)

    Lyubenova L.

    2013-04-01

    Full Text Available The major topic of the present experiment was the investigation of the antioxidative enzymes and the root exudate excretion after plant exposure to copper. The copper was added for each treatment as copper sulphate and copper nitrate in the concentrations of 10 μM, 50 μM and 100 μM, respectively. The plant species chosen for the study was Typha latifolia. The experiment gives insight into the plant responses to different copper supplies during the same conditions of exposure. Remarkable results were obtained during the time course about the excretion of organic acids from Typha latifolia roots during one week of copper exposure. Oxalic acid, malic acid, acetic acid and lactic acid were detected. Interestingly, not all organic acids are excreted from the roots in the first hours after copper addition.

  8. Dendritic Solidification in a Copper Nickel Alloy

    OpenAIRE

    DÜNDAR, Sacit

    2014-01-01

    The distribution of nickel in dendrite arms and in interdendritic regions of copper-10% nickel alloy solidified under production conditions designed to provide 4 different cooling rates was investigated. The results indicate that at different rates of solidification undercooling, diffusion and convection mechanisms affect the microsegregation of nickel and copper in the cast materials to various extents.

  9. High Copper Amalgam Alloys in Dentistry

    Directory of Open Access Journals (Sweden)

    Gaurav Solanki

    2012-07-01

    Full Text Available Amalgam Restoration is an example of the material giving its name to the process. Amalgam fillings are made up of mercury, powdered silver and tin. They are mixed and packed into cavities in teeth where it hardens slowly and replaces the missing tooth substance. The high copper have become material of choice as compared to low copper alloys nowadays because of their improved mechanical properties, corrosion resistance, better marginal integrity and improved performance in clinical trial. The high copper amalgam was used as a restorative material. The application of high copper amalgam was found to be much more useful than low copper amalgam. High copper had much more strength, corrosion resistance, durability and resistance to tarnish as compared to low copper amalgams. No marked expansion or condensation was noted in the amalgam restoration after its setting after 24 hrs. By using the high copper alloy, the chances of creep were also minimized in the restored tooth. No discomfort or any kind of odd sensation in the tooth was noted after few days of amalgam restoration in the tooth.

  10. DIETARY SELENIUM AND COPPER INTAKE BY RESIDENT ...

    African Journals Online (AJOL)

    hi-tech

    2004-01-01

    Jan 1, 2004 ... Less common features of copper deficiency include loss of pigmentation, neurolological and impaired growth(15). Individuals at risk of copper deficiency include premature babies, individuals with malabsorption syndrome including celiac disease, sprue and short bowel syndrome due to surgical removal of.

  11. Material characterization of ancient Indian copper

    Indian Academy of Sciences (India)

    Unknown

    tions on archaeological copper would provide valuable inputs in material selection for canisters for long-term nuclear waste storage (Rosborg et al 2003). In this regard, the inputs from archaeologists would provide valuable insights in the materials selection problem. 2. Experimental. The copper chisel that was utilized in ...

  12. Catalytic kinetic spectrophotometric determination of trace copper ...

    African Journals Online (AJOL)

    A novel catalytic kinetic-spectrophotometric method is proposed for the determination of copper based on this principle. Copper(II) can be determined spectrophotometrically by measuring the decrease in the absorbance of CPApA at the wavelength of 554 nm using the fixed-time method. The optimum reaction conditions ...

  13. Material characterization of ancient Indian copper

    Indian Academy of Sciences (India)

    A chalcolithic (2350–1800 BC) copper chisel from Balathal has been characterized by X-ray diffraction, microstructural and electrochemical methods. The surface patina was composed of sulfates and oxysulfates in the outer layers while the inner layers were rich in copper oxides. The chisel exhibited smaller grain sizes ...

  14. Photocleavage of DNA by copper (II) complexes

    Indian Academy of Sciences (India)

    The chemistry of ternary and binary copper(II) complexes showing efficient visible lightinduced DNA cleavage activity is summarized in this article. The role of the metal in photo-induced DNA cleavage reactions is explored by designing complex molecules having a variety of ligands. Ternary copper(II) complexes with amino ...

  15. 21 CFR 73.1647 - Copper powder.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Copper powder. 73.1647 Section 73.1647 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR... use in color additive mixtures for coloring externally applied drugs. (b) Specifications. Copper...

  16. Additive monitoring and interactions during copper electroprocessing

    Science.gov (United States)

    Collins, Dale Wade

    The electrochemical deposition of copper has been a major focus of research for decades. Renewed interest in copper electroplating is not limited to the copper producers but is also a major concern of semiconductor manufacturers. The focus on copper electrochemistry by the semiconductor manufacturers has increased since IBM's announcement in 1997 that copper will be used for metallization in high speed/power semiconductors [1--3]. The desire to use copper instead of aluminum is simply a reflection on copper's superior conductivity (lower RC time constants) and resistance to electromigration (generally proportional to the melting point). This dissertation is the compilation of the research into analytical techniques for monitoring surface-active additives in common sulfuric acid/copper sulfate plating baths. Chronopotentiometric, DC and AC voltammetry were the major analytical techniques used in this research. Several interactions between the additives will also be presented along with their apparent decline in activity. The decline in activity is well known in the industry and is also detected by these methods as presented in chapters 4 and 5. Finally, a systemic approach for monitoring the additive Galactosal, which is commonly used in electrowinning, will be outlined. The monitoring system proposed herein would have to be adjusted for each electrowinning facility because each has a unique chemistry and cell configuration.

  17. Copper(II) complexes with aroylhydrazones

    Indian Academy of Sciences (India)

    Unknown

    The coordination chemistry of copper(II) with tridentate aroylhydrazones is briefly discussed in this article. ... the metal ions 3. In the following account, the results obtained in our study on copper(II) chemistry with these ..... Rev.77165;. (b) Fenton D E 1983 Advances in inorganic and bio-organic mechanisms (ed.) A G Sykes.

  18. Downstream Intensification Effects Associated with CO2 Laser Mitigation of Fused Silica

    Energy Technology Data Exchange (ETDEWEB)

    Matthews, M J; Bass, I L; Guss, G M; Widmayer, C C; Ravizza, F L

    2007-10-29

    Mitigation of 351nm laser-induced damage sites on fused silica exit surfaces by selective CO{sub 2} treatment has been shown to effectively arrest the exponential growth responsible for limiting the lifetime of optics in high-fluence laser systems. However, the perturbation to the optical surface profile following the mitigation process introduces phase contrast to the beam, causing some amount of downstream intensification with the potential to damage downstream optics. Control of the laser treatment process and measurement of the associated phase modulation is essential to preventing downstream 'fratricide' in damage-mitigated optical systems. In this work we present measurements of the surface morphology, intensification patterns and damage associated with various CO{sub 2} mitigation treatments on fused silica surfaces. Specifically, two components of intensification pattern, one on-axis and another off-axis can lead to damage of downstream optics and are related to rims around the ablation pit left from the mitigation process. It is shown that control of the rim structure around the edge of typical mitigation sites is crucial in preventing damage to downstream optics.

  19. Measurement of the airflow velocity upstream and downstream a wire mesh using constant temperature anemometry

    Directory of Open Access Journals (Sweden)

    Lizal Frantisek

    2014-03-01

    Full Text Available Measurement of velocity upstream and downstream a special wire mesh was performed to ascertain the effect of the mesh on the flow. The mesh consisted of two components, a basic rectangular mesh with mesh width 1.22 mm and wire diameter 0.2 mm, and a top steel wool with random position of wires and wire diameter 0.05 mm. The velocity was measured by Constant Temperature Anemometry using single wire probe in a Plexiglas channel of rectangular cross-section. As a first step, measurement of one horizontal and one vertical measuring line was performed 10 mm upstream and 6 mm downstream the wire mesh. A spatial velocity profile upstream of the wire mesh was smooth, while the downstream velocity profile was highly disturbed. However, velocity fluctuations expressed in terms of turbulence intensity downstream of the wire mesh were attenuated down to 1%. Further measurements of the area downstream the wire mesh will be performed to describe the development of the flow.

  20. Activation of ADAM 12 protease by copper

    DEFF Research Database (Denmark)

    Loechel, F; Wewer, Ulla M.

    2001-01-01

    Conversion of latent proteases to the active form occurs by various mechanisms characteristic for different protease families. Here we report that the disintegrin metalloprotease ADAM 12-S is activated by Cu(II). Copper activation is distinct from the cysteine switch component of latency: elimina......Conversion of latent proteases to the active form occurs by various mechanisms characteristic for different protease families. Here we report that the disintegrin metalloprotease ADAM 12-S is activated by Cu(II). Copper activation is distinct from the cysteine switch component of latency......: elimination of the ADAM 12 cysteine switch by a point mutation in the propeptide had no effect on copper activation, whereas mutation of an unpaired cysteine residue in the catalytic domain resulted in a mutant form of ADAM 12-S that was insensitive to copper. This suggests a multi-step activation mechanism...... for ADAM 12 involving both furin cleavage and copper binding....

  1. Synthesis of copper chromite catalyst

    Energy Technology Data Exchange (ETDEWEB)

    Kawamoto, A.M.; Claudio Rezende, L. [Space Aeronautical Institute/Aerospace Center, Chemistry Div., Sao Jose dos Campos, SP (Brazil); Claudio Pardini, L. [Space Aeronautical Institute/Aerospace Center, Materials Div., Sao Jose dos Campos, SP (Brazil)

    2004-10-01

    The present work has the objective to investigate the catalytic behaviour of copper chromite (CuCr{sub 2}O{sub 4}) in the burning rate of poly-butadiene hydroxyl terminated (HTPB) which is an ammonium perchlorate propellant for solid fueled rockets. Copper chromite catalysts were prepared by ceramic and coprecipitation methods and characterized by X-ray diffraction, scanning electron microscopy (SEM), elemental, differential calorimetric (DSC), thermogravimetric and granulometric analysis, mass spectroscopy and infrared spectroscopy (IR). Elemental and IR analysis have shown similarities among the samples for both synthetic methods. However, DSC, SEM and X-ray analysis of the samples synthesized by coprecipitation method presented different physical properties. For those samples, DSC could identify a tetragonal {yields} cubic phase transition, SEM showed particles with defined crystalline shapes and X-ray analysis contains the main assignments which identify the formation of CuCr{sub 2}O{sub 4}. HTPB propellants containing CuCr{sub 2}O{sub 4} samples were manufactured, then burning rate and mechanical properties have been measured. The results were compared with HTPB propellants containing iron (III) oxide as catalyst. The highest burning rate values were obtained with samples which present a more defined crystalline shape, i.e., the ones synthesized by the coprecipitation method. (authors)

  2. Penicillin-binding protein encoded by pbp4 is involved in mediating copper stress in Listeria monocytogenes.

    Science.gov (United States)

    Parsons, Cameron; Costolo, Ben; Brown, Phillip; Kathariou, Sophia

    2017-11-01

    Listeria monocytogenes raises major food safety and public health concerns due to its potential for severe foodborne disease and persistent colonization of food processing facilities. Copper is often employed to control pathogens in agriculture and is increasingly used in healthcare facilities, but mechanisms mediating tolerance of L. monocytogenes to copper remain poorly understood. A mariner-based mutant library of L. monocytogenes 2011L-2858, implicated in the 2011 listeriosis outbreak via whole cantaloupe, was screened for growth at sublethal levels of copper yielding mutant G2B4 with decreased copper tolerance. The transposon was localized in pbp4 (lmo2229 homolog), encoding a penicillin-binding protein (PBP). In addition to reduced copper tolerance, G2B4 exhibited increased susceptibility to β-lactam antibiotics, reduced biofilm formation and reduced virulence in the Galleria mellonella model. Mutant phenotypes were fully restored upon genetic complementation of G2B4 with intact pbp4. Findings provide the first evidence for the role of a PBP in copper tolerance of L. monocytogenes and suggest that pbp4 may be a suitable target to enable the use of lower levels of copper or enhance the effectiveness of levels currently in use. Given the wide distribution of PBPs and their highly conserved nature, this could have profound impacts in regard to ecology and control of L. monocytogenes and other microorganisms. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. A dulal-functional medium voltage level DVR to limit downstream fault currents

    DEFF Research Database (Denmark)

    Blaabjerg, Frede; Li, Yun Wei; Vilathgamuwa, D. Mahinda

    2007-01-01

    on the other parallel feeders connected to PCC. Furthermore, if not controlled properly, the DVR might also contribute to this PCC voltage sag in the process of compensating the missing voltage, thus further worsening the fault situation. To limit the flow of large line currents, and therefore restore the PCC......, the DVR will therefore be tasked to mitigate even more faults involving downstream loads. Large fault currents would flow through the DVR during a downstream fault before the opening of a circuit breaker. This will cause the voltage at point of common coupling (PCC) to drop, which would affect the loads...... voltage as well as protect the DVR system components, a downstream fault limiting function is proposed and integrated in the DVR operation. A flux-charge-model feedback algorithm is implemented so that the DVR would act as a large virtual inductance in series with the distribution feeder in fault...

  4. 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.

  5. Therapeutic potential of copper chelation with triethylenetetramine in managing diabetes mellitus and Alzheimer's disease.

    Science.gov (United States)

    Cooper, Garth J S

    2011-07-09

    This article reviews recent evidence, much of which has been generated by my group's research programme, which has identified for the first time a previously unknown copper-overload state that is central to the pathogenesis of diabetic organ damage. This state causes tissue damage in the blood vessels, heart, kidneys, retina and nerves through copper-mediated oxidative stress. This author now considers this copper-overload state to provide an important new target for therapeutic intervention, the objective of which is to prevent or reverse the diabetic complications. Triethylenetetramine (TETA) has recently been identified as the first in a new class of anti-diabetic molecules through the original work reviewed here, thus providing a new use for this molecule, which was previously approved by the US FDA in 1985 as a second-line treatment for Wilson's disease. TETA acts as a highly selective divalent copper (Cu(II)) chelator that prevents or reverses diabetic copper overload, thereby suppressing oxidative stress. TETA treatment of diabetic animals and patients has identified and quantified the interlinked defects in copper metabolism that characterize this systemic copper overload state. Copper overload in diabetes mellitus differs from that in Wilson's disease through differences in their respective causative molecular mechanisms, and resulting differences in tissue localization and behaviour of the excess copper. Elevated pathogenetic tissue binding of copper occurs in diabetes. It may well be mediated by advanced-glycation endproduct (AGE) modification of susceptible amino-acid residues in long-lived fibrous proteins, for example, connective tissue collagens in locations such as blood vessel walls. These AGE modifications can act as localized, fixed endogenous chelators that increase the chelatable-copper content of organs such as the heart and kidneys by binding excessive amounts of catalytically active Cu(II) in specific vascular beds, thereby focusing the

  6. The structural flexibility of the human copper chaperone Atox1: Insights from combined pulsed EPR studies and computations.

    Science.gov (United States)

    Levy, Ariel R; Turgeman, Meital; Gevorkyan-Aiapetov, Lada; Ruthstein, Sharon

    2017-08-01

    Metallochaperones are responsible for shuttling metal ions to target proteins. Thus, a metallochaperone's structure must be sufficiently flexible both to hold onto its ion while traversing the cytoplasm and to transfer the ion to or from a partner protein. Here, we sought to shed light on the structure of Atox1, a metallochaperone involved in the human copper regulation system. Atox1 shuttles copper ions from the main copper transporter, Ctr1, to the ATP7b transporter in the Golgi apparatus. Conventional biophysical tools such as X-ray or NMR cannot always target the various conformational states of metallochaperones, owing to a requirement for crystallography or low sensitivity and resolution. Electron paramagnetic resonance (EPR) spectroscopy has recently emerged as a powerful tool for resolving biological reactions and mechanisms in solution. When coupled with computational methods, EPR with site-directed spin labeling and nanoscale distance measurements can provide structural information on a protein or protein complex in solution. We use these methods to show that Atox1 can accommodate at least four different conformations in the apo state (unbound to copper), and two different conformations in the holo state (bound to copper). We also demonstrate that the structure of Atox1 in the holo form is more compact than in the apo form. Our data provide insight regarding the structural mechanisms through which Atox1 can fulfill its dual role of copper binding and transfer. © 2017 The Protein Society.

  7. 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.

  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. Pipe flow pattern downstream of local restrictions studied by an optical method

    Science.gov (United States)

    Molochnikov, V. M.; Kratirov, D. V.; Mikheev, A. N.

    2017-09-01

    An approach to the study of gas flow patterns in circular pipes using 2D methods (PIV, SIV) has been proposed. The approach is based on a special device which is similar to a closed test section of a wind tunnel. It allows measurements of flow parameters downstream of local flow restrictions in circular channels without any optical distortions caused by curved pipe walls. The test results are submitted together with some data on the flow pattern downstream of a gate valve at different channel blockage ratios.

  10. Industrial Tests to Modify Molten Copper Slag for Improvement of Copper Recovery

    Science.gov (United States)

    Guo, Zhengqi; Zhu, Deqing; Pan, Jian; Zhang, Feng; Yang, Congcong

    2017-11-01

    In this article, to improve the recovery of copper from copper slag by flotation process, industrial tests of the modification process involving addition of a composite additive into molten copper slag were conducted, and the modified slag was subjected to the flotation process to confirm the modification effect. The phase evolution of the slag in the modification process was revealed by thermodynamic calculations, x-ray diffraction, optical microscopy and scanning electron microscopy. The results show that more copper was transformed and enriched in copper sulfide phases. The magnetite content in the modified slag decreased, and that of "FeO" increased correspondingly, leading to a better fluidity of the molten slag, which improved the aggregation and growth of fine particles of the copper sulfide minerals. Closed-circuit flotation tests of the original and modified slags were conducted, and the results show that the copper recovery increased obviously from 69.15% to 73.38%, and the copper grade of concentrates was elevated slightly from 20.24% to 21.69%, further confirming that the industrial tests of the modification process were successful. Hence, the modification process has a bright future in industrial applications for enhancing the recovery of copper from the copper slag.

  11. Molecular responses of mouse macrophages to copper and copper oxide nanoparticles inferred from proteomic analyses.

    Science.gov (United States)

    Triboulet, Sarah; Aude-Garcia, Catherine; Carrière, Marie; Diemer, Hélène; Proamer, Fabienne; Habert, Aurélie; Chevallet, Mireille; Collin-Faure, Véronique; Strub, Jean-Marc; Hanau, Daniel; Van Dorsselaer, Alain; Herlin-Boime, Nathalie; Rabilloud, Thierry

    2013-11-01

    The molecular responses of macrophages to copper-based nanoparticles have been investigated via a combination of proteomic and biochemical approaches, using the RAW264.7 cell line as a model. Both metallic copper and copper oxide nanoparticles have been tested, with copper ion and zirconium oxide nanoparticles used as controls. Proteomic analysis highlighted changes in proteins implicated in oxidative stress responses (superoxide dismutases and peroxiredoxins), glutathione biosynthesis, the actomyosin cytoskeleton, and mitochondrial proteins (especially oxidative phosphorylation complex subunits). Validation studies employing functional analyses showed that the increases in glutathione biosynthesis and in mitochondrial complexes observed in the proteomic screen were critical to cell survival upon stress with copper-based nanoparticles; pharmacological inhibition of these two pathways enhanced cell vulnerability to copper-based nanoparticles, but not to copper ions. Furthermore, functional analyses using primary macrophages derived from bone marrow showed a decrease in reduced glutathione levels, a decrease in the mitochondrial transmembrane potential, and inhibition of phagocytosis and of lipopolysaccharide-induced nitric oxide production. However, only a fraction of these effects could be obtained with copper ions. In conclusion, this study showed that macrophage functions are significantly altered by copper-based nanoparticles. Also highlighted are the cellular pathways modulated by cells for survival and the exemplified cross-toxicities that can occur between copper-based nanoparticles and pharmacological agents.

  12. Molecular Responses of Mouse Macrophages to Copper and Copper Oxide Nanoparticles Inferred from Proteomic Analyses*

    Science.gov (United States)

    Triboulet, Sarah; Aude-Garcia, Catherine; Carrière, Marie; Diemer, Hélène; Proamer, Fabienne; Habert, Aurélie; Chevallet, Mireille; Collin-Faure, Véronique; Strub, Jean-Marc; Hanau, Daniel; Van Dorsselaer, Alain; Herlin-Boime, Nathalie; Rabilloud, Thierry

    2013-01-01

    The molecular responses of macrophages to copper-based nanoparticles have been investigated via a combination of proteomic and biochemical approaches, using the RAW264.7 cell line as a model. Both metallic copper and copper oxide nanoparticles have been tested, with copper ion and zirconium oxide nanoparticles used as controls. Proteomic analysis highlighted changes in proteins implicated in oxidative stress responses (superoxide dismutases and peroxiredoxins), glutathione biosynthesis, the actomyosin cytoskeleton, and mitochondrial proteins (especially oxidative phosphorylation complex subunits). Validation studies employing functional analyses showed that the increases in glutathione biosynthesis and in mitochondrial complexes observed in the proteomic screen were critical to cell survival upon stress with copper-based nanoparticles; pharmacological inhibition of these two pathways enhanced cell vulnerability to copper-based nanoparticles, but not to copper ions. Furthermore, functional analyses using primary macrophages derived from bone marrow showed a decrease in reduced glutathione levels, a decrease in the mitochondrial transmembrane potential, and inhibition of phagocytosis and of lipopolysaccharide-induced nitric oxide production. However, only a fraction of these effects could be obtained with copper ions. In conclusion, this study showed that macrophage functions are significantly altered by copper-based nanoparticles. Also highlighted are the cellular pathways modulated by cells for survival and the exemplified cross-toxicities that can occur between copper-based nanoparticles and pharmacological agents. PMID:23882024

  13. MicroRNA-184 is a downstream effector of albuminuria driving renal fibrosis in rats with diabetic nephropathy.

    Science.gov (United States)

    Zanchi, Cristina; Macconi, Daniela; Trionfini, Piera; Tomasoni, Susanna; Rottoli, Daniela; Locatelli, Monica; Rudnicki, Michael; Vandesompele, Jo; Mestdagh, Pieter; Remuzzi, Giuseppe; Benigni, Ariela; Zoja, Carlamaria

    2017-06-01

    Renal fibrosis is a common complication of diabetic nephropathy and is a major cause of end-stage renal disease. Despite the suggested link between renal fibrosis and microRNA (miRNA) dysregulation in diabetic nephropathy, the identification of the specific miRNAs involved is still incomplete. The aim of this study was to investigate miRNA profiles in the diabetic kidney and to identify potential downstream targets implicated in renal fibrosis. miRNA expression profiling was investigated in the kidneys of 8-month-old Zucker diabetic fatty (ZDF) rats during overt nephropathy. Localisation of the most upregulated miRNA was established by in situ hybridisation. The candidate miRNA target was identified by in silico analysis and its expression documented in the diabetic kidney associated with fibrotic markers. Cultured tubule cells served to assess which of the profibrogenic stimuli acted as a trigger for the overexpressed miRNA, and to investigate underlying epigenetic mechanisms. In ZDF rats, miR-184 showed the strongest differential upregulation compared with lean rats (18-fold). Tubular localisation of miR-184 was associated with reduced expression of lipid phosphate phosphatase 3 (LPP3) and collagen accumulation. Transfection of NRK-52E cells with miR-184 mimic reduced LPP3, promoting a profibrotic phenotype. Albumin was a major trigger of miR-184 expression. Anti-miR-184 counteracted albumin-induced LPP3 downregulation and overexpression of plasminogen activator inhibitor-1. In ZDF rats, ACE-inhibitor treatment limited albuminuria and reduced miR-184, with tubular LPP3 preservation and tubulointerstitial fibrosis amelioration. Albumin-induced miR-184 expression in tubule cells was epigenetically regulated through DNA demethylation and histone lysine acetylation and was accompanied by binding of NF-κB p65 subunit to miR-184 promoter. These results suggest that miR-184 may act as a downstream effector of albuminuria through LPP3 to promote tubulointerstitial

  14. Kinetics of the conversion of copper sulfide to blister copper

    Directory of Open Access Journals (Sweden)

    Carrillo, F.

    2002-10-01

    Full Text Available The desulfurization of copper sulfide by air and oxygen has been studied in two laboratory reactors where the gas is blown onto the melt surface. Rates of oxidation in a vertical resistance furnace may be explained by the mass transfer control in the gas phase. However, results for a horizontal tube suggest that the chemical resistance is controlling.

    La desulfuración del sulfuro cuproso con aire y oxígeno se ha estudiado en dos reactores de laboratorio, en los cuales el gas se sopla sobre la superficie del fundido. La velocidad de reacción en un horno de resistencias verticales se puede explicar considerando como controlante la resistencia a la transferencia de materia de la fase gas. Sin embargo, los resultados del horno horizontal indican que la resistencia química es la controlante.

  15. Characterization of copper SERS-active substrates prepared by electrochemical deposition

    Energy Technology Data Exchange (ETDEWEB)

    Cejkova, Jitka, E-mail: jitka.cejkova@vscht.cz [Institute of Chemical Technology Prague, Department of Chemical Engineering, Technicka 5, 166 28 Prague 6 (Czech Republic); Prokopec, Vadym; Brazdova, Sona; Kokaislova, Alzbeta; Matejka, Pavel [Institute of Chemical Technology Prague, Department of Analytical Chemistry, Technicka 5, 166 28 Prague 6 (Czech Republic); Stepanek, Frantisek [Institute of Chemical Technology Prague, Department of Chemical Engineering, Technicka 5, 166 28 Prague 6 (Czech Republic)

    2009-06-30

    Surface Enhanced Raman Scattering (SERS) on copper substrates of various morphologies, prepared by electrochemical deposition on platinum targets, was investigated. The substrate preparation procedures differed by the coating bath compositions, applied current densities and the duration of individual steps. The surface morphology of the substrates was visualized by means of Atomic Force Microscopy (AFM) and Scanning Electron Microscopy (SEM). SERS spectra of selected organic thiols were measured and the relation between SERS spectral intensity and the surface structure of SERS-active substrates was studied. It has been shown that good Raman surface enhancement can be achieved on the copper substrates prepared by electrochemical deposition from ammoniac baths. Copper substrates fabricated from acidic baths did not show efficient Raman surface enhancement. The results of microscopic measurements demonstrated that the average surface roughness value does not play a substantial role, whereas the shape of the surface nanostructures is a key parameter.

  16. Copper and selenium supplementation of ewes gnazing on pastures ...

    African Journals Online (AJOL)

    Influence of copper and selenium supplementation in SA Mutton. Merino ewes, kept on pastures with low copper ... plasma copper, pregnancy, selenium supplementation,. Low copper concentrations are frequently ... very weak at birth, their mortality rate was high and growth rate poor (Van Niekerk & Van Niekerk, 1989c).

  17. Copper and selenium supplementation of ewes grazing on pastures ...

    African Journals Online (AJOL)

    Influence of copper and selenium supplementationi n SA Mutton Merino ewes, kept on pastures with low copper and selenium concentrations, was investigated. Ewes which came into oestrus and conceived during March to April, were found to have concentrations of plasma copper of 60 to 80 pg /dl. Inadequare copper ...

  18. Effects of copper and the sea lice treatment Slice on nutrient release from marine sediments.

    Science.gov (United States)

    Mayor, D J; Solan, M; McMillan, H; Killham, K; Paton, G I

    2009-04-01

    Copper-based antifoulant paints and the sea lice treatment Slice are widely used, and often detectable in the sediments beneath farms where they are administered. Ten-day, whole sediment mesocosm experiments were conducted to examine how increasing sediment concentrations of copper or Slice influenced final water column concentrations of ammonium-nitrogen (NH(4)-N), nitrate+nitrite-nitrogen (NO(X)-N) and phosphate-phosphorus (PO(4)-P) in the presence of the non-target, benthic organisms Corophium volutator and Hediste diversicolor. Nominal sediment concentrations of copper and Slice had significant effects on the resulting concentrations of almost all nutrients examined. The overall trends in nutrient concentrations at the end of the 10-day incubations were highly similar between the trials with either copper or Slice, irrespective of the invertebrate species present. This suggests that nutrient exchange from the experimental sediments was primarily influenced by the direct effect of copper/Slice dose on the sediment microbial community, rather than the indirect effect of reduced bioturbation/irrigation due to increased macrofaunal mortality.

  19. Surface modification of an epoxy resin with polyamines and polydopamine: Adhesion toward electroless deposited copper

    Energy Technology Data Exchange (ETDEWEB)

    Schaubroeck, David, E-mail: David.Schaubroeck@elis.ugent.be [Center for Microsystems Technology (CMST), IMEC and Ghent University, Technologiepark 914A, B-9052 Ghent (Belgium); Mader, Lothar [Center for Microsystems Technology (CMST), IMEC and Ghent University, Technologiepark 914A, B-9052 Ghent (Belgium); Dubruel, Peter [Polymer Chemistry and Biomaterials Research Group, Ghent University, Krijgslaan 281 S4 bis, B-9000 Ghent (Belgium); Vanfleteren, Jan [Center for Microsystems Technology (CMST), IMEC and Ghent University, Technologiepark 914A, B-9052 Ghent (Belgium)

    2015-10-30

    Highlights: • Surface modifications of epoxy resins with polydopamine and grafted polyamines can significantly increase the adhesion toward electroless deposited copper. • A clear characterization of the copper/epoxy interphase is provided by SEM analyses of cross sections. • Tailored conditions such as etching time (roughness) and electroless deposition temperature are needed to increase the adhesion of the modified surfaces. - Abstract: In this paper the influence of the epoxy roughness, surface modifications and ELD (electroless copper deposition) temperatures on the adhesive strength of the copper is studied. Good adhesion at low roughness values is targeted due to their applicability in high density electronic circuits. Roughened epoxy surfaces are modified with adsorbed polyamines, polydopamine and polyamines grafted to polydopamine. Next the, adhesive strength of ELD copper is determined with peel strength measurements and the interphases are examined with SEM (scanning electron microscopy). Polydopamine and polyamines grafted to polydopamine can lead to increased adhesive strength at lower roughness values compared to the non-modified samples at specific plating temperatures.

  20. Selective mechanical transfer of graphene from seed copper foil using rate effects.

    Science.gov (United States)

    Na, Seung Ryul; Suk, Ji Won; Tao, Li; Akinwande, Deji; Ruoff, Rodney S; Huang, Rui; Liechti, Kenneth M

    2015-02-24

    A very fast, dry transfer process based on mechanical delamination successfully effected the transfer of large-area, CVD grown graphene on copper foil to silicon. This has been achieved by bonding silicon backing layers to both sides of the graphene-coated copper foil with epoxy and applying a suitably high separation rate to the backing layers. At the highest separation rate considered (254.0 μm/s), monolayer graphene was completely transferred from the copper foil to the target silicon substrate. On the other hand, the lowest rate (25.4 μm/s) caused the epoxy to be completely separated from the graphene. Fracture mechanics analyses were used to determine the adhesion energy between graphene and its seed copper foil (6.0 J/m(2)) and between graphene and the epoxy (3.4 J/m(2)) at the respective loading rates. Control experiments for the epoxy/silicon interface established a rate dependent adhesion, which supports the hypothesis that the adhesion of the graphene/epoxy interface was higher than that of the graphene/copper interface at the higher separation rate, thereby providing a controllable mechanism for selective transfer of graphene in future nanofabrication systems such as roll-to-roll transfer.

  1. Gold-Copper alloy "nano-dumplings" with tunable compositions and plasmonic properties

    Science.gov (United States)

    Verma, Manoj; Kedia, Abhitosh; Kumar, P. Senthil

    2016-05-01

    The unique yet tunable optical properties of plasmonic metal nanoparticles have made them attractive targets for a wide range of applications including nanophotonics, molecular sensing, catalysis etc. Such diverse applications that require precisely stable / reproducible plasmonic properties depend sensitively on the particle morphology ie. the shape, size and constituents. Herein, we systematically study the size / shape controlled synthesis of gold-copper "dumpling" shaped alloy nanoparticles by simultaneous reduction of gold and copper salts in the PVP-methanol solute-solvent system, by effectively utilizing the efficient but mild reduction as well as capping abilities of Poly (N-vinylpyrrolidone). Introduction of copper salts not only yielded the alloy nanoparticles, but also slowed down the growth process to maintain high mono-dispersity of the new shapes evolved. Copper and gold has different lattice constants (0.361 and 0.408 nm respectively) and hence doping/addition/replacement of copper atoms to gold FCC unit cell introduces strain into the lattice which is key parameter to the shape evolution in anisotropic nanoparticles. Synthesized alloy nanoparticles were characterized by UV-visible absorption spectroscopy, XRD and TEM imaging.

  2. Histopathology biomarker responses in Asian sea bass, Lates calcarifer (Bloch exposed to copper

    Directory of Open Access Journals (Sweden)

    A. Maharajan

    2016-10-01

    Full Text Available Copper is a trace element necessary for the normal growth and metabolism of living organisms. If exceeds its limit it becomes pollutant and causes pathological effects. Asian sea bass (Lates calcarifer was exposed to sublethal concentrations of copper for 28 days and histopathological alterations were noticed in the gill, liver, muscle and intestine. Epithelial necrosis, hypertrophy, rupture of gill epithelium and haemorrhage at primary lamellae were observed after 7 days of exposure. Lifting of epithelium, oedema and fusion of adjacent secondary lamellae were conspicuous at 28 days of exposure. The experimental liver tissue showed reduction in the size of hepatocytes, vacuolisation, and hypertrophy. The intestine displayed fused microvilli, sloughing of mucus membrane and swollen cells. Muscle bundles with severe oedema and their thickening and separation were more pronounced in sublethal treatment of copper in the muscle. Several histopathological changes observed in various fish organs would serve a useful purpose in evaluating the toxic effects of copper. The present study clearly demonstrated that all the treated body organs exhibited significant damage with response; amongst the body organs the liver is an important target organ for copper toxicity in L. calcarifer and this species could be possibly used as a model organism for toxicity studies.

  3. The Effective Electrolytic Recovery of Dilute Copper from Industrial Wastewater

    Directory of Open Access Journals (Sweden)

    Teng-Chien Chen

    2013-01-01

    Full Text Available Electroplating copper industry was discharged huge amount wastewater and cause serious environmental and health damage in Taiwan. This research applied electrical copper recovery system to recover copper metal. In this work, electrotreatment of a industrial copper wastewater ([Cu] = 30000 mg L−1 was studied with titanium net coated with a thin layer of RuO2/IrO2 (DSA reactor. The optimal result for simulated copper solution was 99.9% copper recovery efficiency in current density 0.585 A/dm2 and no iron ion. Due to high concentration of iron and chloride ions in real industrial wastewater, the copper recovery efficiency was down to 60%. Although, the copper recovery efficiency was not high as simulated copper solution, high environmental economic value was included in the technology. The possibility of pretreating the wastewater with iron is the necessary step, before the electrical recovery copper system.

  4. Copper localization, elemental content, and thallus colour in the copper hyperaccumulator lichen Lecanora sierra from California

    Science.gov (United States)

    Purvis, O.W.; Bennett, J.P.; Spratt, J.

    2011-01-01

    An unusual dark blue-green lichen, Lecanora sierrae, was discovered over 30 years ago by Czehura near copper mines in the Lights Creek District, Plumas County, Northern California. Using atomic absorption spectroscopy, Czehura found that dark green lichen samples from Warren Canyon contained 4% Cu in ash and suggested that its colour was due to copper accumulation in the cortex. The present study addressed the hypothesis that the green colour in similar material we sampled from Warren Canyon in 2008, is caused by copper localization in the thallus. Optical microscopy and electron microprobe analysis of specimens of L. sierrae confirmed that copper localization took place in the cortex. Elemental analyses of L. sierrae and three other species from the same localities showed high enrichments of copper and selenium, suggesting that copper selenates or selenites might occur in these lichens and be responsible for the unusual colour.

  5. Copper localization, elemental content, and thallus colour in the copper hyperaccumulator lichen Lecanora sierrae from California

    Science.gov (United States)

    Purvis, O.W.; Bennett, J.P.; Spratt, J.

    2011-01-01

    An unusual dark blue-green lichen, Lecanora sierrae, was discovered over 30 years ago by Czehura near copper mines in the Lights Creek District, Plumas County, Northern California. Using atomic absorption spectroscopy, Czehura found that dark green lichen samples from Warren Canyon contained 4% Cu in ash and suggested that its colour was due to copper accumulation in the cortex. The present study addressed the hypothesis that the green colour in similar material we sampled from Warren Canyon in 2008, is caused by copper localization in the thallus. Optical microscopy and electron microprobe analysis of specimens of L. sierrae confirmed that copper localization took place in the cortex. Elemental analyses of L. sierrae and three other species from the same localities showed high enrichments of copper and selenium, suggesting that copper selenates or selenites might occur in these lichens and be responsible for the unusual colour. Copyright ?? 2011 British Lichen Society.

  6. Graphene-protected copper and silver plasmonics

    DEFF Research Database (Denmark)

    Kravets, V. G.; Jalil, R.; Kim, Y. J.

    2014-01-01

    suitable for plasmonic applications. To this end, there has been a continuous search for alternative plasmonic materials that are also compatible with complementary metal oxide semiconductor technology. Here we show that copper and silver protected by graphene are viable candidates. Copper films covered...... with one to a few graphene layers show excellent plasmonic characteristics. They can be used to fabricate plasmonic devices and survive for at least a year, even in wet and corroding conditions. As a proof of concept, we use the graphene-protected copper to demonstrate dielectric loaded plasmonic...... waveguides and test sensitivity of surface plasmon resonances. Our results are likely to initiate wide use of graphene-protected plasmonics....

  7. Quantifying fish swimming behavior in response to acute exposure of aqueous copper using computer assisted video and digital image analysis

    Science.gov (United States)

    Calfee, Robin D.; Puglis, Holly J.; Little, Edward E.; Brumbaugh, William G.; Mebane, Christopher A.

    2016-01-01

    Behavioral responses of aquatic organisms to environmental contaminants can be precursors of other effects such as survival, growth, or reproduction. However, these responses may be subtle, and measurement can be challenging. Using juvenile white sturgeon (Acipenser transmontanus) with copper exposures, this paper illustrates techniques used for quantifying behavioral responses using computer assisted video and digital image analysis. In previous studies severe impairments in swimming behavior were observed among early life stage white sturgeon during acute and chronic exposures to copper. Sturgeon behavior was rapidly impaired and to the extent that survival in the field would be jeopardized, as fish would be swept downstream, or readily captured by predators. The objectives of this investigation were to illustrate protocols to quantify swimming activity during a series of acute copper exposures to determine time to effect during early lifestage development, and to understand the significance of these responses relative to survival of these vulnerable early lifestage fish. With mortality being on a time continuum, determining when copper first affects swimming ability helps us to understand the implications for population level effects. The techniques used are readily adaptable to experimental designs with other organisms and stressors.

  8. 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)

  9. European downstream oil industry safety performance : statistical summary of reported incidents, 1996

    Science.gov (United States)

    1997-12-01

    This report is the third by CONCAWE reviewing the safety performance of the downstream oil industry in Western Europe. It includes the results of 28 companies which together represent over 90% of the oil refining capacity in Europe. It is therefore a...

  10. European downstream oil industry safety performance : statistical summary of reported incidents, 1998

    Science.gov (United States)

    1999-07-01

    This report is the fifth by CONCAWE reviewing the safety performance of the downstream oil industry in Europe. The area of coverage is primarily the EU, EEA and Hungary, but for some companies the data for other European countries such as Poland, Cze...

  11. 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.

  12. From Process Development to Manufacturing: Lab-Intensive Courses in Downstream Bioprocessing

    Science.gov (United States)

    Gilleskie, Gary L.; Reeves, Baley A.

    2014-01-01

    Most chemical engineering graduates work in industry, a fact that underscores the need for courses to provide experiences that prepare them for industry. The Biomanufacturing Training and Education Center (BTEC) at North Carolina State University has addressed this need by developing and delivering a comprehensive downstream bioprocessing program…

  13. 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.

  14. 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

  15. 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...

  16. 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...

  17. Effect of stilling basin shape on the hydraulic characteristics of the flow downstream radial gates

    Directory of Open Access Journals (Sweden)

    Abdelazim M. Ali

    2010-12-01

    Full Text Available Barrage regulators are considered as one of the most important projects in the Egyptian irrigation practice, which is obvious by its controlling of the released discharge and both of upstream and downstream water levels. In the present time, the ministry of water resources and irrigation starts to construct new barrages on the River Nile instead of the oldest ones, which are not able to withstand the requirements of increasing head difference between the upstream and downstream water levels upon the gates. The present study was focused on investigating the effect of different shapes of stilling basins of regulator on the length of the submerged hydraulic jump, velocity profiles along the apron, and local scour downstream regulator floor. Extensive experimental program was conducted on a re-circulating flume with 1.0 m wide, 26.0 m long and 1.2 m deep, with discharges range from 40 to 190 l/s. The relative velocity near bed, and shear Reynolds number were studied to fix the best shape of stilling basin that could reduce both of length of submerged hydraulic jump and local scour downstream stilling basin. Statistical equation was developed to correlate the length of submerged jump with the other independent parameters. Finally, clear matching of results from the length of jump and velocity analysis was investigated.

  18. 40 CFR 80.220 - What are the downstream standards for GPA gasoline?

    Science.gov (United States)

    2010-07-01

    ... GPA gasoline? 80.220 Section 80.220 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Sulfur Geographic Phase-in Program § 80.220 What are the downstream standards for GPA gasoline? (a) GPA gasoline. (1) During...

  19. 40 CFR 80.219 - Designation and downstream requirements for GPA gasoline.

    Science.gov (United States)

    2010-07-01

    ... requirements for GPA gasoline. 80.219 Section 80.219 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Sulfur Geographic Phase-in Program § 80.219 Designation and downstream requirements for GPA gasoline. The requirements and...

  20. Full-scale observation of the flow downstream of a suspension bridge deck

    DEFF Research Database (Denmark)

    Cheynet, Etienne; Jakobsen, Jasna Bogunović; Snæbjörnsson, Jónas

    2017-01-01

    The paper presents a full-scale observation of the flow conditions downstream of a suspension bridge by a system of synchronized short-range dual-Doppler wind lidars. The lidar units were deployed directly on the bridge walkway during a four-day pilot experiment. The wind velocity was monitored...

  1. Climate change impact on infection risks during bathing downstream of sewage emissions from CSOs or WWTPs

    NARCIS (Netherlands)

    Sterk, Ankie; de Man, Heleen; Schijven, Jack F; de Nijs, Ton; de Roda Husman, Ana Maria

    2016-01-01

    Climate change is expected to influence infection risks while bathing downstream of sewage emissions from combined sewage overflows (CSOs) or waste water treatment plants (WWTPs) due to changes in pathogen influx, rising temperatures and changing flow rates of the receiving waters. In this study,

  2. Climate change impact on infection risks during bathing downstream of sewage emissions from CSOs or WWTPs.

    Science.gov (United States)

    Sterk, Ankie; de Man, Heleen; Schijven, Jack F; de Nijs, Ton; de Roda Husman, Ana Maria

    2016-11-15

    Climate change is expected to influence infection risks while bathing downstream of sewage emissions from combined sewage overflows (CSOs) or waste water treatment plants (WWTPs) due to changes in pathogen influx, rising temperatures and changing flow rates of the receiving waters. In this study, climate change impacts on the surface water concentrations of Campylobacter, Cryptosporidium and norovirus originating from sewage were modelled. Quantitative microbial risk assessment (QMRA) was used to assess changes in risks of infection. In general, infection risks downstream of WWTPs are higher than downstream CSOs. Even though model outputs show an increase in CSO influxes, in combination with changes in pathogen survival, dilution within the sewage system and bathing behaviour, the effects on the infection risks are limited. However, a decrease in dilution capacity of surface waters could have significant impact on the infection risks of relatively stable pathogens like Cryptosporidium and norovirus. Overall, average risks are found to be higher downstream WWTPs compared to CSOs. Especially with regard to decreased flow rates, adaptation measures on treatment at WWTPs may be more beneficial for human health than decreasing CSO events. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Drifting plankton from a reservoir subsidize downstream food webs and alter community structure.

    Science.gov (United States)

    Doi, Hideyuki; Chang, Kwang-Hyeon; Ando, Takamitsu; Imai, Hiroyuki; Nakano, Shin-ichi; Kajimoto, Akio; Katano, Izumi

    2008-05-01

    Subsidy between ecosystems has been considered in many natural ecosystems, and should alter food webs and communities in human-impacted ones. We estimated how drifting plankton from a reservoir contribute to downstream food webs and showed that they alter community structures over a 10-km reach below the dam. To estimate the contribution of the drifting plankton to macroinvertebrates, we used C and N isotopes and an IsoSource mixing model. In spring and autumn, contributions of plankton to collector-filterer species were highest 0.2 km downstream of the dam, and clearly decreased from 0.2 to 10 km. At 0.2 km, the contribution of plankton to a predator stonefly was remarkably high. These results indicated that drifting plankton from a dam reservoir could subsidize downstream food webs and alter their energy base, but the importance of this subsidy decreased as distance from the reservoir increased. The general linear models indicated that the abundance of collector-filterers and predators was related positively to zooplankton density in stream water. Thus, food source alteration by drifting plankton also influenced the community structures downstream of the dam.

  4. A comparison of machine learning techniques for predicting downstream acid mine drainage

    CSIR Research Space (South Africa)

    van Zyl, TL

    2014-07-01

    Full Text Available We consider the challenge of providing downstream predictions of water quality using a time-series of upstream insitu measurements and a time-series of remote sensed precipitation data from the Tropical Rainfall Measuring Mission (TRMM). We use a...

  5. Stress analysis of the modified Pulsed Neutron Activation system downstream shield support structure

    Energy Technology Data Exchange (ETDEWEB)

    Mosby, W.R.

    1980-05-28

    The modified LOFT Pulsed Neutron Activation (PNA) System downstream shielding support structure was stress analyzed for deadweight and worst-case LOCE loads. No deficiencies were found in the structure. This stress analysis was performed for the PNA Shielding Configuration that has been used on Test L3-2 and that is to be used on Test L3-7.

  6. 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

  7. Novel Techniques for Quantification of Correlation Between Primary Liquid Jet Breakup and Downstream Spray Characteristics

    Science.gov (United States)

    2016-10-05

    unlimited. 5 1. Introduction Several liquid -fuelled combustion systems, such as liquid propellant rocket engines and gas turbines... liquid sheet[1], [2], [3]. Considering the challenges in studying spray combustion due to interacting complex physical and chemical processes...AFRL-AFOSR-JP-TR-2016-0084 Novel techniques for quantification of correlation between primary liquid jet breakup and downstream spray characteristics

  8. Copper doped borate dosimeters revisited

    Energy Technology Data Exchange (ETDEWEB)

    Alajerami, Y.S.M. [Department of Physics, Universiti Teknologi Malaysia, 81310 Skudai, Johor (Malaysia); Department of Medical Radiography, Al-Azhar University, Gaza Strip, Palestine (Country Unknown); Hashim, S., E-mail: suhairul@utm.my [Department of Physics, Universiti Teknologi Malaysia, 81310 Skudai, Johor (Malaysia); Oncology Treatment Centre, Sultan Ismail Hospital, 81100 Johor Bahru (Malaysia); Ghoshal, S.K. [Department of Physics, Universiti Teknologi Malaysia, 81310 Skudai, Johor (Malaysia); Bradley, D.A. [Centre for Nuclear and Radiation Physics, Department of Physics, University of Surrey, Guildford GU2 7XH (United Kingdom); Department of Physics, Faculty of Science, University of Malaya, 50603 Kuala Lumpur (Malaysia); Mhareb, M. [Department of Physics, Universiti Teknologi Malaysia, 81310 Skudai, Johor (Malaysia); Saleh, M.A. [Department of Physics, Universiti Teknologi Malaysia, 81310 Skudai, Johor (Malaysia); National Atomic Energy Commission (NATEC), Sana' a (Yemen)

    2014-11-15

    We render a panoramic overview on copper (Cu) doped borate dosimeters. Preparing a dosimeter by mixing specific materials with precise weights and methods is a never-ending quest. The recommended composition is highly decisive for accurate estimation of the absorbed dose, prediction of the biological outcome, determination of the treatment dose for radiation therapy and facilitation of personal monitoring. Based on these principles, the proposed dosimeter must cover a series of dosimetric properties to realize the exact results and assessment. The doped borate dosimeters indeed demonstrate attractive thermoluminescence (TL) features. Several dedicated efforts are attempted to improve the luminescence properties by doping various transition metals or rare-earth elements. The Cu ion being one of the preferred activators shows excellent TL properties as revealed via detail comparison with other dosimeters. Two oxide states of Cu (Cu{sup +} and Cu{sup ++}) with reasonable atomic number allow easy interaction with boron network. Interestingly, the intrinsic luminescent centers of borate lattice are in cross linked with that of Cu{sup +} ions. Thus, the activation of borate dosimeter with Cu ions for the enhancement of the TL sensitivity is recognized. These dosimeters reveal similar glow curves as the standard TLD-100 (LiF:Mg,Ti) one irrespective of the use of modifiers and synthesis techniques. They display high sensitivity, low fading, dose response linearity over wide range and practical minimum detectable dose. Furthermore, the effective atomic number being the most beneficial aspect (equivalent to that of human tissue) of borate dosimeters do not show any change due to Cu ion activations. The past development, major challenges, excitement, applications, recent progress and the future promises of Cu doped borate TL dosimeters are highlighted. - Highlights: • The manuscript gives a panoramic overview on copper doped borate dosimeters. • Cu ions activated

  9. 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.

  10. 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

  11. C, N, P export regimes in rivers from headwater to downstream catchments

    Science.gov (United States)

    Dupas, Rémi; Musolff, Andreas; Jawitz, James W.; Rao, P. Suresh C.; Fleckenstein, Jan H.; Rode, Michael; Borchardt, Dietrich

    2017-04-01

    Excessive amounts of nutrients and dissolved organic matter in freshwater bodies affect aquatic ecosystems. In this study, the spatial and temporal variability of nitrate (NO3), dissolved organic carbon (DOC) and soluble reactive phosphorus (SRP) was analyzed along the Selke river continuum from 1 - 3 km2 headwater catchments to 184 - 456 km2 downstream catchments, within the TERENO Harz/Central German Lowland Observatory. Three headwater catchments were selected as archetypes of the main landscape units (land use x soil type) present in the Selke catchment. Export regimes in these catchments were interpreted in terms of NO3, DOC and SRP land-to-stream transfer processes. Differences between export regimes in headwater and downstream catchments were interpreted in terms of in-stream processes and contribution of point source emissions. The results showed that the NO3 seasonal dynamics were opposite compared to DOC and SRP in all three headwater catchments. These dynamics were interpreted as the result of the interplay of hydrological and biogeochemical processes, for which riparian wetlands were hypothesized to play a determining role. In the two downstream catchments, NO3 was transported almost conservatively, except during the summer period where in-stream retention could exceed 50%. Allochtonous DOC was consumed in the upstream river section (with low light and nutrient availability) and autochthonous DOC was produced in the downstream river section (with high light and nutrients availability); the natural export regime of SRP mimicked a point source signal, which may lead to misattribution and thus overestimation of domestic contribution to phosphorus loads in rivers. Monitoring the river continuum from headwater to downstream rivers proved effective to investigate jointly land-to-stream and in-stream transport and transformation processes.

  12. Carbon and nutrient export regimes from headwater catchments to downstream reaches

    Science.gov (United States)

    Dupas, Rémi; Musolff, Andreas; Jawitz, James W.; Rao, P. Suresh C.; Jäger, Christoph G.; Fleckenstein, Jan H.; Rode, Michael; Borchardt, Dietrich

    2017-09-01

    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 (Germany) river continuum from three headwaters draining 1-3 km2 catchments to two downstream reaches representing spatially integrated signals from 184-456 km2 catchments. Three headwater catchments were selected as archetypes of the main landscape units (land use × 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 contributions from point sources. 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 (high SRP during summer low flow), which may lead to overestimation of domestic contributions in the downstream reaches. Monitoring the river continuum from headwaters to downstream reaches proved effective to jointly investigate land-to-stream and in-stream transport, and transformation processes.

  13. 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

  14. Effects of stimulation of copper bioleaching on microbial community in vineyard soil and copper mining waste.

    Science.gov (United States)

    Andreazza, Robson; Okeke, Benedict C; Pieniz, Simone; Bortolon, Leandro; Lambais, Márcio R; Camargo, Flávio A O

    2012-04-01

    Long-term copper application in vineyards and copper mining activities cause heavy metal pollution sites. Such sites need remediation to protect soil and water quality. Bioremediation of contaminated areas through bioleaching can help to remove copper ions from the contaminated soils. Thus, the aim of this work was to evaluate the effects of different treatments for copper bioleaching in two diverse copper-contaminated soils (a 40-year-old vineyard and a copper mining waste) and to evaluate the effect on microbial community by applying denaturing gradient gel electrophoresis (DGGE) of 16S ribosomal DNA amplicons and DNA sequence analysis. Several treatments with HCl, H(2)SO(4), and FeSO(4) were evaluated by stimulation of bioleaching of copper in the soils. Treatments and extractions using FeSO(4) and H(2)SO(4) mixture at 30°C displayed more copper leaching than extractions with deionized water at room temperature. Treatment with H(2)SO(4) supported bioleaching of as much as 120 mg kg(-1) of copper from vineyard soil after 115 days of incubation. DGGE analysis of the treatments revealed that some treatments caused greater diversity of microorganisms in the vineyard soil compared to the copper mining waste. Nucleotide Blast of PCR-amplified fragments of 16S rRNA gene bands from DGGE indicated the presence of Rhodobacter sp., Silicibacter sp., Bacillus sp., Paracoccus sp., Pediococcus sp., a Myxococcales, Clostridium sp., Thiomonas sp., a firmicute, Caulobacter vibrioides, Serratia sp., and an actinomycetales in vineyard soil. Contrarily, Sphingomonas was the predominant genus in copper mining waste in most treatments. Paracoccus sp. and Enterobacter sp. were also identified from DGGE bands of the copper mining waste. Paracoccus species is involved in the copper bioleaching by sulfur oxidation system, liberating the copper bounded in the soils and hence promoting copper bioremediation. Results indicate that stimulation of bioleaching with a combination of FeSO(4

  15. Effort on calibration of infrared spark ablation of copper with synthetic copper standards

    Energy Technology Data Exchange (ETDEWEB)

    Wienold, Julia, E-mail: julia.wienold@bam.de; Traub, Heike; Bresch, Harald; Seeger, Stefan; Recknagel, Sebastian; Kipphardt, Heinrich

    2011-06-15

    Two types of copper samples, compact certified copper reference materials and calibration samples prepared from liquid doped, pressed copper powders, were studied in terms of accuracy of obtained calibration functions originating from infrared spark ablation. Additionally, corresponding particle size distributions of the aerosols from infrared spark ablation were recorded. It is shown that the differences in quantification results, originating from the two sets of calibration functions, could not mainly be ascribed to different particle size distributions of the two copper sample types. Possible other causes, as different ablation rates, parts of melting and differences of the chemical constitutions of the two sample types were explored.

  16. Oxalic acid overproduction by copper-tolerant brown-rot basidiomycetes on southern yellow pine treated with copper-based preservatives

    Science.gov (United States)

    Carol A. Clausen; Frederick Green

    2003-01-01

    Accumulation of oxalic acid (OA) by brown-rot fungi and precipitation of copper oxalate crystals in wood decayed by copper-tolerant decay fungi has implicated OA in the mechanism of copper tolerance. Understanding the role of OA in copper tolerance is important due to an increasing reliance on copper-based wood preservatives. In this study, four copper-tolerant brown-...

  17. Copper Supplementation in Parenteral Nutrition of Cholestatic Infants

    Science.gov (United States)

    Frem, Juliana; Sarson, Yvonne; Sternberg, Tom; Cole, Conrad R.

    2009-01-01

    Background Conventional practice is to reduce or eliminate copper supplementation in the parenteral nutrition of infants with cholestasis due to the increased risk of hepatotoxicity. However, there are reports of copper deficiency in cholestatic infants due to copper reduction in their parenteral nutrition. Objectives 1) To determine the proportion of cholestatic infants who develop elevated serum copper while receiving a non-reduced dose of parenteral copper, 2) To evaluate potential clinical factors that affect serum copper in cholestatic infants, and 3) To evaluate the impact of serum copper on liver disease. Methods This is a retrospective review of 28 cholestatic infants receiving 20 mcg/kg/d of copper via parenteral nutrition. Age-adjusted references were used to determine normality of serum copper levels. Multiple linear regression analyses were performed to determine predictors of serum copper and alanine aminotransferase. Results Serum copper levels were elevated in 2 infants (7%). On average, infants received 80% of their energy intake from parenteral nutrition for 3 months. Intestinal failure was present in 50% of the patients. Birth weight, gestational age and alanine aminotransferase were identified as predictors of serum copper (R2=0.53; p= 0.0001). Serum copper, gestational age and total bilirubin were associated with serum alanine aminotransferase (R2 = 0.43; p = 0.001). Conclusion Supplementation of parenteral copper at 20 mcg/kg/day does not lead to a significant increase in copper toxicity or worsening of liver disease in cholestatic infants. PMID:20400915

  18. Selection of Fecal Enterococci Exhibiting tcrB-Mediated Copper Resistance in Pigs Fed Diets Supplemented with Copper † ▿

    OpenAIRE

    Amachawadi, R. G.; Shelton, N. W.; Shi, X.; Vinasco, J.; Dritz, S.S.; M. D. Tokach; Nelssen, J. L.; Scott, H. M.; Nagaraja, T G

    2011-01-01

    Copper, as copper sulfate, is increasingly used as an alternative to in-feed antibiotics for growth promotion in weaned piglets. Acquired copper resistance, conferred by a plasmid-borne, transferable copper resistance (tcrB) gene, has been reported in Enterococcus faecium and E. faecalis. A longitudinal field study was undertaken to determine the relationship between copper supplementation and the prevalence of tcrB-positive enterococci in piglets. The study was done with weaned piglets, hous...

  19. Antimicrobial Properties of Copper Nanoparticles and Amino Acid Chelated Copper Nanoparticles Produced by Using a Soya Extract

    OpenAIRE

    DeAlba-Montero, I.; Guajardo-Pacheco, Jesús; Morales-Sánchez, Elpidio; Araujo-Martínez, Rene; Loredo-Becerra, G. M.; Martínez-Castañón, Gabriel-Alejandro; Ruiz, Facundo; Compeán Jasso, M. E.

    2017-01-01

    This paper reports a comparison of the antibacterial properties of copper-amino acids chelates and copper nanoparticles against Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis. These copper-amino acids chelates were synthesized by using a soybean aqueous extract and copper nanoparticles were produced using as a starting material the copper-amino acids chelates species. The antibacterial activity of the samples was evaluated by using the standard microdilution method (CLSI M...

  20. Copper foil provides uniform heat sink path

    Science.gov (United States)

    Phillips, I. E., Jr.; Schreihans, F. A.

    1966-01-01

    Thermal path prevents voids and discontinuities which make heat sinks in electronic equipment inefficient. The thermal path combines the high thermal conductivity of copper with the resiliency of silicone rubber.

  1. Electroless Copper Deposition: A Sustainable Approach

    Science.gov (United States)

    Kutnahorsky, Marika Renee

    A sustainable electroless copper coating process was developed for plating automotive fasteners shaped from AISI 9255 low carbon, high silicon steel. The objective was to minimize the ionic and organic species present in each step of the plating process. A sulfuric acid solution inhibited with quinine was defined to clean the steel prior to plating. The corrosivity of the solution was examined through electrochemical and weight loss measurements to evaluate the efficiency of the cleaning process at high temperatures and high acid concentrations. An electroless copper coating process was then developed using a simple copper sulfate chemistry inhibited with quinine to extend the possible operating window. Finally, benzotriazole was evaluated as a possible anti-oxidant coating. Accelerated thioacetamide corrosion tests were used to evaluate the corrosion inhibition of benzotriazole on copper coatings.

  2. Map and table of world copper smelters

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This map and table comprise information on 124 world copper smelters (2 of which are closed and 1 of which is under development) and 4 (low-grade solvent...

  3. Copper catalysed synthesis of indolylquinazolinone alkaloid ...

    Indian Academy of Sciences (India)

    We describe the total synthesis of indolylquinazolinone alkaloid bouchardatine and some of the quinazolinone derivatives. The aerobic oxidation induced by copper(I) bromide, followed by Vilsmeier-Haack formylation gives the natural product bouchardatine alkaloid in good yield.

  4. Porphyry copper deposits of the world

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — Information on porphyry copper deposits from around the world with grade and tonnage models, a general classification based on geologic setting, mineralogy, with...

  5. Synthesis, Characterization and Properties of Copper Clusters

    OpenAIRE

    Vilar Vidal, Noelia

    2013-01-01

    This study displays the electrochemical synthesis of different copper clusters (CuCLs) sizes, their characterization and possible applications. These CuCLs exhibit great photoluminescence and catalytic properties, making them promising materials in a wide range of applications.

  6. Effects of urine composition on epithelial Na+ channel-targeted protease activity.

    Science.gov (United States)

    Berman, Jonathan M; Awayda, Ryan G; Awayda, Mouhamed S

    2015-11-01

    We examined human urinary proteolytic activity toward the Epithelial Sodium Channel (ENaC). We focused on two sites in each of alpha and gamma ENaC that are targets of endogenous and exogenous proteases. We examined the effects of ionic strength, pH and urinary H(+)-buffers, metabolic intermediates, redox molecules, and large urinary proteins. Monoatomic cations caused the largest effect, with sodium inhibiting activity in the 15-515 mEq range. Multivalent cations zinc and copper inhibited urinary proteolytic activity at concentrations below 100 μmol/L. Similar to sodium, urea caused a 30% inhibition in the 0-500 mmol/L range. This was not observed with acetone and ethanol. Modulating urinary redox status modified activity with H2O2 stimulated and ascorbate inhibited activity. Minimal effects (<10%) were observed with caffeine, glucose, several TCA cycle intermediates, salicylic acid, inorganic phosphate, albumin, creatinine, and Tamm-Horsfall protein. The cumulative activity of ENaC-cleaving proteases was highest at neutral pH, however, alpha and gamma proteases exhibited an inverse dependence with alpha stimulated at acidic and gamma stimulated at alkaline pH. These data indicate that ENaC-targeting urinary proteolytic activity is sensitive to sodium, urea and pH and changes in these components can modify channel cleavage and activation status, and likely downstream sodium absorption unrelated to changes in protein or channel density. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  7. Electrochemical detection of protein based on hybridization chain reaction-assisted formation of copper nanoparticles.

    Science.gov (United States)

    Zhao, Jing; Hu, Suisui; Cao, Ya; Zhang, Bin; Li, Genxi

    2015-04-15

    In this paper, we report an electrochemical method for highly sensitive and specific detection of protein based on hybridization chain reaction (HCR)-assisted formation of copper nanoparticles by using small molecule such as folate-linked DNA as probe. In the presence of target protein, taking folate receptor (FR) as the model protein in this study, its binding with folate can protect the probe DNA from exonuclease I-catalyzed degradation, thus the probe DNA can be immobilized onto the electrode surface through the hybridization with capture DNA, triggering HCR on the electrode surface. Subsequently, copper nanoparticles can be formed on the electrode surface by using long duplex DNA oligomers from HCR as templates. Furthermore, copper ions released from acid-dissolution of copper nanoparticles can catalyze the oxidation of ο-phenylenediamine by dissolved oxygen, leading to significant electrochemical responses. As a result, our method can sensitively detect FR in the linear range from 0.01ng/mL to 100ng/mL with a detection limit of 3pg/mL. It can also specifically distinguish the target protein in both buffer and complex serum samples. Since many other proteins can be assayed by changing the corresponding small molecule, this method may be promising for the development of the technique for protein detections. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Oxidation Behavior of GRCop-84 Copper Alloy Assessed

    Science.gov (United States)

    Thomas-Ogbuji, Linus U.

    2002-01-01

    NASA's goal of safe, affordable space transportation calls for increased reliability and lifetimes of launch vehicles, and significant reductions of launch costs. The areas targeted for enhanced performance in the next generation of reusable launch vehicles include combustion chambers and nozzle ramps; therefore, the search is on for suitable liner materials for these components. GRCop-84 (Cu-8Cr-4Nb), an advanced copper alloy developed at the NASA Glenn Research Center in conjunction with Case Western Reserve University, is a candidate. The current liner of the Space Shuttle Main Engine is another copper alloy, NARloy-Z (Cu-3Ag-0.1Zr). It provides a benchmark against which to compare the properties of candidate successors. The thermomechanical properties of GRCop-84 have been shown to be superior, and its physical properties comparable, to those of NARloy-Z. However, environmental durability issues control longevity in this application: because copper oxide scales are not highly protective, most copper alloys are quickly consumed in oxygen environments at elevated temperatures. In consequence, NARloy-Z and most other copper alloys are prone to blanching, a degradation process that occurs through cycles of oxidation-reduction as the oxide is repeatedly formed and removed because of microscale fluctuations in the oxygen-hydrogen fuel systems of rocket engines. The Space Shuttle Main Engine lining typically degraded by blanching-induced hot spots that lead to surface roughening, pore formation, and coolant leakage. Therefore, resistance to oxidation and blanching are key requirements for second-generation reusable launch vehicle liners. The rocket engine ambient includes H2 (fuel) and H2O (combustion product) and is, hence, under reduced oxygen partial pressures. Accordingly, our studies were expanded to include oxygen partial pressures as low as 322 parts per million (ppm) at the temperatures likely to be experienced in service. A comparison of 10-hr weight gains of

  9. Electrodialytic Remediation of Copper Mine Tailings

    DEFF Research Database (Denmark)

    Hansen, H.K.; Rojo, A.; Ottosen, L.M.

    2012-01-01

    This work compares and evaluates sixteen electrodialytic laboratory remediation experiments on copper mine tailings. Different parameters were analysed, such as remediation time, addition of desorbing agents, and the use of pulsed electrical fields.......This work compares and evaluates sixteen electrodialytic laboratory remediation experiments on copper mine tailings. Different parameters were analysed, such as remediation time, addition of desorbing agents, and the use of pulsed electrical fields....

  10. Divalent Copper as a Major Triggering Agent in Alzheimer's Disease.

    Science.gov (United States)

    Brewer, George J

    2015-01-01

    Alzheimer's disease (AD) is at epidemic proportions in developed countries, with a steady increase in the early 1900 s, and then exploding over the last 50 years. This epidemiology points to something causative in the environment of developed countries. This paper will review the considerable evidence that that something could be inorganic copper ingestion. The epidemic parallels closely the spread of copper plumbing, with copper leached from the plumbing into drinking water being a main causal feature, aided by the increasingly common use of supplement pills containing copper. Inorganic copper is divalent copper, or copper-2, while we now know that organic copper, or copper in foods, is primarily monovalent copper, or copper-1. The intestinal transport system, Ctr1, absorbs copper-1 and the copper moves to the liver, where it is put into safe channels. Copper-2 is not absorbed by Ctr1, and some of it bypasses the liver and goes directly into the blood, where it appears to be exquisitely toxic to brain cognition. Thus, while aggregation of amyloid-β has been postulated to be the cause of AD under current dogma, the great increase in prevalence over the last century appears to be due to ingestion of copper-2, which may be causing the aggregation, and/or increasing the oxidant toxicity of the aggregates. An alternative hypothesis proposes that oxidant stress is the primary injuring agent, and under this hypothesis, copper-2 accumulation in the brain may be a causal factor of the oxidant injury. Thus, irrespective of which hypothesis is correct, AD can be classified, at least in part, as a copper-2 toxicity disease. It is relatively easy to avoid copper-2 ingestion, as discussed in this review. If most people begin avoiding copper-2 ingestion, perhaps the epidemic of this serious disease can be aborted.

  11. Dietary management of labrador retrievers with subclinical hepatic copper accumulation.

    Science.gov (United States)

    Fieten, H; Biourge, V C; Watson, A L; Leegwater, P A J; van den Ingh, T S G A M; Rothuizen, J

    2015-01-01

    Genetic and environmental factors, including dietary copper intake, contribute to the pathogenesis of copper-associated hepatitis in Labrador retrievers. Clinical disease is preceded by a subclinical phase in which copper accumulates in the liver. To investigate the effect of a low-copper, high-zinc diet on hepatic copper concentration in Labrador retrievers with increased hepatic copper concentrations. Twenty-eight clinically healthy, client-owned Labrador retrievers with a mean hepatic copper concentration of 919 ± 477 mg/kg dry weight liver (dwl) that were related to dogs previously diagnosed with clinical copper-associated hepatitis. Clinical trial in which dogs were fed a diet containing 1.3 ± 0.3 mg copper/Mcal and 64.3 ± 5.9 mg zinc/Mcal. Hepatic copper concentrations were determined in liver biopsy samples approximately every 6 months. Logistic regression was performed to investigate effects of sex, age, initial hepatic copper concentration and pedigree on the ability to normalize hepatic copper concentrations. In responders (15/28 dogs), hepatic copper concentrations decreased from a mean of 710 ± 216 mg/kg dwl copper to 343 ± 70 mg/kg dwl hepatic copper after a median of 7.1 months (range, 5.5-21.4 months). Dogs from a severely affected pedigree were at increased risk for inability to have their hepatic copper concentrations normalized with dietary treatment. Feeding a low-copper, high-zinc diet resulted in a decrease in hepatic copper concentrations in a subset of clinically normal Labrador retrievers with previous hepatic copper accumulation. A positive response to diet may be influenced by genetic background. Determination of clinical benefit requires further study. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  12. Comparative genomic analyses of copper transporters and cuproproteomes reveal evolutionary dynamics of copper utilization and its link to oxygen.

    Directory of Open Access Journals (Sweden)

    Perry G Ridge

    2008-01-01

    Full Text Available Copper is an essential trace element in many organisms and is utilized in all domains of life. It is often used as a cofactor of redox proteins, but is also a toxic metal ion. Intracellular copper must be carefully handled to prevent the formation of reactive oxygen species which pose a threat to DNA, lipids, and proteins. In this work, we examined patterns of copper utilization in prokaryotes by analyzing the occurrence of copper transporters and copper-containing proteins. Many organisms, including those that lack copper-dependent proteins, had copper exporters, likely to protect against copper ions that inadvertently enter the cell. We found that copper use is widespread among prokaryotes, but also identified several phyla that lack cuproproteins. This is in contrast to the use of other trace elements, such as selenium, which shows more scattered and reduced usage, yet larger selenoproteomes. Copper transporters had different patterns of occurrence than cuproproteins, suggesting that the pathways of copper utilization and copper detoxification are independent of each other. We present evidence that organisms living in oxygen-rich environments utilize copper, whereas the majority of anaerobic organisms do not. In addition, among copper users, cuproproteomes of aerobic organisms were larger than those of anaerobic organisms. Prokaryotic cuproproteomes were small and dominated by a single protein, cytochrome c oxidase. The data are consistent with the idea that proteins evolved to utilize copper following the oxygenation of the Earth.

  13. Stage specific effects of soluble copper and copper oxide nanoparticles during sea urchin embryo development and their relation to intracellular copper uptake.

    Science.gov (United States)

    Torres-Duarte, Cristina; Ramos-Torres, Karla M; Rahimoff, René; Cherr, Gary N

    2017-08-01

    The effects of exposure to either soluble copper (copper sulfate) or copper oxide nanoparticles (nano-CuO) during specific early developmental stages of sea urchin embryos were analyzed. Soluble copper caused significant malformations in embryos (skeletal malformations, delayed development or gut malformations) when present at any given stage, while cleavage stage was the most sensitive to nano-CuO exposure causing skeletal malformations and decreased total antioxidant capacity. The stage specificity was linked to higher endocytic activity during the first hours of development that leads to higher accumulation of copper in specific cells critical for development. Results indicate that nano-CuO results in higher accumulation of copper inside of embryos and this intracellular copper is more persistent as compared to soluble copper. The possible implications later in development are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Bitrex: A new levelling agent for copper

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, J.F.K., E-mail: J.F.K.Cooper@gmail.com [Department of Physics, Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE (United Kingdom); Barnes, C.H.W. [Department of Physics, Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE (United Kingdom)

    2011-10-30

    Highlights: > Bitrex is a new levelling agent for copper. > The addition of Bitrex increases corrosion resistance of copper films. > The nature of pure copper electrodeposits depends on the growth template size. > Bitrex increases coppers current efficiency. - Abstract: We investigate the effects of denatonium benzoate (Bitrex) on the electrodeposition of copper films from a boric acid bath using scanning electron microscopy, cyclic voltammetry, electrochemical quartz microbalance (EQCM) measurements and corrosion studies. In the absence of Bitrex, pure copper films grown by this method are optically black owing to the appearance of complex surface nanostructures. The addition of Bitrex acts as a levelling agent preventing the formation of these nanostructures even for concentrations as low as 0.02 mM producing a lustrous film with low surface roughness. Bitrex is also found to improve the corrosion resistance by up to a factor of 20 and increase the current efficiency by over a factor of two. Bitrex is hypothesised to act directly on the cathode, partially inhibiting the growth or lowering the deposition current.

  15. Sorption of copper by vegetated copper-mine tailings

    Science.gov (United States)

    de Coninck, A.; Karam, A.; Jaouich, A.

    2009-04-01

    The lixiviation of copper (Cu) from vegetated mine tailings may present an environmental risk because of the potential adverse effects it may pose to ground and surface water around mines. However, bonding of Cu to mine tailings can limit transfer to surrounding water. The main objective of the present study is to assess Cu sorption by cultivated Cu-mine tailings containing calcite (pH 7.7) as influenced by commercial peat moss-shrimp waste compost (PSC) and chelating solution. Fresh tailing and tailing that had been used in pot experiments were tested and compared. Samples (0.50 g) of tailings were equilibrated with 20 cm3 of 0.01 M CaCl2 solution containing 100 mg Cu dm-3, as CuCl2, for 72 h at room temperature. After equilibration period, the samples were centrifuged and filtered. Concentration of Cu in the equilibrium solution was measured by atomic absorption spectrophotometry. The sorption coefficient (Ks) was used to interpret the sorption data. The sorption experiment was replicated two times. Compost was the most effective organic amendment in enhancing Cu sorption. The Ks values were positively and significantly correlated with organic matter content and Cu associated with the organic fraction of tailing samples. The mineralogy and organic matter content can influence the sorption capacity of Cu-mine tailings. Calcite-containing mine tailings amended with PSC can be used to sorb Cu from chloride solutions.

  16. Copper stable isotopes to trace copper behavior in wetland systems.

    Science.gov (United States)

    Babcsányi, Izabella; Imfeld, Gwenaël; Granet, Mathieu; Chabaux, François

    2014-05-20

    Wetlands are reactive zones of the landscape that can sequester metals released by industrial and agricultural activities. Copper (Cu) stable isotope ratios (δ(65)Cu) have recently been used as tracers of transport and transformation processes in polluted environments. Here, we used Cu stable isotopes to trace the behavior of Cu in a stormwater wetland receiving runoff from a vineyard catchment (Alsace, France). The Cu loads and stable isotope ratios were determined in the dissolved phase, suspended particulate matter (SPM), wetland sediments, and vegetation. The wetland retained >68% of the dissolved Cu and >92% of the SPM-bound Cu, which represented 84.4% of the total Cu in the runoff. The dissolved Cu became depleted in (65)Cu when passing through the wetland (Δ(65)Cuinlet-outlet from 0.03‰ to 0.77‰), which reflects Cu adsorption to aluminum minerals and organic matter. The δ(65)Cu values varied little in the wetland sediments (0.04 ± 0.10‰), which stored >96% of the total Cu mass within the wetland. During high-flow conditions, the Cu flowing out of the wetland became isotopically lighter, indicating the mobilization of reduced Cu(I) species from the sediments and Cu reduction within the sediments. Our results demonstrate that the Cu stable isotope ratios may help trace Cu behavior in redox-dynamic environments such as wetlands.

  17. 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

  18. 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

  19. Synthesis of the copper chelator TGTA and evaluation of its ability to protect biomolecules from copper induced degradation during copper catalyzed azide-alkyne bioconjugation reactions.

    Science.gov (United States)

    Ekholm, F S; Pynnönen, H; Vilkman, A; Koponen, J; Helin, J; Satomaa, T

    2016-01-21

    One of the most successful bioconjugation strategies to date is the copper(I)-catalyzed cycloaddition reaction (CuAAC), however, the typically applied reaction conditions have been found to degrade sensitive biomolecules. Herein, we present a water soluble copper chelator which can be utilized to protect biomolecules from copper induced degradation.

  20. Passivation Behaviour of Anode in Copper Electrorefining Using Recycled Low-grade Copper Anode

    National Research Council Canada - National Science Library

    Koudai TOKUSHIGE; Kohei MORI; Satoshi OUE; Hiroshi MATSUSHIMA; Kazunari SUZUKI; Hiroaki NAKANO

    2017-01-01

    ... of 11.4 hours in the solution containing Ni2+ ions as impurity. At normal dissolution of copper anode, copper parent phase dissolved in the form of dendrite and the framework of anode slime was composed of remained Cu-Ni-Sb-Sn-As compound...

  1. Aspartate aminotransferase is potently inhibited by copper complexes: Exploring copper complex-binding proteome.

    Science.gov (United States)

    Jia, Yuqi; Lu, Liping; Yuan, Caixia; Feng, Sisi; Zhu, Miaoli

    2017-05-01

    Recent researches indicated that a copper complex-binding proteome that potently interacted with copper complexes and then influenced cellular metabolism might exist in organism. In order to explore the copper complex-binding proteome, a copper chelating ion-immobilized affinity chromatography (Cu-IMAC) column and mass spectrometry were used to separate and identify putative Cu-binding proteins in primary rat hepatocytes. A total of 97 putative Cu-binding proteins were isolated and identified. Five higher abundance proteins, aspartate aminotransferase (AST), malate dehydrogenase (MDH), catalase (CAT), calreticulin (CRT) and albumin (Alb) were further purified using a SP-, and (or) Q-Sepharose Fast Flow column. The interaction between the purified proteins and selected 11 copper complexes and CuCl2 was investigated. The enzymes inhibition tests demonstrated that AST was potently inhibited by copper complexes while MDH and CAT were weakly inhibited. Schiff-based copper complexes 6 and 7 potently inhibited AST with the IC50 value of 3.6 and 7.2μM, respectively and exhibited better selectivity over MDH and CAT. Fluorescence titration results showed the two complexes tightly bound to AST with binding constant of 3.89×10(6) and 3.73×10(6)M(-1), respectively and a stoichiometry ratio of 1:1. Copper complex 6 was able to enter into HepG2 cells and further inhibit intracellular AST activity. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Impact of copper ligand mutations on a cupredoxin with a green copper center.

    Science.gov (United States)

    Roger, Magali; Sciara, Giuliano; Biaso, Frédéric; Lojou, Elisabeth; Wang, Xie; Bauzan, Marielle; Giudici-Orticoni, Marie-Thérèse; Vila, Alejandro J; Ilbert, Marianne

    2017-05-01

    Mononuclear cupredoxins contain a type 1 copper center with a trigonal or tetragonal geometry usually maintained by four ligands, a cystein, two histidines and a methionine. The recent discovery of new members of this family with unusual properties demonstrates, however, the versatility of this class of proteins. Changes in their ligand set lead to drastic variation in their metal site geometry and in the resulting spectroscopic and redox features. In our work, we report the identification of the copper ligands in the recently discovered cupredoxin AcoP. We show that even though AcoP possesses a classical copper ligand set, it has a highly perturbed copper center. In depth studies of mutant's properties suggest a high degree of constraint existing in the copper center of the wild type protein and even the addition of exogenous ligands does not lead to the reconstitution of the initial copper center. Not only the chemical nature of the axial ligand but also constraints brought by its covalent binding to the protein backbone might be critical to maintain a green copper site with high redox potential. This work illustrates the importance of experimentally dissecting the molecular diversity of cupredoxins to determine the molecular determinants responsible for their copper center geometry and redox potential. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Interesting properties of some iron(II), copper(I) and copper(II ...

    Indian Academy of Sciences (India)

    Administrator

    Tridendate ligands with nitrogen centers, generally well-known as the tripod ligands, have been of considerable interest to inorganic chemists dealing with the preparation of model compounds for hemocyanin, tyrosinase etc. We have found that such ligands when complexed with iron(II) and copper(II) and copper(I) ions ...

  4. Association of dietary copper and zinc levels with hepatic copper and zinc concentration in Labrador Retrievers

    NARCIS (Netherlands)

    Fieten, H.; Hooijer-Nouwens, B.D.; Biourge, V.; Leegwater, P.A.J.; Watson, A.L.; van den Ingh, T.S.G.A.M.; Rothuizen, J.

    2012-01-01

    J Vet Intern Med. 2012 Nov;26(6):1274-80. doi: 10.1111/j.1939-1676.2012.01001.x. Epub 2012 Sep 24. Association of dietary copper and zinc levels with hepatic copper and zinc concentration in labrador retrievers. Fieten H, Hooijer-Nouwens BD, Biourge VC, Leegwater PA, Watson AL, van den Ingh TS,

  5. Application of mercapto ordered carbohydrate-derived porous carbons for trace detection of cadmium and copper ions in agricultural products.

    Science.gov (United States)

    Behbahani, Mohammad; Abolhasani, Jafar; Amini, Mostafa M; Sadeghi, Omid; Omidi, Fariborz; Bagheri, Akbar; Salarian, Mani

    2015-04-15

    In this paper, we have introduced nanoporous carbon modified with mercapto groups as a new solid-phase method for extraction of cadmium(II) and copper(II) ions. The modified nanoporous carbon sorbent was characterised by thermogravimetric analysis, differential thermal analysis, transmission electron microscopy, Fourier transform infrared spectrometry, X-ray diffraction, and nitrogen adsorption surface area (BET) measurements. Effects of pH value, flow rates, type, concentration and volume of the eluent, breakthrough volume, and effect of other ions were studied. The experimental results show that simultaneous trace cadmium(II) and copper(II) ions can be quantitatively preconcentrated at pH 6.0 with recoveries >97%. Under optimised conditions, limits of detection are 0.04 and 0.09 ng mL(-1) for the ions of cadmium and copper respectively, and the precision of the method for analysis of cadmium and copper ions (5.0 μg of each target ions, N=8) are 2.4% and 2.1%, respectively. The obtained capacities of mercapto-nanoporous carbon were found to be 145 and 95 mg g(-1) for cadmium and copper ions, respectively. The accuracy of the proposed procedure was verified by analysing standard reference material. Finally, the introduced sorbent was successfully applied for trace determination of cadmium and copper ions in food samples. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Extraction and purification methods in downstream processing of plant-based recombinant proteins.

    Science.gov (United States)

    Łojewska, Ewelina; Kowalczyk, Tomasz; Olejniczak, Szymon; Sakowicz, Tomasz

    2016-04-01

    During the last two decades, the production of recombinant proteins in plant systems has been receiving increased attention. Currently, proteins are considered as the most important biopharmaceuticals. However, high costs and problems with scaling up the purification and isolation processes make the production of plant-based recombinant proteins a challenging task. This paper presents a summary of the information regarding the downstream processing in plant systems and provides a comprehensible overview of its key steps, such as extraction and purification. To highlight the recent progress, mainly new developments in the downstream technology have been chosen. Furthermore, besides most popular techniques, alternative methods have been described. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Downstream management practices of transnational companies in institutionally vulnerable countries: Export and use of hazardous products

    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...

  8. Physical modeling of the flow downstream of the butterfly valve of a carburetor

    Energy Technology Data Exchange (ETDEWEB)

    Lahbabi, F.Z.; Nuglish, H.J.; Couteau, G.; Charnay, G. (Institut de Mecanique des Fluides de Toulouse, Toulouse (France))

    1993-07-01

    The flow downstream of the carburetor of a spark ignition piston-engine was experimentally investigated, the geometry was simplified, and single-phase flow was used. Experiments were carried out in a straight cylindrical tube in which a butterfly valve was mounted. Tests were made with water and air. Qualitative and quantitative flow-visualization techniques and hot wire anemometry were used. The existence of several zones of low downstream of the valve was shown by local velocity measurements and measurement of three-dimensional particle trajectories. These results permitted estimation of the location of regions with high, medium, and low rates of deposition of fuel droplets on the walls under actual operating conditions of engines.

  9. 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.

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

    Science.gov (United States)

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

    2005-09-01

    In this research we examined the hypothesis that upper reaches of rivers and streams can experience eutrophication as a consequence of deep releases from dams. Field studies were conducted in four mountain rivers (Tormes, Riaza, Eresma and Miraflores Rivers) of Central Spain. The watersheds of these rivers are underlain by siliceous rocks. A small deep-release storage reservoir is found in the upper reaches of each river. Two sampling sites, upstream and downstream from the reservoir, were established in stony riffles of each impounded river. Significant (P rivers, can act as nutrient sources, causing eutrophication downstream. Nutrients would ultimately come from land/forest runoff. The fact that terrestrial vegetation was not completely removed before filling reservoirs could also contribute to the eutrophication process.

  11. Analysis of velocity fluctuations downstream of a bileaflet mechanical heart valve

    Science.gov (United States)

    Forleo, Marcio; Dasi, Lakshmi

    2010-11-01

    Bileaflet mechanical heart valves are widely used to replace diseased aortic heart valves. The stresses induced by the rich and unsteady non-physiological flow structures have been the focus to evaluate red blood cells damage and platelet activation, develop flow control strategies, or improve valve designs. In this study, we analyzed the flow fields obtained downstream of a bileaflet mechanical heart valve using time-resolved particle image velocimetry under pulsatile and steady flow conditions. Our study demonstrates the rich dynamics downstream of the valve and weighs the relevance of unsteady effects vs inertia effects on the different flow structures. Power spectrum analyses of the turbulent fluctuations highlight the highly anisotropic influence and the limited applicability of classical self-similar turbulence theory in describing the small-scale structures in the immediate vicinity of the valve.

  12. The Copper Balance of Cities

    Science.gov (United States)

    Kral, Ulrich; Lin, Chih-Yi; Kellner, Katharina; Ma, Hwong-wen; Brunner, Paul H

    2014-01-01

    Material management faces a dual challenge: on the one hand satisfying large and increasing demands for goods and on the other hand accommodating wastes and emissions in sinks. Hence, the characterization of material flows and stocks is relevant for both improving resource efficiency and environmental protection. This article focuses on the urban scale, a dimension rarely investigated in past metal flow studies. We compare the copper (Cu) metabolism of two cities in different economic states, namely, Vienna (Europe) and Taipei (Asia). Substance flow analysis is used to calculate urban Cu balances in a comprehensive and transparent form. The main difference between Cu in the two cities appears to be the stock: Vienna seems close to saturation with 180 kilograms per capita (kg/cap) and a growth rate of 2% per year. In contrast, the Taipei stock of 30 kg/cap grows rapidly by 26% per year. Even though most Cu is recycled in both cities, bottom ash from municipal solid waste incineration represents an unused Cu potential accounting for 1% to 5% of annual demand. Nonpoint emissions are predominant; up to 50% of the loadings into the sewer system are from nonpoint sources. The results of this research are instrumental for the design of the Cu metabolism in each city. The outcomes serve as a base for identification and recovery of recyclables as well as for directing nonrecyclables to appropriate sinks, avoiding sensitive environmental pathways. The methodology applied is well suited for city benchmarking if sufficient data are available. PMID:25866460

  13. Grain Boundary Energies in Copper.

    Science.gov (United States)

    Omar, Ramli

    Available from UMI in association with The British Library. Requires signed TDF. The dependence of grain boundary energy on boundary orientation was studied in copper annealed at 1000 ^circC. Grain boundary orientations and the disorientations across the boundaries were measured. A rotation matrix notation is used to interpret selected area electron channelling patterns observed in a scanning electron microscope. The Herring and Shewmon torque terms were investigated using wire specimens having a "bamboo" structure. The Herring torque terms were determined using the Hess relation. The (110) section of the Sigma 11 gamma-plot (i.e. the variation of grain boundary energy with boundary orientation) was evaluated. In this plot, minima in energies were found at the (311) and (332) mirror planes. Sigma 3 and Sigma9 boundaries were investigated in sheet specimens. The (110) and (111) sections of the Sigma3 gamma -plot were evaluated. In addition to the sharp cusps occurring at the Sigma3 {111} planes, the further shallower cusps occur at the incoherent Sigma 3 boundaries with the interfacial planes approximately parallel to {322} in one crystal and {11.44} in the other crystal. Flat and curved Sigma9 boundaries were investigated. The break up of Sigma9 boundaries into two Sigma3 boundaries and the relation between the Sigma3 and Sigma 9 gamma-plots was also examined. The (110) section of the Sigma9 gamma-plot was constructed.

  14. Vitrification of copper flotation waste.

    Science.gov (United States)

    Karamanov, Alexander; Aloisi, Mirko; Pelino, Mario

    2007-02-09

    The vitrification of an hazardous iron-rich waste (W), arising from slag flotation of copper production, was studied. Two glasses, containing 30wt% W were melted for 30min at 1400 degrees C. The first batch, labeled WSZ, was obtained by mixing W, blast furnace slag (S) and zeolite tuff (Z), whereas the second, labeled WG, was prepared by mixing W, glass cullet (G), sand and limestone. The glass frits showed high chemical durability, measured by the TCLP test. The crystallization of the glasses was evaluated by DTA. The crystal phases formed were identified by XRD resulting to be pyroxene and wollastonite solid solutions, magnetite and hematite. The morphology of the glass-ceramics was observed by optical and scanning electron microscopy. WSZ composition showed a high rate of bulk crystallization and resulted to be suitable for producing glass-ceramics by a short crystallization heat-treatment. WG composition showed a low crystallization rate and good sinterability; glass-ceramics were obtained by sinter-crystallization of the glass frit.

  15. Phototunable Magnetism in Copper Octacyanomolybdate

    Directory of Open Access Journals (Sweden)

    Jun Ohara

    2014-01-01

    Full Text Available We introduce copper molybdenum cyanides of general formula Cu2[Mo(CN8]·nH2O, which can serve as optofunctional magnetic devices. Their ground states generally stay paramagnetic down to temperatures of the K order but exhibit a spontaneous magnetization upon photoirradiation usually below a few tens of K. To interest us still further, such a ferromagnetic stateinduced by blue-laser irradiation is demagnetized step by step through further application of red or near-infrared laser pulses. We solve this intriguing photomagnetism. The ground-state properties are fully revealed by means of a group-theoretical technique. Taking account of experimental observations, we simulate applying pump laser pulses to a likely ground state and successfully reproduce both the magnetization and demagnetization dynamics. We monitor the photorelaxation process through angle-resolved photoemission spectroscopy. Electrons are fully itinerant in any of the photoinduced steady states, forming a striking contrast to the initial equilibrium state of atomic aspect. The fully demagnetized final steady state looks completely different from the initial paramagnetism but bears good analogy to one of the possible ground states available with the Coulomb repulsion on Cu sites suppressed.

  16. Regulating water extraction in a river basin with upstream-downstream communities

    DEFF Research Database (Denmark)

    Graversen, Mette Kildegaard

    This paper proposes a tax mechanism modelled for water extraction in a river system with upstream and downstream farmers. The tax mechanism is based on the regulator’s own estimation of aggregate extraction and for that reason the tax addresses the problem of asymmetric information....... It is demonstrated that the tax mechanism ensures approximately correct marginal extraction incentives for the individual farmer. Consequently, it is concluded that the tax mechanism proposed here has a practical application....

  17. Suitability of air sampling locations downstream of bends and static mixing elements.

    Science.gov (United States)

    McFarland, A R; Gupta, R; Anand, N K

    1999-12-01

    The revised standard for sampling effluent air from stacks and ducts of the nuclear industry places limits on the non-uniformity of velocity and contaminant profiles at the sampling location; namely, the coefficients of variation must not exceed 20% over an area that encompasses at least the center 2/3 of the cross sectional area. Tests were conducted to characterize the degree of mixing at downstream locations as affected by several types of flow disturbances, including 90 degree elbows and commercial static mixing devices. Flow straighteners were incorporated into the ducting upstream of the mixer to be tested to simulate the dampening of flow turbulence that might occur because of upstream HEPA filters. The coefficients of variation of velocity and tracer gas concentration measured in a straight tube at a distance of 3 diameters downstream from a 90 degree elbow were 17% and 69%, respectively. The mixing is impacted by the upstream flow turbulence. Without a flow straightener, the tracer gas concentration coefficient of variation was reduced to 33% at the 3-diameter location. The use of static mixing elements can greatly enhance the mixing process. A ring placed just downstream of a 90 degree elbow, which blocks the outer 56% of the cross sectional area, results in a coefficient of variation of 19% for tracer gas concentration at the 3-diameter location. Pressure loss across the elbow with the ring is about nine times that of the basic elbow. One of the commercially available static mixers provides coefficients of variation that are less than 10% for both velocity and tracer gas concentration at 4 diameters downstream from the mixer with a pressure loss that is only about 3.5 times as large as that of a 90 degree elbow.

  18. Production of structured lipids: acyl migration during enzymatic interesterification and downstream processing

    DEFF Research Database (Denmark)

    Xu, Xuebing

    1997-01-01

    -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...... to the required products. In this paper, the reasons of acyl migration and factors affecting the acyl migration were reviewed and discussed. The possible solutions were also evaluated....

  19. 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...

  20. Scleroglucan compatibility with thickeners, alcohols and polyalcohols and downstream processing implications.

    Science.gov (United States)

    Viñarta, Silvana C; Yossen, Mariana M; Vega, Jorge R; Figueroa, Lucía I C; Fariña, Julia I

    2013-02-15

    Thickening capacity and compatibility of scleroglucan with commercial thickeners (corn starch, gum arabic, carboxymethylcellulose, gelatin, xanthan and pectin), glycols (ethylene glycol and polyethylene glycol), alcohols (methanol, ethanol, 1-propanol and isopropanol) and polyalcohols (sorbitol, xylitol and mannitol) was explored. Exopolysaccharides (EPSs) from Sclerotium rolfsii ATCC 201126 and a commercial scleroglucan were compared. Compatibility and synergism were evaluated taking into account rheology, pH and sensory properties of different thickener/scleroglucan mixtures in comparison with pure solutions. S. rolfsii ATCC 201126 EPSs induced or increased pseudoplastic behaviour with a better performance than commercial scleroglucan, showing compatibility and synergy particularly with corn starch, xanthan, pectin and carboxymethylcellulose. Compatibility and a slight synergistic behaviour were also observed with 30% (w/v) ethylene glycol whereas mixtures with polyethylene glycol (PEG) precipitated. Scleroglucan was compatible with polyalcohols, whilst lower alcohols led to scleroglucan precipitation at 20% (v/v) and above. PEG-based scleroglucan downstream processing was compared to the usual alcohol precipitation. Downstream processed EPSi (with isopropanol) and EPS-p (with PEG) were evaluated on their yield, purity, rheological properties and visual aspect pointing to alcohol downstream processing as the best methodology, whilst PEG recovery would be unsuitable. The highest purified EPSi attained a recovery yield of ~23%, similar to ethanol purification, with a high degree of purity (88%, w/w vs. EPS-p, 8%, w/w) and exhibited optimal rheological properties, water solubility and appearance. With a narrower molecular weight distribution (M(w), 2.66×10(6) g/mol) and a radius of gyration (R(w), 245 nm) slightly lower than ethanol-purified EPSs, isopropanol downstream processing showed to be a proper methodology for obtaining a refined-grade scleroglucan