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Sample records for phase ii antioxidant

  1. Regulation of Nrf2-Mediated Phase II Detoxification and Anti-oxidant Genes

    PubMed Central

    Keum, Young-Sam

    2012-01-01

    The molecular mechanisms by which a variety of naturally-occurring dietary compounds exert chemopreventive effects have been a subject of intense scientific investigations. Induction of phase II detoxification and anti-oxidant enzymes through activation of Nrf2/ARE-dependent gene is recognized as one of the major cellular defense mechanisms against oxidative or xenobiotic stresses and currently represents a critical chemopreventive mechanism of action. In the present review, the functional significance of Keap1/Nrf2 protein module in regulating ARE-dependent phase II detoxification and anti-oxidant gene expression is discussed. The biochemical mechanisms underlying the phosphorylation and expression of Keap1/Nrf2 proteins that are controlled by the intracellular signaling kinases and ubiquitin-mediated E3 ligase system as well as control of nucleocytoplasmic translocation of Nrf2 by its innate nuclear export signal (NES) are described. PMID:24116287

  2. Schisandra Chinensis Baillon regulates the gene expression of phase II antioxidant/detoxifying enzymes in hepatic damage induced rats

    PubMed Central

    Jang, Han I; Do, Gyeong-Min; Lee, Hye Min; Ok, Hyang Mok; Shin, Jae-Ho

    2014-01-01

    BACKGROUND/OBJECTIVES This study investigated the antioxidant activities and hepatoprotective effects of Schisandra chinensis Baillon extract (SCE) against tert-butyl hydroperoxide (t-BHP)-induced oxidative hepatic damage in rats. MATERIALS/METHODS Sprague-Dawley (SD) rats were pretreated with SCE (300, 600, and 1,200 mg/kg BW) or saline once daily for 14 consecutive days. On day 14, each animal, except those belonging to the normal control group, were injected with t-BHP (0.8 mmol/kg BW/i.p.), and all of the rats were sacrificed 16 h after t-BHP injection. RESULTS Although no significant differences in AST and ALT levels were observed among the TC and SCE groups, the high-dose SCE group showed a decreasing tendency compared to the TC group. However, erythrocyte SOD activity showed a significant increase in the low-dose SCE group compared with the TC group. On the other hand, no significant differences in hepatic total glutathione (GSH) level, glutathione reductase (GR), and glutathione peroxidase (GSH-Px) activities were observed among the TC and SCE groups. Hepatic histopathological evaluation revealed that pretreatment with SCE resulted in reduced t-BHP-induced incidence of lesions, such as neutrophil infiltration, swelling of liver cells, and necrosis. In particular, treatment with a high dose of SCE resulted in induction of phase II antioxidant/detoxifying enzyme expression, such as glutathione S-transferase (GST) and glutamate-cysteine ligase catalytic subunit (GCLC). CONCLUSIONS Based on these results, we conclude that SCE exerts protective effects against t-BHP induced oxidative hepatic damage through the reduction of neutrophil infiltration, swelling of liver cells, and necrosis. In addition, SCE regulates the gene expression of phase II antioxidant/detoxifying enzymes independent of hepatic antioxidant enzyme activity. PMID:24944771

  3. Chemoprevention by Hippophae rhamnoides: effects on tumorigenesis, phase II and antioxidant enzymes, and IRF-1 transcription factor.

    PubMed

    Padmavathi, Bandhuvula; Upreti, Meenakshi; Singh, Virendra; Rao, A Ramesha; Singh, Rana P; Rath, Pramod C

    2005-01-01

    Fruits or berries of Hippophae rhamnoides (sea buckthorn), a rich source of vitamins A, C, and E, carotenes, flavonoids, and microelements such as sulfur, selenium, zinc, and copper, are edible and have been shown to protect from atopic dermatitis, hepatic injury, cardiac disease, ulcer, and atherosclerosis. However, its mechanism of action is not clear. We show that Hippophae inhibits benzo(a)pyrene-induced forestomach and DMBA-induced skin papillomagenesis in mouse. This decrease in carcinogenesis may be attributed to the concomitant induction of phase II enzymes such as glutathione S-transferase and DT-diaphorase and antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase in the mouse liver. This was accompanied by a remarkable induction of the transcription factor interferon regulatory factor-1 in the Hippophae-treated liver. Our results strongly suggest that Hippophae fruit is able to decrease carcinogen-induced forestomach and skin tumorigenesis, which might involve up-regulation of phase II and antioxidant enzymes as well as DNA-binding activity of IRF-1, a known antioncogenic transcription factor causing growth suppression and apoptosis induction for its anticancer effect. PMID:15749631

  4. Pharmacokinetics and pharmacodynamics of phase II drug metabolizing/antioxidant enzymes gene response by anticancer agent sulforaphane in rat lymphocytes.

    PubMed

    Wang, Hu; Khor, Tin Oo; Yang, Qian; Huang, Ying; Wu, Tien-Yuan; Saw, Constance Lay-Lay; Lin, Wen; Androulakis, Ioannis P; Kong, Ah-Ng Tony

    2012-10-01

    This study assesses the pharmacokinetics (PK) and pharmacodynamics (PD) of Nrf2-mediated increased expression of phase II drug metabolizing enzymes (DME) and antioxidant enzymes which represents an important component of cancer chemoprevention in rat lymphocytes following intravenous (iv) administration of an anticancer phytochemical sulforaphane (SFN). SFN was administered intravenously to four groups of male Sprague-Dawley JVC rats each group comprising four animals. Blood samples were drawn at selected time points. Plasma were obtained from half of each of the blood samples and analyzed using a validated LC-MS/MS method. Lymphocytes were collected from the remaining blood samples using Ficoll-Paque Plus centrifuge medium. Lymphocyte RNAs were extracted and converted to cDNA, quantitative real-time PCR analyses were performed, and fold changes were calculated against those at time zero for the relative expression of Nrf2-target genes of phase II DME/antioxidant enzymes. PK-PD modeling was conducted based on Jusko's indirect response model (IDR) using GastroPlus and bootstrap method. SFN plasma concentration declined biexponentially and the pharmacokinetic parameters were generated. Rat lymphocyte mRNA expression levels showed no change for GSTM1, SOD, NF-κB, UGT1A1, or UGT1A6. Moderate increases (2-5-fold) over the time zero were seen for HO-1, Nrf2, and NQO1, and significant increases (>5-fold) for GSTT1, GPx1, and Maf. PK-PD analyses using GastroPlus and the bootstrap method provided reasonable fitting for the PK and PD profiles and parameter estimates. Our present study shows that SFN could induce Nrf2-mediated phase II DME/antioxidant mRNA expression for NQO1, GSTT1, Nrf2, GPx, Maf, and HO-1 in rat lymphocytes after iv administration, suggesting that Nrf2-mediated mRNA expression in lymphocytes may serve as surrogate biomarkers. The PK-PD IDR model simultaneously linking the plasma concentrations of SFN and the PD response of lymphocyte mRNA expression is

  5. Non-thermal Plasma Activates Human Keratinocytes by Stimulation of Antioxidant and Phase II Pathways

    PubMed Central

    Schmidt, Anke; Dietrich, Stephan; Steuer, Anna; Weltmann, Klaus-Dieter; von Woedtke, Thomas; Masur, Kai; Wende, Kristian

    2015-01-01

    Non-thermal atmospheric pressure plasma provides a novel therapeutic opportunity to control redox-based processes, e.g. wound healing, cancer, and inflammatory diseases. By spatial and time-resolved delivery of reactive oxygen and nitrogen species, it allows stimulation or inhibition of cellular processes in biological systems. Our data show that both gene and protein expression is highly affected by non-thermal plasma. Nuclear factor erythroid-related factor 2 (NRF2) and phase II enzyme pathway components were found to act as key controllers orchestrating the cellular response in keratinocytes. Additionally, glutathione metabolism, which is a marker for NRF2-related signaling events, was affected. Among the most robustly increased genes and proteins, heme oxygenase 1, NADPH-quinone oxidoreductase 1, and growth factors were found. The roles of NRF2 targets, investigated by siRNA silencing, revealed that NRF2 acts as an important switch for sensing oxidative stress events. Moreover, the influence of non-thermal plasma on the NRF2 pathway prepares cells against exogenic noxae and increases their resilience against oxidative species. Via paracrine mechanisms, distant cells benefit from cell-cell communication. The finding that non-thermal plasma triggers hormesis-like processes in keratinocytes facilitates the understanding of plasma-tissue interaction and its clinical application. PMID:25589789

  6. Non-thermal plasma activates human keratinocytes by stimulation of antioxidant and phase II pathways.

    PubMed

    Schmidt, Anke; Dietrich, Stephan; Steuer, Anna; Weltmann, Klaus-Dieter; von Woedtke, Thomas; Masur, Kai; Wende, Kristian

    2015-03-13

    Non-thermal atmospheric pressure plasma provides a novel therapeutic opportunity to control redox-based processes, e.g. wound healing, cancer, and inflammatory diseases. By spatial and time-resolved delivery of reactive oxygen and nitrogen species, it allows stimulation or inhibition of cellular processes in biological systems. Our data show that both gene and protein expression is highly affected by non-thermal plasma. Nuclear factor erythroid-related factor 2 (NRF2) and phase II enzyme pathway components were found to act as key controllers orchestrating the cellular response in keratinocytes. Additionally, glutathione metabolism, which is a marker for NRF2-related signaling events, was affected. Among the most robustly increased genes and proteins, heme oxygenase 1, NADPH-quinone oxidoreductase 1, and growth factors were found. The roles of NRF2 targets, investigated by siRNA silencing, revealed that NRF2 acts as an important switch for sensing oxidative stress events. Moreover, the influence of non-thermal plasma on the NRF2 pathway prepares cells against exogenic noxae and increases their resilience against oxidative species. Via paracrine mechanisms, distant cells benefit from cell-cell communication. The finding that non-thermal plasma triggers hormesis-like processes in keratinocytes facilitates the understanding of plasma-tissue interaction and its clinical application.

  7. Modulation of hepatic phase II phenol sulfotransferase and antioxidant status by phenolic acids in rats.

    PubMed

    Yeh, Chi-Tai; Yen, Gow-Chin

    2006-08-01

    Phenolic acids have significant biological and pharmacological properties and some have demonstrated remarkable ability to alter sulfate conjugation. However, the modulatory effects of phenolic acids on phenol sulfotransferases (PSTs) in vivo have not been described. The present investigation evaluates the role of phenolic acid on the expression of PSTs in male Sprague-Dawley rat liver. According to the results, gentisic acid, gallic acid and p-coumaric acid in a dosage of 100 mg/kg of body weight for 14 consecutive days significantly increased P-form PST (PST-P) activity as compared with that of the control rats (P<.05), whereas the activity of M-form PST (PST-M) in rats that received gallic acid and p-coumaric acid were also significantly (P<.05) higher than in the control rats. Reverse transcriptase-polymerase chain reaction results indicated that the changes in both PST-P and PST-M mRNA levels by phenolic acids were similar to those noted in the enzyme activity levels. The plasma obtained from phenolic acid-administered rats had significantly (P<.05) increased oxygen radical absorbance capacity (ORAC(ROO*) values than that from control rats. In a bioavailability study, following oral administration of gallic acid and p-coumaric acid, the phenolic acids were detected in the plasma, and the Cmax values after 2.0-h administration were 665+/-23 and 550+/-33 nmol/L, respectively. There was a significant correlation between the activity of both forms of PSTs and the antioxidant capacity of ORAC(ROO*) value by phenolic acids (r=.74, P<.05 and r=.77, P<.05). These data suggest that phenolic acids might alter sulfate conjugation and antioxidant capacity in living systems. PMID:16443358

  8. Fisetin inhibits osteoclastogenesis through prevention of RANKL-induced ROS production by Nrf2-mediated up-regulation of phase II antioxidant enzymes.

    PubMed

    Sakai, Eiko; Shimada-Sugawara, Megumi; Yamaguchi, Yu; Sakamoto, Hiroshi; Fumimoto, Reiko; Fukuma, Yutaka; Nishishita, Kazuhisa; Okamoto, Kuniaki; Tsukuba, Takayuki

    2013-01-01

    Osteoclasts (OCLs) are multinucleated bone-resorbing cells that are differentiated by stimulation with receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor. We recently demonstrated that regulation of heme-oxygenase 1 (HO-1), a stress-induced cytoprotective enzyme, also functions in OCL differentiation. In this study, we investigated effects of fisetin, a natural bioactive flavonoid that has been reported to induce HO-1 expression, on the differentiation of macrophages into OCLs. Fisetin inhibited the formation of OCLs in a dose-dependent manner and suppressed the bone-resorbing activity of OCLs. Moreover, fisetin-treated OCLs showed markedly decreased phosphorylation of extracellular signal-regulated kinase, Akt, and Jun N-terminal kinase, but fisetin did not inhibit p38 phosphorylation. Fisetin up-regulated mRNA expression of phase II antioxidant enzymes including HO-1 and interfered with RANKL-mediated reactive oxygen species (ROS) production. Studies with RNA interference showed that suppression of NF-E2-related factor 2 (Nrf2), a key transcription factor for phase II antioxidant enzymes, rescued fisetin-mediated inhibition of OCL differentiation. Furthermore, fisetin significantly decreased RANKL-induced nuclear translocation of cFos and nuclear factor of activated T cells cytoplasmic-1 (NFATc1), which is a transcription factor critical for osteoclastogenic gene regulation. Therefore, fisetin inhibits OCL differentiation through blocking RANKL-mediated ROS production by Nrf2-mediated up-regulation of phase II antioxidant enzymes.

  9. Phase II-inducing, polyphenols content and antioxidant capacity of corn (Zea mays L.) from phenotypes of white, blue, red and purple colors processed into masa and tortillas.

    PubMed

    Lopez-Martinez, Leticia X; Parkin, Kirk L; Garcia, Hugo S

    2011-03-01

    White, blue, red and purple corns (Zea mays L.) were lime-cooked to obtain masa for tortillas. The total phenolics and anthocyanins content, antioxidant activity expressed as total reducing power (TRP), peroxyl radical bleaching (PRAC), total antioxidant activity (TAA) and quinone reductase (QR) induction in the murine hepatoma (Hepa 1 c1c7 cell line) as a biological marker for phase II detoxification enzymes were investigated. Among the extracts prepared from raw corn varieties the highest concentration of total phenolics, anthocyanins, antioxidant index and induction of QR-inducing activity were found in the Veracruz 42 (Ver 42) genotype. The nixtamalization process (masa) reduced total phenolics, anthocyanins and antioxidant activities and the ability for QR induction when was compared to raw grain. Processing masa into tortillas also negatively affected total phenolics, anthocyanin concentration, antioxidant activities, and QR induction in the colored corn varieties. The blue variety and its corresponding masa and tortillas did not induce QR. Ver 42 genotype and their products (masa and tortilla) showed the greatest antioxidant activity and capacity to induce QR.

  10. Phase II-inducing, polyphenols content and antioxidant capacity of corn (Zea mays L.) from phenotypes of white, blue, red and purple colors processed into masa and tortillas.

    PubMed

    Lopez-Martinez, Leticia X; Parkin, Kirk L; Garcia, Hugo S

    2011-03-01

    White, blue, red and purple corns (Zea mays L.) were lime-cooked to obtain masa for tortillas. The total phenolics and anthocyanins content, antioxidant activity expressed as total reducing power (TRP), peroxyl radical bleaching (PRAC), total antioxidant activity (TAA) and quinone reductase (QR) induction in the murine hepatoma (Hepa 1 c1c7 cell line) as a biological marker for phase II detoxification enzymes were investigated. Among the extracts prepared from raw corn varieties the highest concentration of total phenolics, anthocyanins, antioxidant index and induction of QR-inducing activity were found in the Veracruz 42 (Ver 42) genotype. The nixtamalization process (masa) reduced total phenolics, anthocyanins and antioxidant activities and the ability for QR induction when was compared to raw grain. Processing masa into tortillas also negatively affected total phenolics, anthocyanin concentration, antioxidant activities, and QR induction in the colored corn varieties. The blue variety and its corresponding masa and tortillas did not induce QR. Ver 42 genotype and their products (masa and tortilla) showed the greatest antioxidant activity and capacity to induce QR. PMID:21327968

  11. Pharmacodynamics of dietary phytochemical indoles I3C and DIM: Induction of Nrf2-mediated phase II drug metabolizing and antioxidant genes and synergism with isothiocyanates.

    PubMed

    Saw, Constance Lay-Lay; Cintrón, Melvilí; Wu, Tien-Yuan; Guo, Yue; Huang, Ying; Jeong, Woo-Sik; Kong, Ah-Ng Tony

    2011-07-01

    The antioxidant response element (ARE) is a critical regulatory element for the expression of many phase II drug metabolizing enzymes (DME), phase III transporters and antioxidant enzymes, mediated by the transcription factor Nrf2. The aim of this study was to examine the potential activation and synergism of Nrf2-ARE-mediated transcriptional activity between four common phytochemicals present in cruciferous vegetables; the indoles: indole-3-carbinol (I3C), 3,3'-diindolylmethane (DIM); and the isothiocyanates (ITCs): phenethyl isothiocyanate (PEITC) and sulforaphane (SFN). The cytotoxicity of the compounds was determined in a human liver hepatoma cell line (HepG2-C8). The combination index was calculated to assess the synergistic effects on the induction of ARE-mediated gene expressions. Quantitative real-time polymerase chain reaction (qPCR) was employed to measure the mRNA expressions of Nrf2 and Nrf2-mediated genes. I3C and DIM showed less cytotoxicity than SFN and PEITC. Compared with I3C, DIM was found to be a stronger inducer of ARE. Synergism was observed after combined treatments of 6.25 µm I3C + 1 µm SFN, 6.25 µm I3C + 1 µm PEITC and 6.25 µm DIM + 1 µm PEITC, while an additive effect was observed for 6.25 µm DIM + 1 µm SFN. Induction of endogenous Nrf2, phase II genes (GSTm2, UGT1A1 and NQO1) and antioxidant genes (HO-1 and SOD1) was also observed. In summary, the indole I3C or DIM alone could induce or syngergistically induce in combination with the ITCs SFN or PEITC, Nrf2-ARE-mediated gene expression, which could potentially enhance cancer chemopreventive activity. PMID:21656528

  12. Long Term Effect of Curcumin in Restoration of Tumour Suppressor p53 and Phase-II Antioxidant Enzymes via Activation of Nrf2 Signalling and Modulation of Inflammation in Prevention of Cancer

    PubMed Central

    Das, Laxmidhar; Vinayak, Manjula

    2015-01-01

    Inhibition of carcinogenesis may be a consequence of attenuation of oxidative stress via activation of antioxidant defence system, restoration and stabilization of tumour suppressor proteins along with modulation of inflammatory mediators. Previously we have delineated significant role of curcumin during its long term effect in regulation of glycolytic pathway and angiogenesis, which in turn results in prevention of cancer via modulation of stress activated genes. Present study was designed to investigate long term effect of curcumin in regulation of Nrf2 mediated phase-II antioxidant enzymes, tumour suppressor p53 and inflammation under oxidative tumour microenvironment in liver of T-cell lymphoma bearing mice. Inhibition of Nrf2 signalling observed during lymphoma progression, resulted in down regulation of phase II antioxidant enzymes, p53 as well as activation of inflammatory signals. Curcumin potentiated significant increase in Nrf2 activation. It restored activity of phase-II antioxidant enzymes like GST, GR, NQO1, and tumour suppressor p53 level. In addition, curcumin modulated inflammation via upregulation of TGF-β and reciprocal regulation of iNOS and COX2. The study suggests that during long term effect, curcumin leads to prevention of cancer by inducing phase-II antioxidant enzymes via activation of Nrf2 signalling, restoration of tumour suppressor p53 and modulation of inflammatory mediators like iNOS and COX2 in liver of lymphoma bearing mice. PMID:25860911

  13. Modulatory effect of henna leaf (Lawsonia inermis) on drug metabolising phase I and phase II enzymes, antioxidant enzymes, lipid peroxidation and chemically induced skin and forestomach papillomagenesis in mice.

    PubMed

    Dasgupta, Trisha; Rao, A R; Yadava, P K

    2003-03-01

    Henna leaf (Lawsonia inermis), commonly known as Mehndi is cultivated throughout India and is a very popular natural dye to color hand and hair. It is an integral part of indigenous culture, and is also known for its medicinal value. The effect of 200 and 400 mg/kg body weight of 80% ethanolic extract of the fresh leaves of Lawsonia inermis were examined on drug metabolizing phase-I and phase-II enzymes, antioxidant enzymes, glutathione content, lactate dehydrogenase and lipid peroxidation in the liver of 7 weeks old Swiss albino mice. Also anticarcinogenic potential of Henna leaf extract was studied adopting the protocol of benzo(a)pyrene induced forestomach and 7,12 dimethylbenz(a)anthracene (DMBA)-initiated and croton oil-promoted skin papillomagenesis. Our primary findings reveal the 'duel-acting' nature of henna leaf as deduced from its potential to induce only the phase-II enzyme activity, associated mainly with carcinogen detoxification in liver of mice and inhibit the phase I enzyme activities. The hepatic glutathione S-transferase and DT-diaphorase specific activities were elevated above basal (p < 0.005) level by Lawsonia inermis extract treatment. With reference to antioxidant enzymes the investigated doses were effective in increasing the hepatic glutathione reductase (GR), superoxide dismutase (SOD) and catalase activities significantly (from p < 0.05 to p < 0.005) at both the dose levels. Reduced glutathione (GSH) measured as non-protein sulphydryl was found to be significantly elevated in liver (p < 0.005) and in all the extrahepatic organs studied (from p < 0.05 to p < 0.005). Among the extrahepatic organs examined (forestomach, kidney and lung) glutathione S-transferase and DT-diaphorase level were increased in a dose independent manner (from p < 0.05 to p < 0.005). Chemopreventive response was measured by the average number of papillomas per mouse (tumor burden) as well as percentage of tumor bearing animals and tumor multiplicity. There was a

  14. Hepatic metabolism, phase I and II biotransformation enzymes in Atlantic salmon (Salmo Salar, L) during a 12 week feeding period with graded levels of the synthetic antioxidant, ethoxyquin.

    PubMed

    Berdikova Bohne, Victoria J; Hamre, Kristin; Arukwe, Augustine

    2007-05-01

    The synthetic antioxidant ethoxyquin (EQ) is a widely used additive in animal feeds, including farmed fish feed. The use of EQ as food additive is prohibited and it is also undesirable in farmed meat and fish products. The possible negative aspects of EQ in fish feeds, such as modulation of hepatic detoxifying enzymes and possible effects through "carry-over" to edible parts of fish are not known. In addition, the subsequent consequences for human consumers have not been previously studied. In the present work, the alteration in gene and protein expression patterns, and catalytic activities of phase I and II hepatic biotransformation enzymes due to prolonged exposure to graded levels of dietary EQ in the range of 11-1800 mg EQ/kg feed were studied. The kinetics of parent EQ and its major metabolite, ethoxyquin dimer (EQDM) was also studied. In general two weeks seem to be the critical point in the entire toxicological response of salmon to dietary consumed EQ. Biotransformation of EQ to EQDM is shown to be a rapid process. However, the decrease in biotransformation rate results in the accumulation of EQ metabolites, high concentration of which was postulated to alter translation and post-translational modification of CYP3A, GST and UDPGT at feeding day 14 and 42, with subsequent decreases in the biotransformation of consumed EQ. Decrease in the biotransformation of consumed EQ produced the retention of un-metabolized EQ rather than metabolites in salmon liver. This may be considered as undesirable effect, since it could lead to the transport and accumulation in other organs and edible tissues. It may also cause a new wave of biotransformation with formation of metabolites inhibiting detoxifying enzymes. In general, these processes may prolong the excretion of dietary EQ from the fish body and produce EQ-derived residues in the ready-to-consume salmon or fish products. These EQ residues may have higher toxicological effects for human consumers than the parent

  15. Phase II Final Report

    SciTech Connect

    Schuknecht, Nate; White, David; Hoste, Graeme

    2014-09-11

    The SkyTrough DSP will advance the state-of-the-art in parabolic troughs for utility applications, with a larger aperture, higher operating temperature, and lower cost. The goal of this project was to develop a parabolic trough collector that enables solar electricity generation in the 2020 marketplace for a 216MWe nameplate baseload power plant. This plant requires an LCOE of 9¢/kWhe, given a capacity factor of 75%, a fossil fuel limit of 15%, a fossil fuel cost of $6.75/MMBtu, $25.00/kWht thermal storage cost, and a domestic installation corresponding to Daggett, CA. The result of our optimization was a trough design of larger aperture and operating temperature than has been fielded in large, utility scale parabolic trough applications: 7.6m width x 150m SCA length (1,118m2 aperture), with four 90mm diameter × 4.7m receivers per mirror module and an operating temperature of 500°C. The results from physical modeling in the System Advisory Model indicate that, for a capacity factor of 75%: The LCOE will be 8.87¢/kWhe. SkyFuel examined the design of almost every parabolic trough component from a perspective of load and performance at aperture areas from 500 to 2,900m2. Aperture-dependent design was combined with fixed quotations for similar parts from the commercialized SkyTrough product, and established an installed cost of $130/m2 in 2020. This project was conducted in two phases. Phase I was a preliminary design, culminating in an optimum trough size and further improvement of an advanced polymeric reflective material. This phase was completed in October of 2011. Phase II has been the detailed engineering design and component testing, which culminated in the fabrication and testing of a single mirror module. Phase II is complete, and this document presents a summary of the comprehensive work.

  16. Options Study - Phase II

    SciTech Connect

    R. Wigeland; T. Taiwo; M. Todosow; W. Halsey; J. Gehin

    2010-09-01

    The Options Study has been conducted for the purpose of evaluating the potential of alternative integrated nuclear fuel cycle options to favorably address the issues associated with a continuing or expanding use of nuclear power in the United States. The study produced information that can be used to inform decisions identifying potential directions for research and development on such fuel cycle options. An integrated nuclear fuel cycle option is defined in this study as including all aspects of the entire nuclear fuel cycle, from obtaining natural resources for fuel to the ultimate disposal of used nuclear fuel (UNF) or radioactive wastes. Issues such as nuclear waste management, especially the increasing inventory of used nuclear fuel, the current uncertainty about used fuel disposal, and the risk of nuclear weapons proliferation have contributed to the reluctance to expand the use of nuclear power, even though it is recognized that nuclear power is a safe and reliable method of producing electricity. In this Options Study, current, evolutionary, and revolutionary nuclear energy options were all considered, including the use of uranium and thorium, and both once-through and recycle approaches. Available information has been collected and reviewed in order to evaluate the ability of an option to clearly address the challenges associated with the current implementation and potential expansion of commercial nuclear power in the United States. This Options Study is a comprehensive consideration and review of fuel cycle and technology options, including those for disposal, and is not constrained by any limitations that may be imposed by economics, technical maturity, past policy, or speculated future conditions. This Phase II report is intended to be used in conjunction with the Phase I report, and much information in that report is not repeated here, although some information has been updated to reflect recent developments. The focus in this Options Study was to

  17. Combustion 2000: Phase II

    SciTech Connect

    Unknown

    1999-11-01

    The goals of the program are to develop a coal-fired high performance power generation system (HIPPS) that is capable of: thermal efficiency (HHV) {ge} 47%; NOx, SOx, and particulates {le} 10% NSPS (New Source Performance Standard); coal providing {ge} 65% of heat input; all solid wastes benign; and cost of electricity {le} 90% of present plants. Phase 1, which began in 1992, focused on the analysis of various configurations of indirectly fired cycles and on technical assessments of alternative plant subsystems and components, including performance requirements, developmental status, design options, complexity and reliability, and capital and operating costs. Phase 1 also included preliminary R and D and the preparation of designs for HIPPS commercial plants approximately 300 MWe in size. This Phase, Phase 2, had as its initial objective the development of a complete design base for the construction and operation of a HIPPS prototype plant to be constructed in Phase 3. As part of a descoping initiative, the Phase 3 program has been eliminated and work related to the commercial plant design has been ended. The rescoped program retained a program of engineering research and development focusing on high temperature heat exchangers, e.g. HITAF development (Task 2); a rescoped Task 6 that is pertinent to Vision 21 objectives and focuses on advanced cycle analysis and optimization, integration of gas turbines into complex cycles, and repowering designs; and preparation of the Phase 2 Technical Report (Task 8). This rescoped program deleted all subsystem testing (Tasks 3, 4,and 5) and the development of a site-specific engineering design and test plan for the HIPPS prototype plant (Task 7). Work reported herein is from: Task 2.1 HITAF Combustors; Task 2.2 HITAF Air Heaters; and Task 6 HIPPS Commercial Plant Design Update.

  18. Influence of bacterial N-acyl-homoserine lactones on growth parameters, pigments, antioxidative capacities and the xenobiotic phase II detoxification enzymes in barley and yam bean.

    PubMed

    Götz-Rösch, Christine; Sieper, Tina; Fekete, Agnes; Schmitt-Kopplin, Philippe; Hartmann, Anton; Schröder, Peter

    2015-01-01

    Bacteria are able to communicate with each other and sense their environment in a population density dependent mechanism known as quorum sensing (QS). N-acyl-homoserine lactones (AHLs) are the QS signaling compounds of Gram-negative bacteria which are frequent colonizers of rhizospheres. While cross-kingdom signaling and AHL-dependent gene expression in plants has been confirmed, the responses of enzyme activities in the eukaryotic host upon AHLs are unknown. Since AHL are thought to be used as so-called plant boosters or strengthening agents, which might change their resistance toward radiation and/or xenobiotic stress, we have examined the plants' pigment status and their antioxidative and detoxifying capacities upon AHL treatment. Because the yield of a crop plant should not be negatively influenced, we have also checked for growth and root parameters. We investigated the influence of three different AHLs, namely N-hexanoyl- (C6-HSL), N-octanoyl- (C8-HSL), and N-decanoyl- homoserine lactone (C10-HSL) on two agricultural crop plants. The AHL-effects on Hordeum vulgare (L.) as an example of a monocotyledonous crop and on the tropical leguminous crop plant Pachyrhizus erosus (L.) were compared. While plant growth and pigment contents in both plants showed only small responses to the applied AHLs, AHL treatment triggered tissue- and compound-specific changes in the activity of important detoxification enzymes. The activity of dehydroascorbate reductase in barley shoots after C10-HSL treatment for instance increased up to 384% of control plant levels, whereas superoxide dismutase activity in barley roots was decreased down to 23% of control levels upon C6-HSL treatment. Other detoxification enzymes reacted similarly within this range, with interesting clusters of positive or negative answers toward AHL treatment. In general the changes on the enzyme level were more severe in barley than in yam bean which might be due to the different abilities of the plants to

  19. Influence of bacterial N-acyl-homoserine lactones on growth parameters, pigments, antioxidative capacities and the xenobiotic phase II detoxification enzymes in barley and yam bean

    PubMed Central

    Götz-Rösch, Christine; Sieper, Tina; Fekete, Agnes; Schmitt-Kopplin, Philippe; Hartmann, Anton; Schröder, Peter

    2015-01-01

    Bacteria are able to communicate with each other and sense their environment in a population density dependent mechanism known as quorum sensing (QS). N-acyl-homoserine lactones (AHLs) are the QS signaling compounds of Gram-negative bacteria which are frequent colonizers of rhizospheres. While cross-kingdom signaling and AHL-dependent gene expression in plants has been confirmed, the responses of enzyme activities in the eukaryotic host upon AHLs are unknown. Since AHL are thought to be used as so-called plant boosters or strengthening agents, which might change their resistance toward radiation and/or xenobiotic stress, we have examined the plants’ pigment status and their antioxidative and detoxifying capacities upon AHL treatment. Because the yield of a crop plant should not be negatively influenced, we have also checked for growth and root parameters. We investigated the influence of three different AHLs, namely N-hexanoyl- (C6-HSL), N-octanoyl- (C8-HSL), and N-decanoyl- homoserine lactone (C10-HSL) on two agricultural crop plants. The AHL-effects on Hordeum vulgare (L.) as an example of a monocotyledonous crop and on the tropical leguminous crop plant Pachyrhizus erosus (L.) were compared. While plant growth and pigment contents in both plants showed only small responses to the applied AHLs, AHL treatment triggered tissue- and compound-specific changes in the activity of important detoxification enzymes. The activity of dehydroascorbate reductase in barley shoots after C10-HSL treatment for instance increased up to 384% of control plant levels, whereas superoxide dismutase activity in barley roots was decreased down to 23% of control levels upon C6-HSL treatment. Other detoxification enzymes reacted similarly within this range, with interesting clusters of positive or negative answers toward AHL treatment. In general the changes on the enzyme level were more severe in barley than in yam bean which might be due to the different abilities of the plants to

  20. A Proof of Concept, Phase II Randomized European Trial, on the Efficacy of ALF-5755, a Novel Extracellular Matrix-Targeted Antioxidant in Patients with Acute Liver Diseases

    PubMed Central

    Nalpas, Bertrand; Ichaï, Philippe; Jamot, Laure; Carbonell, Nicolas; Rudler, Marika; Mathurin, Philippe; Durand, François; Gerken, Guido; Manns, Michael; Trautwein, Christian; Larrey, Dominique; Radenne, Sylvie; Duvoux, Christophe; Leroy, Vincent; Bernuau, Jacques; Faivre, Jamila; Moniaux, Nicolas; Bréchot, Christian; Amouyal, Gilles; Amouyal, Paul; Samuel, Didier

    2016-01-01

    Objective No efficient medical treatment is available for severe acute hepatitis (SAH) except N-acetylcysteine for acetaminophen-induced acute liver failure. The human C-type lectin Reg3α, referred to as ALF-5755, improved survival in an animal model of acute liver failure and was well tolerated in a phase 1 trial in humans. We performed a phase 2a trial of ALF5755 in non-acetaminophen induced SAH. Design double-blind, randomized, placebo-controlled study. The primary end-point was the improvement in the coagulation protein synthesis assessed by the change of Prothrombin (PR) during the 72 hours following treatment initiation calculated as PRH0 minus PRH72 divided by 72 (PR slope H0H72). Intention to treat (ITT) and per-protocol (PP) analysis of the entire group and the Hepatitis B virus (HBV)/AIH (auto-immune hepatitis) sub-group were done separately. Results 57 patients were included. Twenty-eight received ALF-5755, 29 the placebo. Etiologies were: Hepatitis A (n = 10), HBV (n = 13), AIH (n = 9), drug-induced (n = 8), other (n = 17). On the whole group, nor the PR slope H0H72 (0.18±0.31 vs 0.25±0.32), nor the transplant-free survival rate at day 21 (75 vs 86%) differed between groups. Conversely, in the HBV-AIH subgroup, in which ALF was more severe, PR slope H0-H72 was higher in the ALF-5755 arm, the difference being significant in PP analysis (0.048±0.066 vs -0.040±0.099, p = 0.04); the median length of hospitalization was lower in the ALF-5755 group (8 vs 14 days, p = 0.02). Conclusion ALF-5755 was not efficient in a ITT analysis performed on the whole sample; however it led to a significant, although moderate, clinical benefit in a PP analysis of the sub-group of patients with HBV or AIH related SAH. As HBV is the major cause of SAH in Asia and Africa and AIH a growing cause, this study emphasizes the need to pursuit the evaluation of this novel medical treatment of SAH. Trial Registration ClinicalTrials.gov NCT01318525 PMID:26983031

  1. Phase II metabolism of benzene.

    PubMed Central

    Schrenk, D; Orzechowski, A; Schwarz, L R; Snyder, R; Burchell, B; Ingelman-Sundberg, M; Bock, K W

    1996-01-01

    The hepatic metabolism of benzene is thought to be a prerequisite for its bony marrow toxicity. However, the complete pattern of benzene metabolites formed in the liver and their role in bone marrow toxicity are not fully understood. Therefore, benzene metabolism was studied in isolated rodent hepatocytes. Rat hepatocytes released benzene-1,2-dihydrodiol, hydroquinone (HQ), catechol (CT), phenol (PH), trans-trans-muconic acid, and a number of phase II metabolites such as PH sulfate and PH glucuronide. Pretreatment of animals with 3-methylcholantrene (3-MC) markedly increased PH glucuronide formation while PH sulfate formation was decreased. Likewise, V79 cells transfected with the 3-MC-inducible rat UGT1.6 cDNA showed a considerable rate of PH and HQ glucuronidation. In addition to inducing glucuronidation of phenols, 3-MC treatment (reported to protect rats from the myelotoxicity of benzene) resulted in a decrease of hepatic CYP2E1. In contrast, pretreatment of rats with the CYP2E1-inducer isopropanol strongly enhanced benzene metabolism and the formation of phenolic metabolites. Mouse hepatocytes formed much higher amounts of HQ than rat hepatocytes and considerable amounts of 1,2,4-trihydroxybenzene (THB) sulfate and HQ sulfate. In conclusion, the protective effect of 3-MC in rats is probably due to a shift from the labile PH sulfate to the more stable PH glucuronide, and to a decrease in hepatic CYP2E1. The higher susceptibility of mice toward benzene may be related to the high rate of formation of the myelotoxic metabolite HQ and the semistable phase II metabolites HQ sulfate and THB sulfate. Images Figure 4. PMID:9118891

  2. Geology of the Phase II System

    SciTech Connect

    Laney, R.; Laughlin, A. William

    1980-11-19

    This is a report on the analysis of EE-2 cuttings and thin sections, geologic characterization of the Phase II system, comparison with Phase 1, and geologic speculations and recommendations concerning Phase II. The EE-2 litholog has been included in the pocket.

  3. Sample Exchange Evaluation (SEE) Report - Phase II

    SciTech Connect

    Winters, W.I.

    1994-09-28

    This report describes the results from Phase II of the Sample Exchange Evaluation (SEE) Program, a joint effort to compare analytical laboratory performance on samples from the Hanford Site`s high-level waste tanks. In Phase II, the program has been expanded to include inorganic constituents in addition to radionuclides. Results from Phase II that exceeded 20% relative percent difference criteria are identified.

  4. Centrifuge workers study. Phase II, completion report

    SciTech Connect

    Wooten, H.D.

    1994-09-01

    Phase II of the Centrifuge Workers Study was a follow-up to the Phase I efforts. The Phase I results had indicated a higher risk than expected among centrifuge workers for developing bladder cancer when compared with the risk in the general population for developing this same type of cancer. However, no specific agent could be identified as the causative agent for these bladder cancers. As the Phase II Report states, Phase I had been limited to workers who had the greatest potential for exposure to substances used in the centrifuge process. Phase II was designed to expand the survey to evaluate the health of all employees who had ever worked in Centrifuge Program Departments 1330-1339 but who had not been interviewed in Phase I. Employees in analytical laboratories and maintenance departments who provided support services for the Centrifuge Program were also included in Phase II. In December 1989, the Oak Ridge Associated Universities (ORAU), now known as Oak Ridge Institute for Science and Education (ORISE), was contracted to conduct a follow-up study (Phase II). Phase H of the Centrifuge Workers Study expanded the survey to include all former centrifuge workers who were not included in Phase I. ORISE was chosen because they had performed the Phase I tasks and summarized the corresponding survey data therefrom.

  5. Small Business Innovation Research GRC Phase I, Phase II, and Post-Phase II Opportunity Assessment for 2015

    NASA Technical Reports Server (NTRS)

    Nguyen, Hung D.; Steele, Gynelle C.

    2016-01-01

    This report outlines the 2015 Small Business Innovation Research/Small Business Technology Transfer (SBIR/STTR) Phase I, Phase II, and Post-Phase II opportunity contract award results associated with NASA's Aeronautics Research Mission Directorate (ARMD), Human Exploration and Operations Mission Directorate (HEOMD), Science Mission Directorate (SMD), and Space Technology Mission Directorate (STMD) for NASA Glenn Research Center. The report also highlights the number of Phase I, Phase II, and Post-Phase II contracts awarded by mission directorate. The 2015 Phase I contract awards to companies in Ohio and their corresponding technologies are also discussed.

  6. Upregulation of phase II enzymes through phytochemical activation of Nrf2 protects cardiomyocytes against oxidant stress.

    PubMed

    Reuland, Danielle J; Khademi, Shadi; Castle, Christopher J; Irwin, David C; McCord, Joe M; Miller, Benjamin F; Hamilton, Karyn L

    2013-03-01

    Increased production of reactive oxygen species has been implicated in the pathogenesis of cardiovascular disease (CVD), and enhanced endogenous antioxidants have been proposed as a mechanism for regulating redox balance. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a transcriptional regulator of phase II antioxidant enzymes, and activation of Nrf2 has been suggested to be an important step in attenuating oxidative stress associated with CVD. A well-defined combination of five widely studied medicinal plants derived from botanical sources (Bacopa monniera, Silybum marianum (milk thistle), Withania somnifera (Ashwagandha), Camellia sinensis (green tea), and Curcuma longa (turmeric)) has been shown to activate Nrf2 and induce phase II enzymes through the antioxidant response element. The purpose of these experiments was to determine if treatment of cardiomyocytes with this phytochemical composition, marketed as Protandim, activates Nrf2, induces phase II detoxification enzymes, and protects cardiomyocytes from oxidant-induced apoptosis in a Nrf2-dependent manner. In cultured HL-1 cardiomyocytes, phytochemical treatment was associated with nuclear accumulation of Nrf2, significant induction of phase II enzymes, and concomitant protection against hydrogen peroxide-induced apoptosis. The protection against oxidant stress was abolished when Nrf2 was silenced by shRNA, suggesting that our phytochemical treatment worked through the Nrf2 pathway. Interestingly, phytochemical treatment was found to be a more robust activator of Nrf2 than oxidant treatment, supporting the use of the phytochemicals as a potential treatment to increase antioxidant defenses and protect heart cells against an oxidative challenge.

  7. SLUDGE BATCH 6 PHASE II FLOWSHEET SIMULATIONS

    SciTech Connect

    Koopman, D.; Best, D.

    2010-03-30

    Two Sludge Receipt and Adjustment Tank (SRAT) runs were used to demonstrate that a fairly wide window of acid stoichiometry was available for processing SB6 Phase II flowsheet simulant (Tank 40 simulant) while still meeting the dual goals of acceptable nitrate destruction and controlled hydrogen generation. Phase II was an intermediate flowsheet study for the projected composition of Tank 40 after transfer of SB6/Tank 51 sludge to the heel of SB5. The composition was based on August 2009 projections. A window of about 50% in total acid was found between acceptable nitrite destruction and excessive hydrogen generation.

  8. Antioxidant activity and ACE-inhibitory of Class II hydrophobin from wild strain Trichoderma reesei.

    PubMed

    Khalesi, Mohammadreza; Jahanbani, Raheleh; Riveros-Galan, David; Sheikh-Hassani, Vahid; Sheikh-Zeinoddin, Mahmoud; Sahihi, Mehdi; Winterburn, James; Derdelinckx, Guy; Moosavi-Movahedi, Ali Akbar

    2016-10-01

    There are several possible uses of the Class II hydrophobin HFBII in clinical applications. To fully understand and exploit this potential however, the antioxidant activity and ACE-inhibitory potential of this protein need to be better understood and have not been previously reported. In this study, the Class II hydrophobin HFBII was produced by the cultivation of wild type Trichoderma reesei. The crude hydrophobin extract obtained from the fermentation process was purified using reversed-phase liquid chromatography and the identity of the purified HFBII verified by MALDI-TOF (molecular weight: 7.2kDa). Subsequently the antioxidant activities of different concentrations of HFBII (0.01-0.40mg/mL) were determined. The results show that for HFBII concentrations of 0.04mg/mL and upwards the protein significantly reduced the presence of ABTS(+) radicals in the medium, the IC50 value found to be 0.13mg/mL. Computational modeling highlighted the role of the amino acid residues located in the conserved and exposed hydrophobic patch on the surface of the HFBII molecule and the interactions with the aromatic rings of ABTS. The ACE-inhibitory effect of HFBII was found to occur from 0.5mg/mL and upwards, making the combination of HFBII with strong ACE-inhibitors attractive for use in the healthcare industry. PMID:27211298

  9. {sup 129}I Interlaboratory comparison: phase I and phase II

    SciTech Connect

    Caffee, M W; Roberts, M L

    1999-09-30

    An interlaboratory comparison exercise for {sup 129}I was organized and conducted. Nine laboratories participated in the exercise to either a full or limited extent. In Phase I of the comparison, 11 samples were measured. The suite of samples contained both synthetic ''standard type'' materials (i.e., AgI) and environmental materials. The isotopic {sup 129}I/{sup 127}I ratios of the samples varied from 10{sup {minus}8} to 10{sup {minus}14}. In this phase, each laboratory was responsible for its own chemical preparation of the samples. In Phase I, the {sup 129}I AMS measurements for prepared AgI were in good agreement. However, large discrepancies were seen in {sup 129}I AMS measurements of environmental samples. Because of the large discrepancies seen in the Phase I {sup 129}I intercomparison, a subsequent study was conducted. In Phase II of the {sup 129}I intercomparison, three separate laboratories prepared AgI from two environmental samples (IAEA 375 soil and maples leaves). Each laboratory used its own chemical preparation method with each of the methods being distinctly different. The resulting six samples (two sets of three) were then re-distributed to the participating {sup 129}I AMS facilities and {sup 129}I/{sup 127}I ratios measured. Results and discussion of both the Phase I and Phase II interlaboratory comparison are presented.

  10. 129I interlaboratory comparison: phase I and phase II results

    SciTech Connect

    Roberts, M.I.; Caffee, M.W.; Proctor, I.D.

    1997-07-01

    An interlaboratory comparison exercise for 129I was organized and conducted. A total of nine laboratories participated in the exercise to either a full or limited extent. In Phase I of the comparison, a suite of 11 samples were measured. The suite of samples contained both synthetic `standard type` materials (i.e., AgI) and environmental materials. The isotopic 129I/127I ratios of the samples varied from 10`-8 to 10`-14. In this phase, each laboratory was responsible for its own chemical preparation of the environmental samples. The 129I AMS measurements obtained at different laboratories for prepared AgI were in good agreement. However, large discrepancies were seen in 129I AMS measurements of environmental samples. Because of the large discrepancies seen in the Phase I intercomparison, a subsequent study was conducted. In Phase II of the comparison, AgI was prepared from two environmental samples (IAEA 375 soil and maples leaves) by three separate laboratories. Each laboratory used its own chemical preparation method with each of the methods being distinctly different. The resulting six samples (two sets of three) were then redistributed to the participating 129I AMS facilities and 129I/127I ratios measured. Results and discussion of both the Phase I and Phase II interlaboratory comparison are presented.

  11. The Long Valley Well: Phase II operations

    SciTech Connect

    Finger, J.T.

    1992-01-01

    Phase II of the Long Valley Exploratory Well was completed to a depth of 7588 feet in November 1991. The drilling comprised two sub-phases: (1) drilling 17-1/2 inch hole from the Phase I casing shoe at 2558 feet to a depth of 7130 feet, plugging back to 6826 feet, and setting 13-3/8 inch casing at 6825 feet, all during August--September 1991; and (2) returning in November to drill a 3.85-inch core hole deviated out of the previous wellbore at 6868 feet and extending to 7588 feet. Ultimate depth of the well is planned to be 20,000 feet, or at a bottomhole temperature of 500{degrees}C, whichever comes first. Total cost of this drilling phase was approximately $2.3 million, and funding was shared about equally between the California Energy Commission and the Department of Energy. Phase II scientific work will commence in July 1992 and will be supported by DOE Office of Basic Energy Sciences, DOE Geothermal Division, and other funding sources.

  12. The Long Valley Well - Phase II Operations

    SciTech Connect

    Finger, John T.

    1992-03-24

    Phase II of the Long Valley Exploratory Well was completed to a depth of 7588 feet in November 1991. The drilling comprised two sub-phases: (1) drilling 17-1/2 inch hole from the Phase I casing shoe at 2558 feet to a depth of 7130 feet, plugging back to 6826 feet, and setting 13-3/8 inch casing at 6825 feet, all during August-September 1991; and (2) returning in November to drill a 3.85-inch core hole deviated out of the previous wellbore at 6808 feet and extending to 7588 feet. Ultimate depth of the well is planned to be 20,000 feet, or at a bottomhole temperature of 500 C, whichever comes first. Total cost of this drilling phase was approximately $2.3 million, and funding was shared about equally between the California Energy Commission and the Department of Energy. Phase II scientific work will commence in July 1992 and will be supported by DOE Office of Basic Energy Sciences, DOE Geothermal Division, and other funding sources.

  13. Robotic dry stripping of airframes - Phase II

    NASA Astrophysics Data System (ADS)

    Pauli, Robert A.; Wittenberg, Art M.

    1989-03-01

    This paper describes a program for the development of a dust-free closed-cycle robotic system for dry stripping of airframes, designed to insure dust-free work environment and reduce plastic-media loss, the contamination risk, and the media inventory requirement. Phase I of the program involved building a prototype of the proposed robotic arm and its dust enclosure to prove basic automation concepts, showing reasonable paint removal rate from a curved surface, and establishing that the process is dust-free and recovers plastic media in a closed-cycle fashion. This paper contains calculations on the effect of different blasting parameters in order to determine optimum values required for the completion of Phase I. Also presented is the progress achieved by the Phase II of the program, which is to prove the total concept by building the complete system and demonstrating its capability.

  14. Phase II enzyme induction by a carotenoid, lutein, in a PC12D neuronal cell line.

    PubMed

    Miyake, Seiji; Kobayashi, Saori; Tsubota, Kazuo; Ozawa, Yoko

    2014-04-01

    The mechanism by which lutein, a carotenoid, acts as an antioxidant in retinal cells is still not fully understood. Here, lutein treatment of a neuronal cell line (PC12D) immediately resulted in reduced intracellular ROS levels, implying that it has a direct role in ROS scavenging. Significantly, lutein treatment also induced phase II antioxidative enzyme expression, probably via a nuclear factor-like 2 (Nrf2) independent pathway. This latter mechanism could explain why lutein acts diversely to protect against oxidative/cytotoxic stress, and why it is physiologically involved in the human neural tissue, such as the retina.

  15. EIS issued for Unocal Phase II expansion

    SciTech Connect

    Not Available

    1986-09-01

    The draft Environmental Impact Statement discusses the impacts of construction and operation of an 80,000 barrels per day expansion of Union's completed Phase I oil shale project at Parachute Creek, Colorado. With the demise of the United States Synthetic Fuels Corporation, there is, of course, no chance that the project will proceed under current economic conditions. If and when the project is able to proceed, the EIS indicates that it would be possible without exceeding the allowable PSD increments for air quality. This paper describes the proposed Phase II, which includes a new room and pillar mine, new surface retorting facilities, water supply system, synthetic crude pipelines, retorted shale disposal systems, and associated housing, roads, and power supplies. Summaries of the environmental impacts are given.

  16. Spray Forming Aluminum - Final Report (Phase II)

    SciTech Connect

    D. D. Leon

    1999-07-08

    The U.S. Department of Energy - Office of Industrial Technology (DOE) has an objective to increase energy efficient and enhance competitiveness of American metals industries. To support this objective, ALCOA Inc. entered into a cooperative program to develop spray forming technology for aluminum. This Phase II of the DOE Spray Forming Program would translate bench scale spray forming technology into a cost effective world class process for commercialization. Developments under DOE Cooperative Agreement No. DE-FC07-94ID13238 occurred during two time periods due to budgetary constraints; April 1994 through September 1996 and October 1997 and December 1998. During these periods, ALCOA Inc developed a linear spray forming nozzle and specific support processes capable of scale-up for commercial production of aluminum sheet alloy products. Emphasis was given to alloys 3003 and 6111, both being commercially significant alloys used in the automotive industry. The report reviews research performed in the following areas: Nozzel Development, Fabrication, Deposition, Metal Characterization, Computer Simulation and Economics. With the formation of a Holding Company, all intellectual property developed in Phases I and II of the Project have been documented under separate cover for licensing to domestic producers.

  17. Measurement of antioxidant activity and antioxidant compounds under versatile extraction conditions: II. The immuno-biochemical antioxidant properties of black sour cherry (Prunus cerasus) extracts.

    PubMed

    Haddad, John J; Ghadieh, Rana M; Hasan, Hiba A; Nakhal, Yasmine K; Hanbali, Lama B

    2013-01-01

    Retrospectively, we have measured the antioxidant activity and a variety of antioxidant compounds under versatile extraction conditions of sweet cherry (Prunus avium) extracts. Further in this study, in order to understand the biochemical constituents and antioxidant activities of a variety of extracts of black sour cherries (P. cerasus), a related species, antioxidant compounds, including L-ascorbic acid (vitamin C), phenols, flavonoids, and anthocyanins, and the total antioxidant activity were simultaneously measured under varying extraction conditions (mild heating and brief microwave exposure) for: i) whole juice extracts (WJE), ii) methanol-extracted juice (MEJ), iii) ddH2O-extracted pomace (dPOM), and iv) methanol-extracted pomace (mPOM). The antioxidant activity for WJE was substantially increased with mild and prolonged exposure to either heating or microwave, such that the % inhibition against 2,2-diphenyl-1-bspicrylhydrazyl (DPPH) followed a positive correlation (heating, 5-20 min.; microwave, 1-2 min.), insignificant with MEJ and dPOM, whereas with mPOM there was sharp downregulation. L-Ascorbic acid content was not affected with mild to prolonged heating or microwave exposure (WEJ and mPOM), except a mild increase with MEJ and dPOM. Similarly, total phenols assessed showed no significant variations, as compared with control extracts, except a mild decrease with exposure for mPOM. In a manner similar to L-ascorbic acid, total flavonoid content was increased under varying conditions for WEJ and MEJ, and slightly decreased for dPOM and mPOM. On the other hand, anthocyanins showed differential variations with exposure (up- and downregulation). Assessment of extraction means as compared with WJE revealed sharp increase in the antioxidant activity for MEJ, dPOM and mPOM, significant increase in L-ascorbic acid, total phenol, and flavonoid contents for MEJ, dPOM and mPOM, and mild decrease in anthocyanin contents for MEJ, dPOM, and mPOM. These results

  18. Monorail bridge conveyor. Phase II report

    SciTech Connect

    Gonski, J

    1982-04-30

    This report covers the second phase of a four-phase contract to develop and test a roof hung monorail bridge conveyor coal haulage system working behind a continuous miner. Phase II covers the fabrication and assembly of all the components in making up the Monoral Bridge Conveyor System. The original concept presented had to be analyzed before final design could proceed. The analysis revealed that 24 ft. long bridge conveyor segments were the optimum length; the suspension system must have the vertical hinge point between bridges, the impact point of the coal transfer point and the suspension point itself, coincidental. The propulsion system is such that each bridge is self propelled in order to minimize side loading on the monorail. The conveyor belt drive is simple since it only has to drive one single 24 ft. conveyor. The entire assembly of twelve conveyors has been pre-tested in our Murfreesboro, Tennessee, shop. The electric circuit proved successful to operate from a manual control or automatically, and successfully proved the cycle of sequential strating and stopping.

  19. Induction of Phase 2 Antioxidant Enzymes by Broccoli Sulforaphane: Perspectives in Maintaining the Antioxidant Activity of Vitamins A, C, and E

    PubMed Central

    Boddupalli, Sekhar; Mein, Jonathan R.; Lakkanna, Shantala; James, Don R.

    2012-01-01

    Consumption of fruits and vegetables is recognized as an important part of a healthy diet. Increased consumption of cruciferous vegetables in particular has been associated with a decreased risk of several degenerative and chronic diseases, including cardiovascular disease and certain cancers. Members of the cruciferous vegetable family, which includes broccoli, Brussels sprouts, cauliflower, and cabbage, accumulate significant concentrations of glucosinolates, which are metabolized in vivo to biologically active isothiocyanates (ITCs). The ITC sulforaphane, which is derived from glucoraphanin, has garnered particular interest as an indirect antioxidant due to its extraordinary ability to induce expression of several enzymes via the KEAP1/Nrf2/ARE pathway. Nrf2/ARE gene products are typically characterized as Phase II detoxification enzymes and/or antioxidant (AO) enzymes. Over the last decade, human clinical studies have begun to provide in vivo evidence of both Phase II and AO enzyme induction by SF. Many AO enzymes are redox cycling enzymes that maintain redox homeostasis and activity of free radical scavengers such as vitamins A, C, and E. In this review, we present the existing evidence for induction of PII and AO enzymes by SF, the interactions of SF-induced AO enzymes and proposed maintenance of the essential vitamins A, C, and E, and, finally, the current view of genotypic effects on ITC metabolism and AO enzyme induction and function. PMID:22303412

  20. Low Noise Borehole Triaxial Seismometer Phase II

    SciTech Connect

    Kerr, James D; McClung, David W

    2006-11-06

    This report describes the preliminary design and the effort to date of Phase II of a Low Noise Borehole Triaxial Seismometer for use in networks of seismic stations for monitoring underground nuclear explosions. The design uses the latest technology of broadband seismic instrumentation. Each parameter of the seismometer is defined in terms of the known physical limits of the parameter. These limits are defined by the commercially available components, and the physical size constraints. A theoretical design is proposed, and a preliminary prototype model of the proposed instrument has been built. This prototype used the sensor module of the KS2000. The installation equipment (hole locks, etc.) has been designed and one unit has been installed in a borehole. The final design of the sensors and electronics and leveling mechanism is in process. Noise testing is scheduled for the last quarter of 2006.

  1. Busted Butte Phase II Excavation Analysis

    SciTech Connect

    J.W. Keifer

    2000-11-29

    The purpose of this analysis is to provide an engineering excavation and ground support design for the Busted Butte phase II mine back. The analysis will apply engineering practices and previous proven design methods for pillar design and ground support in accordance with applicable Integrated Safety Management principles and functions. The scope of this analysis is limited to the Busted Butte Test Facility. The intended use of this analysis is to provide testing excavation boundaries, ground support and pillar design input to drawing(s) to support test operations implementation. This design activity has been prepared under ''Technical Work Plan For Test Facilities Design FY01 Work Activities'' (TWP) (CRWMS M&O 2000b). No deviations from the TWP have been necessary for this analysis.

  2. Antioxidants

    MedlinePlus

    Antioxidants are man-made or natural substances that may prevent or delay some types of cell damage. Antioxidants are found in many foods, including fruits and ... are also available as dietary supplements. Examples of antioxidants include Beta-carotene Lutein Lycopene Selenium Vitamin A ...

  3. MesoNAM Verification Phase II

    NASA Technical Reports Server (NTRS)

    Watson, Leela R.

    2011-01-01

    The 45th Weather Squadron Launch Weather Officers use the 12-km resolution North American Mesoscale model (MesoNAM) forecasts to support launch weather operations. In Phase I, the performance of the model at KSC/CCAFS was measured objectively by conducting a detailed statistical analysis of model output compared to observed values. The objective analysis compared the MesoNAM forecast winds, temperature, and dew point to the observed values from the sensors in the KSC/CCAFS wind tower network. In Phase II, the AMU modified the current tool by adding an additional 15 months of model output to the database and recalculating the verification statistics. The bias, standard deviation of bias, Root Mean Square Error, and Hypothesis test for bias were calculated to verify the performance of the model. The results indicated that the accuracy decreased as the forecast progressed, there was a diurnal signal in temperature with a cool bias during the late night and a warm bias during the afternoon, and there was a diurnal signal in dewpoint temperature with a low bias during the afternoon and a high bias during the late night.

  4. Utility-based optimization of phase II/III programs.

    PubMed

    Kirchner, Marietta; Kieser, Meinhard; Götte, Heiko; Schüler, Armin

    2016-01-30

    Phase II and phase III trials play a crucial role in drug development programs. They are costly and time consuming and, because of high failure rates in late development stages, at the same time risky investments. Commonly, sample size calculation of phase III is based on the treatment effect observed in phase II. Therefore, planning of phases II and III can be linked. The performance of the phase II/III program crucially depends on the allocation of the resources to phases II and III by appropriate choice of the sample size and the rule applied to decide whether to stop the program after phase II or to proceed. We present methods for a program-wise phase II/III planning that aim at determining optimal phase II sample sizes and go/no-go decisions in a time-to-event setting. Optimization is based on a utility function that takes into account (fixed and variable) costs of the drug development program and potential gains after successful launch. The proposed methods are illustrated by application to a variety of scenarios typically met in oncology drug development.

  5. Toxic metals and antioxidants: Part II. The role of antioxidants in arsenic and cadmium toxicity.

    PubMed

    Patrick, Lyn

    2003-05-01

    Exposure to toxic metals has become an increasingly recognized source of illness worldwide. Both cadmium and arsenic are ubiquitous in the environment, and exposure through food and water as well as occupational sources can contribute to a well-defined spectrum of disease. The symptom picture of arsenic toxicity is characterized by dermal lesions, anemia, and an increased risk for cardiovascular disease, diabetes, and liver damage. Cadmium has a significant effect on renal function, and as a result alters bone metabolism, leading to osteoporosis and osteomalacia. Cadmium-induced genotoxicity also increases risk for several cancers. The mechanisms of arsenic- and cadmium-induced damage include the production of free radicals that alter mitochondrial activity and genetic information. The metabolism and excretion of these heavy metals depend on the presence of antioxidants and thiols that aid arsenic methylation and both arsenic and cadmium metallothionein-binding. S-adenosylmethionine, lipoic acid, glutathione, selenium, zinc, N-acetylcysteine (NAC), methionine, cysteine, alpha-tocopherol, and ascorbic acid have specific roles in the mitigation of heavy metal toxicity. Several antioxidants including NAC, zinc, methionine, and cysteine, when used in conjunction with standard chelating agents, can improve the mobilization and excretion of arsenic and cadmium.

  6. Phase II Final Scientific/Technical Report

    SciTech Connect

    Grigg, Reid; McPherson, Brian; Lee, Rober

    2011-08-01

    The Southwest Regional Partnership on Carbon Sequestration (SWP) one of seven regional partnerships sponsored by the U.S. Department of Energy (USDOE) carried out five field pilot tests in its Phase II Carbon Sequestration Demonstration effort, to validate the most promising sequestration technologies and infrastructure concepts, including three geologic pilot tests and two terrestrial pilot programs. This field testing demonstrated the efficacy of proposed sequestration technologies to reduce or offset greenhouse gas emissions in the region. Risk mitigation, optimization of monitoring, verification, and accounting (MVA) protocols, and effective outreach and communication were additional critical goals of these field validation tests. The program included geologic pilot tests located in Utah, New Mexico, Texas, and a region-wide terrestrial analysis. Each geologic sequestration test site was intended to include injection of a minimum of ~75,000 tons/year CO{sub 2}, with minimum injection duration of one year. These pilots represent medium- scale validation tests in sinks that host capacity for possible larger-scale sequestration operations in the future. These validation tests also demonstrated a broad variety of carbon sink targets and multiple value-added benefits, including testing of enhanced oil recovery and sequestration, enhanced coalbed methane production and a geologic sequestration test combined with a local terrestrial sequestration pilot. A regional terrestrial sequestration demonstration was also carried out, with a focus on improved terrestrial MVA methods and reporting approaches specific for the Southwest region.

  7. Phase Noise Measurement in PEP II and the Linac

    SciTech Connect

    Getaneh, Mesfin

    2003-09-05

    The Goal of this project is to provide a measurement of the phase of the radio frequency (RF) relative to electron beam traveling down the Stanford Linear Accelerator Center (SLAC). Because the Main Drive Line (MDL) supplies the RF drive and phase reference for the entire accelerator system, the phase accuracy and amount of phase noise present in the MDL are very critical to the functionality of the accelerator. Therefore, a Phase Noise Measurement System was built to measure the phase noise in the liner accelerator (Linac) and PEP II. The system was used to determine the stability of the PEP II RF reference system. In this project a low noise Phase Locked Loop system (PLL) was built to measure timing jitter about sub picoseconds level. The phase noise measured in Master Oscillator using PLL indicates that phase noise is low enough for PEP II to run.

  8. 40 CFR 790.52 - Phase II test rule.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 33 2013-07-01 2013-07-01 false Phase II test rule. 790.52 Section 790.52 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT... Modification of Test Rules § 790.52 Phase II test rule. (a) If EPA determines that the proposed study...

  9. 40 CFR 72.44 - Phase II repowering extensions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... (CONTINUED) PERMITS REGULATION Acid Rain Compliance Plan and Compliance Options § 72.44 Phase II repowering... the requirements of paragraph (a)(1)(i) of this section may include in the unit's Phase II Acid Rain... authority shall issue the Acid Rain portion of the operating permit including: (A) The approved...

  10. 40 CFR 72.44 - Phase II repowering extensions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) PERMITS REGULATION Acid Rain Compliance Plan and Compliance Options § 72.44 Phase II repowering... the requirements of paragraph (a)(1)(i) of this section may include in the unit's Phase II Acid Rain... authority shall issue the Acid Rain portion of the operating permit including: (A) The approved...

  11. 40 CFR 72.44 - Phase II repowering extensions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... (CONTINUED) PERMITS REGULATION Acid Rain Compliance Plan and Compliance Options § 72.44 Phase II repowering... the requirements of paragraph (a)(1)(i) of this section may include in the unit's Phase II Acid Rain... authority shall issue the Acid Rain portion of the operating permit including: (A) The approved...

  12. 40 CFR 72.44 - Phase II repowering extensions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... (CONTINUED) PERMITS REGULATION Acid Rain Compliance Plan and Compliance Options § 72.44 Phase II repowering... the requirements of paragraph (a)(1)(i) of this section may include in the unit's Phase II Acid Rain... authority shall issue the Acid Rain portion of the operating permit including: (A) The approved...

  13. Antioxidative effects of cinnamomi cortex: A potential role of iNOS and COX-II

    PubMed Central

    Chung, Jin-Won; Kim, Jeong-Jun; Kim, Sung-Jin

    2011-01-01

    Background: Cinnamomi cortex has wide varieties of pharmacological actions such as anti-inflammatory action, anti-platelet aggregation, and improving blood circulation. In this study, we tested to determine whether the Cinnamomi cortex extract has antioxidant activities. Materials and Methods: Antioxidative actions were explored by measuring free radical scavenging activity, NO levels, and reducing power. The mechanism of antioxidative action of Cinnamomi cortex was determined by measuring iNOS and COX-II expression in lipopolysaccharide (LPS) stimulated Raw cells. Results: Seventy percent methanolic extract of Cinnamomi cortex exerted significant 1,1-diphenyl--2--picrylhydrazyl (DPPH) free radicals and NO scavenging activities in a dose-dependent manner. More strikingly, the Cinnamomi cortex extract exerted dramatic reducing power activity (13-fold over control). Production of iNOS induced by LPS was significantly inhibited by the Cinnamomi cortex extract, suggesting that it inhibits NO production by suppressing iNOS expression. Additionally, COX-2 induced by LPS was dramatically inhibited by the Cinnamomi cortex extract. Conclusion: These results suggest that 70% methanolic extract of Cinnamomi cortex exerts significant antioxidant activity via inhibiting iNOS and COX-II induction. PMID:22262934

  14. Phase II enzyme induction by a carotenoid, lutein, in a PC12D neuronal cell line

    SciTech Connect

    Miyake, Seiji; Kobayashi, Saori; Tsubota, Kazuo; Ozawa, Yoko

    2014-04-04

    Highlights: • Lutein reduced ROS levels in a PC12D neuronal cell line. • Lutein induced mRNAs of phase II antioxidative enzymes in PC12D neuronal cells. • Lutein increased protein levels of HO-1, SOD2, and NQO-1 in PC12D neuronal cells. • Lutein had no effect on intranuclear Nrf2 levels in PC12D neuronal cells. • Lutein did not activate potential upstream Nrf2 nuclear translocation pathways. - Abstract: The mechanism by which lutein, a carotenoid, acts as an antioxidant in retinal cells is still not fully understood. Here, lutein treatment of a neuronal cell line (PC12D) immediately resulted in reduced intracellular ROS levels, implying that it has a direct role in ROS scavenging. Significantly, lutein treatment also induced phase II antioxidative enzyme expression, probably via a nuclear factor-like 2 (Nrf2) independent pathway. This latter mechanism could explain why lutein acts diversely to protect against oxidative/cytotoxic stress, and why it is physiologically involved in the human neural tissue, such as the retina.

  15. Effects of Hg(II) exposure on MAPK phosphorylation and antioxidant system in D. melanogaster.

    PubMed

    Paula, M T; Zemolin, A P; Vargas, A P; Golombieski, R M; Loreto, E L S; Saidelles, A P; Picoloto, R S; Flores, E M M; Pereira, A B; Rocha, J B T; Merritt, T J S; Franco, J L; Posser, T

    2014-06-01

    The heavy metal mercury is a known toxin, but while the mechanisms involved in mercury toxicity have been well demonstrated in vertebrates, little is known about toxicological effects of this metal in invertebrates. Here, we present the results of our study investigating the effects associated with exposure of fruit fly Drosophila melanogaster to inorganic mercury (HgCl2 ). We quantify survival and locomotor performance as well as a variety of biochemical parameters including antioxidant status, MAPK phosphorylation and gene expression following mercury treatment. Our results demonstrate that exposure to Hg(II) through diet induced mortality and affected locomotor performance as evaluated by negative geotaxis, in D. melanogaster. We also saw a significant impact on the antioxidant system including an inhibition of acetylcholinesterase (Ache), glutathione S-transferase (GST) and superoxide dismutase (SOD) activities. We found no significant alteration in the levels of mRNA of antioxidant enzymes or NRF-2 transcriptional factor, but did detect a significant up regulation of the HSP83 gene. Mercury exposure also induced the phosphorylation of JNK and ERK, without altering p38(MAPK) and the concentration of these kinases. In parallel, Hg(II) induced PARP cleavage in a 89 kDa fragment, suggesting the triggering of apoptotic cell death in response to the treatment. Taken together, this data clarifies and extends our understanding of the molecular mechanisms mediating Hg(II) toxicity in an invertebrate model.

  16. Synthesis, characterization, and antioxidant/cytotoxic activity of new chromone Schiff base nano-complexes of Zn(II), Cu(II), Ni(II) and Co(II)

    NASA Astrophysics Data System (ADS)

    Saif, M.; El-Shafiy, Hoda F.; Mashaly, Mahmoud M.; Eid, Mohamed F.; Nabeel, A. I.; Fouad, R.

    2016-08-01

    A chromone Schiff base complexes of Zn(II) (1), Cu(II) (2), Ni(II) (3) and Co(II) (4) were successfully prepared in nano domain with crystalline or amorphous structures. The spectroscopic data revealed that the Schiff base ligand behaves as a monoanionic tridentate ligand. The metal complexes exhibited octahedral geometry. Transmission electron microscope (TEM) analysis showed that Cu(II) complex have aggregated nanospheres morphology. The obtained nano-complexes were tested as antioxidant and antitumor agents. The H2L and its Cu(II) complex (2) were found to be more potent antioxidant (IC50(H2L) = 0.93 μM; IC50(Cu(II) complex) = 1.1 μM than standard ascorbic acid (IC50 = 2.1 μM) as evaluated by DPPH• method. The H2L and its complexes (1-4) were tested for their in vitro cytotoxicity against Ehrlich Ascites Carcinoma cell line (EAC). The Cu(II) nano-complex (2) effectively inhibited EAC growth with IC50 value of 47 μM in comparison with its parent compound and other prepared complexes. The high antioxidant activity and antitumor activity of Cu(II) nano-complex (2) were attributed to their chemical structure, Cu(II) reducing capacity, and nanosize property. The toxicity test on mice showed that Zn(II) (1) and Cu(II) (2) nano-complex have lower toxicity than the standard cis-platin.

  17. BADD phase II: DDS information management architecture

    NASA Astrophysics Data System (ADS)

    Stephenson, Thomas P.; DeCleene, Brian T.; Speckert, Glen; Voorhees, Harry L.

    1997-06-01

    The DARPA Battlefield Awareness and Data Dissemination (BADD) Phase II Program will provide the next generation multimedia information management architecture to support the warfighter. One goal of this architecture is proactive dissemination of information to the warfighter through strategies such as multicast and 'smart push and pull' designed to minimize latency and make maximum use of available communications bandwidth. Another goal is to support integration of information from widely distributed legacy repositories. This will enable the next generation of battlefield awareness applications to form a common operational view of the battlefield to aid joint service and/or multi-national peacekeeping forces. This paper discusses the approach we are taking to realize such an architecture for BADD. Our architecture and its implementation, known as the Distributed Dissemination Serivces (DDS) are based on two key concepts: a global database schema and an intelligent, proactive caching scheme. A global schema provides a common logical view of the information space in which the warfighter operates. This schema (or subsets of it) is shared by all warfighters through a distributed object database providing local access to all relevant metadata. This approach provides both scalability to a large number of warfighters, and it supports tethered as well as autonomous operations. By utilizing DDS information integration services that provide transparent access to legacy databases, related information from multiple 'stovepipe' systems are now available to battlefield awareness applications. The second key concept embedded in our architecture is an intelligent, hierarchical caching system supported by proactive dissemination management services which push both lightweight and heavyweight data such as imagery and video to warfighters based on their information profiles. The goal of this approach is to transparently and proactively stage data which is likely to be requested by

  18. Modular microfluidic system for emulation of human phase I/phase II metabolism.

    PubMed

    Kampe, Thomas; König, Anna; Schroeder, Hendrik; Hengstler, Jan G; Niemeyer, Christof M

    2014-03-18

    We present a microfluidic device for coupled phase I/phase II metabolic reactions in vitro. The chip consists of microchannels, which are used as packed bed reactor compartments, filled with superparamagnetic microparticles bearing recombinant microsomal phase I cytochrome P450 or phase II conjugating enzymes (UDP-glucuronosyltransferase). Online coupling of the microfluidic device with LC/MS enabled the quantitative assessment of coupled phase I/phase II transformations, as demonstrated for two different substrates, 7-benzyloxy-4-trifluoromethylcoumarin (BFC) and dextromethorphan (DEX). In contrast, conventional sequential one-pot incubations did not generate measurable amounts of phase II metabolites. Because the microfluidic device is readily assembled from standard parts and can be equipped with a variety of recombinant enzymes, it provides a modular platform to emulate and investigate hepatic metabolism processes, with particular potential for targeted small-scale synthesis and identification of metabolites formed by sequential action of specific enzymes. PMID:24597510

  19. Polyphenolic flavanols as scavengers of aqueous phase radicals and as chain-breaking antioxidants.

    PubMed

    Salah, N; Miller, N J; Paganga, G; Tijburg, L; Bolwell, G P; Rice-Evans, C

    1995-10-01

    The purpose of this investigation was to establish the relative antioxidant activities in vitro of the flavanolic polyphenols, the catechins, and catechin-gallate esters. The relative antioxidant potentials were measured against radicals generated in the aqueous phase and against propagating lipid peroxyl radicals. The results show that in the aqueous phase their order of effectiveness as radical scavengers is epicatechin gallate (ECG) > epigallocatechin gallate (EGCG) > epigallocatechin (EGC) > gallic acid (GA) > epicatechin congruent to catechin; against propagating lipid peroxyl radical species, epicatechin and catechin are as effective as ECG and EGCG, the least efficacious being EGC and GA. This is consistent with their relative abilities to protect against consumption of LDL alpha-tocopherol. The results are discussed in the context of the most relevant antioxidant constituents of green tea extracts.

  20. Digitizing Images for Curriculum 21: Phase II.

    ERIC Educational Resources Information Center

    Walker, Alice D.

    Although visual databases exist for the study of art, architecture, geography, health care, and other areas, readily accessible sources of quality images are not available for engineering faculty interested in developing multimedia modules or for student projects. Presented here is a brief review of Phase I of the Engineering Visual Database…

  1. Thermodynamics of mantle minerals - II. Phase equilibria

    NASA Astrophysics Data System (ADS)

    Stixrude, Lars; Lithgow-Bertelloni, Carolina

    2011-03-01

    We complete the development and description of a thermodynamic method for the computation of phase equilibria and physical properties of multiphase mantle assemblages. Our previous paper focused on the computation of physical properties. In this paper, our focus shifts to the phase equilibria. We further develop our theory to specify the ideal and excess contributions to solution properties and derive properties of multiphase assemblages. We discuss our global inversion strategy for determining the values of the free parameters in our theory and compare inverted parameter values with expectations based on scaling arguments. Comparisons between our method and experimental phase equilibria data encompass the pressure-temperature regime of Earth's mantle. Finally, we present applications of our method that illustrate how it may be used to explore the origins of mantle structure and mantle dynamics. Continuing rapid advances in experimental and theoretical petrology and mineral physics have motivated an expansion of the scope of our model via the addition of several new phases, and of the soda component: an appendix lists all parameters in our model and references to the experimental and theoretical studies that constrain them. Our algorithm for global minimization of the Gibbs free energy is embodied in a code called HeFESTo, and is detailed in a second appendix.

  2. Antioxidant-Based Phase-Change Thermal Interface Materials with High Thermal Stability

    NASA Astrophysics Data System (ADS)

    Aoyagi, Yasuhiro; Chung, D. D. L.

    2008-04-01

    This work provides phase-change thermal interface materials (TIMs) with high thermal stability and high heat of fusion. They are based on antioxidants mainly in the form of hydrocarbons with linear segments. The thermal stability is superior to paraffin wax and four commercial phase-change materials (PCMs). The use of 98.0 wt.% thiopropionate antioxidant (SUMILIZER TP-D) with 2.0 wt.% sterically half-hindered phenolic antioxidant (GA80) as the matrix and the use of 16 vol.% boron nitride particles as the solid component give a PCM with a 100°C lifetime indicator of 5.3 years, in contrast to 0.95 year or less for the commercial PCMs. The heat of fusion is much higher than those of commercial PCMs; the values for antioxidants with nonbranched molecular structures exceed that of wax; the value for one with a branched structure is slightly below that of wax. The phase-change properties are degraded by heating at 150°C much less than those of the commercial PCMs. The stability of the heat of fusion upon phase-change cycling is also superior. The viscosity is essentially unaffected by heating at 150°C. Commercial PCMs give slightly lower values of the thermal contact conductance for the case of rough (12 μm) mating surfaces, in spite of the lower values of the bond-line thickness.

  3. ADMX Phase II : Relocation and Millikelvin Cooling

    NASA Astrophysics Data System (ADS)

    Heilman, Jesse; Tracy, Kyle

    2010-08-01

    Low mass axions are an attractive candidate for making up dark matter. While there are several models for how the Axion couples with other matter, were they to be the majority of the local galactic dark matter halo, they would have a number density on the order of 1014 cm-3. The Axion Dark Matter eXperiment (ADMX) is a microwave cavity experiment searching for axion Dark Matter via the axion's electromagnetic coupling. While the original ADMX did not see evidence of axions, the experiment is planned to go through two phases of upgrades to expand its sensitivity and provide a definitive search for axion dark matter. The first phase established the use of a SQUID amplifier which can reduce the amplifier noise temperature to the 100 mK range. In the second phase we will first move the experiment from LLNL to CENPA at the University of Washington. Once the experiment has been moved successfully we will install a dilution refrigerator to cool the cavity to the 100 mK range thus increasing the sensititivity to the level required to scan the remainder of the allowed model space.

  4. The chemical inducibility of mouse cardiac antioxidants and phase 2 enzymes in vivo.

    PubMed

    Cao, Zhuoxiao; Li, Yunbo

    2004-05-14

    The recognition of the critical involvement of oxidative and electrophilic stress in cardiac disorders has led to extensive investigation of the protective effects of exogenous antioxidants on cardiac injury. On the other hand, another strategy for protecting against oxidative/electrophilic cardiac injury may be through induction of the endogenous antioxidants and phase 2 enzymes in myocardium by chemical inducers. However, our understanding of the chemical inducibility of cardiac antioxidants/phase 2 enzymes in vivo is very limited. In addition, careful studies on the basal levels of a scope of endogenous antioxidants/phase 2 enzymes in myocardium as compared with other tissues, such as liver, are lacking. Accordingly, this study was undertaken to determine the basal levels of endogenous antioxidants/phase 2 enzymes, including superoxide dismutase (SOD), catalase, reduced glutathione (GSH), GSH peroxidase (GPx), glutathione reductase (GR), GSH S-transferase (GST), and NAD(P)H:quinone oxidoreductase 1 (NQO1), and investigate the inducibility of the above antioxidants/phase 2 enzymes by the chemoprotectant, 1,2-dithiole-3-thione (D3T), in cardiac as well as hepatic tissues in C57BL/6 mice. Our results demonstrated that in C57BL/6 mice, the levels of catalase, GSH, GPx, GR, and GST were significantly lower in cardiac tissue than in hepatic tissue. The level of total SOD did not differ significantly between mouse heart and liver. Notably, heart contained a much higher NQO1 activity than liver. Immunoblotting and RT-PCR analyses further demonstrated the high expression of NQO1 protein and mRNA in myocardium. Oral administration of D3T at 0.25 and 0.5 mmol/kg body weight for 3 consecutive days resulted in a significant induction of cardiac SOD, catalase, GR, GST, and NQO1. No significant induction of cardiac GSH and GPx was observed with the above D3T treatment. Only GR, GST, and NQO1 in mouse liver were induced by the D3T treatment. Unexpectedly, we observed a

  5. Nucleoside-2',3'/3',5'-bis(thio)phosphate antioxidants are also capable of disassembly of amyloid beta42-Zn(ii)/Cu(ii) aggregates via Zn(ii)/Cu(ii)-chelation.

    PubMed

    Hevroni, Bosmat Levi; Major, Dan Thomas; Dixit, Mudit; Mhashal, Anil Ranu; Das, Susanta; Fischer, Bilha

    2016-05-18

    Currently, there is an urgent need for biocompatible metal-ion chelators capable of antioxidant activity and disassembly of amyloid beta (Aβ)-aggregates as potential therapeutics for Alzheimer's disease (AD). We recently demonstrated the promising antioxidant activity of adenine/guanine 2',3' or 3',5'-bis(thio)phosphate analogues, 2'-dA/G3'5'PO/S and A2'3'PO/S, and their affinity to Zn(ii)-ions. These findings encouraged us to evaluate them as agents for the dissolution of Aβ42-Zn(ii)/Cu(ii) aggregates. Specifically, we explored their ability to bind Cu(ii)/Zn(ii)-ions, the geometry and stoichiometry of these complexes, Cu(ii)/Zn(ii)-binding-sites and binding mode, and the ability of these analogues to dissolve Aβ42-Zn(ii)/Cu(ii) aggregates, as well as their effect on the secondary structure of those aggregates. Finally, we identified the most promising agents for dissolution of Aβ42-Zn(ii)/Cu(ii) aggregates. Specifically, we observed the formation of a 1 : 1 complex between 2'-dG3'5'PO and Cu(ii), involving O4 ligands. Zn(ii) was coordinated by both thiophosphate groups of 2'-dA3'5'PS and A2'3'PS involving O2S2 ligands in a 1 : 1 stoichiometry. A2'3'PS dissolves Aβ42-Zn(ii) and Aβ42-Cu(ii) aggregates as effectively as, and 2.5-fold more effectively than EDTA, respectively. Furthermore, 2'-dG3'5'PS and A2'3'PS reverted the Aβ42-M(ii) structure, back to that of the free Aβ42. Finally, cryo-TEM and TEM images confirmed the disassembly of Aβ42 and Aβ42-M(ii) aggregates by A2'3'PS. Hence, 2'-dG3'5'PS and A2'3'PS may serve as promising scaffolds for new AD therapeutics, acting as both effective antioxidants and agents for solubilization of Aβ42-Cu(ii)/Zn(ii) aggregates. PMID:27109038

  6. Nucleoside-2',3'/3',5'-bis(thio)phosphate antioxidants are also capable of disassembly of amyloid beta42-Zn(ii)/Cu(ii) aggregates via Zn(ii)/Cu(ii)-chelation.

    PubMed

    Hevroni, Bosmat Levi; Major, Dan Thomas; Dixit, Mudit; Mhashal, Anil Ranu; Das, Susanta; Fischer, Bilha

    2016-05-18

    Currently, there is an urgent need for biocompatible metal-ion chelators capable of antioxidant activity and disassembly of amyloid beta (Aβ)-aggregates as potential therapeutics for Alzheimer's disease (AD). We recently demonstrated the promising antioxidant activity of adenine/guanine 2',3' or 3',5'-bis(thio)phosphate analogues, 2'-dA/G3'5'PO/S and A2'3'PO/S, and their affinity to Zn(ii)-ions. These findings encouraged us to evaluate them as agents for the dissolution of Aβ42-Zn(ii)/Cu(ii) aggregates. Specifically, we explored their ability to bind Cu(ii)/Zn(ii)-ions, the geometry and stoichiometry of these complexes, Cu(ii)/Zn(ii)-binding-sites and binding mode, and the ability of these analogues to dissolve Aβ42-Zn(ii)/Cu(ii) aggregates, as well as their effect on the secondary structure of those aggregates. Finally, we identified the most promising agents for dissolution of Aβ42-Zn(ii)/Cu(ii) aggregates. Specifically, we observed the formation of a 1 : 1 complex between 2'-dG3'5'PO and Cu(ii), involving O4 ligands. Zn(ii) was coordinated by both thiophosphate groups of 2'-dA3'5'PS and A2'3'PS involving O2S2 ligands in a 1 : 1 stoichiometry. A2'3'PS dissolves Aβ42-Zn(ii) and Aβ42-Cu(ii) aggregates as effectively as, and 2.5-fold more effectively than EDTA, respectively. Furthermore, 2'-dG3'5'PS and A2'3'PS reverted the Aβ42-M(ii) structure, back to that of the free Aβ42. Finally, cryo-TEM and TEM images confirmed the disassembly of Aβ42 and Aβ42-M(ii) aggregates by A2'3'PS. Hence, 2'-dG3'5'PS and A2'3'PS may serve as promising scaffolds for new AD therapeutics, acting as both effective antioxidants and agents for solubilization of Aβ42-Cu(ii)/Zn(ii) aggregates.

  7. Continuous fiber ceramic composites. Phase II - Final report

    SciTech Connect

    Bird, James

    1997-10-31

    This report documents Atlantic Research Corporation's (ARC) Phase 11 effort on the Department of Energy's (DOE) Continuous Fiber Ceramic Composite (CFCC) program. This project is supported by the DOE cooperative agreement DE-FCO2-92CE40998. Such DOE support does not constitute an endorsement of the views expressed in this report. ARC'S CFCC Phase II effort began during October 1993 and was suspended in March of 1997 when, for business considerations, ARC closed the Amercom operation. This report covers progress from Phase II program inception through Amercom closure. ARC'S Phase II effort built upon the results of the Phase I Applications Assessment and Process Engineering developments to produce CFCC test components for end-user evaluation. Initially, the Phase 11 effort planned to develop and produce three CFCC components: CFCC compression rings for stationary diesel engines, CFCC hot gas fans for industrial furnace applications, and CFCC hot gas filters for current and advanced coal fired power cycles. As the program progressed, the development effort for the diesel engine piston rings was suspended. This decision was based on technical issues, cost factors and reduced program funding; the status of CFCC diesel engine piston ring development will be discussed in detail in section 2.2.1.

  8. Alberta Education Energy Conservation Project. Phase II: Internal Evaluation.

    ERIC Educational Resources Information Center

    Sundmark, Dana

    This report is based on the Alberta Education Energy Conservation Project - Phase II. The project was a follow-up to an earlier study, extending from June 1980 to June 1983, in which government funding and engineering manpower were used to conduct an energy management program in 52 selected pilot schools in 5 areas of the province. The report…

  9. Interservice Procedures for Instructional Systems Development. Phase II: Design.

    ERIC Educational Resources Information Center

    Branson, Robert K.; And Others

    The document is the second of a five-part series focusing in minute detail on the processes involved in the formulation of an instructional systems development (ISD) program for military interservice training that will adequately train individuals to do a particular job. Phase II, Design, is concerned with designing instructional materials based…

  10. Synthesis, characterization, molecular modeling and antioxidant activity of (1E,5E)-1,5-bis(1-(pyridin-2-yl)ethylidene)carbonohydrazide (H2APC) and its zinc(II), cadmium(II) and mercury(II) complexes

    NASA Astrophysics Data System (ADS)

    El-Gammal, O. A.; Abu El-Reash, G. M.; Ghazy, S. E.; Radwan, A. H.

    2012-08-01

    A new series of Zn(II), Cd(II) and Hg(II) complexes of (1E,5E)-1,5-bis(1-(pyridin-2-yl)ethylidene)carbonohydrazide (H2APC) have been prepared and characterized by elemental analyses, spectral (IR, UV-visible, mass and 1H NMR) as well as magnetic and thermal measurements. The data revealed that the ligand acts a monobasic hexadentate, neutral tri- and monodentate in Zn(II), Cd(II) and Hg(II) complexes, respectively. An octahedral geometry is proposed for Zn(II) complex, a trigonal bi-pyramid for Cd(II) complex and a tetrahedral one for Hg(II) complex. The bond length, bond angle, HOMO, LUMO and charges on the atoms have been calculated to confirm the geometry of the ligand and the investigated complexes using material studio program. Kinetic parameters were determined for each thermal degradation stage of some complexes using Coats-Redfern and Horowitz-Metzger methods. The antioxidant, anti-hemolytic, and cytotoxic activities of the compounds have been screened. H2APC showed moderate antioxidant activity using ABTS and DPPH methods. With respect to erythrocyte hemolysis and in vitro Ehrlich ascites assay, H2APC exhibited the potent antioxidative activity followed by Cd(II) and Zn(II) complexes while Hg(II) complex showed very weak activity.

  11. 78 FR 30951 - SBIR/STTR Phase I to Phase II Transition Benchmarks

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-23

    ... INFORMATION: Section 4(a)(3)(iii) of the SBIR Policy Directive (77 FR 46806) and the STTR Policy Directive (77 FR 46855) require each agency to establish an SBA-approved Phase I-Phase II Transition Rate benchmark... benchmarks can take effect. As a result, on October 16, 2012, at 77 FR 63410, SBA published the...

  12. Effects of ethylene on photosystem II and antioxidant enzyme activity in Bermuda grass under low temperature.

    PubMed

    Hu, Zhengrong; Fan, Jibiao; Chen, Ke; Amombo, Erick; Chen, Liang; Fu, Jinmin

    2016-04-01

    The phytohormone ethylene has been reported to mediate plant response to cold stress. However, it is still debated whether the effect of ethylene on plant response to cold stress is negative or positive. The objective of the present study was to explore the role of ethylene in the cold resistance of Bermuda grass (Cynodon dactylon (L).Pers.). Under control (warm) condition, there was no obvious effect of the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC) or the antagonist Ag(+) of ethylene signaling on electrolyte leakage (EL) and malondialdehyde (MDA) content. Under cold stress conditions, ACC-treated plant leaves had a greater level of EL and MDA than the untreated leaves. However, the EL and MDA values were lower in the Ag(+) regime versus the untreated. In addition, after 3 days of cold treatment, ACC remarkably reduced the content of soluble protein and also altered antioxidant enzyme activity. Under control (warm) condition, there was no significant effect of ACC on the performance of photosystem II (PS II) as monitored by chlorophyll α fluorescence transients. However, under cold stress, ACC inhibited the performance of PS II. Under cold condition, ACC remarkably reduced the performance index for energy conservation from excitation to the reduction of intersystem electron acceptors (PI(ABS)), the maximum quantum yield of primary photochemistry (φP0), the quantum yield of electron transport flux from Q(A) to Q(B) (φE0), and the efficiency/probability of electron transport (ΨE0). Simultaneously, ACC increased the values of specific energy fluxes for absorption (ABS/RC) and dissipation (DI0/RC) after 3 days of cold treatment. Additionally, under cold condition, exogenous ACC altered the expressions of several related genes implicated in the induction of cold tolerance (LEA, SOD, POD-1 and CBF1, EIN3-1, and EIN3-2). The present study thus suggests that ethylene affects the cold tolerance of Bermuda grass by impacting the antioxidant system

  13. Study of phase I NOx control: Lessons learned for phase II NOx control strategies

    SciTech Connect

    Myers, B.

    1996-12-31

    Title IV of the Clean Air Act Amendments of 1990 (CAAA) is concerned with lowering the levels of acid rain in the USA. One of the contributions to acid rain is nitric oxides referred to as NO{sub x}. Title IV seeks NO{sub x} reductions from two groupings of utility steam generators. The first group, known as Phase I, was to have their reductions made by January 1, 1996. The purpose of this paper is to look back at Phase I to see what one can learn for use in Phase II compliance planning. Phase II units are scheduled to be in compliance by January 1, 2000. As such, this paper looks to answer four questions about Phase I units.

  14. Urban Integrated Industrial Cogeneration Systems Analysis. Phase II final report

    SciTech Connect

    Not Available

    1984-01-01

    Through the Urban Integrated Industrial Cogeneration Systems Analysis (UIICSA), the City of Chicago embarked upon an ambitious effort to identify the measure the overall industrial cogeneration market in the city and to evaluate in detail the most promising market opportunities. This report discusses the background of the work completed during Phase II of the UIICSA and presents the results of economic feasibility studies conducted for three potential cogeneration sites in Chicago. Phase II focused on the feasibility of cogeneration at the three most promising sites: the Stockyards and Calumet industrial areas, and the Ford City commercial/industrial complex. Each feasibility case study considered the energy load requirements of the existing facilities at the site and the potential for attracting and serving new growth in the area. Alternative fuels and technologies, and ownership and financing options were also incorporated into the case studies. Finally, site specific considerations such as development incentives, zoning and building code restrictions and environmental requirements were investigated.

  15. Small Business Innovation Research, Post-Phase II Opportunity Assessment

    NASA Technical Reports Server (NTRS)

    Nguyen, Hung D.; Steele, Gynelle C.

    2015-01-01

    This report outlines current Small Business Innovation Research (SBIR) Post-Phase II opportunity contract award results for the SBIR technology program from 2007 to 2011 for NASA's Aeronautics Research Mission Directorate (ARMD), Human Exploration and Operations Mission Directorate (HEOMD), Science Mission Directorate (SMD), and Space Technology Mission Directorate (STMD). The report provides guidelines for incorporating SBIR technology into NASA programs and projects and provides a quantitative overview of the post-Phase II award patterns that correspond with each mission directorate at NASA Glenn Research Center (GRC). In recent years, one of NASA's goals has been to not only transfer SBIR technologies to commercial industries, but to ensure that NASA mission directorates incorporate SBIR technologies into their program and project activities. Before incorporating technologies into MD programs, it is important to understand each mission directorate structure because each directorate has different objectives and needs. The directorate program structures follow.

  16. Microbial Dark Matter Phase II: Stepping deeper into unknown territory

    SciTech Connect

    Jarett, Jessica; Dunfield, Peter; Peura, Sari; Wielen, Paul van der; Hedlund, Brian; Elshahed, Mostafa; Kormas, Konstantinos; Stott, Andreas Teske8, Matt; Birkeland, Nils-Kare; Zhang, Chuanlun; Rengefors, Karin; Lindemann, Stephen; Ravin, Nikolai V.; Spear, John; Hallam, Steven; Crowe, Sean; Steele, Jillian; Goudeau, Danielle; Malmstrom, Rex; Kyrpides, Nikos; Stepanauskas, Ramunas; Woyke, Tanja

    2014-10-27

    Currently available microbial genomes are of limited phylogenetic breadth due to our historical inability to cultivate most microorganisms in the laboratory. The first phase of the Microbial Dark Matter project used single-cell genomics to sequence 201 single cells from uncultivated lineages, and was able to resolve new superphyla and reveal novel metabolic features in bacteria and archaea. However, many fundamental questions about the evolution and function of microbes remain unanswered, and many candidate phyla remain uncharacterized. Phase II of the Microbial Dark Matter project will target candidate phyla with no sequenced representatives at a variety of new sites using a combination of single-cell sequencing and shotgun metagenomics approaches.

  17. PWR steam generator chemical cleaning. Phase II. Final report

    SciTech Connect

    Not Available

    1980-01-01

    Two techniques believed capable of chemically dissolving the corrosion products in the annuli between tubes and support plates were developed in laboratory work in Phase I of this project and were pilot tested in Indian Point Unit No. 1 steam generators. In Phase II, one of the techniques was shown to be inadequate on an actual sample taken from an Indian Point Unit No. 2 steam generator. The other technique was modified slightly, and it was demonstrated that the tube/support plate annulus could be chemically cleaned effectively.

  18. OSAS Surgery and Postoperative Discomfort: Phase I Surgery versus Phase II Surgery

    PubMed Central

    Gasparini, Giulio; Pelo, Sandro; Foresta, Enrico; Boniello, Roberto; Romandini, Mario; Cervelli, Daniele; Azzuni, Camillo; Marianetti, Tito Matteo

    2015-01-01

    Introduction. This study aims to investigate the reasons that discourage the patients affected by OSAS to undergo orthognathic surgery and compares the postoperative discomfort of phase I (soft tissue surgery) and phase II (orthognathic surgery) procedures for treatment of OSAS. Material and Methods. A pool of 46 patients affected by OSAS was divided into two groups: “surgery patients” who accepted surgical treatments of their condition and “no surgery patients” who refused surgical procedures. The “surgery patients” group was further subdivided into two arms: patients who accepted phase I procedures (IP) and those who accepted phase II (IIP). To better understand the motivations behind the refusal of II phase procedures, we asked the patients belonging to both the IP group and “no surgery” group to indicate the main reason that influenced their decision to avoid II phase procedures. We also monitored and compared five parameters of postoperative discomfort: pain, painkiller assumption, length of hospitalization, foreign body sensation, and diet assumption following IP and IIP procedures. Results. The main reason to avoid IIP procedures was the concern of a more severe postoperative discomfort. Comparison of the postoperative discomfort following IP versus IIP procedures showed that the former scored worse in 4 out of 5 parameters analyzed. Conclusion. IIP procedures produce less postoperative discomfort. IIP procedures, namely, orthognathic surgery, should be the first choice intervention in patients affected by OSAS and dentoskeletal malformation. PMID:25695081

  19. Orally active antioxidative copper(II) aspirinate: synthesis, structure characterization, superoxide scavenging activity, and in vitro and in vivo antioxidative evaluations.

    PubMed

    Fujimori, T; Yamada, S; Yasui, H; Sakurai, H; In, Y; Ishida, T

    2005-12-01

    Ever since it was proposed that reactive oxygen species (ROS) are involved in the pathogeneses of various diseases, superoxide dismutase (SOD)-mimetic complexes have been intensively studied. We prepared copper(II) aspirinate [Cu2(asp)4] from Cu(II) and aspirin, which has been in use for many years as an antipyretic, an analgesic, and an anti-inflammatory agent. However, Cu2(asp)4 has been found to have additional activities, including anti-inflammatory, antiulcer, anti-ischemic/reperfusion agent, anticancer, antimutagenic, and antimicrobial activities. The activity of copper salicylate [Cu(sal)2] was also compared with that of Cu2(asp)4. The structure of the Cu2(asp)4 was determined using X-ray structure analysis. Its SOD-mimetic activity was determined using cytochrome c, electron spin resonance (ESR) spectroscopy, and ESR spin trap methods. The activity of Cu2(asp)4 was slightly greater than CuSO4 and copper acetate [Cu(ace)2] and slightly less than that of Cu(sal)2. The in vitro antioxidant activity, evaluated in human epithelial or transformed neoplastic keratinocyte cells, HaCaT, and normal dermal fibroblasts in terms of cell survival following ultraviolet B (UVB) irradiation, was significantly increased in the presence of Cu2(asp)4, Cu(sal)2, and CuSO4. Further, ROS generation following UVA irradiation in the skin of hairless mice following oral treatment with Cu2(asp)4 for three consecutive days was significantly suppressed compared to the vehicle- or Cu(ace)2-treated mice. On the basis of these results, Cu2(asp)4 was observed to be a potent antioxidative compound possessing antioxidative activity in biological systems. In conclusion, Cu2(asp)4 is a potent antioxidative agent that may be useful for future treatment of diseases resulting from ROS. PMID:16261369

  20. Solid phase extraction of lead (II), copper (II), cadmium (II) and nickel (II) using gallic acid-modified silica gel prior to determination by flame atomic absorption spectrometry.

    PubMed

    Xie, Fazhi; Lin, Xucong; Wu, Xiaoping; Xie, Zenghong

    2008-01-15

    The immobilization of gallic acid on the surface of amino group-containing silica gel phases for the formation of a newly chelating matrix (GASG) is described. The newly synthesized extractant, characterized by the diffuse reflectance infrared Fourier transformation spectroscopy and elemental analysis, was used to preconcentrate Pb(II), Cu(II), Cd(II) and Ni(II). The pH ranges for quantitative sorption and the concentrations of HCl for eluting Pb(II), Cd(II), Cu(II) and Ni(II) were opimized, respectively. The sorption capacity of the matrix has been found to be 12.63, 6.09, 15.38, 4.62mg/g for Pb(II), Cd(II), Cu(II) and Ni(II), respectively, with the preconcentration factor of approximately 200 ( approximately 100 for Cd(II)). The effects of flow rates, the eluants, the electrolytes and cations on the metal ions extraction, as well as the chelating matrix stability and reusability, were also studied. The extraction behavior of the matrix was conformed with Langmuir's equation. The present preconcentration and determination method was successfully applied to the analysis of synthetic metal mixture solution and river water samples. The 3sigma detection limit and 10sigma quantification limit for Pb(II), Cu(II), Cd(II) and Ni(II) were found to be 0.58, 0.86, 0.65, 0.92microg/L and 1.08, 1.23, 0.87, 1.26microg/L, respectively. PMID:18371717

  1. Type II Collagen and Gelatin from Silvertip Shark (Carcharhinus albimarginatus) Cartilage: Isolation, Purification, Physicochemical and Antioxidant Properties

    PubMed Central

    Jeevithan, Elango; Bao, Bin; Bu, Yongshi; Zhou, Yu; Zhao, Qingbo; Wu, Wenhui

    2014-01-01

    Type II acid soluble collagen (CIIA), pepsin soluble collagen (CIIP) and type II gelatin (GII) were isolated from silvertip shark (Carcharhinus albimarginatus) cartilage and examined for their physicochemical and antioxidant properties. GII had a higher hydroxyproline content (173 mg/g) than the collagens and cartilage. CIIA, CIIP and GII were composed of two identical α1 and β chains and were characterized as type II. Amino acid analysis of CIIA, CIIP and GII indicated imino acid contents of 150, 156 and 153 amino acid residues per 1000 residues, respectively. Differing Fourier transform infrared (FTIR) spectra of CIIA, CIIP and GII were observed, which suggested that the isolation process affected the secondary structure and molecular order of collagen, particularly the triple-helical structure. The denaturation temperature of GII (32.5 °C) was higher than that of CIIA and CIIP. The antioxidant activity against 1,1-diphenyl-2-picrylhydrazyl radicals and the reducing power of CIIP was greater than that of CIIA and GII. SEM microstructure of the collagens depicted a porous, fibrillary and multi-layered structure. Accordingly, the physicochemical and antioxidant properties of type II collagens (CIIA, CIIP) and GII isolated from shark cartilage were found to be suitable for biomedical applications. PMID:24979271

  2. Type II collagen and gelatin from silvertip shark (Carcharhinus albimarginatus) cartilage: isolation, purification, physicochemical and antioxidant properties.

    PubMed

    Jeevithan, Elango; Bao, Bin; Bu, Yongshi; Zhou, Yu; Zhao, Qingbo; Wu, Wenhui

    2014-07-01

    Type II acid soluble collagen (CIIA), pepsin soluble collagen (CIIP) and type II gelatin (GII) were isolated from silvertip shark (Carcharhinus albimarginatus) cartilage and examined for their physicochemical and antioxidant properties. GII had a higher hydroxyproline content (173 mg/g) than the collagens and cartilage. CIIA, CIIP and GII were composed of two identical α1 and β chains and were characterized as type II. Amino acid analysis of CIIA, CIIP and GII indicated imino acid contents of 150, 156 and 153 amino acid residues per 1000 residues, respectively. Differing Fourier transform infrared (FTIR) spectra of CIIA, CIIP and GII were observed, which suggested that the isolation process affected the secondary structure and molecular order of collagen, particularly the triple-helical structure. The denaturation temperature of GII (32.5 °C) was higher than that of CIIA and CIIP. The antioxidant activity against 1,1-diphenyl-2-picrylhydrazyl radicals and the reducing power of CIIP was greater than that of CIIA and GII. SEM microstructure of the collagens depicted a porous, fibrillary and multi-layered structure. Accordingly, the physicochemical and antioxidant properties of type II collagens (CIIA, CIIP) and GII isolated from shark cartilage were found to be suitable for biomedical applications. PMID:24979271

  3. Mercury Oxidation via Catalytic Barrier Filters Phase II

    SciTech Connect

    Wayne Seames; Michael Mann; Darrin Muggli; Jason Hrdlicka; Carol Horabik

    2007-09-30

    In 2004, the Department of Energy National Energy Technology Laboratory awarded the University of North Dakota a Phase II University Coal Research grant to explore the feasibility of using barrier filters coated with a catalyst to oxidize elemental mercury in coal combustion flue gas streams. Oxidized mercury is substantially easier to remove than elemental mercury. If successful, this technique has the potential to substantially reduce mercury control costs for those installations that already utilize baghouse barrier filters for particulate removal. Completed in 2004, Phase I of this project successfully met its objectives of screening and assessing the possible feasibility of using catalyst coated barrier filters for the oxidation of vapor phase elemental mercury in coal combustion generated flue gas streams. Completed in September 2007, Phase II of this project successfully met its three objectives. First, an effective coating method for a catalytic barrier filter was found. Second, the effects of a simulated flue gas on the catalysts in a bench-scale reactor were determined. Finally, the performance of the best catalyst was assessed using real flue gas generated by a 19 kW research combustor firing each of three separate coal types.

  4. Combined Analysis of Phase I and Phase II Data to Enhance the Power of Pharmacogenetic Tests.

    PubMed

    Tessier, A; Bertrand, J; Chenel, M; Comets, E

    2016-03-01

    We show through a simulation study how the joint analysis of data from phase I and phase II studies enhances the power of pharmacogenetic tests in pharmacokinetic (PK) studies. PK profiles were simulated under different designs along with 176 genetic markers. The null scenarios assumed no genetic effect, while under the alternative scenarios, drug clearance was associated with six genetic markers randomly sampled in each simulated dataset. We compared penalized regression Lasso and stepwise procedures to detect the associations between empirical Bayes estimates of clearance, estimated by nonlinear mixed effects models, and genetic variants. Combining data from phase I and phase II studies, even if sparse, increases the power to identify the associations between genetics and PK due to the larger sample size. Design optimization brings a further improvement, and we highlight a direct relationship between η-shrinkage and loss of genetic signal. PMID:27069775

  5. Preliminary Exploratory Study of Different Phase II Collimators

    SciTech Connect

    Lari, L.; Assmann, R.W.; Bertarelli, A.; Bracco, C.; Brugger, M.; Cerutti, F.; Dallocchio, A.; Ferrari, A.; Mauri, M.; Roesler, S.; Sarchiapone, L.; Vlachoudis, Vasilis; Doyle, J.E.; Keller, L.; Lundgren, S.A.; Markiewicz, Thomas W.; Smith, J.C.; Lari, L.; /LPHE, Lausanne

    2011-11-02

    The Large Hadron Collider (LHC) collimation system is installed and commissioned in different phases, following the natural evolution of the LHC performance. To improve cleaning efficiency towards the end of the low beta squeeze at 7TeV, and in stable physics conditions, it is foreseen to complement the 30 highly robust Phase I secondary collimators with low impedance Phase II collimators. At this stage, their design is not yet finalized. Possible options include metallic collimators, graphite jaws with a movable metallic foil, or collimators with metallic rotating jaws. As part of the evaluation of the different designs, the FLUKA Monte Carlo code is extensively used for calculating energy deposition and studying material damage and activation. This report outlines the simulation approach and defines the critical quantities involved.

  6. Cannabidiol Post-Treatment Alleviates Rat Epileptic-Related Behaviors and Activates Hippocampal Cell Autophagy Pathway Along with Antioxidant Defense in Chronic Phase of Pilocarpine-Induced Seizure.

    PubMed

    Hosseinzadeh, Mahshid; Nikseresht, Sara; Khodagholi, Fariba; Naderi, Nima; Maghsoudi, Nader

    2016-04-01

    Abnormal and sometimes severe behavioral and molecular symptoms are usually observed in epileptic humans and animals. To address this issue, we examined the behavioral and molecular aspects of seizure evoked by pilocarpine. Autophagy can promote both cell survival and death, but there are controversial reports about the neuroprotective or neurodegenerative effects of autophagy in seizure. Cannabidiol has anticonvulsant properties in some animal models when used as a pretreatment. In this study, we investigated alteration of seizure scores, autophagy pathway proteins, and antioxidant status in hippocampal cells during the chronic phase of pilocarpine-induced epilepsy after treatment with cannabidiol. Cannabidiol (100 ng, intracerebroventricular injection) delayed the chronic phase of epilepsy. Single administration of cannabidiol during the chronic phase of seizure significantly diminished seizure scores such as mouth clonus, head nodding, monolateral and bilateral forelimb clonus and increased the activity of catalase enzyme and reduced glutathione content. Such a protective effect in the behavioral scores of epileptic rats was also observed after repeated administrations of cannabidiol at the onset of the silent phase. Moreover, the amount of Atg7, conjugation of Atg5/12, Atg12, and LC3II/LC3I ratio increased significantly in epileptic rats treated with repeated injections of cannabidiol. In short, our results suggest that post-treatment of Cannabidiol could enhance the induction of autophagy pathway and antioxidant defense in the chronic phase of epilepsy, which could be considered as the protective mechanisms of cannabidiol in a temporal lobe epilepsy model.

  7. 48 CFR 1852.219-81 - Limitation on subcontracting-SBIR Phase II program.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... subcontracting-SBIR Phase II program. 1852.219-81 Section 1852.219-81 Federal Acquisition Regulations System... CLAUSES Texts of Provisions and Clauses 1852.219-81 Limitation on subcontracting—SBIR Phase II program. As prescribed in 1819.7302(b), insert the following clause: Limitation on Subcontracting—SBIR Phase II...

  8. 48 CFR 1852.219-81 - Limitation on subcontracting-SBIR Phase II program.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... subcontracting-SBIR Phase II program. 1852.219-81 Section 1852.219-81 Federal Acquisition Regulations System... CLAUSES Texts of Provisions and Clauses 1852.219-81 Limitation on subcontracting—SBIR Phase II program. As prescribed in 1819.7302(b), insert the following clause: Limitation on Subcontracting—SBIR Phase II...

  9. DNA interaction, antioxidant activity, and bioactivity studies of two ruthenium(II) complexes

    NASA Astrophysics Data System (ADS)

    Han, Bing-Jie; Jiang, Guang-Bin; Yao, Jun-Hua; Li, Wei; Wang, Ji; Huang, Hong-Liang; Liu, Yun-Jun

    2015-01-01

    Two new ruthenium(II) polypyridyl complexes [Ru(dmb)2(dcdppz)](ClO4)2 (1) and [Ru(bpy)2(dcdppz)](ClO4)2 (2) were prepared and characterized. The crystal structure of the complex 2 was solved by single crystal X-ray diffraction. The complex crystallizes in the monoclinic system, space group P21/n with a = 12.9622(14) Å, b = 17.1619(19) Å, c = 22.7210(3) Å, β = 100.930(2)°, R = 0.0536, Rω = 0.1111. The DNA-binding constants for complexes 1 and 2 were determined to be 1.92 × 105 (s = 1.72) and 2.24 × 105 (s = 1.86) M-1, respectively. The DNA-binding behaviors showed that complexes 1 and 2 interact with DNA by intercalative mode. The antioxidant activities of the ligand and the complexes were performed. Ligand, dcdppz, has no cytotoxicity against the selected cell lines. Complex 1 shows higher cytotoxicity than complex 2, but lower than cisplatin toward selected cell lines. The apoptosis and cell cycle arrest were investigated, and the apoptotic mechanism of BEL-7402 cells was studied by reactive oxygen species (ROS), mitochondrial membrane potential and western blot analysis. Complex 1 induces apoptosis in BEL-7402 cells through ROS-mediated mitochondrial dysfunction pathway and by regulating the expression of Bcl-2 family proteins.

  10. Physics Detector Simulation Facility Phase II system software description

    SciTech Connect

    Scipioni, B.; Allen, J.; Chang, C.; Huang, J.; Liu, J.; Mestad, S.; Pan, J.; Marquez, M.; Estep, P.

    1993-05-01

    This paper presents the Physics Detector Simulation Facility (PDSF) Phase II system software. A key element in the design of a distributed computing environment for the PDSF has been the separation and distribution of the major functions. The facility has been designed to support batch and interactive processing, and to incorporate the file and tape storage systems. By distributing these functions, it is often possible to provide higher throughput and resource availability. Similarly, the design is intended to exploit event-level parallelism in an open distributed environment.

  11. Phase II study of lonidamine in metastatic breast cancer.

    PubMed Central

    Pronzato, P.; Amoroso, D.; Bertelli, G.; Conte, P. F.; Cusimano, M. P.; Ciottoli, G. B.; Gulisano, M.; Lionetto, R.; Rosso, R.

    1989-01-01

    Thirty patients with previously treated metastatic breast cancer were entered in a phase II study with oral lonidamine. Twenty-eight patients are evaluable for toxicity and 25 for response. A partial remission was obtained in four patients (16%) and disease stability in 11 (44%): 10 patients progressed (40%). Toxicity was acceptable, consisting mainly of myalgias (39% of patients) and asthenia (21.4%). No myelotoxicity was observed. The drug is active in previously treated metastatic breast cancer and, because of its peculiar pattern of action and toxicity, deserves to be evaluated in combination with cytotoxic chemotherapy. PMID:2930690

  12. Randomized Phase II Trials: A Long-term Investment With Promising Returns

    PubMed Central

    Sharma, Manish R.; Stadler, Walter M.

    2011-01-01

    Given the multitude of novel anticancer drugs and the limited resources available to study them, phase II trials should identify drugs with the highest probability of succeeding in subsequent phase III trials. Currently, single-arm phase II trial results are interpreted relative to historical control subjects, introducing selection bias and confounding that may limit the validity of the conclusions. The rate of success (defined as a statistically significant difference between arms) in phase III oncology trials is only 40%, suggesting that current phase II trials are insufficiently informative. However, simulation studies suggest that randomized phase II trials would have lower error rates and greater predictive power for phase III results. Randomized phase II trials may also be more informative than single-arm phase II trials because of the hypotheses being tested, the variety of possible endpoints, and the opportunities for biomarker discovery. There are a wide variety of randomized phase II designs that can be used, including the randomized discontinuation design, the delayed-start design, adaptive (Bayesian) designs, selection designs, and phase II/III designs. The barriers to widespread adoption of randomized phase II trials include time to completion, sample size considerations, and ethical concerns, but none are insurmountable. We conclude that randomized phase II trials are a worthy investment considering finite patient and financial resources and should be the rule rather than the exception for evaluating novel therapies in oncology. PMID:21709274

  13. Phase I Report, US DOE GRED II Program

    SciTech Connect

    Fairbank Engineering Ltd.

    2003-04-23

    Noramex Corporation Inc, a Nevada company, owns a 100% interest in geothermal leases at the Blue Mountain Geothermal Area, Humboldt County, Nevada. The company is exploring the site for a geothermal resource suitable for development for electric power generation or In the spring of 2002, Noramex drilled the first geothermal observation hole at Blue Mountain, under a cost-share program with the U.S Department of Energy (DOE), under the DOE's Geothermal Exploration and Resource Definition (GRED) program, (Cooperative Agreement No. DE-FC04-00AL66972). DEEP BLUE No.1 was drilled to a total depth of 672.1 meters (2205 feet) and recorded a maximum temperature of 144.7 C (292.5 F). Noramex Corporation will now drill a second slim geothermal observation test hole at Blue Mountain, designated DEEP BLUE No.2. The hole will be drilled under a cost-share program with the DOE, under the DOE's Geothermal Exploration and Resource Definition II (GRED II) program, (Cooperative Agreement No. DE-FC04-2002AL68297). This report comprises Phase I of Cooperative Agreement No. DE-FC04-2002AL68297 of the GRED II program. The report provides an update on the status of resource confirmation at the Blue Mountain Geothermal Area, incorporating the results from DEEP BLUE No.1, and provides the technical background for a second test hole. The report also outlines the proposed drilling program for slim geothermal observation test hole DEEP BLUE No.2.

  14. Synergism between soluble and dietary fiber bound antioxidants.

    PubMed

    Çelik, Ecem Evrim; Gökmen, Vural; Skibsted, Leif H

    2015-03-01

    This study investigates the synergism between antioxidants bound to dietary fibers (DF) of grains and soluble antioxidants of highly consumed beverages or their pure antioxidants. The interaction between insoluble fractions of grains containing bound antioxidants and soluble antioxidants was investigated using (i) a liposome-based system by measuring the lag phase before the onset of oxidation and (ii) an ESR-based system by measuring the reduction percentage of Fremy's salt radical. In both procedures, antioxidant capacities of DF-bound and soluble antioxidants were measured as well as their combinations, which were prepared at different ratios. The simple addition effects of DF-bound and soluble antioxidants were compared with measured values. The results revealed a clear synergism for almost all combinations in both liposome- and ESR-based systems. The synergism observed in DF-bound-soluble antioxidant system paints a promising picture considering the role of fiber in human gastrointestinal (GI) tract health.

  15. Effect of Carbon Ion Radiotherapy for Sacral Chordoma: Results of Phase I-II and Phase II Clinical Trials

    SciTech Connect

    Imai, Reiko; Kamada, Tadashi; Tsuji, Hiroshi; Sugawara, Shinji; Serizawa, Itsuko; Tsujii, Hirohiko; Tatezaki, Shin-ichiro

    2010-08-01

    Purpose: To summarize the results of treatment for sacral chordoma in Phase I-II and Phase II carbon ion radiotherapy trials for bone and soft-tissue sarcomas. Patients and Methods: We performed a retrospective analysis of 38 patients with medically unresectable sacral chordomas treated with the Heavy Ion Medical Accelerator in Chiba, Japan between 1996 and 2003. Of the 38 patients, 30 had not received previous treatment and 8 had locally recurrent tumor after previous resection. The applied carbon ion dose was 52.8-73.6 Gray equivalents (median, 70.4) in a total of 16 fixed fractions within 4 weeks. Results: The median patient age was 66 years. The cranial tumor extension was S2 or greater in 31 patients. The median clinical target volume was 523 cm{sup 3}. The median follow-up period was 80 months. The 5-year overall survival rate was 86%, and the 5-year local control rate was 89%. After treatment, 27 of 30 patients with primary tumor remained ambulatory with or without supportive devices. Two patients experienced severe skin or soft-tissue complications requiring skin grafts. Conclusion: Carbon ion radiotherapy appears effective and safe in the treatment of patients with sacral chordoma and offers a promising alternative to surgery.

  16. Advanced Simulation Capability for Environmental Management (ASCEM) Phase II Demonstration

    SciTech Connect

    Freshley, M.; Hubbard, S.; Flach, G.; Freedman, V.; Agarwal, D.; Andre, B.; Bott, Y.; Chen, X.; Davis, J.; Faybishenko, B.; Gorton, I.; Murray, C.; Moulton, D.; Meyer, J.; Rockhold, M.; Shoshani, A.; Steefel, C.; Wainwright, H.; Waichler, S.

    2012-09-28

    quality assurance. The Platform and HPC capabilities are being tested and evaluated for EM applications through a suite of demonstrations being conducted by the Site Applications Thrust. In 2010, the Phase I Demonstration focused on testing initial ASCEM capabilities. The Phase II Demonstration, completed in September 2012, focused on showcasing integrated ASCEM capabilities. For Phase II, the Hanford Site Deep Vadose Zone (BC Cribs) served as an application site for an end-to-end demonstration of ASCEM capabilities on a site with relatively sparse data, with emphasis on integration and linkages between the Platform and HPC components. Other demonstrations included in this Phase II report included addressing attenuation-based remedies at the Savannah River Site F-Area, to exercise linked ASCEM components under data-dense and complex geochemical conditions, and conducting detailed simulations of a representative waste tank. This report includes descriptive examples developed by the Hanford Site Deep Vadose Zone, the SRS F-Area Attenuation-Based Remedies for the Subsurface, and the Waste Tank Performance Assessment working groups. The integrated Phase II Demonstration provides test cases to accompany distribution of the initial user release (Version 1.0) of the ASCEM software tools to a limited set of users in 2013. These test cases will be expanded with each new release, leading up to the release of a version that is qualified for regulatory applications in the 2015 time frame.

  17. PHASE II VAULT TESTING OF THE ARGONNE RFID SYSTEM

    SciTech Connect

    Willoner, T.; Turlington, R.; Koenig, R.

    2012-06-25

    The U.S. Department of Energy (DOE) (Environmental Management [EM], Office of Packaging and Transportation [EM-45]) Packaging and Certification Program (DOE PCP) has developed a Radio Frequency Identification (RFID) tracking and monitoring system, called ARG-US, for the management of nuclear materials packages during transportation and storage. The performance of the ARG-US RFID equipment and system has been fully tested in two demonstration projects in April 2008 and August 2009. With the strong support of DOE-SR and DOE PCP, a field testing program was completed in Savannah River Site's K-Area Material Storage (KAMS) Facility, an active Category I Plutonium Storage Facility, in 2010. As the next step (Phase II) of continued vault testing for the ARG-US system, the Savannah River Site K Area Material Storage facility has placed the ARG-US RFIDs into the 910B storage vault for operational testing. This latest version (Mark III) of the Argonne RFID system now has the capability to measure radiation dose and dose rate. This paper will report field testing progress of the ARG-US RFID equipment in KAMS, the operability and reliability trend results associated with the applications of the system, and discuss the potential benefits in enhancing safety, security and materials accountability. The purpose of this Phase II K Area test is to verify the accuracy of the radiation monitoring and proper functionality of the ARG-US RFID equipment and system under a realistic environment in the KAMS facility. Deploying the ARG-US RFID system leads to a reduced need for manned surveillance and increased inventory periods by providing real-time access to status and event history traceability, including environmental condition monitoring and radiation monitoring. The successful completion of the testing program will provide field data to support a future development and testing. This will increase Operation efficiency and cost effectiveness for vault operation. As the next step (Phase

  18. Adaptive two-stage designs in phase II clinical trials.

    PubMed

    Banerjee, Anindita; Tsiatis, Anastasios A

    2006-10-15

    Two-stage designs have been widely used in phase II clinical trials. Such designs are desirable because they allow a decision to be made on whether a treatment is effective or not after the accumulation of the data at the end of each stage. Optimal fixed two-stage designs, where the sample size at each stage is fixed in advance, were proposed by Simon when the primary outcome is a binary response. This paper proposes an adaptive two-stage design which allows the sample size at the second stage to depend on the results at the first stage. Using a Bayesian decision-theoretic construct, we derive optimal adaptive two-stage designs; the optimality criterion being minimum expected sample size under the null hypothesis. Comparisons are made between Simon's two-stage fixed design and the new design with respect to this optimality criterion. PMID:16479547

  19. Small Business Innovation Research. Abstracts of Phase II awards, 2000

    SciTech Connect

    2000-12-01

    The SBIR program enables DOE to obtain effective, innovative solutions to important problems through the private sector, which has a commercial incentive to pursue the resulting technology and bring it to the marketplace. The growing number of awardees, many of them started in business in response to SBIR solicitations, is becoming a significant resource for the solution of high risk, high technology problems for the Department. As detailed below, this publication describes the technical efforts and commercialization possibilities for SBIR Phase II awards in Fiscal Year (FY) 2000. It is intended for the educated layman, and maybe of particular interest to potential investors who wish to get in on the ground floor of exciting opportunities.

  20. Lunar Quest in Second Life, Lunar Exploration Island, Phase II

    NASA Astrophysics Data System (ADS)

    Ireton, F. M.; Day, B. H.; Mitchell, B.; Hsu, B. C.

    2010-12-01

    Linden Lab’s Second Life is a virtual 3D metaverse created by users. At any one time there may be 40,000-50,000 users on line. Users develop a persona and are seen on screen as a human figure or avatar. Avatars move through Second Life by walking, flying, or teleporting. Users form communities or groups of mutual interest such as music, computer graphics, and education. These groups communicate via e-mail, voice, and text within Second Life. Information on downloading the Second Life browser and joining can be found on the Second Life website: www.secondlife.com. This poster details Phase II in the development of Lunar Exploration Island (LEI) located in Second Life. Phase I LEI highlighted NASA’s LRO/LCROSS mission. Avatars enter LEI via teleportation arriving at a hall of flight housing interactive exhibits on the LRO/ LCROSS missions including full size models of the two spacecraft and launch vehicle. Storyboards with information about the missions interpret the exhibits while links to external websites provide further information on the mission, both spacecraft’s instrument suites, and related EPO. Other lunar related activities such as My Moon and NLSI EPO programs. A special exhibit was designed for International Observe the Moon Night activities with links to websites for further information. The sim includes several sites for meetings, a conference stage to host talks, and a screen for viewing NASATV coverage of mission and other televised events. In Phase II exhibits are updated to reflect on-going lunar exploration highlights, discoveries, and future missions. A new section of LEI has been developed to showcase NASA’s Lunar Quest program. A new exhibit hall with Lunar Quest information has been designed and is being populated with Lunar Quest information, spacecraft models (LADEE is in place) and kiosks. A two stage interactive demonstration illustrates lunar phases with static and 3-D stations. As NASA’s Lunar Quest program matures further

  1. What Works in Oklahoma Schools: A Comprehensive Needs Assessment of Oklahoma Schools. Phase II State Report

    ERIC Educational Resources Information Center

    Marzano Research Laboratory, 2010

    2010-01-01

    Phase II provides a more detailed examination of classroom variables important to achievement in Oklahoma schools. Where Phase I addressed all nine of the Oklahoma essential elements using survey data, Phase II focuses on what occurs in Oklahoma classrooms primarily using data from principal interviews, classroom observations (on-site), and video…

  2. 7 CFR 3403.8 - Proposal format for phase II applications.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...) Commercialization Plan. A succinct commercialization plan must be included in each SBIR Phase II proposal moving toward commercialization. Elements of a commercialization plan may include the following: (i) Company... commercialization. (ii) Customer and competition. Clear description of key technology objectives,...

  3. Analysis of SBIR phase I and phase II review results at the National Institutes of Health.

    PubMed

    Vener, K J; Calkins, B M

    1991-09-01

    A cohort of phase I and phase II summary statements for the SBIR grant applications was evaluated to determine the strengths and weaknesses in approved and disapproved applications. An analysis of outcome variables (disapproval or unfunded status) was examined with respect to exposure variables (strengths or shortcomings). Logistic regression models were developed for comparisons to measure the predictive value of shortcomings and strengths to the outcomes. Disapproved phase I results were compared with an earlier 1985 study. Although the magnitude of the frequencies of shortcomings was greater in the present study, the relative rankings within shortcoming class were more alike than different. Also, the frequencies of shortcomings were, with one exception, not significantly different in the two studies. Differences in the summary statement review may have accounted for some differences observed between the 1985 data and results of the present study. Comparisons of Approved/Disapproved and Approved-Unfunded/Funded yielded the following observations. For phase I applicants, a lack of a clearly stated, testable hypothesis, a poorly qualified or described investigative team, and inadequate methodological approaches contributed significantly (in that order) to a rating of disapproval. A critical flaw for phase II proposals was failure to accomplish objectives of the phase I study. Methodological issues also dominate the distinctions in both comparison groups. A clear result of the data presented here and that published previously is that SBIR applicants need continuing assistance to improve the chances of their success. These results should serve as a guide to assist NIH staff as they provide information to prospective applicants focusing on key elements of the application. A continuing review of the SBIR program would be helpful to evaluate the quality of the submitted science. PMID:1916087

  4. Rooftop PV system. Final technical progress report, Phase II

    SciTech Connect

    1995-08-01

    Under this four-year PV:BONUS Program, ECD and United Solar are developing and demonstrating two new lightweight flexible building integrated Photovoltaic (BIPV) modules specifically designed as exact replacements for conventional asphalt shingles and standing seam metal roofing. These modules can be economically and aesthetically integrated into new residential and commercial buildings, and address the even larger roofing replacement market. The modules are designed to be installed by roofing contractors without special training which minimizes the installation and balance of system costs. The modules will be fabricated from high-efficiency, multiple-junction a-Si alloy solar cells developed by ECD and United Solar. Under the Phase I Program, which ended in March 1994, we developed two different concept designs for rooftop PV modules: (1) the United Solar overlapping (asphalt shingle replacement) shingle-type modules and (2) the ECD metal roof-type modules. We also developed a plan for fabricating, testing and demonstrating these modules. Candidate demonstration sites for our rooftop PV modules were identified and preliminary engineering designs for these demonstrations were developed; a marketing study plan was also developed. The major objectives of the Phase II Program, which started in June 1994 was (1) to develop, test, and qualify these new rooftop modules; (2) to develop mechanical and electrical engineering specifications for the demonstration projects; and (3) to develop a marketing/commercialization plan.

  5. Overview of SBIR Phase II Work on Hollow Graphite Fibers

    NASA Technical Reports Server (NTRS)

    Stallcup, Michael; Brantley, Lott W. (Technical Monitor)

    2001-01-01

    Ultra-Lightweight materials are enabling for producing space based optical components and support structures. Heretofore, innovative designs using existing materials has been the approach to produce lighter-weight optical systems. Graphite fiber reinforced composites, because of their light weight, have been a material of frequent choice to produce space based optical components. Hollow graphite fibers would be lighter than standard solid graphite fibers and, thus, would save weight in optical components. The Phase I SBIR program demonstrated it is possible to produce hollow carbon fibers that have strengths up to 4.2 GPa which are equivalent to commercial fibers, and composites made from the hollow fibers had substantially equivalent composite strengths as commercial fiber composites at a 46% weight savings. The Phase II SBIR program will optimize processing and properties of the hollow carbon fiber and scale-up processing to produce sufficient fiber for fabricating a large ultra-lightweight mirror for delivery to NASA. Information presented here includes an overview of the strength of some preliminary hollow fibers, photographs of those fibers, and a short discussion of future plans.

  6. Easier Phase IIs: Recent Improvements to the Gemini User Tools

    NASA Astrophysics Data System (ADS)

    Miller, Bryan; Nuñez, A.

    2013-01-01

    During 2011 and 2012 Gemini Observatory undertook a significant project to improve the software tools used by investigators to propose for and prepare observations. The main goal was to make the definition of observation details (the Phase II process) easier and faster. The main initiatives included rewriting the observing proposal tool (Phase I Tool) and making several major improvements to the Observing Tool, including automatic settings for arc and flat exposures, automatic guide star selection for all instruments and wavefront sensors, and more complete initial template observations with capabilities for simultaneous editing of many observations. This poster explains these major changes as well as outlines future development plans. The Gemini Observatory is operated by the Association of Universities for Research in Astronomy, Inc., under a cooperative agreement with the NSF on behalf of the Gemini partnership: the National Science Foundation (United States), the Science and Technology Facilities Council (United Kingdom), the National Research Council (Canada), CONICYT (Chile), the Australian Research Council (Australia), Ministério da Ciência, Tecnologia e Inovação (Brazil), and Ministerio de Ciencia, Tecnología e Innovación Productiva (Argentina).

  7. ALTERNATE REDUCTANT COLD CAP EVALUATION FURNACE PHASE II TESTING

    SciTech Connect

    Johnson, F.; Stone, M.; Miller, D.

    2014-09-03

    Savannah River Remediation (SRR) conducted a Systems Engineering Evaluation (SEE) to determine the optimum alternate reductant flowsheet for the Defense Waste Processing Facility (DWPF). Specifically, two proposed flowsheets (nitric–formic–glycolic and nitric–formic–sugar) were evaluated based upon results from preliminary testing. Comparison of the two flowsheets among evaluation criteria indicated a preference towards the nitric–formic–glycolic flowsheet. Further research and development of this flowsheet eliminated the formic acid, and as a result, the nitric–glycolic flowsheet was recommended for further testing. Based on the development of a roadmap for the nitric–glycolic acid flowsheet, Waste Solidification Engineering (WS-E) issued a Technical Task Request (TTR) to address flammability issues that may impact the implementation of this flowsheet. Melter testing was requested in order to define the DWPF flammability envelope for the nitric-glycolic acid flowsheet. The Savannah River National Laboratory (SRNL) Cold Cap Evaluation Furnace (CEF), a 1/12th scale DWPF melter, was selected by the SRR Alternate Reductant project team as the melter platform for this testing. The overall scope was divided into the following sub-tasks as discussed in the Task Technical and Quality Assurance Plan (TTQAP):  Phase I - A nitric–formic acid flowsheet melter test (unbubbled) to baseline the CEF cold cap and vapor space data to the benchmark melter flammability models;  Phase II - A nitric–glycolic acid flowsheet melter test (unbubbled and bubbled) to: o Define new cold cap reactions and global kinetic parameters in support of the melter flammability model development; o Quantify off-gas surging potential of the feed; o Characterize off-gas condensate for complete organic and inorganic carbon species. After charging the CEF with cullet from Phase I CEF testing, the melter was slurry-fed with glycolic flowsheet based SB6-Frit 418 melter feed at 36

  8. MHD seed recovery and regeneration, Phase II. Final report

    SciTech Connect

    Not Available

    1994-10-01

    This final report summarizes the work performed by the Space and Technology Division of the TRW Space and Electronics Group for the U.S. Department of Energy, Pittsburgh Energy Technology Center for the Econoseed process. This process involves the economical recovery and regeneration of potassium seed used in the MHD channel. The contract period of performance extended from 1987 through 1994 and was divided into two phases. The Phase II test results are the subject of this Final Report. However, the Phase I test results are presented in summary form in Section 2.3 of this Final Report. The Econoseed process involves the treatment of the potassium sulfate in spent MHD seed with an aqueous calcium formate solution in a continuously stirred reactor system to solubilize, as potassium formate, the potassium content of the seed and to precipitate and recover the sulfate as calcium sulfate. The slurry product from this reaction is centrifuged to separate the calcium sulfate and insoluble seed constituents from the potassium formate solution. The dilute solids-free potassium formate solution is then concentrated in an evaporator. The concentrated potassium formate product is a liquid which can be recycled as a spray into the MHD channel. Calcium formate is the seed regenerant used in the Econoseed process. Since calcium formate is produced in the United States in relatively small quantities, a new route to the continuous production of large quantities of calcium formate needed to support an MHD power industry was investigated. This route involves the reaction of carbon monoxide gas with lime solids in an aqueous medium.

  9. Glycerol and NEFA kinetics in long-term fasting king penguins: phase II versus phase III.

    PubMed

    Bernard, S F; Fayolle, C; Robin, J-P; Groscolas, R

    2002-09-01

    In spontaneously fasting birds such as penguins, below a body mass threshold corresponding to the phase II-phase III transition, a metabolic and hormonal shift occurs and feeding behaviour is stimulated ('refeeding signal'). The major aim of this study was to determine whether a decrease in non-esterified fatty acid (NEFA) release from adipose tissue could be a component of this signal. Lipolytic fluxes and primary triacylglycerol:fatty acid (TAG:FA) cycling were determined in vivo in breeding, fasting king penguins (Aptenodytes patagonicus) using continuous infusions of 2-[3H]glycerol and 1-[14C]palmitate under field conditions. In phase II (after approximately 8 days of fasting, large fat stores, body protein spared, N=8), the rate of appearance (R(a)) of glycerol and of NEFA were 5.7+/-0.8 and 10.5+/-0.4 micromol kg(-1) min(-1), respectively, and the percentage of primary TAG:FA cycling was 41+/-7%. In phase III (after approximately 25 days of fasting, fat stores reduced by fourfold, increased body protein catabolism, N=9), R(a) glycerol kg(-1) body mass remained unchanged, whereas R(a) glycerol kg(-1) fat mass and R(a) NEFA kg(-1) body mass were increased by 2.8-fold and 1.5-fold, respectively. Increased R(a) glycerol kg(-1) fat mass was possibly the result of a 3.5-fold increase in circulating glucagon, the increased R(a) NEFA kg(-1) body mass being attributable to decreased primary TAG:FA cycling. Thus, triggering of the refeeding signal that redirects the behavior of fasting, incubating penguins from incubation towards the search for food after entrance into phase III cannot be ascribed to a reduction in lipolytic fluxes and NEFA availability. PMID:12151380

  10. Synthesis, spectral characterization and antioxidant activity studies of a bidentate Schiff base, 5-methyl thiophene-2-carboxaldehyde-carbohydrazone and its Cd(II), Cu(II), Ni(II) and Zn(II) complexes

    NASA Astrophysics Data System (ADS)

    Harinath, Y.; Harikishore Kumar Reddy, D.; Naresh Kumar, B.; Apparao, Ch.; Seshaiah, K.

    2013-01-01

    A new Schiff base bidentate ligand (L), 5-methyl thiophene-2-carboxaldehyde-carbohydrazone and its metal (Cu(II), Cd(II), Ni(II) and Zn(II)) complexes with general stoichiometry [M(L)2X2] (where X = Cl) were synthesized. The ligand and its metal complexes were characterized by elemental analyses, IR, 1H NMR, ESR spectral analyses, and molar conductance studies. The molar conductance data revealed that all the metal chelates are non-electrolytes. IR spectra showed that ligand (L) is coordinated to the metal ions in a bidentate manner with N and O donor sites of the azomethine-N, and carbonyl-O. ESR and UV-Vis spectral data showed that the geometrical structure of the complexes are Orthorhombic. Furthermore, the antioxidant activity of the ligand and its complexes was determined by hydroxyl radical scavenging, DPPH, NO, reducing power methods in vitro. The obtained IC50 value of the DPPH activity for the copper complex (IC50 = 66.4 μm) was higher than other compounds. Microbial assay of the above complexes against Staphylococcus aureus, Escherichia coli, Rhizocotonia bataticola and Alternaria alternata showed that copper complex exhibited higher activity than the other complexes.

  11. 7 CFR 3403.8 - Proposal format for phase II applications.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... budget category must be included. (6) Organizational management information. Each Phase II awardee will..., financial statements or balance sheet) and report any changes in management or principals....

  12. 7 CFR 3403.8 - Proposal format for phase II applications.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... budget category must be included. (6) Organizational management information. Each Phase II awardee will..., financial statements or balance sheet) and report any changes in management or principals....

  13. 7 CFR 3403.8 - Proposal format for phase II applications.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... budget category must be included. (6) Organizational management information. Each Phase II awardee will..., financial statements or balance sheet) and report any changes in management or principals....

  14. A New Approach to Designing Phase I-II Cancer Trials for Cytotoxic Chemotherapies

    PubMed Central

    Bartroff, Jay; Lai, Tze Leung; Narasimhan, Balasubramanian

    2014-01-01

    Recently there has been much work on early phase cancer designs that incorporate both toxicity and efficacy data, called Phase I-II designs because they combine elements of both phases. However, they do not explicitly address the Phase II hypothesis test of H0: p ≤ p0, where p is the probability of efficacy at the estimated maximum tolerated dose (MTD) η̂ from Phase I and p0 is the baseline efficacy rate. Standard practice for Phase II remains to treat p as a fixed, unknown parameter and to use Simon’s 2-stage design with all patients dosed at η̂. We propose a Phase I-II design that addresses the uncertainty in the estimate p = p(η̂) in H0 by using sequential generalized likelihood theory. Combining this with a Phase I design that incorporates efficacy data, the Phase I-II design provides a common framework that can be used all the way from the first dose of Phase I through the final accept/reject decision about H0 at the end of Phase II, utilizing both toxicity and efficacy data throughout. Efficient group sequential testing is used in Phase II that allows for early stopping to show treatment effect or futility. The proposed Phase I-II design thus removes the artificial barrier between Phase I and Phase II, and fulfills the objectives of searching for the MTD and testing if the treatment has an acceptable response rate to enter into a Phase III trial. PMID:24577750

  15. NRF2 and the Phase II Response in Acute Stress Resistance Induced by Dietary Restriction

    PubMed Central

    Hine, Christopher M.; Mitchell, James R.

    2013-01-01

    Dietary restriction (DR) as a means to increase longevity is well-established in a number of model organisms from yeast to primates. DR also improves metabolic fitness and increases resistance to acute oxidative, carcinogenic and toxicological stressors - benefits with more immediate potential for clinical translation than increased lifespan. While the detailed mechanism of DR action remains unclear, a conceptual framework involving an adaptive, or hormetic response to the stress of nutrient/energy deprivation has been proposed. A key prediction of the hormesis hypothesis of DR is that beneficial adaptations occur in response to an increase in reactive oxygen/nitrogen species (ROS). These ROS may be derived either from increased mitochondrial respiration or increased xenobiotic metabolism in the case of some DR mimetics. This review will focus on the potential role of the redox-sensing transcription factor NF-E2-related factor 2 (NRF2) and its control of the evolutionarily conserved antioxidant/redox cycling and detoxification systems, collectively known as the Phase II response, in the adaptive response to DR. PMID:23505614

  16. Influence of heat stress on the cortisol and oxidant-antioxidants balance during oestrous phase in buffalo-cows (Bubalus bubalis): thermo-protective role of antioxidant treatment.

    PubMed

    Megahed, G A; Anwar, M M; Wasfy, S I; Hammadeh, M E

    2008-12-01

    In the present study, the effect of heat stress, which is commonly observed in the animals of Upper Egypt area in summer, as well as the effect of antioxidant treatment as a thermo-protective was examined. In this study, the animals (n = 120) were divided into winter group (n = 40, bred during winter) and summer group (n = 80, bred during summer) as well as, animals in the summer group were divided into first subgroup animals (n = 40) and injected with Viteselen intramuscularly (15 ml) twice weekly for 10 weeks and second subgroup animals (n = 40) were not treated (as control). Serum levels of progesterone (P4), oestradiol (E2), cortisol, superoxide dismutase (SOD), lipid peroxidase (LPO) and nitric oxide (NO) were measured. The pregnancy rate of all animals was detected rectally. The levels of oestradiol and the activity of the antioxidant SOD were decreased in serum of animals in behavioural oestrus during summer as compared with those in winter. During the same time period the levels of oxidants such as LPO and NO were increased in the serum of animals again in the phase of oestrus. In another group of animals treated by intramuscular injection with 15 ml viteselen (antioxidant) twice weekly for 6 weeks during hot months, the activities of serum SOD showed an increase and the levels of oxidants and cortisol decreased. Moreover, the levels of oestradiol were increased during the oestrous behaviour. The pregnancy rate was decreased in animals under heat stress and the pregnancy rate was enhanced dramatically when these animals received antioxidants during the heat stress. This means that the heat-stress in Upper Egypt may affect the fertility of animals and pregnancy rate and this effect may be through an increased production of free radicals and decreased production of antioxidants as well as increased levels of cortisol. Treatment of animals or supplementation with antioxidants before the beginning of months of heat-stress and also during the stress period may

  17. 40 CFR 300.305 - Phase II-Preliminary assessment and initiation of action.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... SUBSTANCES POLLUTION CONTINGENCY PLAN Operational Response Phases for Oil Removal § 300.305 Phase II... effective and immediate removal of the discharge or mitigation or prevention of a substantial threat of...

  18. 40 CFR 300.305 - Phase II-Preliminary assessment and initiation of action.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... SUBSTANCES POLLUTION CONTINGENCY PLAN Operational Response Phases for Oil Removal § 300.305 Phase II... effective and immediate removal of the discharge or mitigation or prevention of a substantial threat of...

  19. 40 CFR 300.305 - Phase II-Preliminary assessment and initiation of action.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... SUBSTANCES POLLUTION CONTINGENCY PLAN Operational Response Phases for Oil Removal § 300.305 Phase II... effective and immediate removal of the discharge or mitigation or prevention of a substantial threat of...

  20. 40 CFR 300.305 - Phase II-Preliminary assessment and initiation of action.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... SUBSTANCES POLLUTION CONTINGENCY PLAN Operational Response Phases for Oil Removal § 300.305 Phase II... effective and immediate removal of the discharge or mitigation or prevention of a substantial threat of...

  1. 40 CFR 300.305 - Phase II-Preliminary assessment and initiation of action.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... SUBSTANCES POLLUTION CONTINGENCY PLAN Operational Response Phases for Oil Removal § 300.305 Phase II... effective and immediate removal of the discharge or mitigation or prevention of a substantial threat of...

  2. An Overview of 2014 SBIR Phase I and Phase II Materials Structures for Extreme Environments

    NASA Technical Reports Server (NTRS)

    Nguyen, Hung D.; Steele, Gynelle C.; Morris, Jessica R.

    2015-01-01

    NASA's Small Business Innovation Research (SBIR) program focuses on technological innovation by investing in development of innovative concepts and technologies to help NASA mission directorates address critical research needs for Agency programs. This report highlights nine of the innovative SBIR 2014 Phase I and Phase II projects that emphasize one of NASA Glenn Research Center's six core competencies-Materials and Structures for Extreme Environments. The technologies cover a wide spectrum of applications such as high temperature environmental barrier coating systems, deployable space structures, solid oxide fuel cells, and self-lubricating hard coatings for extreme temperatures. Each featured technology describes an innovation, technical objective, and highlights NASA commercial and industrial applications. This report provides an opportunity for NASA engineers, researchers, and program managers to learn how NASA SBIR technologies could help their programs and projects, and lead to collaborations and partnerships between the small SBIR companies and NASA that would benefit both.

  3. The role of technology in reducing health care costs. Phase II and phase III.

    SciTech Connect

    Cilke, John F.; Parks, Raymond C.; Funkhouser, Donald Ray; Tebo, Michael A.; Murphy, Martin D.; Hightower, Marion Michael; Gallagher, Linda K.; Craft, Richard Layne, II; Garcia, Rudy John

    2004-04-01

    In Phase I of this project, reported in SAND97-1922, Sandia National Laboratories applied a systems approach to identifying innovative biomedical technologies with the potential to reduce U.S. health care delivery costs while maintaining care quality. The effort provided roadmaps for the development and integration of technology to meet perceived care delivery requirements and an economic analysis model for development of care pathway costs for two conditions: coronary artery disease (CAD) and benign prostatic hypertrophy (BPH). Phases II and III of this project, which are presented in this report, were directed at detailing the parameters of telemedicine that influence care delivery costs and quality. These results were used to identify and field test the communication, interoperability, and security capabilities needed for cost-effective, secure, and reliable health care via telemedicine.

  4. Clean Air Act Title IV: Lessons learned from Phase I; getting ready for Phase II

    SciTech Connect

    Miller, M.J.

    1997-12-31

    The 1990 Clean Air Act Amendments have required significant reductions in SO{sub 2} and NO{sub x} emissions from fossil fuel-fired power plants in the US. This paper examines some of the key technical lessons learned in Phase I following retrofit of low NO{sub x} systems, FGD systems, and continuous emissions monitors. Some of the key problems encountered have been waterwall wastage as a result of low NO{sub x} burner retrofits; high LOI (carbon) ash as a result of low NO{sub x} operation; high O&M costs associated with CEMs; and the heat rate discrepancy which has arisen between CEMs and conventional heat rate calculations. As Phase II approaches, EPRI and the electric utility industry are investigating improvements in FGD systems (e.g., clear liquor scrubbing), advances in NO{sub x} control technologies, more robust CEM systems, and tools to help in the technology decision-making process.

  5. Photosystem II functionality and antioxidant system changes during leaf rolling in post-stress emerging Ctenanthe setosa exposed to drought.

    PubMed

    Terzi, Rabiye; Saruhan, Neslihan; Sağlam, A; Nar, Hatice; Kadioğlu, A

    2009-12-01

    We studied the changes in antioxidant system and chlorophyll fluorescence parameters in post-stress emerging Ctenanthe setosa (Rosc.) Eichler (Marantaceae) plants (PSE plants) having reduced leaf area under drought stress causing leaf rolling and re-watering. PSE plants were compared to primary stressed plants (PS) in previous studies. The parameters were measured at different visual leaf rolling scores from 1 to 4 (1 is unrolled, 4 is tightly rolled and the others is intermediate form). Water potentials and stomatal conductance of leaves were gradually decreased during leaf rolling. Similarly, maximum quantum efficiency of open PS II center and quantum yield of PS II decreased during the rolling period. Non-photochemical quenching of chlorophyll fluorescence decreased at score 2 then increased while photochemical quenching did not change during leaf rolling. Electron transport rate decreased only at score 4 but approximately reached to score 1 level after re-watering. Superoxide dismutase activity was not constant at all leaf rolling scores. Ascorbate peroxidase, catalase and glutathione reductase activities generally tended to increase during leaf rolling. Lipid peroxidation and H 2 O 2 content increased at score 2 but decreased at the later scores. On the other hand, O 2 .- production increased during the rolling period. After re-watering of the plants having score 4 of leaf rolling, antioxidant enzyme activities were lower than those of score 1. Other physiological parameters also tended to reach the value of score 1. The results indicated that PSE plants gained drought tolerance by reducing leaf area effectively induced their antioxidant systems and protected the photosynthesis under drought stress similar to PS plants. PMID:20015833

  6. Photosystem II functionality and antioxidant system changes during leaf rolling in post-stress emerging Ctenanthe setosa exposed to drought.

    PubMed

    Terzi, Rabiye; Saruhan, Neslihan; Sağlam, A; Nar, Hatice; Kadioğlu, A

    2009-12-01

    We studied the changes in antioxidant system and chlorophyll fluorescence parameters in post-stress emerging Ctenanthe setosa (Rosc.) Eichler (Marantaceae) plants (PSE plants) having reduced leaf area under drought stress causing leaf rolling and re-watering. PSE plants were compared to primary stressed plants (PS) in previous studies. The parameters were measured at different visual leaf rolling scores from 1 to 4 (1 is unrolled, 4 is tightly rolled and the others is intermediate form). Water potentials and stomatal conductance of leaves were gradually decreased during leaf rolling. Similarly, maximum quantum efficiency of open PS II center and quantum yield of PS II decreased during the rolling period. Non-photochemical quenching of chlorophyll fluorescence decreased at score 2 then increased while photochemical quenching did not change during leaf rolling. Electron transport rate decreased only at score 4 but approximately reached to score 1 level after re-watering. Superoxide dismutase activity was not constant at all leaf rolling scores. Ascorbate peroxidase, catalase and glutathione reductase activities generally tended to increase during leaf rolling. Lipid peroxidation and H 2 O 2 content increased at score 2 but decreased at the later scores. On the other hand, O 2 .- production increased during the rolling period. After re-watering of the plants having score 4 of leaf rolling, antioxidant enzyme activities were lower than those of score 1. Other physiological parameters also tended to reach the value of score 1. The results indicated that PSE plants gained drought tolerance by reducing leaf area effectively induced their antioxidant systems and protected the photosynthesis under drought stress similar to PS plants.

  7. Yakima River Basin Phase II Fish Screen Evaluations, 2002

    SciTech Connect

    Carter, Jessica A.; McMichael, Geoffrey A.; Chamness, Mickie A.

    2003-03-01

    In 2002, the Pacific Northwest National Laboratory evaluated 23 Phase II fish screen sites in the Yakima River Basin as part of a multi-year project for the Bonneville Power Administration on the effectiveness of fish screening devices. Pacific Northwest National Laboratory collected data to determine whether velocities in front of the screens and in the bypasses met National Marine Fisheries Service criteria to promote safe and timely fish passage and whether bypass outfall conditions allowed fish to safely return to the river. In addition, Pacific Northwest National Laboratory conducted underwater video surveys to evaluate the environmental and operational conditions of the screen sites with respect to fish passage. Based on evaluations in 2002, PNNL concluded that: (1) In general, water velocity conditions at the screen sites met fish passage criteria set by the National Marine Fisheries Service. (2) Conditions at most facilities would be expected to provide for safe juvenile fish passage. (3) Conditions at some facilities indicate that operation and/or maintenance should be modified to increase safe juvenile fish passage. (4) Automated cleaning brushes generally functioned properly; chains and other moving parts were typically well greased and operative. (5) Removal of sediment buildup and accumulated leafy and woody debris should be improved at some sites.

  8. Yakima River Basin Phase II Fish Screen Evaluations, 2003

    SciTech Connect

    Vucelick, Jessica A.; McMichael, Geoffrey A.; Chamness, Mickie A.

    2004-05-01

    In 2003, the Pacific Northwest National Laboratory (PNNL) evaluated 23 Phase II fish screen sites in the Yakima River Basin as part of a multi-year project for the Bonneville Power Administration on the effectiveness of fish screening devices. PNNL collected data to determine whether velocities in front of the screens and in the bypasses met the Nation Oceanic and Atmospheric Administration Fisheries (NOAA Fisheries, formerly the National Marine Fisheries Service (NMFS)) criteria to promote safe and timely fish passage. In addition, PNNL conducted underwater video surveys to evaluate the environmental and operational conditions of the screen sites with respect to fish passage. Based on evaluations in 2003, PNNL concluded that: (1) In general, water velocity conditions at the screen sites met fish passage criteria set by the National Oceanic and Atmospheric Administration Fisheries. (2) Conditions at most facilities would be expected to provide for safe juvenile fish passage. (3) Conditions at some facilities indicate that operation and/or maintenance should be modified to improve juvenile fish passage conditions. (4) Automated cleaning brushes generally functioned properly; chains and other moving parts were typically well greased and operative. (5) Removal of sediment buildup and accumulated leafy and woody debris could be improved at some sites.

  9. Understanding pharmacology in humans: Phase I and Phase II (data generation).

    PubMed

    Merlo Pich, Emilio

    2011-10-01

    The discovery of novel drugs is a complex and highly regulated process organized around a critical moment, that is, when the novel compound is tested in humans. This process encompasses a series of clinical studies, identified as Phase I and Phase II, whose composite outcome should deliver the data needed for an informed decision about progressing or not the compound in full development (Phase III). Over the last 10 years the global delivery of novel treatments from the pharmaceutical industry has plunged to the level of the '70ies in spite of a 10-fold larger investment, the differential mostly due to failures in Phase III. There is the need to improve the decision making at the early clinical stage by using innovation and the high-profile achievements of basic science generated in academic and biomedical labs. A specific attention should be paid to applied biotechnologies, in particular nanotechnology and biomedical devices not only for drug deliver but also for biomarker detection. This path, also supported by regulatory agencies, is calling for an important change of perspective about how drug discovery is made, which we believe should start from the full implementation of the paradigm of Translational Medicine. PMID:21783419

  10. PBN derived amphiphilic spin-traps. II/Study of their antioxidant properties in biomimetic membranes.

    PubMed

    Ortial, Stéphanie; Morandat, Sandrine; Bortolato, Muriel; Roux, Bernard; Polidori, Ange; Pucci, Bernard; Durand, Grégory

    2014-01-01

    The work reported herein deals with the evaluation of the antioxidant properties of bitailed amphiphilic α-phenyl-N-tert-butylnitrone derivatives (BPBNs) towards oxidation of an unsaturated lipid, the 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLoPC). Oxidation was induced either by UV light irradiation or radical initiators, i.e. the water soluble AAPH and the Fenton reaction, and the antioxidant evaluation was carried out using two biomimetic systems, namely Langmuir monolayers and large unilamellar vesicles. Measurement of the molecular area and the membrane fluidity of pure nitrone monolayers before and after UV-irradiation demonstrated the better stability and antioxidant properties of B17PBN, the derivative with two C17H35 alkyl chains, compared to its analogue B11PBN with two C11H23 alkyl chains. At only 5% molar ratio of nitrone in mixed DLoPC/nitrone monolayers, a complete inhibition of the molecular area decrease was observed for B17PBN whereas B11PBN showed lower protection. The oxidation of mixed DLoPC/nitrones large unilamellar vesicles in the presence of free radicals arising from AAPH decomposition or Fenton reaction was assessed by measuring lipid conjugated dienes and thiobarbituric acid reactive substances on the whole series of nitrone, i.e. C11-, C13-, C15- and C17-based compounds. Compared to the saturated 1,2-dimyristoyl-sn-glycero-3-phosphocholine, all bitailed amphiphilic nitrones were able to decrease conjugated dienes and TBARS in both oxidative paradigms, demonstrating therefore antioxidant property. The inhibition of phospholipids oxidation was increased when increasing the concentration of nitrone with the two B11PBN and B13PBN derivatives exhibiting higher potency. This study underlines the importance in the choice of a model membrane system when evaluating the potency of antioxidants against lipid oxidation. PMID:24121081

  11. Piotron. II. Methods and initial results of dynamic pion therapy in phase II studies

    SciTech Connect

    von Essen, C.F.; Blattmann, H.; Bodendoerfer, G.; Mizoe, J.; Pedroni, E.; Walder, E.; Zimmermann, A.

    1985-02-01

    Negative pi-meson (pion) therapy employing dynamic scanning with a focused spot of convergent beams has been in use since 1981 at SIN. Three-dimensional conformation of the treatment volume to the target volume can thus be achieved. Following previously reported Phase I and Ib clinical trials, a Phase II trial was initiated with the goal of treating primary deep-seated tumors in a dose optimization schedule which included stepwise increase of total pion dose and of target volume. Patients with multicentric superficial bladder tumors who were cystectomy candidates were initially selected. Since then, more invasive cases have been treated. Treatment reactions ranged from a faint erythema and increase of bladder frequency to dry desquamation, mild nausea, moderate dysuria, and moderate proctitis or diarrhea with mucus. These reactions were closely related to treatment volume and site. One severe late cystitis has occurred in a patient treated with 2 courses of pions (4475 rad). Mild to moderate late proctitis has been seen in 4 patients. Ten of 13 bladder cancer patients had local control of disease while all 3 pancreas or biliary tract cancer patients had microscopic residual disease locally at time of death from metastasis. A total of 11 of 17 patients are thus clinically or pathologically free of local tumor to time of last observation.

  12. Artwork: Johnson Space Center U.S./International Cooperation Phase II -- This is a representation

    NASA Technical Reports Server (NTRS)

    1994-01-01

    Artwork: Johnson Space Center U.S./International Cooperation Phase II -- This is a representation illustrating the United States' international cooperation in space. Phase II of the International Space Station is depicted with elements provided by the United States and Russia comprising the Human Tended Space Station. The scene was produced by John Frassanito and Associates. (JSC ref: S94-30086)

  13. TNX GeoSiphon Cell (TGSC-1) Phase II Single Cell Deployment/Demonstration Final Report

    SciTech Connect

    Phifer, M.A.

    1999-04-15

    This Phase II final report documents the Phase II testing conducted from June 18, 1998 through November 13, 1998, and it focuses on the application of the siphon technology as a sub-component of the overall GeoSiphon Cell technology. [Q-TPL-T-00004

  14. 40 CFR 72.74 - Federal issuance of Phase II permits.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... PROGRAMS (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.74 Federal issuance of Phase II permits. (a)(1) The Administrator will be responsible for administering and enforcing Acid Rain... and enforcing Acid Rain permits for such sources under § 72.73(a). (2) After and to the extent...

  15. 40 CFR 72.74 - Federal issuance of Phase II permits.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... PROGRAMS (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.74 Federal issuance of Phase II permits. (a)(1) The Administrator will be responsible for administering and enforcing Acid Rain... and enforcing Acid Rain permits for such sources under § 72.73(a). (2) After and to the extent...

  16. 40 CFR 72.73 - State issuance of Phase II permits.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.73 State issuance of Phase II permits... permit program under part 70 of this chapter and that has a State Acid Rain program accepted by the Administrator under § 72.71 shall be responsible for administering and enforcing Acid Rain permits effective...

  17. 40 CFR 72.73 - State issuance of Phase II permits.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.73 State issuance of Phase II permits... permit program under part 70 of this chapter and that has a State Acid Rain program accepted by the Administrator under § 72.71 shall be responsible for administering and enforcing Acid Rain permits effective...

  18. 40 CFR 72.74 - Federal issuance of Phase II permits.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... PROGRAMS (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.74 Federal issuance of Phase II permits. (a)(1) The Administrator will be responsible for administering and enforcing Acid Rain... and enforcing Acid Rain permits for such sources under § 72.73(a). (2) After and to the extent...

  19. 40 CFR 72.74 - Federal issuance of Phase II permits.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... PROGRAMS (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.74 Federal issuance of Phase II permits. (a)(1) The Administrator will be responsible for administering and enforcing Acid Rain... and enforcing Acid Rain permits for such sources under § 72.73(a). (2) After and to the extent...

  20. 40 CFR 72.73 - State issuance of Phase II permits.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.73 State issuance of Phase II permits... permit program under part 70 of this chapter and that has a State Acid Rain program accepted by the Administrator under § 72.71 shall be responsible for administering and enforcing Acid Rain permits effective...

  1. 40 CFR 72.73 - State issuance of Phase II permits.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.73 State issuance of Phase II permits... permit program under part 70 of this chapter and that has a State Acid Rain program accepted by the Administrator under § 72.71 shall be responsible for administering and enforcing Acid Rain permits effective...

  2. 40 CFR 72.73 - State issuance of Phase II permits.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.73 State issuance of Phase II permits... permit program under part 70 of this chapter and that has a State Acid Rain program accepted by the Administrator under § 72.71 shall be responsible for administering and enforcing Acid Rain permits effective...

  3. 40 CFR 72.74 - Federal issuance of Phase II permits.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PROGRAMS (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.74 Federal issuance of Phase II permits. (a)(1) The Administrator will be responsible for administering and enforcing Acid Rain... and enforcing Acid Rain permits for such sources under § 72.73(a). (2) After and to the extent...

  4. 47 CFR 54.310 - Connect America Fund for Price Cap Territories-Phase II

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 3 2014-10-01 2014-10-01 false Connect America Fund for Price Cap Territories... Connect America Fund for Price Cap Territories—Phase II (a) Geographic areas eligible for support. Connect... identified by public notice. (b) Term of support. Connect America Phase II model-based support shall...

  5. 78 FR 8184 - DEEPWATER HORIZON Oil Spill; Final Phase II Early Restoration Plan and Environmental Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-05

    ... availability of the Phase II DERP/ER was published in the Federal Register on November 6, 2012. (77 FR 66626... DEEPWATER HORIZON Oil Spill; Final Phase II Early Restoration Plan and Environmental Review AGENCY: Interior... (OPA), the National Environmental Policy Act (NEPA), and the Framework Agreement for Early...

  6. Investing in Our Nation's Youth. National Youth Anti-Drug Media Campaign: Phase II (Final Report).

    ERIC Educational Resources Information Center

    Office of National Drug Control Policy, Washington, DC.

    This publication presents the findings from an evaluation of Phase II of the National Youth Anti-Drug Media Campaign. The number one goal of the campaign was to educate youth to reject illegal drugs. This report evaluates Phase II and focuses on the effect of paid television advertising on awareness of anti-drug messages among youth, teens, and…

  7. A steerable/distance enhanced penetrometer delivery system: Phase II. Topical report

    SciTech Connect

    Amini, A.; Shenhar, J.; Lum, K.D.

    1996-05-01

    This report summarizes the phase II work on the Position Location Device (POLO) for penetrometers. Phase II was carried out to generate an integrated design of a full-scale steerable/distance enhanced penetrometer delivery system. Steering provides for the controlled and directional use of the penetrometer, while vibratory thrusting can provide greater penetration ability.

  8. Sigma S-Dependent Antioxidant Defense Protects Stationary-Phase Escherichia coli against the Bactericidal Antibiotic Gentamicin

    PubMed Central

    Wang, Jing-Hung; Singh, Rachna; Benoit, Michael; Keyhan, Mimi; Sylvester, Matthew; Hsieh, Michael; Thathireddy, Anuradha; Hsieh, Yi-Ju

    2014-01-01

    Stationary-phase bacteria are important in disease. The σs-regulated general stress response helps them become resistant to disinfectants, but the role of σs in bacterial antibiotic resistance has not been elucidated. Loss of σs rendered stationary-phase Escherichia coli more sensitive to the bactericidal antibiotic gentamicin (Gm), and proteomic analysis suggested involvement of a weakened antioxidant defense. Use of the psfiA genetic reporter, 3′-(p-hydroxyphenyl) fluorescein (HPF) dye, and Amplex Red showed that Gm generated more reactive oxygen species (ROS) in the mutant. HPF measurements can be distorted by cell elongation, but Gm did not affect stationary-phase cell dimensions. Coadministration of the antioxidant N-acetyl cysteine (NAC) decreased drug lethality particularly in the mutant, as did Gm treatment under anaerobic conditions that prevent ROS formation. Greater oxidative stress, due to insufficient quenching of endogenous ROS and/or respiration-linked electron leakage, therefore contributed to the greater sensitivity of the mutant; infection by a uropathogenic strain in mice showed this to be the case also in vivo. Disruption of antioxidant defense by eliminating the quencher proteins, SodA/SodB and KatE/SodA, or the pentose phosphate pathway proteins, Zwf/Gnd and TalA, which provide NADPH for ROS decomposition, also generated greater oxidative stress and killing by Gm. Thus, besides its established mode of action, Gm also kills stationary-phase bacteria by generating oxidative stress, and targeting the antioxidant defense of E. coli can enhance its efficacy. Relevant aspects of the current controversy on the role of ROS in killing by bactericidal drugs of exponential-phase bacteria, which represent a different physiological state, are discussed. PMID:25070093

  9. Sigma S-dependent antioxidant defense protects stationary-phase Escherichia coli against the bactericidal antibiotic gentamicin.

    PubMed

    Wang, Jing-Hung; Singh, Rachna; Benoit, Michael; Keyhan, Mimi; Sylvester, Matthew; Hsieh, Michael; Thathireddy, Anuradha; Hsieh, Yi-Ju; Matin, A C

    2014-10-01

    Stationary-phase bacteria are important in disease. The σ(s)-regulated general stress response helps them become resistant to disinfectants, but the role of σ(s) in bacterial antibiotic resistance has not been elucidated. Loss of σ(s) rendered stationary-phase Escherichia coli more sensitive to the bactericidal antibiotic gentamicin (Gm), and proteomic analysis suggested involvement of a weakened antioxidant defense. Use of the psfiA genetic reporter, 3'-(p-hydroxyphenyl) fluorescein (HPF) dye, and Amplex Red showed that Gm generated more reactive oxygen species (ROS) in the mutant. HPF measurements can be distorted by cell elongation, but Gm did not affect stationary-phase cell dimensions. Coadministration of the antioxidant N-acetyl cysteine (NAC) decreased drug lethality particularly in the mutant, as did Gm treatment under anaerobic conditions that prevent ROS formation. Greater oxidative stress, due to insufficient quenching of endogenous ROS and/or respiration-linked electron leakage, therefore contributed to the greater sensitivity of the mutant; infection by a uropathogenic strain in mice showed this to be the case also in vivo. Disruption of antioxidant defense by eliminating the quencher proteins, SodA/SodB and KatE/SodA, or the pentose phosphate pathway proteins, Zwf/Gnd and TalA, which provide NADPH for ROS decomposition, also generated greater oxidative stress and killing by Gm. Thus, besides its established mode of action, Gm also kills stationary-phase bacteria by generating oxidative stress, and targeting the antioxidant defense of E. coli can enhance its efficacy. Relevant aspects of the current controversy on the role of ROS in killing by bactericidal drugs of exponential-phase bacteria, which represent a different physiological state, are discussed. PMID:25070093

  10. Synthesis, spectral, antitumor, antioxidant and antimicrobial studies on Cu(II), Ni(II) and Co(II) complexes of 4-[(1H-Benzoimidazol-2-ylimino)-methyl]-benzene-1,3-diol

    NASA Astrophysics Data System (ADS)

    El-wakiel, Nadia; El-keiy, Mai; Gaber, Mohamed

    2015-08-01

    A new Schiff base of 2-aminobenzimidazole with 2,4-dihydroybezaldehyde (H3L), and its Cu(II), Ni(II) and Co(II) complexes have been synthesized and characterized by elemental analyses, molar conductance, thermal analysis (TGA), inductive coupled plasma (ICP), magnetic moment measurements, IR, EI-mass, UV-Vis. and ESR spectral studies. On the basis of spectral studies and analytical data, it is evident that the Schiff base acts as dibasic tridentate ligand coordinating via deprotonated OH, NH and azomethine nitrogen atom. The results showed that Co(II) and Ni(II) complexes have tetrahedral structure while Cu(II) complexes has octahedral geometry. The kinetic and thermodynamic parameters of the thermal decomposition stages have been evaluated. The studied complexes were tested for their in vitro antimicrobial activities against some bacterial strains. The anticancer activity of the ligand and its metal complexes is evaluated against human liver Carcinoma (HEPG2) cell. These compounds exhibited a moderate and weak activity against the tested HEPG2 cell lines with IC50 of 9.08, 18.2 and 19.7 μg/ml for ligand, Cu(II) and Ni(II) complexes, respectively. In vitro antioxidant activity of the newly synthesized compounds has also been evaluated.

  11. Acute phase protein and antioxidant responses in dogs with experimental acute monocytic ehrlichiosis treated with rifampicin.

    PubMed

    Karnezi, Dimitra; Ceron, Jose J; Theodorou, Konstantina; Leontides, Leonidas; Siarkou, Victoria I; Martinez, Silvia; Tvarijonaviciute, Asta; Harrus, Shimon; Koutinas, Christos K; Pardali, Dimitra; Mylonakis, Mathios E

    2016-02-29

    There is currently lack of information on the changes of acute phase proteins (APP) and antioxidant markers and their clinical relevance as treatment response indicators in canine monocytic ehrlichiosis (CME). The objective of this study was to investigate the patterns of C-reactive protein (CRP), haptoglobin (Hp), ferritin and paraoxonase-1 (PON-1) during treatment of dogs with acute CME with rifampicin. Blood serum samples from ten Beagle dogs with experimental acute CME were retrospectively examined. Five dogs (Group A) were treated with rifampicin (10mg/Kg/24h), per os, for 3 weeks and 5 dogs (Group B) received no treatment (infected controls). Two Beagle dogs served as uninfected controls. Blood serum samples were serially examined prior to Ehrlichia canis inoculation and on post-inoculation days 14, 21, 28, 35 and 42. Significant changes of CRP, Hp, ferritin and PON-1 values were found in the majority of infected dogs. However, their concentrations did not differ between the two groups during the treatment observation period. The results of this study indicate that although several APP and PON-1 tend to significantly change in the majority of dogs with acute CME, they were of limited clinical relevance as treatment response indicators in this experimental setting.

  12. Acute phase protein and antioxidant responses in dogs with experimental acute monocytic ehrlichiosis treated with rifampicin.

    PubMed

    Karnezi, Dimitra; Ceron, Jose J; Theodorou, Konstantina; Leontides, Leonidas; Siarkou, Victoria I; Martinez, Silvia; Tvarijonaviciute, Asta; Harrus, Shimon; Koutinas, Christos K; Pardali, Dimitra; Mylonakis, Mathios E

    2016-02-29

    There is currently lack of information on the changes of acute phase proteins (APP) and antioxidant markers and their clinical relevance as treatment response indicators in canine monocytic ehrlichiosis (CME). The objective of this study was to investigate the patterns of C-reactive protein (CRP), haptoglobin (Hp), ferritin and paraoxonase-1 (PON-1) during treatment of dogs with acute CME with rifampicin. Blood serum samples from ten Beagle dogs with experimental acute CME were retrospectively examined. Five dogs (Group A) were treated with rifampicin (10mg/Kg/24h), per os, for 3 weeks and 5 dogs (Group B) received no treatment (infected controls). Two Beagle dogs served as uninfected controls. Blood serum samples were serially examined prior to Ehrlichia canis inoculation and on post-inoculation days 14, 21, 28, 35 and 42. Significant changes of CRP, Hp, ferritin and PON-1 values were found in the majority of infected dogs. However, their concentrations did not differ between the two groups during the treatment observation period. The results of this study indicate that although several APP and PON-1 tend to significantly change in the majority of dogs with acute CME, they were of limited clinical relevance as treatment response indicators in this experimental setting. PMID:26854345

  13. Transcriptional up-regulation of antioxidant genes by PPAR{delta} inhibits angiotensin II-induced premature senescence in vascular smooth muscle cells

    SciTech Connect

    Kim, Hyo Jung; Ham, Sun Ah; Paek, Kyung Shin; Hwang, Jung Seok; Jung, Si Young; Kim, Min Young; Jin, Hanna; Kang, Eun Sil; Woo, Im Sun; Kim, Hye Jung; Lee, Jae Heun; Chang, Ki Churl; Han, Chang Woo; Seo, Han Geuk

    2011-03-25

    Research highlights: {yields} Activation of PPAR{delta} by GW501516 significantly inhibited Ang II-induced premature senescence in hVSMCs. {yields} Agonist-activated PPAR{delta} suppressed generation of Ang II-triggered ROS with a concomitant reduction in DNA damage. {yields} GW501516 up-regulated expression of antioxidant genes, such as GPx1, Trx1, Mn-SOD and HO-1. {yields} Knock-down of these antioxidant genes abolished the effects of GW501516 on ROS production and premature senescence. -- Abstract: This study evaluated peroxisome proliferator-activated receptor (PPAR) {delta} as a potential target for therapeutic intervention in Ang II-induced senescence in human vascular smooth muscle cells (hVSMCs). Activation of PPAR{delta} by GW501516, a specific agonist of PPAR{delta}, significantly inhibited the Ang II-induced premature senescence of hVSMCs. Agonist-activated PPAR{delta} suppressed the generation of Ang II-triggered reactive oxygen species (ROS) with a concomitant reduction in DNA damage. Notably, GW501516 up-regulated the expression of antioxidant genes, such as glutathione peroxidase 1, thioredoxin 1, manganese superoxide dismutase and heme oxygenase 1. siRNA-mediated down-regulation of these antioxidant genes almost completely abolished the effects of GW501516 on ROS production and premature senescence in hVSMCs treated with Ang II. Taken together, the enhanced transcription of antioxidant genes is responsible for the PPAR{delta}-mediated inhibition of premature senescence through sequestration of ROS in hVSMCs treated with Ang II.

  14. A phase II study of axitinib in advanced neuroendocrine tumors

    PubMed Central

    Strosberg, J R; Cives, M; Hwang, J; Weber, T; Nickerson, M; Atreya, C E; Venook, A; Kelley, R K; Valone, T; Morse, B; Coppola, D; Bergsland, E K

    2016-01-01

    Neuroendocrine tumors (NETs) are highly vascular neoplasms overexpressing vascular endothelial growth factor (VEGF) as well as VEGF receptors (VEGFR). Axitinib is a potent, selective inhibitor of VEGFR-1, -2 and -3, currently approved for the treatment of advanced renal cell carcinoma. We performed an open-label, two-stage design, phase II trial of axitinib 5 mg twice daily in patients with progressive unresectable/metastatic low-to-intermediate grade carcinoid tumors. The primary end points were progression-free survival (PFS) and 12-month PFS rate. The secondary end points included time to treatment failure (TTF), overall survival (OS), overall radiographic response rate (ORR), biochemical response rate and safety. A total of 30 patients were enrolled and assessable for toxicity; 22 patients were assessable for response. After a median follow-up of 29 months, we observed a median PFS of 26.7 months (95% CI, 11.4–35.1), with a 12-month PFS rate of 74.5% (±10.2). The median OS was 45.3 months (95% CI, 24.4–45.3), and the median TTF was 9.6 months (95% CI, 5.5–12). The best radiographic response was partial response (PR) in 1/30 (3%) and stable disease (SD) in 21/30 patients (70%); 8/30 patients (27%) were unevaluable due to early withdrawal due to toxicity. Hypertension was the most common toxicity that developed in 27 patients (90%). Grade 3/4 hypertension was recorded in 19 patients (63%), leading to treatment discontinuation in six patients (20%). Although axitinib appears to have an inhibitory effect on tumor growth in patients with advanced, progressive carcinoid tumors, the high rate of grade 3/4 hypertension may represent a potential impediment to its use in unselected patients. PMID:27080472

  15. A phase II trial of oral gimatecan for recurrent glioblastoma.

    PubMed

    Hu, Jethro; Wen, Patrick Y; Abrey, Lauren E; Fadul, Camilo E; Drappatz, Jan; Salem, Nadia; Supko, Jeffrey G; Hochberg, Fred

    2013-02-01

    Gimatecan is a lipophilic oral camptothecin analogue with preclinical activity in glioma models. We conducted a multicenter phase II trial to evaluate the efficacy of gimatecan in adults with recurrent glioblastoma. Eligibility criteria included ≤1 prior treatment for recurrent disease, age ≥18, Eastern Cooperative Oncology Group performance status 0-1, and normal organ function. Patients taking enzyme-inducing anti-seizure medications were excluded. Gimatecan 1.22 mg/m(2) was given orally once daily for 5 consecutive days during each 28-day cycle. The primary endpoint was progression-free survival at 6 months. A Simon 2-stage optimal design was used in which 19 patients were evaluated in the 1st stage, with an additional 36 patients accrued if >4 patients in stage 1 achieved PFS at 6 months. 29 patients were enrolled in the study, with median age of 58 years (range, 25-77 years); 58.6 % female. All patients received prior surgery, radiation therapy, and at least one chemotherapy regimen. The daily dose was reduced to 1.0 mg/m(2) after four of the first 10 patients experienced grade 4 hematologic toxicity. Treatment-related grade 3/4 toxicities included thrombocytopenia (17.2 %), leukopenia (17.2 %) and neutropenia (10.3 %). None of the 19 patients treated at 1.0 mg/m(2)/day experienced grade 4 hematologic toxicity. One patient had a partial radiographic response by modified Macdonald criteria. Only 3 patients (12 %) were progression-free at 6 months. Median time to progression was 12.0 weeks (7.0, 17.0).Treatment with gimatecan 1.0 mg/m(2)/day for 5 days, repeated every 28-days showed minimal efficacy.

  16. Phase II study of PX-866 in recurrent glioblastoma

    PubMed Central

    Pitz, Marshall W.; Eisenhauer, Elizabeth A.; MacNeil, Mary V.; Thiessen, Brian; Easaw, Jacob C.; Macdonald, David R.; Eisenstat, David D.; Kakumanu, Ankineedu S.; Salim, Muhammad; Chalchal, Haji; Squire, Jeremy; Tsao, Ming Sound; Kamel-Reid, Suzanne; Banerji, Shantanu; Tu, Dongsheng; Powers, Jean; Hausman, Diana F.; Mason, Warren P.

    2015-01-01

    Background Glioblastoma (GBM) is the most aggressive malignancy of the central nervous system in adults. Increased activity of the phosphatidylinositol-3-OH kinase (PI3K) signal transduction pathway is common. We performed a phase II study using PX-866, an oral PI3K inhibitor, in participants with recurrent GBM. Methods Patients with histologically confirmed GBM at first recurrence were given oral PX-866 at a dose of 8 mg daily. An MRI and clinical exam were done every 8 weeks. Tissue was analyzed for potential predictive markers. Results Thirty-three participants (12 female) were enrolled. Median age was 56 years (range 35–78y). Eastern Cooperative Oncology Group performance status was 0–1 in 29 participants and 2 in the remainder. Median number of cycles was 1 (range 1–8). All participants have discontinued therapy: 27 for disease progression and 6 for toxicity (5 liver enzymes and 1 allergic reaction). Four participants had treatment-related serious adverse events (1 liver enzyme, 1 diarrhea, 2 venous thromboembolism). Other adverse effects included fatigue, diarrhea, nausea, vomiting, and lymphopenia. Twenty-four participants had a response of progression (73%), 1 had partial response (3%, and 8 (24%) had stable disease (median, 6.3 months; range, 3.1–16.8 months). Median 6-month progression-free survival was 17%. None of the associations between stable disease and PTEN, PIK3CA, PIK3R1, or EGFRvIII status were statistically significant. Conclusions PX-866 was relatively well tolerated. Overall response rate was low, and the study did not meet its primary endpoint; however, 21% of participants obtained durable stable disease. This study also failed to identify a statistically significant association between clinical outcome and relevant biomarkers in patients with available tissue. PMID:25605819

  17. NOx control subsystem test plan: LEBS Phase II

    SciTech Connect

    1995-03-16

    It is planned that NO{sub x} control subsystem testing in support of Phase II of the Low-Emissions Boiler Systems (LEBS) Project occur in ABB Power Plant Laboratories` (PPL) pilot scale Boiler Simulation Facility (BSF). This work will be performed to provide necessary design and operational information for inclusion of an optimized NO, control subsystem in the Proof-of-Concept Test Facility (POCTF) and Commercial Generating Unit (CGU) designs. The BSF is a 50 to 90x10{sup 6} BTU/hr (15 to 26 MWt) coal, oil or natural gas fired tangential furnace designed to replicate the residence time/temperature history of a utility scale tangentially fired boiler. All major aspects of a typical utility boiler are duplicated in the BSF including the lower furnace, the ash hopper, multiple burner elevations, the arch section, superheater/reheater panels, and the convective heat transfer surfaces. The furnace walls and heat transfer surfaces are cooled by a surrounding water jacket. Steam generated is vented off at atmospheric pressure so that a constant sink temperature of 100{degrees}C (212{degrees}C) is maintained. The lower furnace water walls are selectively refractory lined to maintain an appropriate furnace gas temperature history. Refractory is required because the sink temperature (100{degrees}C) is cooler than that of a typical, utility boiler, and the surface-to-volume ratio of the BSF is greater than that of a utility boiler due to scale effects. For the subject testing, the BSF will be configured as a coal fired boiler. Design and planning activities associated with the construction of the NO{sub x} control subsystem test unit will continue through June, 1995. Additionally, the schedule for specification of certain low NO{sub x} firing system components was set to allow for precursor, internal and LEBS development activities to occur and subsequently provide necessary design parameters.

  18. Synthesis, characterisation and antioxidant activity of luteolin-vanadium(II) complex.

    PubMed

    Roy, Souvik; Mallick, Sougata; Chakraborty, Tania; Ghosh, Nilanjan; Singh, Amit Kumar; Manna, Subhadip; Majumdar, Sumana

    2015-04-15

    The complex formation between luteolin (L) and vanadium(IV) oxide sulphate monohydrate (VOSO4·H2O) was examined under UV-visible, infra-red spectroscopy, mass spectroscopy and NMR techniques. The spectroscopic data indicated that luteolin reacts with vanadium oxide cation (VO(+2)) through 4-carbonyl-5-hydroxy chelation site in the two luteolin molecule. The free radical antioxidant activity of the complex with respect to the parent molecule was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and 2,2'-azinobis 3-ethylbenzothiazoline-6-sulphonic acid diammonium salt (ABTS) methods. It was observed that the free radical scavenging activity and ferric ion reducing potential of luteolin was increased after the formation of complex with vanadium oxide (VO(+2)) cation.

  19. Potent induction of cellular antioxidants and phase 2 enzymes by resveratrol in cardiomyocytes: protection against oxidative and electrophilic injury.

    PubMed

    Cao, Zhuoxiao; Li, Yunbo

    2004-04-01

    Resveratrol is known to be protective against oxidative cardiovascular disorders. However, the underlying mechanisms remain unclear. This study was undertaken to determine if resveratrol could increase endogenous antioxidants and phase 2 enzymes in cardiomyocytes, and if such increased cellular defenses could provide protection against oxidative and electrophilic cell injury. Incubation of cardiac H9C2 cells with low micromolar resveratrol resulted in a significant induction of a scope of cellular antioxidants and phase 2 enzymes in a concentration- and/or time-dependent fashion. To investigate the protective effects of the resveratrol-induced cellular defenses on oxidative and electrophilic cell injury, H9C2 cells were first incubated with resveratrol, and then exposed to xanthine oxidase (XO)/xanthine, 4-hydroxy-2-nonenal or doxorubicin. We observed that resveratrol pretreatment afforded a marked protection against the above agent-mediated cytotoxicity in H9C2 cells. Moreover, the resveratrol pretreatment led to a great reduction in XO/xanthine-induced intracellular accumulation of ROS. Taken together, this study demonstrates that resveratrol induces antioxidants and phase 2 enzymes in cardiomyocytes, which is accompanied by increased resistance to oxidative and electrophilic cell injury.

  20. Phase II experiment test plan: solar photovoltaic/thermal residential experiment

    SciTech Connect

    Sheldon, D. B.

    1980-01-23

    The Solar Photovoltaic/Thermal Energy Project being carried out by the Massachusetts Institute of Technology Lincoln Laboratory under US Department of Energy funding requires a Phase II test plan for its Solar Energy Research Facility (SERF) located at the University of Texas at Arlington. This Phase II test plan is provided. The purpose of the research being conducted at the SERF is reviewed, and references describing Phase I work are listed.

  1. Antimutagenicity and induction of anticarcinogenic phase II enzymes by basidiomycetes.

    PubMed

    Shon, Y H; Nam, K S

    2001-09-01

    Extracts from Phellinus linteus, Phellinus igniarius, and Agrocybe cylindracea have been tested for their antimutagenic properties against direct-acting mutagens [4-nitro-o-phenylenediamine (NPD) and sodium azide (NaN(3))] and indirect-acting mutagens [2-aminofluorene (2-AF) and benzo[a]pyrene (B[a]P)], using the Salmonella typhimurium tester strains TA 98 and TA 100. In addition, the chemopreventive potentials of these extracts to induce NAD(P)H:quinone oxidoreductase (QR) and glutathione S-transferase (GST) activities and glutathione (GSH) level extracts from the filtrate of the cultured broth of P. linteus, polysaccharide extracts from the cultured broth (PI I) and mycelia (PI II) and water extract of fruiting bodies (PI II) of P. igniarius, and polysaccharide extracts from the cultured broth (AC I) and mycelia (AC II) of A. cylindracea showed inhibitory effects on the mutagenic activities induced by the direct-acting mutagens, NPD and NaN(3), and the indirect-acting mutagens, 2-AF and B[a]P. QR was induced with PI I, PI II, AC I, and AC II, and GST activity was induced with PL I, PL II, PI I, PI II, PI III and AC I in murine Hepa1c1c7 cell culture. In addition, PL I, PL II, PI I, PI II, PI III and AC II increased glutathione level. These results suggest that P. linteus, P. igniarius, and A. cylindracea have antimutagenic activities and may play a role in the prevention of cancer by inducing QR and GST activities and increasing GSH level. PMID:11483385

  2. Designing a series of decision-theoretic phase II trials in a small population.

    PubMed

    Hee, Siew Wan; Stallard, Nigel

    2012-12-30

    This paper introduces a decision-theoretic design for a series of phase II trials. Instead of designing phase II trials individually, we proposed a development plan that consists of a series of phase II trials and one phase III trial such that the long-term expected utility on the whole is optimized. The phase II trials are conducted sequentially, and patients are recruited sequentially to each phase II trial. At each interim stage, a decision is made to continue recruiting patients to the current trial, to stop and recommend the treatment proceeds to a phase III trial, to stop and initiate a new phase II trial or to stop and cease the development plan. The methodology uses a hybrid approach in which it is assumed that the data from the final phase III trial will be analysed using a classical frequentist hypothesis test. The expected power of this test based on some specified prior distribution for the effect of the experimental treatment is then used in a utility function, which is used to obtain the optimal design for the whole series of trials. PMID:22927289

  3. Bioactive compounds extracted from Indian wild legume seeds: antioxidant and type II diabetes-related enzyme inhibition properties.

    PubMed

    Gautam, Basanta; Vadivel, Vellingiri; Stuetz, Wolfgang; Biesalski, Hans K

    2012-03-01

    Seven different wild legume seeds (Acacia leucophloea, Bauhinia variegata, Canavalia gladiata, Entada scandens, Mucuna pruriens, Sesbania bispinosa and Tamarindus indica) from various parts of India were analyzed for total free phenolics, l-Dopa (l-3,4 dihydroxyphenylalanine), phytic acid and their antioxidant capacity (ferric-reducing antioxidant power [FRAP] and 2,2-diphenyl-1-picrylhydrazyl [DPPH] assay) and type II diabetes-related enzyme inhibition activitiy (α-amylase). S. bispinosa had the highest content in both total free phenolics and l-Dopa, and relatively low phytic acid when compared with other seeds. Phytic acid content, being highest in E. scandens, M. pruriens and T. indica, was highly predictive for FRAP (r = 0.47, p < 0.05) and DPPH (r = 0.66, p < 0.001) assays. The phenolic extract from T. indica and l-Dopa extract from E. scandens showed significantly higher FRAP values among others. All seed extracts demonstrated a remarkable reducing power (7-145 mM FeSO4 per mg extract), DPPH radical scavenging activity (16-95%) and α-amylase enzyme inhibition activity (28-40%).

  4. Bioactive compounds extracted from Indian wild legume seeds: antioxidant and type II diabetes-related enzyme inhibition properties.

    PubMed

    Gautam, Basanta; Vadivel, Vellingiri; Stuetz, Wolfgang; Biesalski, Hans K

    2012-03-01

    Seven different wild legume seeds (Acacia leucophloea, Bauhinia variegata, Canavalia gladiata, Entada scandens, Mucuna pruriens, Sesbania bispinosa and Tamarindus indica) from various parts of India were analyzed for total free phenolics, l-Dopa (l-3,4 dihydroxyphenylalanine), phytic acid and their antioxidant capacity (ferric-reducing antioxidant power [FRAP] and 2,2-diphenyl-1-picrylhydrazyl [DPPH] assay) and type II diabetes-related enzyme inhibition activitiy (α-amylase). S. bispinosa had the highest content in both total free phenolics and l-Dopa, and relatively low phytic acid when compared with other seeds. Phytic acid content, being highest in E. scandens, M. pruriens and T. indica, was highly predictive for FRAP (r = 0.47, p < 0.05) and DPPH (r = 0.66, p < 0.001) assays. The phenolic extract from T. indica and l-Dopa extract from E. scandens showed significantly higher FRAP values among others. All seed extracts demonstrated a remarkable reducing power (7-145 mM FeSO4 per mg extract), DPPH radical scavenging activity (16-95%) and α-amylase enzyme inhibition activity (28-40%). PMID:21970446

  5. Structural mechanisms of the Ih–II and II → Ic transitions between the crystalline phases of aqueous ice

    SciTech Connect

    Zheligovskaya, E. A.

    2015-09-15

    Structural mechanisms are proposed for experimentally observed phase transitions between crystalline modifications of aqueous ice, Ih and II, as well as II and Ic. It is known that the Ih–II transition occurs with the conservation of large structural units (hexagonal channels) common for these ices. It is shown that the Ih → II transition may occur with the conservation of 5/6 of all hydrogen bonds in crystal, including all hydrogen bonds in the retained channels (3/4 of the total number of bonds in crystal) and 1/3 of the bonds between these channels (1/12 of the total number). The transformation of other hydrogen bonds between the retained channels leads to the occurrence of proton order in ice II. A structural mechanism is proposed to explain the transformation of single crystals of ice Ih either into single crystals of ice II or into crystalline twins of ice II with c axes rotated by 180° with respect to each other, which is often observed at the Ih → II transition. It is established that up to 7/12 of all hydrogen bonds are retained at the irreversible cooperative II → Ic transition.

  6. Nitrosonifedipine ameliorates angiotensin II-induced vascular remodeling via antioxidative effects.

    PubMed

    Sakurada, Takumi; Ishizawa, Keisuke; Imanishi, Masaki; Izawa-Ishizawa, Yuki; Fujii, Shoko; Tominaga, Erika; Tsuneishi, Teppei; Horinouchi, Yuya; Kihira, Yoshitaka; Ikeda, Yasumasa; Tomita, Shuhei; Aihara, Ken-ichi; Minakuchi, Kazuo; Tsuchiya, Koichiro; Tamaki, Toshiaki

    2013-01-01

    Nifedipine is unstable under light and decomposes to a stable nitroso analog, nitrosonifedipine (NO-NIF). The ability of NO-NIF to block calcium channels is quite weak compared with that of nifedipine. Recently, we have demonstrated that NO-NIF reacts with unsaturated fatty acid leading to generate NO-NIF radical, which acquires radical scavenging activity. However, the effects of NO-NIF on the pathogenesis related with oxidative stress, such as atherosclerosis and hypertension, are unclear. In this study, we investigated the effects of NO-NIF on angiotensin II (Ang II)-induced vascular remodeling. Ang II-induced thickening and fibrosis of aorta were inhibited by NO-NIF in mice. NO-NIF decreased reactive oxygen species (ROS) in the aorta and urinary 8-hydroxy-20-deoxyguanosine. Ang II-stimulated mRNA expressions of p22(phox), CD68, F4/80, monocyte chemoattractant protein-1, and collagen I in the aorta were inhibited by NO-NIF. Moreover, NO-NIF inhibited Ang II-induced cell migration and proliferation of vascular smooth muscle cells (VSMCs). NO-NIF reduced Ang II-induced ROS to the control level detected by dihydroethidium staining and lucigenin chemiluminescence assay in VSMCs. NO-NIF suppressed phosphorylations of Akt and epidermal growth factor receptor induced by Ang II. However, NO-NIF had no effects on intracellular Ca(2+) increase and protein kinase C-δ phosphorylation induced by Ang II in VSMCs. The electron paramagnetic resonance spectra indicated the continuous generation of NO-NIF radical of reaction with cultured VSMCs. These findings suggest that NO-NIF improves Ang II-induced vascular remodeling via the attenuation of oxidative stress.

  7. Chitosan film loaded with silver nanoparticles-sorbent for solid phase extraction of Al(III), Cd(II), Cu(II), Co(II), Fe(III), Ni(II), Pb(II) and Zn(II).

    PubMed

    Djerahov, Lubomir; Vasileva, Penka; Karadjova, Irina; Kurakalva, Rama Mohan; Aradhi, Keshav Krishna

    2016-08-20

    The present study describes the ecofriendly method for the preparation of chitosan film loaded with silver nanoparticles (CS-AgNPs) and application of this film as efficient sorbent for separation and enrichment of Al(III), Cd(II), Cu(II), Co(II), Fe(III), Ni(II), Pb(II) and Zn(II). The stable CS-AgNPs colloid was prepared by dispersing the AgNPs sol in chitosan solution at appropriate ratio and further used to obtain a cast film with very good stability under storage and good mechanical strength for easy handling in aqueous medium. The incorporation of AgNPs in the structure of CS film and interaction between the polymer matrix and nanoparticles were confirmed by UV-vis and FTIR spectroscopy. The homogeneously embedded AgNPs (average diameter 29nm, TEM analysis) were clearly observed throughout the film by SEM. The CS-AgNPs nanocomposite film shows high sorption activity toward trace metals under optimized chemical conditions. The results suggest that the CS-AgNPs nanocomposite film can be feasibly used as a novel sorbent material for solid-phase extraction of metal pollutants from surface waters.

  8. Experimental and DFT characterization, antioxidant and anticancer activities of a Cu(II)-irbesartan complex: structure-antihypertensive activity relationships in Cu(II)-sartan complexes.

    PubMed

    Islas, María S; Luengo, Alicia; Franca, Carlos A; Merino, Mercedes Griera; Calleros, Laura; Rodriguez-Puyol, Manuel; Lezama, Luis; Ferrer, Evelina G; Williams, Patricia A M

    2016-10-01

    The coordination compound of the antihypertensive ligand irbesartan (irb) with copper(II) (CuIrb) was synthesized and characterized by FTIR, FT-Raman, UV-visible, reflectance and EPR spectroscopies. Experimental evidence allowed the implementation of structural and vibrational studies by theoretical calculations made in the light of the density functional theory (DFT). This compound was designed to induce structural modifications on the ligand. No antioxidant effects were displayed by both compounds, though CuIrb behaved as a weak 1,1-diphenyl-2-picrylhydrazyl radical (DPPH(·)) scavenger (IC50 = 425 μM). The measurements of the contractile capacity on human mesangial cell lines showed that CuIrb improved the antihypertensive effects of the parent medication. In vitro cell growth inhibition against prostate cancer cell lines (LNCaP and DU 145) was measured for CuIrb, irbesartan and copper(II). These cell lines have been selected since the angiotensin II type 1 (AT1) receptor (that was blocked by the angiotensin receptor blockers, ARB) has been identified in them. The complex exerted anticancer behavior (at 100 μM) improving the activity of the ligand. Flow cytometry determinations were used to determine late apoptotic mechanisms of cell death. Experimental and DFT characterization of an irbesartan copper(II) complex has been performed. The complex exhibits low scavenging activity against DPPH(·) and significant growth inhibition of LNCaP and DU 145 prostate cancer cell lines. Flow cytometry determinations were used to determine late apoptotic mechanisms of cell death. This compound improved the antihypertensive effect of irbesartan. This effect was observed earlier for the mononuclear Cu-candesartan complex, but not in structurally modified sartans forming dinuclear or octanuclear Cu-sartan compounds.

  9. Metabolism of methandrostenolone in the horse: a gas chromatographic-mass spectrometric investigation of phase I and phase II metabolism.

    PubMed

    McKinney, A R; Ridley, D D; Suann, C J

    2001-12-01

    The phase I and phase II metabolism of the anabolic steroid methandrostenolone was investigated following oral administration to a standardbred gelding. In the phase I study, metabolites were isolated from the urine by solid-phase extraction, deconjugated by acid catalysed methanolysis and converted to their O-methyloxime trimethylsilyl derivatives. GC-MS analysis indicated the major metabolic processes to be sequential reduction of the A-ring and hydroxylation at C6 and C16. In the phase II study, unconjugated, beta-glucuronidated and sulfated metabolites were fractionated and deconjugated using a combination of liquid-liquid extraction, enzyme hydrolysis, solid-phase extraction and acid catalysed methanolysis. Derivatization followed by GC-MS analysis revealed extensive conjugation to both glucuronic and sulfuric acids, with only a small proportion of metabolites occurring in unconjugated form. PMID:11817312

  10. Yakima River Basin Phase II Fish Screen Evaluations, 2001.

    SciTech Connect

    Carter, J.A.; McMichael, Geoffrey A.; Chamness, M.A.

    2002-01-01

    In the summer and fall of 2001 the Pacific Northwest National Laboratory (PNNL) evaluated 23 Phase II fish screen sites in the Yakima River Basin as part of a multi-year study for the Bonneville Power Administration (BPA) on the effectiveness of fish screening devices. Data were collected to determine if velocities in front of the screens and in the bypasses met current National Marine Fisheries Service (NMFS) criteria to promote safe and timely fish passage and whether bypass outfall conditions allowed fish to safely return to the river. Based on our studies in 2001, we concluded that: in general, water velocity conditions at the screen sites met fish passage criteria set forth by the NMFS; most facilities efficiently protected juvenile fish from entrainment, impingement, or migration delay; automated cleaning brushes generally functioned properly; chains and other moving parts were well greased and operative; and removal of sediment build-up and accumulated leafy and woody debris are areas that continue to improve. Continued periodic screen evaluations will increase the effectiveness of screen operation and maintenance practices by confirming the effectiveness (or ineffectiveness) of screen operating procedures at individual sites. Where procedures are being followed and problems still occur, evaluation results can be used to suggest means to better protect fish at screening facilities. There has been a progressive improvement in the maintenance and effectiveness of fish screen facilities in the Yakima River Basin during the last several years, in part, as a result of regular screen evaluations and the rapid feedback of information necessary to improve operations and design of these important fish protection devices. Continued periodic screen evaluations will increase the effectiveness of screen operation and maintenance practices by confirming the effectiveness (or ineffectiveness) of screen operating procedures at individual sites. Where procedures are being

  11. Microgrid Design, Development and Demonstration - Final Report for Phase I and Phase II

    SciTech Connect

    Bose, Sumit; Krok, Michael

    2011-02-08

    This document constitutes GE’s final report for the Microgrid Design, Development and Demonstration program for DOE’s Office of Electricity Delivery and Energy Reliability, Award DE-FC02-05CH11349. It contains the final report for Phase I in Appendix I, and the results the work performed in Phase II. The program goal was to develop and demonstrate a Microgrid Energy Management (MEM) framework for a broad set of Microgrid applications that provides unified controls, protection, and energy management. This project contributed to the achievement of the U.S. Department of Energy’s Renewable and Distributed Systems Integration Program goals by developing a fully automated power delivery microgrid network that: - Reduces carbon emissions and emissions of other air pollutants through increased use of optimally dispatched renewable energy, - Increases asset use through integration of distributed systems, - Enhances reliability, security, and resiliency from microgrid applications in critical infrastructure protection, constrained areas of the electric grid, etc. - Improves system efficiency with on-site, distributed generation and improved economic efficiency through demand-side management.

  12. Biomarker-Guided Adaptive Trial Designs in Phase II and Phase III: A Methodological Review

    PubMed Central

    Antoniou, Miranta; Jorgensen, Andrea L; Kolamunnage-Dona, Ruwanthi

    2016-01-01

    Background Personalized medicine is a growing area of research which aims to tailor the treatment given to a patient according to one or more personal characteristics. These characteristics can be demographic such as age or gender, or biological such as a genetic or other biomarker. Prior to utilizing a patient’s biomarker information in clinical practice, robust testing in terms of analytical validity, clinical validity and clinical utility is necessary. A number of clinical trial designs have been proposed for testing a biomarker’s clinical utility, including Phase II and Phase III clinical trials which aim to test the effectiveness of a biomarker-guided approach to treatment; these designs can be broadly classified into adaptive and non-adaptive. While adaptive designs allow planned modifications based on accumulating information during a trial, non-adaptive designs are typically simpler but less flexible. Methods and Findings We have undertaken a comprehensive review of biomarker-guided adaptive trial designs proposed in the past decade. We have identified eight distinct biomarker-guided adaptive designs and nine variations from 107 studies. Substantial variability has been observed in terms of how trial designs are described and particularly in the terminology used by different authors. We have graphically displayed the current biomarker-guided adaptive trial designs and summarised the characteristics of each design. Conclusions Our in-depth overview provides future researchers with clarity in definition, methodology and terminology for biomarker-guided adaptive trial designs. PMID:26910238

  13. Ni(II), Pd(II) and Pt(II) complexes of (1H-1,2,4-triazole-3-ylimino)methyl]naphthalene-2-ol. Structural, spectroscopic, biological, cytotoxicity, antioxidant and DNA binding

    NASA Astrophysics Data System (ADS)

    Gaber, M.; El-Ghamry, H. A.; Fathalla, S. K.

    2015-03-01

    Metal complexes of the general formula [ML(H2O)Cl]nH2O; n = 1 for M = Ni and Pt and n = 2 for M = Pd, L = Schiff base (HL) derived from the condensation of 3-amino-1,2,4-triazole and 2-hydroxy-1-naphthaldehyde, were prepared. The synthesized ligand and its metal complexes were characterized on the basis of elemental analyses, spectral and magnetic studies as well as thermal analysis. The IR spectra revealed that the ligand is coordinated to the metal ions in bidentate manner via the N-atom of the azomethine group and the phenolic OH group. Square planar geometry was proposed for Pd(II) and Pt(II) complexes and tetrahedral for Ni(II) complex. The ligand and its metal complexes were screened against the sensitive organisms Escherichia coli as Gram-negative bacteria, Staphylococcus aureus as Gram-positive bacteria, Aspergillus flavus and Candida albicans as fungi. Moreover, the anticancer activity of the ligand and its metal complexes was evaluated in liver carcinoma (HEPG2) cell line. The results obtained indicated that the Schiff base ligand is more effective than its metal complexes towards the tested cell line. Ni(II), Pd(II) and Pt(II) complexes as well as the free Schiff base ligand were tested for their antioxidant activities. The DNA-binding properties of the studied complexes have been investigated by electronic absorption and viscosity measurements.

  14. Ni(II), Pd(II) and Pt(II) complexes of (1H-1,2,4-triazole-3-ylimino)methyl]naphthalene-2-ol. Structural, spectroscopic, biological, cytotoxicity, antioxidant and DNA binding.

    PubMed

    Gaber, M; El-Ghamry, H A; Fathalla, S K

    2015-03-15

    Metal complexes of the general formula [ML(H2O)Cl]nH2O; n=1 for M=Ni and Pt and n=2 for M=Pd, L=Schiff base (HL) derived from the condensation of 3-amino-1,2,4-triazole and 2-hydroxy-1-naphthaldehyde, were prepared. The synthesized ligand and its metal complexes were characterized on the basis of elemental analyses, spectral and magnetic studies as well as thermal analysis. The IR spectra revealed that the ligand is coordinated to the metal ions in bidentate manner via the N-atom of the azomethine group and the phenolic OH group. Square planar geometry was proposed for Pd(II) and Pt(II) complexes and tetrahedral for Ni(II) complex. The ligand and its metal complexes were screened against the sensitive organisms Escherichia coli as Gram-negative bacteria, Staphylococcus aureus as Gram-positive bacteria, Aspergillus flavus and Candida albicans as fungi. Moreover, the anticancer activity of the ligand and its metal complexes was evaluated in liver carcinoma (HEPG2) cell line. The results obtained indicated that the Schiff base ligand is more effective than its metal complexes towards the tested cell line. Ni(II), Pd(II) and Pt(II) complexes as well as the free Schiff base ligand were tested for their antioxidant activities. The DNA-binding properties of the studied complexes have been investigated by electronic absorption and viscosity measurements. PMID:25576936

  15. Preparation, spectroscopic, thermal, antihepatotoxicity, hematological parameters and liver antioxidant capacity characterizations of Cd(II), Hg(II), and Pb(II) mononuclear complexes of paracetamol anti-inflammatory drug

    NASA Astrophysics Data System (ADS)

    El-Megharbel, Samy M.; Hamza, Reham Z.; Refat, Moamen S.

    2014-10-01

    Keeping in view that some metal complexes are found to be more potent than their parent drugs, therefore, our present paper aimed to synthesized Cd(II), Hg(II) and Pb(II) complexes of paracetamol (Para) anti-inflammatory drug. Paracetamol complexes with general formula [M(Para)2(H2O)2]·nH2O have been synthesized and characterized on the basis of elemental analysis, conductivity, IR and thermal (TG/DTG), 1H NMR, electronic spectral studies. The conductivity data of these complexes have non-electrolytic nature. Comparative antimicrobial (bacteria and fungi) behaviors and molecular weights of paracetamol with their complexes have been studied. In vivo the antihepatotoxicity effect and some liver function parameters levels (serum total protein, ALT, AST, and LDH) were measured. Hematological parameters and liver antioxidant capacities of both Para and their complexes were performed. The Cd2+ + Para complex was recorded amelioration of antioxidant capacities in liver homogenates compared to other Para complexes treated groups.

  16. Evaluation of the antioxidant capacity of natural polyphenolic compounds using a macrocyclic Ni-(II) complex-catalysed Briggs-Rauscher reaction.

    PubMed

    Li, Mengshuo; Hu, Gang; Chen, Yangyang

    2016-04-15

    This paper reports a method for evaluating antioxidant capacity based on the inhibitory effects of a macrocyclic Ni(II) complex-catalysed Briggs-Rauscher reaction. The macrocyclic Ni(II) complex NiL(ClO4)2, in which L is 5,7,7,12,14,14-hexamethyl-1,4,8,11-tetraazacyclotetradeca-4,11-diene, is a porphyrin-like compound, the structure of which can be found in certain enzymes. The experiments indicated that three natural compounds could temporarily quench the oscillations for a period of time prior to regeneration of oscillations. The inhibition time was related to the compound type and concentration; thus, procedures for evaluating the antioxidant activities of polyphenolic compounds were successfully established. Three polyphenolic compounds were tested to evaluate their antioxidant activities: protocatechuic acid, rutin hydrate and procyanidin. Of these three naturally occurring compounds, procyanidin was found to be the most efficient antioxidant. We have also discussed the reaction of the antioxidant with the hydroperoxyl radical (HOO) present in the oscillating system. PMID:26617044

  17. A Tool for Predicting Regulatory Approval After Phase II Testing of New Oncology Compounds.

    PubMed

    DiMasi, J A; Hermann, J C; Twyman, K; Kondru, R K; Stergiopoulos, S; Getz, K A; Rackoff, W

    2015-11-01

    We developed an algorithm (ANDI) for predicting regulatory marketing approval for new cancer drugs after phase II testing has been conducted, with the objective of providing a tool to improve drug portfolio decision-making. We examined 98 oncology drugs from the top 50 pharmaceutical companies (2006 sales) that first entered clinical development from 1999 to 2007, had been taken to at least phase II development, and had a known final outcome (research abandonment or regulatory marketing approval). Data on safety, efficacy, operational, market, and company characteristics were obtained from public sources. Logistic regression and machine-learning methods were used to provide an unbiased approach to assess overall predictability and to identify the most important individual predictors. We found that a simple four-factor model (activity, number of patients in the pivotal phase II trial, phase II duration, and a prevalence-related measure) had high sensitivity and specificity for predicting regulatory marketing approval. PMID:26239772

  18. Gramicidin-induced hexagonal H/sub II/ phase formation in erythrocyte membranes

    SciTech Connect

    Tournois, H.; Leunissen-Bijvelt, J.; Haest, C.W.M.; de Gier, J.; Kruij, B.

    1987-10-20

    Using /sup 31/P nuclear magnetic resonance (NMR), small-angle X-ray scattering (SAXS), and freeze-fracture electron microscopic (FFEM) techniques, it is shown that gramicidin induces a hexagonal H/sub II/ phase not only in liposomes prepared from total lipids extracted from human erythrocytes but also in isolated human erythrocyte membranes (white ghosts). A 37/sup 0/C, H/sub II/ phase formation is detected at a gramicidin to phospholipid molar ratio exceeding 1:80. The gramicidin-induced H/sub II/ phase exhibits a very small /sup 31/P chemical shift anisotropy indicating decreased head-group order, and it displays a temperature-dependent increase in tube diameter from 60.2 A at 4/sup 0/C to 64.2 A at 37/sup 0/C in ghosts and from 62.8 to 69.4 A at 37/sup 0/C in total lipid extracts, both in the presence of 1 mol of gramicidin/10 mol of phospholipid. /sup 31/P NMR data indicate that the H/sub II/ phase formation by gramicidin is temperature dependent and show the gradual disappearance of the H/sub II/ phase at low temperatures resulting in a bilayer type of /sup 31/P NMR line shape at 4/sup 0/C, whereas SAXS and FFEM data suggest equal amounts of H/sub II/ phases at all temperatures. The induction of the H/sub II/ phase by gramicidin is specific in that N-formylation of the four tryptophan residues of gramicidin completely blocks the hexagonal (H/sub II/) phase inducing ability of the peptide. The striking parallel between hexagonal H/sub II/ phase induction and the enhancement of lysophosphatidylcholine and palmitoylcarnitine transbilayer reorientation by gramicidin as well the lack of effect of the formylated gramicidin strongly suggests the H/sub II/ phase formation and flip enhancement are mechanistically related phenomena. It is suggested that the formation of gramicidin aggregates of specific structure which are intermediates in H/sub II/ phase formation leads to enhancement of transbilayer reorientation of phospholipids.

  19. Analysis of the O-antigen biosynthesis regions of phase II isolates of Coxiella burnetii.

    PubMed

    Denison, Amy M; Massung, Robert F; Thompson, Herbert A

    2007-02-01

    The O-antigen-encoding region in the genomes of 14 isolates of Coxiella burnetii was examined by PCR. Five phase I isolates (Nine Mile clone 7, KAV, Ohio, Henzerling RSA 343, Q173) were analyzed and no deletions were detected. Two other isolates of unknown phase (Scottish, WAV) were examined, but no deletions were detected. In contrast, RSA 514 and three phase II isolates (Nine Mile phase II clone 4, Nine Mile phase II clone 1, Nine Mile Baca) contained large deletions, and the latter two were further characterized by DNA sequencing. Three other phase II isolates (Henzerling RSA 331, M44, Australian QD) contained no apparent deletions. Reactivity to phase I- and phase II-specific antibodies by immunofluorescence assay was used to further characterize isolates. Selected ORFs in Australian QD and M44 DNA were sequenced to detect mutations, and no significant changes were found. Australian QD RNA was examined by reverse transcriptase-PCR specific to the four ORFs hypothesized to encode the O-antigen sugar virenose, which this isolate has been shown to lack, as well as one that is predicted to encode part of the O-antigen ABC transporter. Each of these five genes was found to be expressed.

  20. Phase II clinical trials on Investigational drugs for the Treatment of Pancreatic Cancers

    PubMed Central

    Kim, Edward J.; Semrad, Thomas J.; Bold, Richard J.

    2015-01-01

    Introduction Despite some recent advances in treatment options, pancreatic cancer remains a devastating disease with poor outcomes. In a trend contrary to most malignancies, both incidence and mortality continue to rise due to pancreatic cancer. The majority of patients present with advanced disease and there are no treatment options for this stage that have demonstrated a median survival greater than 1 year. As the penultimate step prior to phase III studies involving hundreds of patients, phase II clinical trials provide an early opportunity to evaluate the efficacy of new treatments that are desperately needed for this disease. Areas Covered This review covers the results of published phase II clinical trials in advanced pancreatic adenocarcinoma published within the past 5 years. The treatment results are framed in the context of the current standards of care and the historic challenge of predicting phase III success from phase II trial results. Expert opinion Promising therapies remain elusive in pancreatic cancer based on recent phase II clinical trial results. Optimization and standardization of clinical trial design in the phase II setting, with consistent incorporation of biomarkers, is needed to more accurately identify promising therapies that warrant phase III evaluation. PMID:25809274

  1. New York State Educational Information System (NYSEIS) Systems Design. Volume I, Phase II. Final Report.

    ERIC Educational Resources Information Center

    Price Waterhouse and Co., New York, NY.

    This volume on Phase II of the New York State Educational Information System (NYSEIS) describes the Gross Systems Analysis and Design, which includes the general flow diagram and processing chart for each of the student, personnel, and financial subsystems. Volume II, Functional Specifications, includes input/output requirements and file…

  2. Functional design criteria for project W-252, phase II liquid effluent treatment and disposal. Revision 2

    SciTech Connect

    Hatch, C.E.

    1995-05-01

    This document is the Functional Design Criteria for Project W-252. Project W-252 provides the scope to provide BAT/AKART (best available technology...) to 200 Liquid Effluent Phase II streams (B-Plant). This revision (Rev. 2) incorporates a major descoping of the project. The descoping was done to reflect a combination of budget cutting measures allowed by a less stringent regulatory posture toward the Phase II streams

  3. High-Lift Flight Tunnel - Phase II Report. Phase 2 Report

    NASA Technical Reports Server (NTRS)

    Lofftus, David; Lund, Thomas; Rote, Donald; Bushnell, Dennis M. (Technical Monitor)

    2000-01-01

    The High-Lift Flight Tunnel (HiLiFT) concept is a revolutionary approach to aerodynamic ground testing. This concept utilizes magnetic levitation and linear motors to propel an aerodynamic model through a tube containing a quiescent test medium. This medium (nitrogen) is cryogenic and pressurized to achieve full flight Reynolds numbers higher than any existing ground test facility world-wide for the range of 0.05 to 0.50 Mach. The results of the Phase II study provide excellent assurance that the HiLiFT concept will provide a valuable low-speed, high Reynolds number ground test facility. The design studies concluded that the HiLiFT facility is feasible to build and operate and the analytical studies revealed no insurmountable difficulties to realizing a practical high Reynolds number ground test facility. It was determined that a national HiLiFT facility, including development, would cost approximately $400M and could be operational by 2013 if fully funded. Study participants included National Aeronautics and Space Administration Langley Research Center as the Program Manager and MSE Technology Applications, Inc., (MSE) of Butte, Montana as the prime contractor and study integrator. MSE#s subcontractors included the University of Texas at Arlington for aerodynamic analyses and the Argonne National Laboratory for magnetic levitation and linear motor technology support.

  4. River Protection Project Integrated safety management system phase II verification report, volumes I and II - 8/19/99

    SciTech Connect

    SHOOP, D.S.

    1999-09-10

    The Department of Energy policy (DOE P 450.4) is that safety is integrated into all aspects of the management and operations of its facilities. In simple and straightforward terms, the Department will ''Do work safely.'' The purpose of this River Protection Project (RPP) Integrated Safety Management System (ISMS) Phase II Verification was to determine whether ISMS programs and processes are implemented within RFP to accomplish the goal of ''Do work safely.'' The goal of an implemented ISMS is to have a single integrated system that includes Environment, Safety, and Health (ES&H) requirements in the work planning and execution processes to ensure the protection of the worker, public, environment, and federal property over the RPP life cycle. The ISMS is comprised of the (1) described functions, components, processes, and interfaces (system map or blueprint) and (2) personnel who are executing those assigned roles and responsibilities to manage and control the ISMS. Therefore, this review evaluated both the ''paper'' and ''people'' aspects of the ISMS to ensure that the system is implemented within RPP. Richland Operations Office (RL) conducted an ISMS Phase I Verification of the TWRS from September 28-October 9, 1998. The resulting verification report recommended that TWRS-RL and the contractor proceed with Phase II of ISMS verification given that the concerns identified from the Phase I verification review are incorporated into the Phase II implementation plan.

  5. Status of trace elements and antioxidants in premenopausal and postmenopausal phase of life: a comparative study

    PubMed Central

    Ansar, Sabah; Alhefdhi, Tayef; Aleem, Ansari M

    2015-01-01

    The aim of the study was to determine the extent of free radical damage in the form of oxidative stress, the antioxidant status and correlate with trace element levels in postmenopausal females as compared to premenopausal females. Participants between the ages of 30-60 years were recruited for the study and status of antioxidant enzymes and trace metals level was determined. The serum Calcium (Ca) levels after menopause was higher than that of the premenopausal group (P<0.001). The changes in copper (Cu) and Zinc (Zn) between the groups were not significant (p>0.05). In postmenopausal women, antioxidant enzymes like superoxide dismutase (SOD) and glutathione peroxidase (GPX), catalase (CAT) significantly decreased (P<0.001) in postmenopausal women showing oxidative stress in the cells. Concentrations of vitamin-C pointed out a significant decrease (P<0.05) in postmenopausal women when compared with premenopausal women. In conclusion. PMID:26770597

  6. Mixed-ligand copper(II) phenolate complexes: Synthesis, spectral characterization, phosphate-hydrolysis, antioxidant, DNA interaction and cytotoxic studies

    NASA Astrophysics Data System (ADS)

    Gurumoorthy, Perumal; Mahendiran, Dharmasivam; Prabhu, Durai; Arulvasu, Chinnasamy; Rahiman, Aziz Kalilur

    2015-01-01

    A series of phenol-based mixed-ligand copper(II) complexes of the type [CuL1-4(diimine)] (1-8), where L1-4 = N1,N2-bis(5-substituted-2-hydroxybenzylidene)-1,2-ethylene/phenylenediimine and diimine = 2,2‧-bipyridyl (bpy) or 1,10-phenanthroline (phen), have been isolated and fully characterized by analytical and spectral techniques. Electronic spectra of complexes suggest Cu(II) cation has a d9 electronic configuration, adopting distorted octahedral geometry with axial elongation, due to Jahn-Teller effect. Electrochemical studies of complexes evidenced one-electron irreversible reduction wave in the cathodic region. The observed rate constant (k) values for the hydrolysis of 4-nitrophenylphosphate (4-NPP) are in the range of 0.25-3.82 × 10-2 min-1. The obtained room temperature magnetic moment values (1.79-1.90 BM) lies within the range observed for octahedral copper(II) complexes. Antioxidant studies revealed that these complexes possess considerable radical scavenging potency against DPPH. The binding studies of complexes with calf thymus DNA (CT-DNA) revealed intercalation with minor-groove binding, and the complex 4 exhibits highest binding activity than the other complexes. The cleavage activity on supercoiled pBR322 DNA revealed the involvement of hydroxyl radical and singlet-oxygen as reactive oxygen species, and complexes encourage binding to minor-groove. Further, the cytotoxicity of complex 4 on human hepatocellular liver carcinoma HepG2 cell line implies the cell death through apoptosis.

  7. Crystal-Phase Control by Solution-Solid-Solid Growth of II-VI Quantum Wires.

    PubMed

    Wang, Fudong; Buhro, William E

    2016-02-10

    A simple and potentially general means of eliminating the planar defects and phase alternations that typically accompany the growth of semiconductor nanowires by catalyzed methods is reported. Nearly phase-pure, defect-free wurtzite II-VI semiconductor quantum wires are grown from solid rather than liquid catalyst nanoparticles. The solid-catalyst nanoparticles are morphologically stable during growth, which minimizes the spontaneous fluctuations in nucleation barriers between zinc blende and wurtzite phases that are responsible for the defect formation and phase alternations. Growth of single-phase (in our cases the wurtzite phase) nanowires is thus favored. PMID:26731426

  8. Phase II Audit Report - Energy & Water Audits of LLNL Facilities

    SciTech Connect

    Horst, B I; Jacobs, P C; Pierce, S M

    2005-08-03

    This report describes Phase II of a project conducted for the Mechanical Utilities Division (UTel), Energy Management Program at Lawrence Livermore National Laboratory (LLNL) by Architectural Energy Corporation (AEC). The overall project covers energy efficiency and water conservation auditing services for 215 modular and prefabricated buildings at LLNL. The primary goal of this project is to demonstrate compliance with DOE Order 430.2A, Contractor Requirements Document section 2.d (2) Document, to demonstrate annual progress of at least 10 percent toward completing energy and water audits of all facilities. Although this project covers numerous buildings, they are all similar in design and use. The approach employed for completing audits for these facilities involves a ''model-similar building'' approach. In the model-similar building approach, similarities between groups of buildings are established and quantified. A model (or test case) building is selected and analyzed for each model-similar group using a detailed DOE-2 simulation. The results are extended to the group of similar buildings based on careful application of quantified similarities, or ''extension measures''. This approach leverages the relatively minor effort required to evaluate one building in some detail to a much larger population of similar buildings. The facility wide energy savings potential was calculated for a select set of measures that have reasonable payback based on the detailed building analysis and are otherwise desirable to the LLNL facilities staff. The selected measures are: (1) HVAC Tune-up. This is considered to be a ''core measure'', based on the energy savings opportunity and the impact on thermal comfort. All HVAC units in the study are assumed to be tuned up under this measure. See the Appendix for a detailed calculation by building and HVAC unit. (2) HVAC system scheduling. This is also considered to be a ''core measure'', based on the energy savings opportunity and

  9. Nickel(II) Oxide Solubility and Phase Stability in High Temperature Aqueous Solutions

    SciTech Connect

    S.E. Ziemniak; M.A. Goyette

    2003-03-17

    A platinum-lined, flowing autoclave facility was used to investigate the solubility behavior of nickel(II) oxide (NiO) in deoxygenated ammonium and sodium hydroxide solutions between 21 and 315 C. Solubilities were found to vary between 0.4 and 400 nanomolal (nm). The measured nickel ion solubilities were interpreted via a Ni(II) ion hydroxo- and amino-complexing model and thermodynamic functions for these equilibria were obtained from a least-squares analysis of the data. Two solid phase transformations were observed: at temperatures below 149 C, the activity of Ni(II) ions in aqueous solution was controlled by a hydrous Ni(II) oxide (theophrastite) solid phase rather than anhydrous NiO (bunsenite); above 247 C, Ni(II) activities were controlled by cubic rather than rhombohedral bunsenite.

  10. Nickel (II) Oxide Solubility and Phase Stability in High Temperature Aqueous Solutions

    SciTech Connect

    SE Ziemniak; MA Goyette

    2004-06-17

    A platinum-lined, flowing autoclave facility was used to investigate the solubility behavior of nickel(II) oxide (NiO) in deoxygenated ammonium and sodium hydroxide solutions between 21 and 315 C. Solubilities were found to vary between 0.4 and 400 nmol kg{sup -1}. The measured nickel ion solubilities were interpreted via a Ni(II) ion hydroxo-and amino-complexing model and thermodynamic functions for these equilibria were obtained from a least-squares analysis of the data. Two solid phase transformations were observed: at temperatures below 149 C, the activity of Ni(II) ions in aqueous solution was controlled by a hydrous Ni(II) oxide (theophrastite) solid phase rather than anhydrous NiO (bunsenite); above 247 C, Ni(II) activities were controlled by cubic rather than rhombohedral bunsenite.

  11. Supplementing antioxidants to pigs fed diets high in oxidants: II. Effects on carcass characteristics, meat quality, and fatty acid profile.

    PubMed

    Lu, T; Harper, A F; Dibner, J J; Scheffler, J M; Corl, B A; Estienne, M J; Zhao, J; Dalloul, R A

    2014-12-01

    concentration of DHA in backfat (P<0.001); switching the diet on d 83 resulted in HO pigs having a similar fatty acid profile to SC at d 118 pigs. Vitamin E concentration in plasma and muscle was greater in HO and SC than VE, AOX, and VE+AOX on d 118. Feeding the high oxidant diet caused a series of changes in carcass characteristics and meat quality. Addition of antioxidant blend attenuated many of these, whereas the protective effects of supplemental vitamin E at 11 IU/kg were minimal during the finisher phase of the study. PMID:25367510

  12. Supplementing antioxidants to pigs fed diets high in oxidants: II. Effects on carcass characteristics, meat quality, and fatty acid profile.

    PubMed

    Lu, T; Harper, A F; Dibner, J J; Scheffler, J M; Corl, B A; Estienne, M J; Zhao, J; Dalloul, R A

    2014-12-01

    concentration of DHA in backfat (P<0.001); switching the diet on d 83 resulted in HO pigs having a similar fatty acid profile to SC at d 118 pigs. Vitamin E concentration in plasma and muscle was greater in HO and SC than VE, AOX, and VE+AOX on d 118. Feeding the high oxidant diet caused a series of changes in carcass characteristics and meat quality. Addition of antioxidant blend attenuated many of these, whereas the protective effects of supplemental vitamin E at 11 IU/kg were minimal during the finisher phase of the study.

  13. SH-2F LAMPS Instructional Systems Development: Phase II. Final Report.

    ERIC Educational Resources Information Center

    Gibbons, Andrew S.; Hymes, Jonah P.

    This project was one of four aircrew training development projects in a continuing study of the methodology, effectiveness, and resource requirements of the Instructional Systems Development (ISD) process. This report covers the Phase II activities of a two-phase project for the development of aircrew training for SH-2F anti-submarine warfare…

  14. 40 CFR 76.8 - Early election for Group 1, Phase II boilers.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source...

  15. 40 CFR 76.8 - Early election for Group 1, Phase II boilers.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source...

  16. 40 CFR 76.8 - Early election for Group 1, Phase II boilers.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source...

  17. 40 CFR 76.8 - Early election for Group 1, Phase II boilers.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source...

  18. 40 CFR 76.8 - Early election for Group 1, Phase II boilers.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source...

  19. DEMONSTRATION OF FUEL CELLS TO RECOVER ENERGY FROM LANDFILL GAS: PHASE II. PRETREATMENT SYSTEM PERFORMANCE MEASUREMENT

    EPA Science Inventory

    The report describes Phase II of a demonstration of the utilization of commercial phosphoric acid fuel cells to recover energy from landfill gas. This phase consisted primarily of the construction and testing of a Gas Pretreatment Unit (GPU) whose function is to remove those impu...

  20. An Experimental Evaluation of Hyperactivity and Food Additives. 1977-Phase II.

    ERIC Educational Resources Information Center

    Harley, J. Preston; And Others

    Phase II of a study on the effectiveness of B. Feingold's recommended diet for hyperactive children involved the nine children (mean age 9 years) who had shown the "best" response to diet manipulation in Phase I. Each child served as his own control and was challenged with specified amounts of placebo and artificial color containing food items…

  1. Proteomic comparison of phase I and II coxiella burnetii cells reveals potential virulence biomarkers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Coxiella burnetii, a category B biological warfare agent, causes several worldwide outbreaks of zoonotic disease each year. In order to identify C. burnetii virulence factors, the virulent phase I and avirulent phase II variants of the Nine Mile RSA strains, were propagated in embryonated hen eggs ...

  2. Phase relations between total solar irradiance and the Mg II index

    NASA Astrophysics Data System (ADS)

    Li, K. J.; Xu, J. C.; Xiang, N. B.; Feng, W.

    2016-01-01

    The Mg II index is usually used to represent the brightening contribution to total solar irradiance (TSI) by solar bright structures, such as faculae and network. In order to understand variations of TSI, phase relations of TSI and the chromospheric Mg II index is investigated on time-scales of one year and longer. The NOAA daily Mg II index at the time interval of November 17, 1978-October 24, 2007 is utilized to carry out correlation analyses respectively with the daily ACRIM and PMOD composites of TSI. The Mg II index is found to lead TSI by about one solar rotation period for time-scales of one year and longer. Correlation of TSI with the Mg II index on the time-scale of one year is sometimes significantly positive, sometimes statistically insignificant, and sometimes even significantly negative. When sunspot darkening is dominant, the correlation between TSI and Mg II is either negative or not significant. When TSI is backward shifted vs the Mg II index by about one rotation period, correlation between them becomes significantly positive in all years. Thus, it is after about one rotation period that a more prominent intensification is inferred to be contributed to TSI than that immediately, by bright constructions, which is represented by the Mg II index. We propose an explanation for the phase relationship of TSI and the Mg II index.

  3. Modifications in the glycerophospholipid composition between the Coxiella burnetii phase I and phase II cells suggest an association with phase variation of the bacterium.

    PubMed

    Frimmelová, M; Toman, R; Pompach, P; Škultéty, L

    2016-03-01

    Glycerophospholipids (GP) extracted from the Coxiella burnetii strain Nine Mile in virulent phase I (NM I) and low virulent phase II (NM II) were analyzed by Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry (MS) that gave a superior mass resolution and mass accuracy allowing unambiguous peak recognition and precise assignment of ions. We showed that GP present in the pathogen's outer membrane underwent considerable modifications during the phase variation that might be related to impact of various environmental factors. It was found that GP from phase I cells were much more complex than those from phase II cells. While glycerophosphoethanolamines (PE), glycerophosphocholines (PC) and glycerophosphoglycerols (PG) were present in both phases of C. burnetii, major differences were observed in the presence of glycerophosphates (PA) and glycerophosphoserines (PS). Thus, PA but no PS were detected in NM I variant in contrast with NM II cells where PS but no PA were identified. It is suggested that enzymes for PA head group modifications to form PS, PE, and PG become active during the phase variation of the bacterium. PMID:26982464

  4. Phase contrast radiography. II. Imaging of complex objects

    NASA Astrophysics Data System (ADS)

    Arhatari, Benedicta D.; Nugent, Keith A.; Peele, Andrew G.; Thornton, John

    2005-11-01

    An image model for phase contrast in projection radiography of complex objects is presented and tested experimentally. The model includes the wavelength distribution of the radiation. The model is used to optimize the contrast of a radiograph of a piece of aluminium containing a fine crack.

  5. Window Treatment Phase I and Other Energy II Conservation Measures.

    ERIC Educational Resources Information Center

    Donohue, Philip E.

    Six different energy-saving treatments for large window areas were tested by Tompkins-Cortland Community College (TCCC) to coordinate energy saving with building design. The TCCC building has an open space design with 33,000 square feet of external glass and other features causing heating problems and high energy costs. Phase I of the…

  6. Technical Analysis of the Hydrogen Energy Station Concept, Phase I and Phase II

    SciTech Connect

    TIAX, LLC

    2005-05-04

    patterns would be most viable for an energy station, TIAX developed several criteria for selecting a representative set of technology configurations. TIAX applied these criteria to all possible technology configurations to determine an optimized set for further analysis, as shown in Table ES-1. This analysis also considered potential energy station operational scenarios and their impact upon hydrogen and power production. For example, an energy station with a 50-kWe reformer could generate enough hydrogen to serve up to 12 vehicles/day (at 5 kg/fill) or generate up to 1,200 kWh/day, as shown in Figure ES-1. Buildings that would be well suited for an energy station would utilize both the thermal and electrical output of the station. Optimizing the generation and utilization of thermal energy, hydrogen, and electricity requires a detailed look at the energy transfer within the energy station and the transfer between the station and nearby facilities. TIAX selected the Baseline configuration given in Table ES-1 for an initial analysis of the energy and mass transfer expected from an operating energy station. Phase II The purpose of this technical analysis was to analyze the development of a hydrogen-dispensing infrastructure for transportation applications through the installation of a 50-75 kW stationary fuel cell-based energy station at federal building sites. The various scenarios, costs, designs and impacts of such a station were quantified for a hypothetical cost-shared program that utilizes a natural gas reformer to provide hydrogen fuel for both the stack(s) and a limited number of fuel cell powered vehicles, with the possibility of using cogeneration to support the building heat load.

  7. Docking studies, synthesis, characterization of some novel oxazine substituted 9-anilinoacridine derivatives and evaluation for their antioxidant and anticancer activities as topoisomerase II inhibitors.

    PubMed

    Kalirajan, R; Kulshrestha, Vivek; Sankar, S; Jubie, S

    2012-10-01

    A series of 9-anilinoacridines substituted with oxazine derivatives were synthesized to evaluate their antioxidant and anticancer activity against Daltons Lymphoma Ascites (DLA) cell growth by in vitro method. It was revealed that these conjugates exhibited significant antioxidant and anticancer activity (inhibition of DLA cell proliferation). Among these agents, compounds 5a, 5h, 5i, 5j were the most cytotoxic with CTC(50) value of 140-250 μg/mL. The docking studies of the synthesized compounds were performed towards the key Topoisomerase II (1QZR) by using Schrodinger Maestro 9.2 version. The oxazine substituted 9-anilinoacridine derivatives 5a, 5h, 5i, 5j have significant anticancer activity as topoisomerase II inhibitors. PMID:22982526

  8. Maximizing return on socioeconomic investment in phase II proof-of-concept trials.

    PubMed

    Chen, Cong; Beckman, Robert A

    2014-04-01

    Phase II proof-of-concept (POC) trials play a key role in oncology drug development, determining which therapeutic hypotheses will undergo definitive phase III testing according to predefined Go-No Go (GNG) criteria. The number of possible POC hypotheses likely far exceeds available public or private resources. We propose a design strategy for maximizing return on socioeconomic investment in phase II trials that obtains the greatest knowledge with the minimum patient exposure. We compare efficiency using the benefit-cost ratio, defined to be the risk-adjusted number of truly active drugs correctly identified for phase III development divided by the risk-adjusted total sample size in phase II and III development, for different POC trial sizes, powering schemes, and associated GNG criteria. It is most cost-effective to conduct small POC trials and set the corresponding GNG bars high, so that more POC trials can be conducted under socioeconomic constraints. If δ is the minimum treatment effect size of clinical interest in phase II, the study design with the highest benefit-cost ratio has approximately 5% type I error rate and approximately 20% type II error rate (80% power) for detecting an effect size of approximately 1.5δ. A Go decision to phase III is made when the observed effect size is close to δ. With the phenomenal expansion of our knowledge in molecular biology leading to an unprecedented number of new oncology drug targets, conducting more small POC trials and setting high GNG bars maximize the return on socioeconomic investment in phase II POC trials. PMID:24526732

  9. Biological Impact of Pd (II) Complexes: Synthesis, Spectral Characterization, In Vitro Anticancer, CT-DNA Binding, and Antioxidant Activities

    PubMed Central

    Sharma, Nitin Kumar; Ameta, Rakesh Kumar; Singh, Man

    2016-01-01

    A new series of Pd (II) complexes of methyl substituted benzylamine ligands (BLs) has been synthesized and characterized via spectroscopic techniques such as UV/Vis. FTIR, LCMS, 1H, and 13C NMR. The UV/Vis study in DMSO, DMSO + water, and DMSO + PBS buffer (pH = 7.2) confirmed their molecular sustainability in liquids. Their in vitro anticancer activity against breast cancer cell lines such as MCF-7 and MDA-MB-231 makes them interesting for in vivo analysis. Their stronger DNA binding activity (DBA) compared with free ligand suggested them as a good DNA binder. DBA was further confirmed by physicochemical studies such as surface tension and viscosity of complex + DNA which inferred the disruption of DNA and intercalation of complexes, respectively. Their % binding activity, % disruption of DNA base pairs (DNABP), and % intercalating strength are reported in this paper for the first time for better understanding of DNA binding mechanism. Along with this, their scavenging activity (SA) determined through DPPH free radical and the results indicate good antioxidant behaviour of complexes. PMID:26989511

  10. Antioxidant properties and neuroprotective effects of isocampneoside II on hydrogen peroxide-induced oxidative injury in PC12 cells.

    PubMed

    Si, Chuan-Ling; Shen, Ting; Jiang, Yun-Yao; Wu, Lei; Yu, Guo-Jing; Ren, Xiao-Dan; Xu, Guang-Hui; Hu, Wei-Cheng

    2013-09-01

    Oxidative stress has been considered as a major cause of cell damage in various neurodegenerative disorders. One of the reasonable strategies for delaying the disease's progression is to prevent reactive oxygen species (ROS) mediated cellular injury by dietary or pharmaceutical augmentation of free radical scavengers. Isocampneoside II (ICD) is an active phenylethanoid glycoside isolated from the medicinal hardwood genus Paulownia. This study was designed to explore free radical scavenging potential of ICD in different in vitro systems and its protective role in hydrogen peroxide (H₂O₂)-induced oxidative stress and apoptotic death in cultured rat pheochromocytoma (PC12) cells. The results showed ICD eliminated approximately 80.75% superoxide radical at the concentration of 0.1mg/ml and inhibited metal chelating by 22.07% at 8 mg/ml. Additionally, ICD showed a strong ability on reducing power and provided protection against oxidative protein damage induced by hydroxyl radicals. Pretreatment of PC12 cells with ICD prior to H₂O₂ exposure elevated cell viability, enhanced activity of superoxide dismutase and catalase, and decreased levels of malondialdehyde and intracellular ROS. Furthermore, ICD inhibited cell apoptosis and Bax/Bcl-2 ratio induced by H₂O₂. These findings suggested ICD may be considered as a potential antioxidant agent and should encourage for further research in neurodegenerative diseases. PMID:23770344

  11. Syntheses, crystal structures and antioxidant study of Zn(II) complexes with morin-5'-sulfonic acid (MSA).

    PubMed

    Pieniążek, Elżbieta; Kalembkiewicz, Jan; Dranka, Maciej; Woźnicka, Elżbieta

    2014-12-01

    The study of modified synthetic procedure of water soluble morin-5'-sulfonic acid sodium salt (NaMSA) involving less aggressive chemicals and carried out at mild conditions was described. The NaMSA salt is a convenient source of anionic morin-5'-sulfonic ligand (MSA) in ion exchange reactions. The coordination ability of MSA ligand towards the zinc cations was investigated in aqueous solution and in solid state. Novel zinc complexes of morin-5'-sulfonate were obtained by a reaction of Zn(NO3)2 with morin-5'-sulfonate in water. Resulting compounds were characterized by single-crystal X-ray diffraction analysis, as well as spectral and thermal methods. The coordination interaction, hydrogen bond and π-π stacking lead to the formation of a 1D chain or 3D coordination polymers. The antioxidant activity of the Zn(II)-MSA complexes was evaluated by means of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging method. In this work, we have shown that the studied compounds are more effective free radical scavengers than the natural flavonoids like plain morin.

  12. Phase II trials in heart failure: The role of cardiovascular imaging

    PubMed Central

    Shah, Sanjiv J.; Fonarow, Gregg C.; Gheorghiade, Mihai; Lang, Roberto M.

    2013-01-01

    The development of new therapies for heart failure (HF), especially acute HF, has proven to be quite challenging; and therapies evaluated in HF have greatly outnumbered treatments that are eventually successful in obtaining regulatory approval. Thus, the development of therapies for HF remains a vexing problem for pharmaceutical and device companies, clinical trialists, and health care professionals. Nowhere is this more apparent than in the phase II HF clinical trial, in which the goal is to determine whether an investigational agent should move forward to a phase III trial. Recent advancements in noninvasive cardiovascular imaging have allowed a new era of comprehensive phenotyping of cardiac structure and function in phase II HF trials. Besides using imaging parameters to predict success of subsequent phase III outcome studies, it is essential to also use imaging in phase II HF trials in a way that increases understanding of drug or device mechanism. Determination of the patients who would benefit most from a particular drug or device could decrease heterogeneity of phase III trial participants and lead to more successful HF clinical trials. In this review, we outline advantages and disadvantages of imaging various aspects of cardiac structure and function that are potential targets for therapy in HF, compare and contrast imaging modalities, provide practical advice for the use of cardiovascular imaging in drug development, and conclude with some novel uses of cardiac imaging in phase II HF trials. PMID:21742085

  13. Phase transitions in tumor growth: II prostate cancer cell lines

    NASA Astrophysics Data System (ADS)

    Llanos-Pérez, J. A.; Betancourt-Mar, A.; De Miguel, M. P.; Izquierdo-Kulich, E.; Royuela-García, M.; Tejera, E.; Nieto-Villar, J. M.

    2015-05-01

    We propose a mechanism for prostate cancer cell lines growth, LNCaP and PC3 based on a Gompertz dynamics. This growth exhibits a multifractal behavior and a "second order" phase transition. Finally, it was found that the cellular line PC3 exhibits a higher value of entropy production rate compared to LNCaP, which is indicative of the robustness of PC3, over to LNCaP and may be a quantitative index of metastatic potential tumors.

  14. Apoptosis Induction by Polygonum minus is related to antioxidant capacity, alterations in expression of apoptotic-related genes, and S-phase cell cycle arrest in HepG2 cell line.

    PubMed

    Mohd Ghazali, Mohd Alfazari; Al-Naqeb, Ghanya; Krishnan Selvarajan, Kesavanarayanan; Hazizul Hasan, Mizaton; Adam, Aishah

    2014-01-01

    Polygonum minus (Polygonaceae) is a medicinal herb distributed throughout eastern Asia. The present study investigated antiproliferative effect of P. minus and its possible mechanisms. Four extracts (petroleum ether, methanol, ethyl acetate, and water) were prepared by cold maceration. Extracts were subjected to phytochemical screening, antioxidant, and antiproliferative assays; the most bioactive was fractionated using vacuum liquid chromatography into seven fractions (F1-F7). Antioxidant activity was measured via total phenolic content (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP) assays. Antiproliferative activity was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Most active fraction was tested for apoptosis induction and cell cycle arrest in HepG2 cells using flow cytometry and confocal microscopy. Apoptotic-related gene expression was studied by RT-PCR. Ethyl acetate extract was bioactive in initial assays. Its fraction, F7, exhibited highest antioxidant capacity (TPC; 113.16 ± 6.2 mg GAE/g extract, DPPH; EC50: 30.5 ± 3.2 μg/mL, FRAP; 1169 ± 20.3 μmol Fe (II)/mg extract) and selective antiproliferative effect (IC50: 25.75 ± 1.5 μg/mL). F7 induced apoptosis in concentration- and time-dependent manner and caused cell cycle arrest at S-phase. Upregulation of proapoptotic genes (Bax, p53, and caspase-3) and downregulation of antiapoptotic gene, Bcl-2, were observed. In conclusion, F7 was antiproliferative to HepG2 cells by inducing apoptosis, cell cycle arrest, and via antioxidative effects. PMID:24955361

  15. Apoptosis Induction by Polygonum minus Is Related to Antioxidant Capacity, Alterations in Expression of Apoptotic-Related Genes, and S-Phase Cell Cycle Arrest in HepG2 Cell Line

    PubMed Central

    Mohd Ghazali, Mohd Alfazari; Al-Naqeb, Ghanya; Krishnan Selvarajan, Kesavanarayanan; Hazizul Hasan, Mizaton; Adam, Aishah

    2014-01-01

    Polygonum minus (Polygonaceae) is a medicinal herb distributed throughout eastern Asia. The present study investigated antiproliferative effect of P. minus and its possible mechanisms. Four extracts (petroleum ether, methanol, ethyl acetate, and water) were prepared by cold maceration. Extracts were subjected to phytochemical screening, antioxidant, and antiproliferative assays; the most bioactive was fractionated using vacuum liquid chromatography into seven fractions (F1–F7). Antioxidant activity was measured via total phenolic content (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP) assays. Antiproliferative activity was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Most active fraction was tested for apoptosis induction and cell cycle arrest in HepG2 cells using flow cytometry and confocal microscopy. Apoptotic-related gene expression was studied by RT-PCR. Ethyl acetate extract was bioactive in initial assays. Its fraction, F7, exhibited highest antioxidant capacity (TPC; 113.16 ± 6.2 mg GAE/g extract, DPPH; EC50: 30.5 ± 3.2 μg/mL, FRAP; 1169 ± 20.3 μmol Fe (II)/mg extract) and selective antiproliferative effect (IC50: 25.75 ± 1.5 μg/mL). F7 induced apoptosis in concentration- and time-dependent manner and caused cell cycle arrest at S-phase. Upregulation of proapoptotic genes (Bax, p53, and caspase-3) and downregulation of antiapoptotic gene, Bcl-2, were observed. In conclusion, F7 was antiproliferative to HepG2 cells by inducing apoptosis, cell cycle arrest, and via antioxidative effects. PMID:24955361

  16. Synthesis and Evaluation of In Vitro DNA/Protein Binding Affinity, Antimicrobial, Antioxidant and Antitumor Activity of Mononuclear Ru(II) Mixed Polypyridyl Complexes.

    PubMed

    Putta, Venkat Reddy; Chintakuntla, Nagamani; Mallepally, Rajender Reddy; Avudoddi, Srishailam; K, Nagasuryaprasad; Nancherla, Deepika; V V N, Yaswanth; R S, Prakasham; Surya, Satyanarayana Singh; Sirasani, Satyanarayana

    2016-01-01

    The four novel Ru(II) complexes [Ru(phen)2MAFIP](2+) (1) [MAFIP = 2-(5-(methylacetate)furan-2-yl)-1 H-imidazo[4,5-f] [1, 10]phenanthroline, phen = 1,10-Phenanthroline], [Ru(bpy)2MAFIP](2+) (2) (bpy = 2,2'-bipyridine) and [Ru(dmb)2MAFIP](2+) (3) (dmb = 4,4'-dimethyl-2,2'-bipyridine) and [Ru(hdpa)2MAFIP](2+) (4) (hdpa = 2,2-dipyridylamine) have been synthesized and fully characterized via elemental analysis, NMR spectroscopy, EI-MS and FT-IR spectroscopy. In addition, the DNA-binding behaviors of the complexes 1-4 with calf thymus DNA were investigated by UV-Vis absorption, fluorescence studies and viscosity measurement. The DNA-binding experiments showed that the complexes 1-4 interact with CT-DNA through an intercalative mode. BSA protein binding affinity of synthesized complexes was determined by UV/Vis absorption and fluorescence emission titrations. The binding affinity of ruthenium complexes was supported by molecular docking. The photoactivated cleavage of plasmid pBR322 DNA by ruthenium complexes 1-4 was investigated. All the synthesized compounds were tested for antimicrobial activity by using three Gram-negative (Escherichia coli, Salmonella typhi and Pseudomonas aeruginosa) and three Gram-positive (Micrococcus luteus, Bacillus subtilis and Bacillus megaterium) organisms, these results indicated that complex 3 was more activity compared to other complexes against all tested microbial strains while moderate antimicrobial activity profile was noticed for complex 4. The antioxidant activity experiments show that the complexes exhibit moderate antioxidant activity. The cytotoxicity of synthesized complexes on HeLa cell lines has been examined by MTT assay. The apoptosis assay was carried out with Acridine Orange (AO) staining methods and the results indicate that complexes can induce the apoptosis of HeLa cells. The cell cycle arrest investigated by flow cytometry and these results indicate that complexes 1-4 induce the cell cycle arrest at G0/G1

  17. Activities of Antioxidant Scavenger Enzymes (Superoxide Dismutase and Glutathione Peroxidase) in Erythrocytes in Adult Women With and Without Type II Diabetes

    PubMed Central

    Coleman, Raymond; Berner, Yitshal N.

    2004-01-01

    It is widely believed that oxidative stress plays an important role in the pathogenesis of type II diabetes. The present study was undertaken to examine the functioning of two antioxidant scavenger enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), in erythrocytes in a population of healthy aging adult women compared with a similar population with type II diabetes. Blood samples were examined from 42 female adult healthy subjects at different ages and from 59 female patients with type II diabetes. A significant increase in SOD activities was correlated with aging in erythrocytes of the healthy control subjects (r = .550, P = .001); however, this correlation was not found in subjects with type II diabetes (r = .250, P < .07). A trend showing a reduction in glutathione peroxidase activities was demonstrated with aging (r = −.331, P = .228); however, this trend was not found in diabetic subjects (r = .031, P < .820). The results indicate a possible imbalance in the antioxidant system in erythrocytes of aging adult women, which is even more pronounced in cases of type II diabetes. This study may indicate possible therapeutic treatment or preventive measures to limit oxidative damage and reduce complications of diabetes. PMID:15203888

  18. Comparing two tetraalkylammonium ionic liquids. II. Phase transitions.

    PubMed

    Lima, Thamires A; Paschoal, Vitor H; Faria, Luiz F O; Ribeiro, Mauro C C; Ferreira, Fabio F; Costa, Fanny N; Giles, Carlos

    2016-06-14

    Phase transitions of the ionic liquids n-butyl-trimethylammonium bis(trifluoromethanesulfonyl)imide, [N1114][NTf2], and methyl-tributylammonium bis(trifluoromethanesulfonyl)imide, [N1444][NTf2], were investigated by differential scanning calorimetry (DSC), X-ray diffraction (XRD) measurements, and Raman spectroscopy. XRD and Raman spectra were obtained as a function of temperature at atmospheric pressure, and also under high pressure at room temperature using a diamond anvil cell (DAC). [N1444][NTf2] experiences glass transition at low temperature, whereas [N1114][NTf2] crystallizes or not depending on the cooling rate. Both the ionic liquids exhibit glass transition under high pressure. XRD and low-frequency Raman spectra provide a consistent physical picture of structural ordering-disordering accompanying the thermal events of crystallization, glass transition, cold crystallization, pre-melting, and melting. Raman spectra in the high-frequency range of some specific cation and anion normal modes reveal conformational changes of the molecular structures along phase transitions.

  19. Optical spectroscopic and reverse-phase HPLC analyses of Hg(II) binding to phytochelatins.

    PubMed

    Mehra, R K; Miclat, J; Kodati, V R; Abdullah, R; Hunter, T C; Mulchandani, P

    1996-02-15

    Optical spectroscopy and reverse-phase HPLC were used to investigate the binding of Hg(II) to plant metal-binding peptides (phytochelatins) with the structure (gammaGlu-Cys)2Gly, (gammaGlu-Cys)3Gly and (gammaGlu-Cys)4Gly. Glutathione-mediated transfer of Hg(II) into phytochelatins and the transfer of the metal ion from one phytochelatin to another was also studied using reverse-phase HPLC. The saturation of Hg(II)-induced bands in the UV/visible and CD spectra of (gammaGlu-Cys)2Gly suggested the formation of a single Hg(II)-binding species of this peptide with a stoichiometry of one metal ion per peptide molecule. The separation of apo-(gammaGlu-Cys)2Gly from its Hg(II) derivative on a C18 reverse-phase column also indicated the same metal-binding stoichiometry. The UV/visible spectra of both (gammaGlu-Cys)3Gly and (gammaGlu-Cys)4Gly at pH 7.4 showed distinct shoulders in the ligand-to-metal charge-transfer region at 280-290 mm. Two distinct Hg(II)-binding species, occurring at metal-binding stoichiometries of around 1.25 and 2.0 Hg(II) ions per peptide molecule, were observed for (gammaGlu-Cys)3Gly. These species exhibited specific spectral features in the charge-transfer region and were separable by HPLC. Similarly, two main Hg(II)-binding species of (gammaGlu-Cys)4Gly were observed by UV/visible and CD spectroscopy at metal-binding stoichiometries of around 1.25 and 2.5 respectively. Only a single peak of Hg(II)-(gammaGlu-Cys)4Gly complexes was resolved under the conditions used for HPLC. The overall Hg(II)-binding stoichiometries of phytochelatins were similar at pH 2.0 and at pH 7.4, indicating that pH did not influence the final Hg(II)-binding capacity of these peptides. The reverse-phase HPLC assays indicated a rapid transfer of Hg(II) from glutathione to phytochelatins. These assays also demonstrated a facile transfer of the metal ion from shorter- to longer-chain phytochelatins. The strength of Hg(II) binding to glutathione and phytochelatins followed the

  20. Generation of phase II in vitro metabolites using homogenized horse liver.

    PubMed

    Wong, Jenny K Y; Chan, George H M; Leung, David K K; Tang, Francis P W; Wan, Terence S M

    2016-02-01

    The successful use of homogenized horse liver for the generation of phase I in vitro metabolites has been previously reported by the authors' laboratory. Prior to the use of homogenized liver, the authors' laboratory had been using mainly horse liver microsomes for carrying out equine in vitro metabolism studies. Homogenized horse liver has shown significant advantages over liver microsomes for in vitro metabolism studies as the procedures are much quicker and have higher capability for generating more in vitro metabolites. In this study, the use of homogenized liver has been extended to the generation of phase II in vitro metabolites (glucuronide and/or sulfate conjugates) using 17β-estradiol, morphine, and boldenone undecylenate as model substrates. It was observed that phase II metabolites could also be generated even without the addition of cofactors. To the authors' knowledge, this is the first report of the successful use of homogenized horse liver for the generation of phase II metabolites. It also demonstrates the ease with which both phase I and phase II metabolites can now be generated in vitro simply by using homogenized liver without the need for ultracentrifuges or tedious preparation steps.

  1. Investigation of high velocity separator for particle removal in coal gasification plants. Phase II report

    SciTech Connect

    Linhardt, H.D.

    1980-01-15

    This report summarizes the results of Phase II of the High Velocity Particle Separator Program performed under Contract EF-77-C-01-2709. This high velocity wedge separator has the potential to reduce equipment size and cost of high temperature and pressurized particulate removal equipment for coal derived gases. Phase II has been directed toward testing and detailed conceptual design of an element suitable for a commercial scale high temperature, high pressure particle separator (HTPS). Concurrently, Phase IA has been conducted, which utilized the ambient analog method (AAM) for aerodynamic and collection performance investigation of each HTPS configuration prior and during hot testing. This report summarizes the results of Phase IA and II. The AAM effort established correlation of theoretical analysis and experiment for HTPS pressure drop, purge flow ratio and collection efficiency potential. Task I defined the initial test conditions to be the contract design point of 1800/sup 0/F and 350 psia. The 1800/sup 0/F, 350 psia testing represents the main high temperature testing with coal-derived particulates in the 2 to 10 micron range. Phase IA and Phase II have demonstrated efficient particle collection with acceptable pressure drop. In view of these encouraging results, it is reasonable to apply the developed technology toward future hot gas particulate cleanup requirements.

  2. Silica Waste Utilisation Phase II - Preliminary Laboratory Results

    SciTech Connect

    Lund, J.W.; Boyd, T.L.

    1995-01-01

    A second phase of laboratory testing is being performed on waste silica from the Cerro Prieto geothermal field in Mexico. The main objective is to produce mixes of various combinations of hydrated lime, portland cement, and plastic fibers with the waste silica from disposal ponds to determine their suitability for use as insulating bricks in low cost housing. Silica-cement mixtures appear to have the highest flexural strength and resistance to weathering. Silica-lime mixtures appear to have the best insulating properties (lowest thermal conductivity). The addition of plastic fibers to the silica-lime mixture appears to improve both strength and weather resistance. Work is still in progress and will be completed in 1996 with the construction of various test walls in the Mexicali, Mexico area.

  3. 75 FR 62530 - Eagle Creek Hydro Power, LLC; Laredo Ridge Wind, LLC; RRI Energy West, Inc.; Goshen Phase II LLC...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-12

    ...; EG10-55-000; EG10-56-000] Eagle Creek Hydro Power, LLC; Laredo Ridge Wind, LLC; RRI Energy West, Inc.; Goshen Phase II LLC; Solar Partners I, LLC; Solar Partners II, LLC; Solar Partners VIII, LLC; Notice...

  4. Solid phase synthesis of somatostatin-28 II. A new biologically active octacosapeptide from anglerfish pancreatic islets.

    PubMed

    Nicolas, P; Delfour, A; Boussetta, H; Morel, A; Rholam, M; Cohen, P

    1986-10-30

    Somatostatin-28 II, an octacosapeptide recently isolated from anglerfish pancreatic islets, was synthetized by the solid phase method along with its somatostatin-14 II and somatostatin-28 II-(1-12) corresponding domains. Homogeneity of the synthetic peptides was demonstrated by analytical RP-HPLC, thin layer chromatography and electrophoresis. The peptides were further characterized by amino acids analysis, fast atomic bombarding mass spectrometry and/or 252Cf plasma desorption mass spectrometry. Synthetic somatostatin-28 II and somatostatin-14 II displace equally well the potent agonist (Tyr0,D-Trp8)-somatostatin-14 from its specific binding sites on anterior pituitary cells membranes. Both peptides activate adenylate cyclase from dispersed rat anterior pituitary cells. PMID:2877662

  5. Optimal and minimax three-stage designs for phase II oncology clinical trials.

    PubMed

    Chen, Kun; Shan, Michael

    2008-01-01

    The common objective of oncology phase II trials is to evaluate the anti-tumor activity of a new agent and to determine whether the new drug warrants further investigation. For cancer drugs that significantly shrink tumors, response (CR and PR) rate is usually the primary endpoint in cancer phase II trials for testing H(0): Por=P(1), where P(0) and P(1) are response rates which does not or does warrant further investigation given the rate of false positive (alpha) and false negative (beta). Multiple-stage designs including two-stage and three-stage have been developed by several authors. For example, Simon's optimal two-stage design [Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials 1989;10:1-10], Ensign et al. optimal three-stage design with restriction at the first stage [Ensign LG, Gehan EA, Kamen DS, Thall PF. An optimal three-stage design for phase II clinical trials. Stat Med 1994;13:1727-1736], Chen's optimal three-stage design without any restriction [Chen TT. Optimal three-stage designs for phase II clinical trials. Stat Med 1997;16:2701-2711], etc. However, all the above designs only early terminate a trial due to lack of activity of the study drug. Fleming's multiple-stage design [Fleming TR. One-sample multiple testing procedure for phase II clinical trials. Biometrics 1982;38:143-151] allows early stopping for either sufficient activity or lack of activity. But his design does not attempt to optimize its efficiency. We extend Chen's [Chen TT. Optimal three-stage designs for phase II clinical trials Stat Med 1997;16:2701-2711] design and propose an optimal and a minimax design for three-stage cancer phase II trials which allows early stopping under both hypotheses. The design is optimal in the sense that the average sample number (ASN) is minimized under P=P(0). The minimax design minimizes the maximal sample size (N) and then given this value of N minimizes the average sample number under P=P(0

  6. RadSTraM: Radiological Source Tracking and Monitoring, Phase II Final Report

    SciTech Connect

    Warren, Tracy A; Walker, Randy M; Hill, David E; Gross, Ian G; Smith, Cyrus M; Abercrombie, Robert K

    2008-12-01

    This report focuses on the technical information gained from the Radiological Source Tracking and Monitoring (RadSTraM) Phase II investigation and its implications. The intent of the RadSTraM project was to determine the feasibility of tracking radioactive materials in commerce, particularly International Atomic Energy Agency (IAEA) Category 3 and 4 materials. Specifically, Phase II of the project addressed tracking radiological medical isotopes in commerce. These categories of materials are susceptible to loss or theft but the problem is not being addressed by other agencies.

  7. OCCIDENTAL VERTICAL MODIFIED IN SITU PROCESS FOR THE RECOVERY OF OIL FROM OIL SHALE. PHASE II

    SciTech Connect

    Nelson, Reid M.

    1980-09-01

    The progress presented in this report covers the period June 1, 1980 through August 31, 1980 under the work scope for.Phase II of the DOE/Occidental Oil Shale, Inc. (OOSI) Cooperative Agreement. The major activities at OOSI 1s Logan Wash site during the quarter were: mining the voids at all levels for Retorts 7, 8 and 8x; completing Mini-Retort (MR) construction; continuing surface facility construction; tracer testing the MR 1 s; conducting Retorts 7 & 8 related Rock Fragmentation tests; setting up and debugging the Sandia B-61 trailer; and preparing the Phase II instrumentation plan.

  8. THE CHEMICAL AND ANTIVIRAL PROPERTIES OF THE SOMATIC ANTIGEN OF PHASE II SHIGELLA SONNEI

    PubMed Central

    Jesaitis, Margeris A.; Goebel, Walther F.

    1952-01-01

    1. The somatic antigen of Phase II Shigella sonnei can be isolated by extracting phenol-killed microorganisms with water. This substance inactivates all T phages to which this bacillus is susceptible. 2. The Phase II antigen is constituted from a protein and a phosphorylated lipocarbohydrate. The major portion of the protein component can be removed by digestion with pancreatin. The enzymatically degraded antigen thus obtained can be further dissociated into its protein and lipocarbohydrate components by treatment with 90 per cent phenol. Glucose, galactose, glucosamine, and an aldoheptose have been identified as the monosaccharide constituents of the lipocarbohydrate. PMID:13000053

  9. MHD coal combustor technology. Final report, phase II

    SciTech Connect

    Not Available

    1980-09-01

    The design, performance, and testing of a 20-MW coal combustor for scaleup to 50 MW for use in an MHD generator are described. The design incorporates the following key features: (1) a two-stage combustor with an intermediate slag separator to remove slag at a low temperture, thus minimizing enthalpy losses required for heating and vaporizing the slag; (2) a first-stage pentad (four air streams impinging on one coal stream) injector design with demonstrated efficient mixing, promoting high carbon burnout; (3) a two-section first-stage combustion chamber; the first stage using a thin slag-protected refractory layer and the second section using a thick refractory layer, both to minimize heat losses; (4) a refractory lining in the slag separator to minimize heat losses; (5) a second-stage combustor, which provided both de-swirl of the combustion products exiting from the slag separator and simple mixing of the vitiated secondary air and seed; (6) a dense-phase coal feed system to minimize cold carrier gas entering the first-stage combustors; (7) a dry seed injection system using pulverized K/sub 2/CO/sub 3/ with a 1% amorphous, fumed silicon dioxide additive to enhance flowability, resulting in rapid vaporization and ionization and ensuring maximum performance; and (8) a performance evaluation module (PEM) of rugged design based on an existing, successfully-fired unit. (WHK)

  10. The pixel detector for the CMS phase-II upgrade

    NASA Astrophysics Data System (ADS)

    Dinardo, M. E.

    2015-04-01

    The high luminosity phase of the Large Hadron Collider (HL-LHC) requires a major pixel detector R&D effort to develop both readout chip and sensor that are capable to withstand unprecedented extremely high radiation. The target integrated luminosity of 3000 fb-1, that the HL-LHC is expected to deliver over about 10 years of operation, translates into a hadron fluence of 2×1016 1 MeV eq.n. / cm2, or equivalently 10 MGy of radiation dose in silicon, at about 3 cm from the interaction region where the first layer of the pixel detector could be located. The CMS collaboration has undertaken two baseline sensor R&D programs on thin n-on-p planar and 3D silicon sensor technologies. Together with the ATLAS collaboration it has also been established a common R&D effort for the development of the readout chip in the 65 nm CMOS technology. Status, progresses, and prospects of the CMS R&D effort are presented and discussed in this article.

  11. Heat Mirror II: an advanced transparent insulation. Phase II. Final report

    SciTech Connect

    Cormia, R.L.

    1982-06-01

    The purpose of this project was to take five separate approaches to achieve an environmentally stable Heat Mirror II. Heat Mirror I is limited to use in hermetically sealed, dessicated environments to avoid risks to its integrity from physical abuse and atmospheric chemical attack. In this report, the following five tasks were addressed, each designed to give Heat Mirror I greater durability: surface preparation of the substrate; alternative thin film stack design; passivation of the thin film stack; overcoating; and laminating. It is concluded that the laminate is very promising and should be further tested.

  12. Syntheses, crystallographic, mass-spectroscopic determination and antioxidant studies of Co(II), Ni(II) and Cu(II) complexes of a new imidazol based Schiff base.

    PubMed

    Demir, Serkan; Güder, Aytaç; Yazıcılar, Turan K; Çağlar, Sema; Büyükgüngör, Orhan

    2015-01-01

    A new imidazole-based Schiff base, 2-((1H-imidazol-4-yl)methyleneamino)benzylalcohol (HL) and corresponding analogous bis(2-((1H-imidazol-4-yl)methyleneimino)benzylalcohol)metal(II) perchlorates (M: Co(1), Ni(2), Cu(3)) have prepared and characterized by elemental analyses, ESI-MS, IR, UV-Vis spectroscopies and conductivity measurements. X-ray single crystal structures of 1 and 2 have been also determined. Elemental analyses, spectroscopic and conductance data of 3 demonstrated similar structural features with these of crystallographically characterized complexes and based upon this relevances, HL ligands are neutrally coordinated to metal(II) ions in tridentate mode and all complexes are isostructural, dicathionic, contain perchlorate anions as complementary ions and, are in octahedral geometry with the formulae of [M(HL)2](ClO4)2 (for 3) and [M(HL)2](ClO4)2·H2O (for 1 and 2). Radical scavenging activities of the complexes have been evaluated by using DPPH, DMPD(+), and ABTS(+) assays. SC50 values (μg/mL) of the complexes and standards on DPPH, DMPD(+), ABTS(+) follow the sequences, BHA (9.06±0.33)>CMPD3 (15.62±0.52)>CMPD2 (17.43±0.29)>Rutin (21.65±0.60)>CMPD1 (25.67±0.51)>Trolox (28.57±0.37), Rutin>BHA>CMPD3>CMPD2>Trolox>CMPD1, and Trolox>BHA>CMPD3>CMPD2>Rutin>CMPD1 respectively.

  13. Reverse-phase HPLC separation of hemp seed (Cannabis sativa L.) protein hydrolysate produced peptide fractions with enhanced antioxidant capacity.

    PubMed

    Girgih, Abraham T; Udenigwe, Chibuike C; Aluko, Rotimi E

    2013-03-01

    Hemp seed protein hydrolysate (HPH) was produced through simulated gastrointestinal tract (GIT) digestion of hemp seed protein isolate followed by partial purification and separation into eight peptide fractions by reverse-phase (RP)-HPLC. The peptide fractions exhibited higher oxygen radical absorbance capacity as well as scavenging of 2,2-diphenyl-1-picrylhydrazyl, superoxide and hydroxyl radicals when compared to HPH. Radical scavenging activities of the fractionated peptides increased as content of hydrophobic amino acids or elution time was increased, with the exception of hydroxyl radical scavenging that showed decreased trend. Glutathione (GSH), HPH and the RP-HPLC peptide fractions possessed low ferric ion reducing ability but all had strong (>60 %) metal chelating activities. Inhibition of linoleic acid oxidation by some of the HPH peptide fractions was higher at 1 mg/ml when compared to that observed at 0.1 mg/ml peptide concentration. Peptide separation resulted in higher concentration of some hydrophobic amino acids (especially proline, leucine and isoleucine) in the fractions (mainly F5 and F8) when compared to HPH. The elution time-dependent increased concentrations of the hydrophobic amino acids coupled with decreased levels of positively charged amino acids may have been responsible for the significantly higher (p < 0.05) antioxidant properties observed for some of the peptide fractions when compared to the unfractionated HPH. In conclusion, the antioxidant activity of HPH after simulated GIT digestion is mainly influenced by the amino acid composition of some of its peptides.

  14. Stable Low Cloud Phase II: Nocturnal Event Study

    NASA Technical Reports Server (NTRS)

    Bauman, William H., III; Barrett, Joe, III

    2007-01-01

    This report describes the work done by the Applied Meteorology Unit (AMU) in developing a database of nights that experienced rapid (< 90 minutes) low cloud formation in a stable atmosphere, resulting in ceilings at the Shuttle Landing Facility (TTS) that violated Space Shuttle Flight Rules (FR). This work is the second phase of a similar AMU task that examined the same phenomena during the day. In the first phase of this work, the meteorological conditions favoring the rapid formation of low ceilings include the presence of any inversion below 8000 ft, high relative humidity (RH) beneath the inversion and a clockwise turning of the winds from the surface to the middle troposphere (-15000 ft). The AMU compared and contrasted the atmospheric and thermodynamic conditions between nights with rapid low ceiling formation and nights with low ceilings resulting from other mechanisms. The AMU found that there was little to discern between the rapidly-forming ceiling nights and other low ceiling nights at TTS. When a rapid development occurred, the average RH below the inversions was 87% while non-events had an average RH of 79%. One key parameter appeared to be the vertical wind profile in the Cape Canaveral, FL radiosonde (XMR) sounding. Eighty-three percent of the rapid development events had veering winds with height from the surface to the middle troposphere (-15,000 ft) while 61% of the non-events had veering winds with height. Veering winds indicate a warm-advection regime, which supports large-scale rising motion and ultimately cloud formation in a moist environment. However, only six of the nights (out of 86 events examined) with low cloud ceilings had an occurrence of rapidly developing ceilings. Since only 7% rapid development events were observed in this dataset, it is likely that rapid low cloud development is not a common occurrence during the night, or at least not as common as during the day. In the AMU work on the daytime rapid low cloud development (Case

  15. Inter-donor variability of phase I/phase II metabolism of three reference drugs in cryopreserved primary human hepatocytes in suspension and monolayer.

    PubMed

    den Braver-Sewradj, Shalenie P; den Braver, Michiel W; Vermeulen, Nico P E; Commandeur, Jan N M; Richert, Lysiane; Vos, J Chris

    2016-06-01

    Cytochrome P450s (CYPs), UDP-glucuronosyltransferases (UGTs) and sulfotransferases (SULTs) are the most important enzymes for metabolic clearance. Characterization of phase I and phase II metabolism of a given drug in cellular models is therefore important for an adequate interpretation of the role of drug metabolism in toxicity. We investigated phase I (CYP) and phase II (UGT and SULT) metabolism of three drugs related to drug-induced liver injury (DILI), namely acetaminophen (APAP), diclofenac (DF) and tolcapone (TC), in cryopreserved primary human hepatocytes from 5 donors in suspension and monolayer. The general phase II substrate 7-hydroxycoumarin (7-HC) was included for comparison. Our results show that the decrease in CYP, UGT and SULT activity after plating is substrate dependent. As a consequence the phase I/phase II metabolism ratio is significantly affected, with a shift in monolayer towards phase I metabolism for TC and towards phase II metabolism for APAP and DF. Inter-donor variability in drug metabolism is significant, especially in sulfation of 7-HC or APAP. As CYP, UGT and SULT metabolism may lead to bioactivation and/or detoxification of drugs, a changed ratio in phase I/phase II metabolism may have important consequences for metabolism-related toxicity. PMID:26921663

  16. Structure of intermediate phase II of LiNH2 under high pressure.

    PubMed

    Yamawaki, Hiroshi; Fujihisa, Hiroshi; Gotoh, Yoshito; Nakano, Satoshi

    2014-08-21

    A new intermediate phase (phase II) was found between phases I and III in LiNH2 in the pressure range of 10 to 13 GPa through the analysis of infrared and powder X-ray diffraction measurements to 25 GPa at room temperature. This result agreed with the prediction of a stable phase between phases I and III through theoretical calculations. Powder X-ray diffraction measurement and DFT calculation showed that this phase has a monoclinic structure with space group C2/c (Z = 8), which is the same structure as that of a slightly tilted crystal lattice of the Fddd structural model. The enthalpy of the C2/c structure was also found to be almost the same as that of the Fddd structure.

  17. Specific threonine-4 phosphorylation and function of RNA polymerase II CTD during M phase progression

    PubMed Central

    Hintermair, Corinna; Voß, Kirsten; Forné, Ignasi; Heidemann, Martin; Flatley, Andrew; Kremmer, Elisabeth; Imhof, Axel; Eick, Dirk

    2016-01-01

    Dynamic phosphorylation of Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7 heptad-repeats in the C-terminal domain (CTD) of the large subunit coordinates progression of RNA polymerase (Pol) II through the transcription cycle. Here, we describe an M phase-specific form of Pol II phosphorylated at Thr4, but not at Tyr1, Ser2, Ser5, and Ser7 residues. Thr4 phosphorylated Pol II binds to centrosomes and midbody and interacts with the Thr4-specific Polo-like kinase 1. Binding of Pol II to centrosomes does not require the CTD but may involve subunits of the non-canonical R2TP-Prefoldin-like complex, which bind to and co-localize with Pol II at centrosomes. CTD Thr4 mutants, but not Ser2 and Ser5 mutants, display severe mitosis and cytokinesis defects characterized by multipolar spindles and polyploid cells. We conclude that proper M phase progression of cells requires binding of Pol II to centrosomes to facilitate regulation of mitosis and cytokinesis in a CTD Thr4-P dependent manner. PMID:27264542

  18. Pharmacologically significant complexes of Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) of novel Schiff base ligand, (E)-N-(furan-2-yl methylene) quinolin-8-amine: Synthesis, spectral, XRD, SEM, antimicrobial, antioxidant and in vitro cytotoxic studies

    NASA Astrophysics Data System (ADS)

    Shakir, M.; Hanif, Summaiya; Sherwani, Mohd. Asif; Mohammad, Owais; Al-Resayes, Saud I.

    2015-07-01

    A novel series of metal complexes of the types, [ML2(H2O)2]Cl2 and [ML2]Cl2 [M = Mn(II), 1; Co(II), 2; Ni(II), 3; Cu(II), 4; and Zn(II), 5] were synthesized by the interaction of ligand, L (E)-N-(furan-2-yl methylene) quinolin-8-amine, derived from the condensation of 2-furaldehyde and 8-aminoquinoline. The synthesized ligand and its metal complexes were characterized on the basis of results obtained from elemental analysis, ESI-MS, XRD, SEM, TGA/DTA, FT-IR, UV-Vis, magnetic moment and 1H and 13C NMR spectroscopic studies. EPR parameters were recorded in case of complex 4. The comparative in-vitro antimicrobial activities against various pathogens with reference to known antibiotics and antioxidant activity against standard control at variable concentrations revealed that the metal complexes show enhanced antimicrobial and free radical scavenging activities in general as compared to free ligand. However, the complexes 1 and 5 have shown best antioxidant activity among all the metal complexes. Furthermore, comparative in-vitro antiproliferative activity on ligand and its metal chelates performed on MDA-MB-231 (breast carcinoma), KCL22 (blood lymphoid carcinoma), HeLa (cervical carcinoma) cell lines and normal cells (PBMC) revealed that metal chelates show moderate to good activity as compared to ligand where as complex 1 seems to be the most promising one possessing a broad spectrum of activity against all the selected cancer cell lines with IC50 < 2.10 μM.

  19. Iowa High School Industrial Arts Curriculum Project. Report on Year One of Phase II.

    ERIC Educational Resources Information Center

    Des Moines Public Schools, IA.

    Phase II of the Iowa High School Industrial Arts project sought to revise industrial arts content to include the infusion of new technologies, structured mathematics and science content, and a less project-oriented approach to teaching. The project identified a philosophical basis and a content structure; set priorities for development and…

  20. Emotional Intelligence and Implications for Counseling Self-Efficacy: Phase II

    ERIC Educational Resources Information Center

    Easton, Crystal; Martin, William E.; Wilson, Sheilah

    2008-01-01

    The authors present Phase II of a 9-month study of the relationship between emotional intelligence and counseling self-efficacy. One-hundred eighteen counselors-in-training and professional counselors completed the Counseling Self-Estimate Inventory (COSE) and Emotional Judgment Inventory (EJI). There was a significant correlation between 2 of the…

  1. 40 CFR 125.91 - What is a “Phase II Existing Facility”?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Applicable to Cooling Water Intake Structures for Phase II Existing Facilities Under Section 316(b) of the...: (1) It is a point source. (2) It uses or proposes to use cooling water intake structures with a total design intake flow of 50 million gallons per day (MGD) or more to withdraw cooling water from waters...

  2. 40 CFR 76.7 - Revised NOX emission limitations for Group 1, Phase II boilers.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 17 2012-07-01 2012-07-01 false Revised NOX emission limitations for Group 1, Phase II boilers. 76.7 Section 76.7 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.7 Revised...

  3. 40 CFR 76.7 - Revised NOX emission limitations for Group 1, Phase II boilers.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Revised NOX emission limitations for Group 1, Phase II boilers. 76.7 Section 76.7 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.7 Revised...

  4. 40 CFR 76.7 - Revised NOX emission limitations for Group 1, Phase II boilers.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 16 2011-07-01 2011-07-01 false Revised NOX emission limitations for Group 1, Phase II boilers. 76.7 Section 76.7 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.7 Revised...

  5. 40 CFR 76.7 - Revised NOX emission limitations for Group 1, Phase II boilers.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 17 2014-07-01 2014-07-01 false Revised NOX emission limitations for Group 1, Phase II boilers. 76.7 Section 76.7 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.7 Revised...

  6. 40 CFR 76.7 - Revised NOX emission limitations for Group 1, Phase II boilers.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 17 2013-07-01 2013-07-01 false Revised NOX emission limitations for Group 1, Phase II boilers. 76.7 Section 76.7 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.7 Revised...

  7. Regulation of phase II enzymes by genistein and daidzein in male and female Swiss Webster mice.

    PubMed

    Froyen, Erik B; Reeves, Jaime L Rudolf; Mitchell, Alyson E; Steinberg, Francene M

    2009-12-01

    The consumption of soy and soy isoflavones has been associated with a decreased risk of certain cancers. A factor contributing to this dietary chemoprevention is the activity of phase I and II biotransformation enzymes. This study evaluated the hypothesis that dietary soy isoflavones will increase hepatic and extrahepatic quinone reductase (QR), UDP-glucuronosyltransferase (UGT), and glutathione S-transferase (GST) phase II enzyme activities, under short-term feeding and basal (non-pharmacologic-induced) conditions. Male and female Swiss Webster mice were fed for 1, 3, 5, or 7 days of one of four treatments: control (casein AIN-93G) or control supplemented with flavone (positive control), genistein, or daidzein aglycones at 1,500 mg/kg of diet. QR activity was increased by daidzein in the liver, by both isoflavones in the kidney and small intestine, and by genistein in the heart. Genistein and daidzein slightly decreased UGT activities in some tissues. Liver GST activity was decreased by genistein in females. In contrast, genistein and daidzein increased kidney GST activity. In general, the greatest effects of isoflavones on phase II enzymes were observed in liver and kidney tissues, occurring at day 3, and peaking at day 5. Sex effects in the liver and kidney included females exhibiting higher QR activities and males exhibiting higher UGT and GST activities. In conclusion, individual soy isoflavones modulate phase II enzymes in mice under short-term feeding and basal conditions. This study provides insights into the actions of isolated isoflavones in mice.

  8. NATO/CCMS PILOT STUDY CLEAN PRODUCTS AND PROCESSES (PHASE II) 2003 ANNUAL REPORT

    EPA Science Inventory

    The 6th annual meeting of the NATO CCMS Pilot Study, Clean Products and Processes, was held in Cetraro, Italy, from May 11 to 15, 2003. This was also the first meeting of its Phase II study. 24 country representatives attended this meeting. This meeting was very ably run by th...

  9. 40 CFR 125.91 - What is a “Phase II Existing Facility”?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Applicable to Cooling Water Intake Structures for Phase II Existing Facilities Under Section 316(b) of the...: (1) It is a point source. (2) It uses or proposes to use cooling water intake structures with a total design intake flow of 50 million gallons per day (MGD) or more to withdraw cooling water from waters...

  10. Washington Phase II Fish Diversion Screen Evaluations in the Yakima River Basin, 1998.

    SciTech Connect

    Blanton, S.L.; McMichael, Geoffrey A.; Neitzel, D.A.

    1999-12-01

    Pacific Northwest National Laboratory (PNNL) evaluated 19 Phase II screen sites in the Yakima River Basin as part of a multi-year study for the Bonneville Power Administration (BPA) on the effectiveness of fish screening devices. The sites were examined to determine if they were being effectively operated and maintained to provide fish a safe, efficient return to the Yakima River.

  11. Income Verification Pilot Project (Phase II): Results of Quality Assurance Evaluation, 1982-83 School Year.

    ERIC Educational Resources Information Center

    Applied Management Sciences, Inc., Silver Spring, MD.

    Presented in this report are selected findings of the Income Verification Pilot Project (IVPP), an investigation examining misreporting of applicant income and family size on applications for government-sponsored school meal benefits. As reported here, Phase II of the project provided for a comprehensive assessment of specific quality assurance…

  12. Analysis of thermophilic fungal populations during phase II of composting for the cultivation of Agaricus subrufescens.

    PubMed

    Souza, Thiago Pereira; Marques, Simone Cristina; da Silveira e Santos, Débora Marques; Dias, Eustáquio Souza

    2014-09-01

    The composition and genetic diversity of fungal populations during phase II of compost production for the cultivation of Agaricus subrufescens was determined using culture-dependent and -independent methods on days 3, 6, 10, 12, and 14 of phase II composting. The isolates were morphologically characterized and subsequently analyzed using repetitive extragenic palindromic sequences (rep-PCR), and the intergenic region was sequenced to genetically identify the isolates. Changes on in the filamentous fungi population were analyzed using denaturing gradient gel electrophoresis (DGGE), and the resulting bands were sequenced. The population did not significantly change from day 3 to 10 (2.55 x 10(5) -6 x 10(5) CFU g(-1)), and maximum counts on day 14 of phase II composting (6.92 log CFU g(-1)). In the morphological characterization, Scytalidium thermophilum, Thermomyces lanuginosus, and Thermomyces ibadanensis were the most abundant identified species. The 26 most abundant isolates identified by morphological analysis were characterized using rep-PCR. A significant amount of genetic diversity was detected among the isolates of all three studied species. Based on the DGGE analysis, the diversity of the fungi was reduced during phase II composting, and S. thermophilum was the predominant species identified throughout the entire process. Thus, this study presents the first report of the involvement of T. ibadanensis in the production of compost for Agaricus mushroom cultivation.

  13. Webcam Delivery of the Camperdown Program for Adolescents Who Stutter: A Phase II Trial

    ERIC Educational Resources Information Center

    Carey, Brenda; O'Brian, Sue; Lowe, Robyn; Onslow, Mark

    2014-01-01

    Purpose: This Phase II clinical trial examined stuttering adolescents' responsiveness to the Webcam-delivered Camperdown Program. Method: Sixteen adolescents were treated by Webcam with no clinic attendance. Primary outcome was percentage of syllables stuttered (%SS). Secondary outcomes were number of sessions, weeks and hours to maintenance,…

  14. Definition of the Semisubmersible Floating System for Phase II of OC4

    SciTech Connect

    Robertson, A.; Jonkman, J.; Masciola, M.; Song, H.; Goupee, A.; Coulling, A.; Luan, C.

    2014-09-01

    Phase II of the Offshore Code Comparison Collaboration Continuation (OC4) project involved modeling of a semisubmersible floating offshore wind system as shown below. This report documents the specifications of the floating system, which were needed by the OC4 participants for building aero-hydro-servo-elastic models.

  15. Community Based Model for Training Ex-Offenders in Entrepreneurial Competencies, Phase II. Final Report.

    ERIC Educational Resources Information Center

    Springfield Urban League, Inc., IL.

    An Urban League project in Springfield, Illinois, provided instruction in small business management to persons who had been convicted of a crime. Phase II of the project required designing a self-instructional workbook and tape to be used when classes were not available. A resource guide listing agencies providing assistance to business persons…

  16. 40 CFR 125.91 - What is a “Phase II Existing Facility”?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Applicable to Cooling Water Intake Structures for Phase II Existing Facilities Under Section 316(b) of the...: (1) It is a point source. (2) It uses or proposes to use cooling water intake structures with a total design intake flow of 50 million gallons per day (MGD) or more to withdraw cooling water from waters...

  17. 40 CFR 125.91 - What is a “Phase II Existing Facility”?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Applicable to Cooling Water Intake Structures for Phase II Existing Facilities Under Section 316(b) of the...: (1) It is a point source. (2) It uses or proposes to use cooling water intake structures with a total design intake flow of 50 million gallons per day (MGD) or more to withdraw cooling water from waters...

  18. 40 CFR 125.91 - What is a “Phase II Existing Facility”?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Applicable to Cooling Water Intake Structures for Phase II Existing Facilities Under Section 316(b) of the...: (1) It is a point source. (2) It uses or proposes to use cooling water intake structures with a total design intake flow of 50 million gallons per day (MGD) or more to withdraw cooling water from waters...

  19. 48 CFR 1852.219-81 - Limitation on subcontracting-SBIR Phase II program.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Limitation on subcontracting-SBIR Phase II program. 1852.219-81 Section 1852.219-81 Federal Acquisition Regulations System... (OCT 2006) The Contractor shall perform a minimum of one-half of the research and/or analytical...

  20. 48 CFR 1852.219-81 - Limitation on subcontracting-SBIR Phase II program.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Limitation on subcontracting-SBIR Phase II program. 1852.219-81 Section 1852.219-81 Federal Acquisition Regulations System... (OCT 2006) The Contractor shall perform a minimum of one-half of the research and/or analytical...

  1. 78 FR 5765 - Wireline Competition Bureau Releases Connect America Phase II Cost Model Virtual Workshop...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-28

    ...] Wireline Competition Bureau Releases Connect America Phase II Cost Model Virtual Workshop Discussion Topics... Competition Bureau releases for discussion a number of virtual workshop topics related to the development and... comments. Virtual Workshop: In addition to the usual methods for filing electronic comments, the...

  2. Career Options Research and Development. Materials From Phase II Final Report.

    ERIC Educational Resources Information Center

    YMCA of Metropolitan Chicago, IL. Career Options Research and Development (CORD).

    The Social Service Aide Project for the training and education of paraprofessionals is a part of the Career Options Research and Development project of the Young Men's Christian Association of Chicago. These materials from the Phase II Final Report include: (1) Fourth Quarterly Progress Report (July-September 1970)," (2) "Systems Approach to Job…

  3. Phase II: Resource and Referral Service, Research and Development Exchange. Final Report.

    ERIC Educational Resources Information Center

    Hull, William L.

    Activities of the Resource and Referral Service (RRS), a central service contractor to the Research and Development Exchange (RDx), are documented for the period between March 1, 1977, when Phase II was funded, to November 30, 1977. Product outputs from RRS are described and related to project objectives. The objectives, which correspond to…

  4. Effect of licorice on the induction of phase II metabolizing enzymes and phase III transporters and its possible mechanism.

    PubMed

    Gong, Hui; Li, Huan-De; Yan, Miao; Zhang, Bi-Kui; Jiang, Pei; Fan, Xin-Rong; Deng, Yang

    2014-12-01

    Licorice has a marked detoxifying effect that can treat drug poisoning and/or relieve adverse effects. However, the exact mechanism of this action is not entirely elucidated, but is believed to be related to the modulation of drug disposition when interacting with other drugs. Additionally, Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a significant role in mediating phase II xenobiotic metabolizing enzymes (XMEs) and phase III transporters. In the present study, we showed that licorice induced the mRNA expression of phase II XMEs UDP-glucuronosyltransferases 1A1 (UGT1A1), glutamate cysteine ligase (GCL), glutathione-s-transferase (GST) and phase III transporters multidrug resistance protein 2 (MRP2), as well as a rapid increase in Nrf2 nuclear accumulation. These findings suggests that licorice may intervene in the Nrf2 signal pathway to induce UGT1A1, GCLC, GST and MRP2, which provide a novel mechanism for the use of licorice to treat drug poisoning and/or relieve adverse effects. PMID:25951662

  5. Phase structure of one-dimensional interacting Floquet systems. II. Symmetry-broken phases

    NASA Astrophysics Data System (ADS)

    von Keyserlingk, C. W.; Sondhi, S. L.

    2016-06-01

    Recent work suggests that a sharp definition of "phase of matter" can be given for periodically driven "Floquet" quantum systems exhibiting many-body localization. In this work, we propose a classification of the phases of interacting Floquet localized systems with (completely) spontaneously broken symmetries; we focus on the one-dimensional case, but our results appear to generalize to higher dimensions. We find that the different Floquet phases correspond to elements of Z (G ) , the center of the symmetry group in question. In a previous paper [C. W. von Keyserlingk and S. L. Sondhi, preceding paper, Phys. Rev. B 93, 245145 (2016)], 10.1103/PhysRevB.93.245145, we offered a companion classification of unbroken, i.e., paramagnetic phases.

  6. Inactivation of human pathogens during phase II composting of manure-based mushroom growth substrate.

    PubMed

    Weil, Jennifer D; Cutter, Catherine N; Beelman, Robert B; LaBorde, Luke F

    2013-08-01

    Commercial production of white button mushrooms (Agaricus bisporus) requires a specialized growth substrate prepared from composted agricultural by-products. Because horse and poultry manures are widely used in substrate formulations, there is a need to determine the extent to which the composting process is capable of eliminating human pathogens. In this study, partially composted substrate was inoculated with a pathogen cocktail (log 10⁶ to 10⁸ CFU/g) containing Listeria monocytogenes, Escherichia coli O157:H7, and Salmonella. Pathogen and indicator-organism reductions were followed at temperatures that typically occurred during a standard 6-day phase II pasteurization and conditioning procedure. Controlled-temperature water bath studies at 48.8, 54.4, and 60°C demonstrated complete destruction of the three pathogens after 36.0, 8.0, and 0.5 h, respectively. Destruction of L. monocytogenes and E. coli O157:H7 at 54.4°C occurred more slowly than E. coli, total coliforms, Enterobacteriaceae, and Salmonella. Microbial reductions that occurred during a standard 6-day phase II pasteurization and conditioning treatment were studied in a small-scale mushroom production research facility. After phase II composting, E. coli, coliforms, and Enterobacteriaceae were below detectable levels, and inoculated pathogens were not detected by direct plating or by enrichment. The results of this study show that a phase II composting process can be an effective control measure for eliminating risks associated with the use of composted animal manures during mushroom production. Growers are encouraged to validate and verify their own composting processes through periodic microbial testing for pathogens and to conduct studies to assure uniform distribution of substrate temperatures during phase II.

  7. Degradation of cellulose at the wet-dry interface. II. Study of oxidation reactions and effect of antioxidants.

    PubMed

    Jeong, Myung-Joon; Dupont, Anne-Laurence; de la Rie, E René

    2014-01-30

    To better understand the degradation of cellulose upon the formation of a tideline at the wet-dry interface when paper is suspended in water, the production of chemical species involved in oxidation reactions was studied. The quantitation of hydroperoxides and hydroxyl radicals was carried out in reverse phase chromatography using triphenylphosphine and terephthalic acid, respectively, as chemical probes. Both reactive oxygen species were found in the tideline immediately after its formation, in the range of micromoles and nanomoles per gram of paper, respectively. The results indicate that hydroxyl radicals form for the most part in paper before the tideline experiment, whereas hydroperoxides appear to be produced primarily during tideline formation. Iron sulfate impregnation of the paper raised the production of hydroperoxides. After hygrothermal aging in sealed vials the hydroxyl radical content in paper increased significantly. When aged together in the same vial, tideline samples strongly influenced the degradation of samples from other areas of the paper (multi-sample aging). Different types of antioxidants were added to the paper before the tideline experiment to investigate their effect on the oxidation reactions taking place. In samples treated with iron sulfate or artificially aged, the addition of Irgafos 168 (tris(2,4-ditert-butylphenyl) phosphate) and Tinuvin 292 (bis(1,2,2,6,6-pentamethyl-4-piperidyl) sebacate and methyl 1,2,2,6,6-pentamethyl-4-piperidyl sebacate) reduced the concentration of hydroperoxides and hydroxyl radicals, respectively. Tinuvin 292 was also found to considerably lower the rate of cellulose chain scission reactions during hygrothermal aging of the paper.

  8. Title IV - Phase II NO{sub x} compliance strategy for Minnesota Power

    SciTech Connect

    Mazzi, E.; Rossi-Lane, C.; Himes, R.; Scharnott, M.

    1995-12-31

    Minnesota Power`s (MP) coal-fired generation system is comprised of Title IV-Phase II boilers. Although Phase II boilers are not required to meet emission limits until January 1, 2000, the standards may be more stringent than Phase I NO{sub x} limits. MP is investigating the merits of foregoing system averaging under a yet to be determined Phase II rule, and pursuing an early election option with current Phase I NO{sub x} limits. Boswell Station is comprised of two Riley Stoker face-fired boilers of nominally 74 gross MW generation that went on-line in 1958-60, and two CE tangentially-fired boilers of 372 MW (1973 operation) and 565 MW (1980 operation). All units are balanced draft. Carnot conducted baseline characterizations of MP`s four units at the Boswell Station as the first step in an assessment of the best course of action. This paper will present the baseline data collected and the approach taken in preparing the NO{sub x} compliance strategy for all boilers within the MP system. The approach takes into accounted the projected system load profile and capacity factors for individual units and the cost effectiveness and system flexibility inherent with NO{sub x} compliance achieved on an individual unit basis or with system averaging.

  9. Phase I and II feasibility study report for the 300-FF-5 operable unit

    SciTech Connect

    1993-12-31

    The purpose of this Phase I/II feasibility study is to assemble and screen a list of alternatives for remediation of the 300-FF-5 operable site on the Hanford Reservation. This screening is based on information gathered in the Phase I Remedial Investigation (RI) and on currently available information on remediation technologies. The alternatives remaining after screening provide a range of response actions for remediation. In addition, key data needs are identified for collection during a Phase II RI (if necessary). This Phase I/II FS represents a primary document as defined by the Tri-Party Agreement, but will be followed by a Phase III FS that will further develop the alternatives and provide a detailed evaluation of them. The following remedial action objectives were identified for the 300-FF-5 operable unit: Limit current human exposure to contaminated groundwater in the unit; Limit discharge of contaminated groundwater to the Columbia River; Reduce contaminant concentrations in groundwater below acceptable levels by the year 2018.

  10. Synthesis and processing of intelligent cost-effective structures phase II (SPICES II): smart materials aircraft applications evaluation

    NASA Astrophysics Data System (ADS)

    Dunne, James P.; Jacobs, Steven W.; Baumann, Erwin W.

    1998-06-01

    The second phase of the synthesis and processing of intelligent cost effective structures (SPICES II) program sought to identify high payoff areas for both naval and aerospace military systems and to evaluate military systems and to evaluate the benefits of smart materials incorporation based on their ability to redefine the mission scenario of the candidate platforms in their respective theaters of operation. The SPICES II consortium, consisting of The Boeing Company, Electric Boat Corporation, United Technologies Research Center, and Pennsylvania State University, surveyed the state-of-the-art in smart structures and evaluated potential applications to military aircraft, marine and propulsion systems components and missions. Eleven baseline platforms comprising a wide variety of missions were chosen for evaluation. Each platform was examined in its field of operation for areas which can be improved using smart materials insertion. Over 250 smart materials applications were proposed to enhance the platforms. The applications were examined and, when possible, quantitatively analyzed for their effect on mission performance. The applications were then ranked for payoff, risk, and time frame for development and demonstration. Details of the efforts made in the SPICES II program pertaining to smart structure applications on military and transport aircraft will be presented. A brief discussion of the core technologies will be followed by presentation of the criteria used in ranking each application. Thereafter, a selection of the higher ranking proposed concepts are presented in detail.

  11. Evaluation of hydrothermal resources of North Dakota. Phase II. Final technical report

    SciTech Connect

    Harris, K.L.; Howell, F.L.; Winczewski, L.M.; Wartman, B.L.; Umphrey, H.R.; Anderson, S.B.

    1981-06-01

    This evaluation of the hydrothermal resources of North Dakota is based on existing data on file with the North Dakota Geological Survey (NDGS) and other state and federal agencies, and field and laboratory studies conducted. The principal sources of data used during the Phase II study were WELLFILE, the computer library of oil and gas well data developed during the Phase I study, and WATERCAT, a computer library system of water well data assembled during the Phase II study. A field survey of the shallow geothermal gradients present in selected groundwater observation holes was conducted. Laboratory determinations of the thermal conductivity of core samples is being done to facilitate heat-flow calculations on those hole-of-convenience cased.

  12. Site-specific phase I, II trials of hyperthermia at Kyoto University.

    PubMed

    Hiraoka, M; Nishimura, Y; Nagata, Y; Mitsumori, M; Okuno, Y; Li, P Y; Abe, M; Takahashi, M; Masunaga, S; Akuta, K

    1994-01-01

    Site-specific phase I, II trials of locoregional hyperthermia undertaken at Kyoto University are briefly reviewed. Thermometry analysis demonstrated the usefulness of RF (radiofrequency) capacitive heating equipment in the treatment of various subsurface or deep-seated tumours including locally advanced breast cancers, soft tissue tumours, lung cancers involving the chest wall, liver tumours, unresectable or recurrent colorectal cancers, and invasive urinary bladder cancers. The difficulty in heating whole tumour volume or hypervascular tumours to therapeutic temperatures was also shown. Non-randomized trials for locally advanced breast cancers, unresectable or recurrent colorectal cancers and invasive urinary bladder cancers demonstrated a higher response rate in thermoradiotherapy than in radiotherapy alone. The complications associated with treatment were not generally serious except for chronic bowel damages in a trial for colorectal cancers. These promising phase I, II trials encourage the future phase III trials.

  13. Synthesis, structure, DNA-binding properties and antioxidant activity of a nickel(II) complex with bis(N-allylbenzimidazol-2-ylmethyl)benzylamine.

    PubMed

    Wu, Huilu; Yuan, Jingkun; Bai, Ying; Pan, Guolong; Wang, Hua; Shu, Xingbin

    2012-02-01

    A V-shape ligand bis(N-allylbenzimidazol-2-ylmethyl)benzylamine (babb) and its nickel complex, [Ni(babb)(2)](pic)(2) (pic=picrate), have been synthesized and characterized by physico-chemical and spectroscopic methods. Single-crystal X-ray revealed that the coordination sphere around Ni(II) is distorted octahedral with a N(6) ligand set, in which six nitrogen atoms were afforded by two tridentate ligand babb. The DNA-binding properties of the free ligand babb and Ni(II) complex have been investigated by electronic absorption, fluorescence, and viscosity measurements. The results suggest that babb and Ni(II) complex both bind to DNA via an intercalative binding mode, and the affinity for DNA is more strong in case of Ni(II) complex when compared with babb. The intrinsic binding constants (K(b)) of the Ni(II) complex and ligand with DNA were 3.65×10(4) M(-1) and 2.26×10(3) M(-1), respectively. Additionally, Ni(II) complex also exhibited potential antioxidant properties in vitro studies. PMID:22226085

  14. 7-Methylsulfinylheptyl and 8-methylsulfinyloctyl isothiocyanates from watercress are potent inducers of phase II enzymes.

    PubMed

    Rose, P; Faulkner, K; Williamson, G; Mithen, R

    2000-11-01

    Watercress is an exceptionally rich dietary source of beta-phenylethyl isothiocyanate (PEITC). This compound inhibits phase I enzymes, which are responsible for the activation of many carcinogens in animals, and induces phase II enzymes, which are associated with enhanced excretion of carcinogens. In this study, we show that watercress extracts are potent inducers of quinone reductase (QR) in murine hepatoma Hepa 1c1c7 cells, a widely adopted assay for measuring phase II enzyme induction. However, contrary to expectations, this induction was not associated with PEITC (which is rapidly lost to the atmosphere upon tissue disruption due to its volatility) or a naturally occurring PEITC-glutathione conjugate, but with 7-methylsulfinyheptyl and 8-methylsulfinyloctyl isothiocyanates (ITCs). While it was confirmed that PEITC does induce QR (5 microM required for a two-fold induction in QR), 7-methylsulfinyheptyl and 8-methylsulfinyloctyl ITCs were more potent inducers (0.2 microM and 0.5 microM, respectively, required for a two-fold induction in QR). Thus, while watercress contains three times more phenylethyl glucosinolate than methylsulfinylalkyl glucosinolates, ITCs derived from methylsulfinylalkyl glucosinolates may be more important phase II enzyme inducers than PEITC, having 10 - to 25-fold greater potency. Analysis of urine by liquid chromatography-mass spectroscopy (LC-MS) following consumption of watercress demonstrated the presence of N:-acetylcysteine conjugates of 7-methylsulfinylheptyl, 8-methylsulfinyloctyl ITCs and PEITC, indicating that these ITCs are taken up by the gut and metabolized in the body. Watercress may have exceptionally good anticarcinogenic potential, as it combines a potent inhibitor of phase I enzymes (PEITC) with at least three inducers of phase II enzymes (PEITC, 7-methylsulfinylheptyl ITC and 8-methylsulfinyloctyl ITC). The study also demonstrates the application of LC-MS for the detection of complex glucosinolate-derived metabolites in

  15. A 2-stage phase II design with direct assignment option in stage II for initial marker validation.

    PubMed

    An, Ming-Wen; Mandrekar, Sumithra J; Sargent, Daniel J

    2012-08-15

    Biomarkers are critical to targeted therapies, as they may identify patients more likely to benefit from a treatment. Several prospective designs for biomarker-directed therapy have been previously proposed, differing primarily in the study population, randomization scheme, or both. Recognizing the need for randomization, yet acknowledging the possibility of promising but inconclusive results after a stage I cohort of randomized patients, we propose a 2-stage phase II design on marker-positive patients that allows for direct assignment in a stage II cohort. In stage I, marker-positive patients are equally randomized to receive experimental treatment or control. Stage II has the option to adopt "direct assignment" whereby all patients receive experimental treatment. Through simulation, we studied the power and type I error rate of our design compared with a balanced randomized two-stage design, and conducted sensitivity analyses to study the effect of timing of stage I analysis, population shift effects, and unbalanced randomization. Our proposed design has minimal loss in power (<1.8%) and increased type I error rate (<2.1%) compared with a balanced randomized design. The maximum increase in type I error rate in the presence of a population shift was between 3.1% and 5%, and the loss in power across possible timings of stage I analysis was less than 1.2%. Our proposed design has desirable statistical properties with potential appeal in practice. The direct assignment option, if adopted, provides for an "extended confirmation phase" as an alternative to stopping the trial early for evidence of efficacy in stage I.

  16. Site Characterization of the Source Physics Experiment Phase II Location Using Seismic Reflection Data

    SciTech Connect

    Sexton, Emily; Snelson, Catherine M; Chipman, Veraun D; Emer, Dudley; White, Bob; Emmit, Ryan; Wright, Al; Drellack, Sigmund; Huckins-Gang, Heather; Mercadante, Jennifer; Floyd, Michael; McGowin, Chris; Cothrun, Chris; Bonal, Nedra

    2013-12-05

    An objective of the Source Physics Experiment (SPE) is to identify low-yield nuclear explosions from a regional distance. Low-yield nuclear explosions can often be difficult to discriminate among the clutter of natural and man-made explosive events (e.g., earthquakes and mine blasts). The SPE is broken into three phases. Phase I has provided the first of the physics-based data to test the empirical models that have been used to discriminate nuclear events. The Phase I series of tests were placed within a highly fractured granite body. The evolution of the project has led to development of Phase II, to be placed within the opposite end member of geology, an alluvium environment, thereby increasing the database of waveforms to build upon in the discrimination models. Both the granite and alluvium sites have hosted nearby nuclear tests, which provide comparisons for the chemical test data. Phase III of the SPE is yet to be determined.

  17. The need for thorough phase II studies in medicines development for Alzheimer's disease.

    PubMed

    Gray, Julian A; Fleet, David; Winblad, Bengt

    2015-10-26

    An important factor in the universal failure in phase III trials in mild to moderate Alzheimer's disease in the past decade is the lack of phase II clinical data prior to entering phase III, with common reliance on biomarker results alone. Conduction of two learn-confirm cycles according to the Sheiner model would allow go/no-go decision making to include reliable clinical efficacy data prior to conducting phase III and would likely bring the rate of late stage failure more into line with that of other neurological indications. In studies in earlier disease stages, combined phase IIB/III adaptive approaches merit consideration in view of the long timelines of each study, though advantages and disadvantages of this approach versus the classical development pathway still need careful assessment.

  18. A Fire Safety Certification System for Board and Care Operators and Staff. SBIR Phase II: Final Report.

    ERIC Educational Resources Information Center

    Walker, Bonnie L.

    This report describes Phase II of a project which developed a system for delivering fire safety training to board and care providers who serve adults with developmental disabilities. Phase II focused on developing and pilot testing a "train the trainers" workshop for instructors and field testing the provider's workshop. Evaluation of the 2-day…

  19. 77 FR 23228 - Notice of Submission for OMB Review; Small Business Innovation Research (SBIR) Program-Phase II...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-18

    ... Notice of Submission for OMB Review; Small Business Innovation Research (SBIR) Program--Phase II--Grant... application for the Small Business Innovation Research (SBIR) Program (CFDA 84.133). This is in response to... Innovation Research (SBIR) Program--Phase II--Grant Application Package. OMB Control Number: 1820-0685....

  20. Solid-phase microextraction for qualitative and quantitative determination of migrated degradation products of antioxidants in an organic aqueous solution.

    PubMed

    Burman, Lina; Albertsson, Ann-Christine; Höglund, Anders

    2005-07-01

    Low molecular weight aromatic substances may migrate out from plastic packaging to their contents, especially if they consist of organic aqueous solutions or oils. It is, therefore, extremely important to be able to identify and quantify any migrated substances in such solutions, even at very low concentrations. We have in this work investigated and evaluated the use of solid-phase microextraction for the specific task of extraction from an organic aqueous solution such as a simulated pharmaceutical solution consisting of 10 vol.% ethanol in water. The goal was furthermore to investigate the possibility of simultaneously identifying and quantifying the substances in spite of differences in their chemical structures. Methods were developed and evaluated for extraction both with direct sampling and with headspace sampling. Difficulties appeared due to the ethanol in the solution and the minute amounts of substances present. We have shown that a simultaneous quantification of migrated low molecular weight degradation products of antioxidants using only one fibre is possible if the extraction method and temperature are adjusted in relation to the concentration levels of the analytes. Comparions were made with solid-phase extraction. PMID:16008048

  1. Functional design criteria for Project W-252, Phase II Liquid Effluent Treatment and Disposal: Revision 1

    SciTech Connect

    Hatch, C.E.

    1994-11-10

    This document provides the functional design criteria required for the Phase 2 Liquid Effluent Treatment and Disposal Project, Project W-252. Project W-252 shall provide new facilities and existing facility modifications required to implement Best Available Technology/All Known, Available, and Reasonable Methods of Prevention, Control, and Treatment (BAT/AKART) for the 200 East Phase II Liquid Effluent Streams. The project will also provide a 200 East Area Phase II Effluent Collection System (PTECS) for connection to a disposal system for relevant effluent streams to which BAT/AKART has been applied. Liquid wastestreams generated in the 200 East Area are currently discharged to the soil column. Included in these wastestreams are cooling water, steam condensate, raw water, and sanitary wastewaters. It is the policy of the DOE that the use of soil columns to treat and retain radionuclides and nonradioactive contaminants be discontinued at the earliest practical time in favor of wastewater treatment and waste minimization. In 1989, the DOE entered into an interagency agreement with Ecology and EPA. This agreement is referred to as the Hanford Federal Facility Agreement and Consent Order (Tri-Party Agreement). Project W-252 is one of the projects required to achieve the milestones set forth in the Tri-Party Agreement. One of the milestones requires BAT/AKART implementation for Phase II streams by October 1997. This Functional Design Criteria (FDC) document provides the technical baseline required to initiate Project W-252 to meet the Tri-Party Agreement milestone for the application of BAT/AKART to the Phase II effluents.

  2. Phase Transition of a Structure II Cubic Clathrate Hydrate to a Tetragonal Form.

    PubMed

    Takeya, Satoshi; Fujihisa, Hiroshi; Yamawaki, Hiroshi; Gotoh, Yoshito; Ohmura, Ryo; Alavi, Saman; Ripmeester, John A

    2016-08-01

    The crystal structure and phase transition of cubic structure II (sII) binary clathrate hydrates of methane (CH4 ) and propanol are reported from powder X-ray diffraction measurements. The deformation of host water cages at the cubic-tetragonal phase transition of 2-propanol+CH4 hydrate, but not 1-propanol+CH4 hydrate, was observed below about 110 K. It is shown that the deformation of the host water cages of 2-propanol+CH4 hydrate can be explained by the restriction of the motion of 2-propanol within the 5(12) 6(4) host water cages. This result provides a low-temperature structure due to a temperature-induced symmetry-lowering transition of clathrate hydrate. This is the first example of a cubic structure of the common clathrate hydrate families at a fixed composition. PMID:27346760

  3. System Integral Test by BWR Drywell Cooler Applied as Phase-II Accident Management

    SciTech Connect

    Nagasaka, Hideo; Tobimatsu, Toshimi; Tahara, Mika; Yokobori, Seiichi; Akinaga, Makoto

    2002-07-01

    This paper deals with the system interaction performance using the BWR drywell local cooler (DWC) in combination with containment spray as a Japanese Phase-II accident management (AM). By using almost full height simulation test facility (GIRAFFE-DWC) with scaling ratio of 1/600, the system integral tests simulating BWR low pressure vessel failure sequence were accomplished during about 14 hours. In case of DWC application, the containment pressure increase was found milder due to DWC heat removal performance. Initial spray timing was delayed about 3 hours and each spray period was reduced almost by half. It was concluded that the application of a BWR DWC to Phase-II AM measure is quite promising from the point of delaying or preventing the containment venting. (authors)

  4. Performance of the Tile PreProcessor Demonstrator for the ATLAS Tile Calorimeter Phase II Upgrade

    NASA Astrophysics Data System (ADS)

    Carrió, F.; Moreno, P.; Valero, A.

    2016-03-01

    The Tile Calorimeter PreProcessor demonstrator is a high performance double AMC board based on FPGA resources and QSFP modules. This board has been designed in the framework of the ATLAS Tile Calorimeter Demonstrator project for the Phase II Upgrade as the first stage of the back-end electronics. The TilePPr demonstrator has been conceived to receive and process the data coming from the front-end electronics of the TileCal Demonstrator module, as well as to configure it. Moreover, the TilePPr demonstrator handles the communication with the Detector Control System to monitor and control the front-end electronics. The TilePPr demonstrator represents 1/8 of the final TilePPr that will be designed and installed into the detector for the ATLAS Phase II Upgrade.

  5. Free-Piston Stirling Power Conversion Unit for Fission Power System, Phase II Final Report

    NASA Technical Reports Server (NTRS)

    Wood, J. Gary; Stanley, John

    2016-01-01

    In Phase II, the manufacture and testing of two 6-kW(sub e)Stirling engines was completed. The engines were delivered in an opposed 12-kW(sub e) arrangement with a common expansion space heater head. As described in the Phase I report, the engines were designed to be sealed both hermetically and with a bolted O-ring seal. The completed Phase II convertor is in the bolted configuration to allow future disassembly. By the end of Phase II, the convertor had passed all of the final testing requirements in preparation for delivery to the NASA Glenn Research Center. The electronic controller also was fabricated and tested during Phase II. The controller sets both piston amplitudes and maintains the phasing between them. It also sets the operating frequency of the machine. Details of the controller are described in the Phase I final report. Fabrication of the direct-current to direct-current (DC-DC) output stage, which would have stepped down the main controller output voltage from 700 to 120 V(sub DC), was omitted from this phase of the project for budgetary reasons. However, the main controller was successfully built, tested with the engines, and delivered. We experienced very few development issues with this high-power controller. The project extended significantly longer than originally planned because of yearly funding delays. The team also experienced several hardware difficulties along the development path. Most of these were related to the different thermal expansions of adjacent parts constructed of different materials. This issue was made worse by the large size of the machine. Thermal expansion problems also caused difficulties in the brazing of the opposed stainless steel sodium-potassium (NaK) heater head. Despite repeated attempts Sunpower was not able to successfully braze the opposed head under this project. Near the end of the project, Glenn fabricated an opposed Inconel NaK head, which was installed prior to delivery for testing at Glenn. Engine

  6. Underground Test Area Subproject Phase I Data Analysis Task. Volume II - Potentiometric Data Document Package

    SciTech Connect

    1996-12-01

    Volume II of the documentation for the Phase I Data Analysis Task performed in support of the current Regional Flow Model, Transport Model, and Risk Assessment for the Nevada Test Site Underground Test Area Subproject contains the potentiometric data. Because of the size and complexity of the model area, a considerable quantity of data was collected and analyzed in support of the modeling efforts. The data analysis task was consequently broken into eight subtasks, and descriptions of each subtask's activities are contained in one of the eight volumes that comprise the Phase I Data Analysis Documentation.

  7. Rigid Polyurethane Foam (RPF) Technology for Countermines (Sea) Program Phase II

    SciTech Connect

    WOODFIN,RONALD L.; FAUCETT,DAVID L.; HANCE,BRADLEY G.; LATHAM,AMY E.; SCHMIDT,C.O.

    1999-10-01

    This Phase II report documents the results of one subtask initiated under the joint Department of Energy (DOE)/Department of Defense (DoD) Memorandum of Understanding (MOU) for Countermine Warfare. The development of Rigid Polyurethane Foams for neutralization of mines and barriers in amphibious assault was the objective of the tasking. This phase of the program concentrated on formation of RPF in water, explosive mine simulations, and development of foam and fabric pontoons. Field experimentation was done primarily at the Energetic Materials Research and Testing Center (EMRTC) of the New Mexico Institute of Mining and Technology, Socorro, NM between February 1996 and September 1998.

  8. An FPGA-based trigger for the phase II of the MEG experiment

    NASA Astrophysics Data System (ADS)

    Baldini, A.; Bemporad, C.; Cei, F.; Galli, L.; Grassi, M.; Morsani, F.; Nicolò, D.; Ritt, S.; Venturini, M.

    2016-07-01

    For the phase II of MEG, we are going to develop a combined trigger and DAQ system. Here we focus on the former side, which operates an on-line reconstruction of detector signals and event selection within 450 μs from event occurrence. Trigger concentrator boards (TCB) are under development to gather data from different crates, each connected to a set of detector channels, to accomplish higher-level algorithms to issue a trigger in the case of a candidate signal event. We describe the major features of the new system, in comparison with phase I, as well as its performances in terms of selection efficiency and background rejection.

  9. Analytical data from phases I and II of the Willamette River basin water quality study, Oregon

    USGS Publications Warehouse

    Harrison, Howard E.; Anderson, Chauncey W.; Rinella, Frank A.; Gasser, Timothy M.; Pogue, Ted R.

    1995-01-01

    The data were collected at 50 sites, representing runoff from agricultural, forested, and urbanized subbasins. In Phase I, water samples were collected during high and low flows in 1992 and 1993 to represent a wide range of hydrologic conditions. Bed-sediment samples were collected during low flows in 1993. In Phase II, water samples were collected in the spring of 1994 after the first high-flow event following the application of agricultural fertilizers and pesticides and in the fall during the first high-flow events following the conclusion of the agricultural season.

  10. Biological screening of 100 plant extracts for cosmetic use (II): anti-oxidative activity and free radical scavenging activity.

    PubMed

    Kim, B J; Kim, J H; Kim, H P; Heo, M Y

    1997-12-01

    Methanol aqueous extracts of 100 plants were screened for anti-oxidative activity using Fenton's reagent/ethyl linoleate system and for free radical scavenging activity using the 1,1-diphenyl-2-picryl hydrazyl free radical generating system. The results suggest that 14 plants - Alpinia officinarum, Areca catechu, Brassica alba, Cannabis sativa, Curcuma longa, Curcuma aromatica, Eugenia caryophyllata, Evodia officinalis, Paeonia suffruticosa, Rhaphanus sativus, Rheum palmatum, Rhus verniciflua, Trapa bispinosa, Zanthoxylum piperitum - may be potential sources of anti-oxidants. Eight plants - Citrus aurantium, Cornus officinalis, Gleditsia japonica, Lindera strychnifolia, Phragmites communis, Prunus mume, Schizandra chinensis, Terminalia chebula - may be the potential source of free radical scavengers from natural plant.

  11. V-shaped ligand 1,3-bis(1-ethylbenzimidazol-2-yl)-2-thiapropane and manganese(II), cobalt(II) and copper(II) complexes: Synthesis, crystal structure, DNA-binding properties and antioxidant activities.

    PubMed

    Wu, Huilu; Yang, Zaihui; Wang, Fei; Peng, Hongping; Zhang, Han; Wang, Cuiping; Wang, Kaitong

    2015-07-01

    A V-shaped ligand 1,3-bis(1-ethylbenzimidazol-2-yl)-2-thiapropane (bebt) and its transition metal complexes, [Mn(bebt)(pic)2]·CH3OH (pic=picrate) 1, [Co(bebt)2](pic)22 and [Cu(bebt)2](pic)2·2DMF 3, have been synthesized and characterized. The coordinate forms of complexes 1 and 2 are basically alike, which can be described as six-coordinated distorted octahedron. The geometric structure around Cu(II) atom can be described as distorted tetrahedral in complex 3. The DNA-binding properties of the ligand bebt and complexes have been investigated by electronic absorption, fluorescence, and viscosity measurements. The results suggest that bebt and complexes bind to DNA via an intercalative binding mode and the order of the binding affinity is 1<2<3antioxidant activity against superoxide and hydroxyl radicals, and the scavenging effects of it are stronger than standard mannitol and vitamin C.

  12. Molecular dynamics simulation of the phase transition between calcite and CaCO3-II

    NASA Astrophysics Data System (ADS)

    Kawano, Jun; Miyake, Akira; Shimobayashi, Norimasa; Kitamura, Masao

    2009-07-01

    Molecular dynamics (MD) simulation of calcium carbonate at high pressure was performed to understand the phase transition between calcite (R\\bar {3}c) and CaCO3-II (P 21/c). In the 300-800 K temperature range, the transition of calcite to CaCO3-II was reproduced at a pressure of around 8 GPa. This transition is of first order and reversible in the MD calculations except for runs at 300 K where a small hysteresis exists. The slope of the dP/dT curve at the phase boundary between calcite and CaCO3-II is negative at 300 K and turns positive at around 600 K, which was confirmed by analyzing the enthalpy change. Just below the transition pressure, the P 21/c structure appears and its orientation switches among three positions with time, resulting in the maintenance of the R\\bar {3}c structure as a whole. The P 21/c structure resembles the structure of CaCO3-II on an increase of temperature. It can be suggested that the existence of the P 21/c structure and the switching of its orientation just below the transition pressure are responsible for the change of the slope of the dP/dT curve at the boundary from negative to positive on an increase of temperature, because the switching increases entropy and results in an expansion of the stability field of calcite.

  13. Development and Testing of a Jet Assisted Polycrystalline Diamond Drilling Bit. Phase II Development Efforts

    SciTech Connect

    David S. Pixton

    1999-09-20

    Phase II efforts to develop a jet-assisted rotary-percussion drill bit are discussed. Key developments under this contract include: (1) a design for a more robust polycrystalline diamond drag cutter; (2) a new drilling mechanism which improves penetration and life of cutters; and (3) a means of creating a high-pressure mud jet inside of a percussion drill bit. Field tests of the new drill bit and the new robust cutter are forthcoming.

  14. Evaluation of Beam Loss and Energy Depositions for a Possible Phase II Design for LHC Collimation

    SciTech Connect

    Lari, L.; Assmann, R.; Bracco, C.; Brugger, M.; Cerutti, F.; Doyle, E.; Ferrari, A.; Keller, L.; Lundgren, S.; Markiewicz, Thomas W.; Mauri, M.; Redaelli, S.; Sarchiapone, L.; Smith, J.; Vlachoudis, V.; Weiler, T.; /CERN

    2011-11-07

    The LHC beams are designed to have high stability and to be stored for many hours. The nominal beam intensity lifetime is expected to be of the order of 20h. The Phase II collimation system has to be able to handle particle losses in stable physics conditions at 7 TeV in order to avoid beam aborts and to allow correction of parameters and restoration to nominal conditions. Monte Carlo simulations are needed in order to evaluate the behavior of metallic high-Z collimators during operation scenarios using a realistic distribution of losses, which is a mix of the three limiting halo cases. Moreover, the consequences in the IR7 insertion of the worst (case) abnormal beam loss are evaluated. The case refers to a spontaneous trigger of the horizontal extraction kicker at top energy, when Phase II collimators are used. These studies are an important input for engineering design of the collimation Phase II system and for the evaluation of their effect on adjacent components. The goal is to build collimators that can survive the expected conditions during LHC stable physics runs, in order to avoid quenches of the SC magnets and to protect other LHC equipments.

  15. Flexible designs for phase II comparative clinical trials involving two response variables.

    PubMed

    Bersimis, S; Sachlas, A; Papaioannou, T

    2015-01-30

    The aim of phase II clinical trials is to determine whether an experimental treatment is sufficiently promising and safe to justify further testing. The need for reduced sample size arises naturally in phase II clinical trials owing to both technical and ethical reasons, motivating a significant part of research in the field during recent years, while another significant part of the research effort is aimed at more complex therapeutic schemes that demand the consideration of multiple endpoints to make decisions. In this paper, our attention is restricted to phase II clinical trials in which two treatments are compared with respect to two dependent dichotomous responses proposing some flexible designs. These designs permit the researcher to terminate the clinical trial when high rates of favorable or unfavorable outcomes are observed early enough requiring in this way a small number of patients. From the mathematical point of view, the proposed designs are defined on bivariate sequences of multi-state trials, and the corresponding stopping rules are based on various distributions related to the waiting time until a certain number of events appear in these sequences. The exact distributions of interest, under a unified framework, are studied using the Markov chain embedding technique, which appears to be very useful in clinical trials for the sample size determination. Tables of expected sample size and power are presented. The numerical illustration showed a very good performance for these new designs.

  16. Phase transitions in Kr -CH4 solid solutions and rotational excitations in phase II

    NASA Astrophysics Data System (ADS)

    Bagatskii, M. I.; Mashchenko, D. A.; Dudkin, V. V.

    2007-06-01

    The heat capacity CP of Kr-nCH4 solid solutions with CH4 concentrations n =0.82, 0.86, and 0.90 and of solutions with n =0.90, 0.95 doped with 0.002 O2 impurity is investigated under equilibrium vapor pressure over the interval 1-24K. The (T,n) phase diagram of Kr-nCH4 solid solutions is refined, and the region of two-phase states is determined. The contribution of the rotational subsystem, Crot, to the heat capacity of the solutions is separated. Analysis of Crot(T ) at T <3K makes it possible to estimate the effective conversion times τ and the energy gaps E1 and E2 between the tunneling levels of the A ,T and A ,E nuclear-spin species of CH4 molecules in the orientationally ordered subsystem and to determine the effective energy gaps E1 between the lowest levels of the A and T species. The relations τ(n ) and E1(n) stem from changes of the effective potential field in result of the replacement of CH4 molecules by Kr atoms at sites of the ordered sublattices. The effective gaps EL between a group of tunneling levels of the librational ground state and the nearest group of excited levels of the librational state of the ordered CH4 molecules in the solutions with n =0.90 (EL=52K) and 0.95 (EL=55K) is estimated.

  17. Solar Ethanol Demonstration Plant: report of Phase I, technology assessment and Phase II, concept selection

    SciTech Connect

    Not Available

    1981-01-01

    The solar ethanol demonstration plant is a most versatile facility for demonstrating the feasibility of on-farm, small scale ethanol production using solar energy as the primary heat source. This facility will be capable of processing the full range of feed stocks - not only the sugar and starch crops but also the cellulose feedstocks on which little data have been collected. This plant is unique in that it will be designed to permit the addition of modules (needed for the processing of cellulose and/or the demonstration of the continuous cycle) and the interchange of components such as fermenters, distillation columns, and molecular sieves which will enable comparative performance data among specific components. The feasibility of solar energy in ethanol production and the utilization of cascaded waste heat for other on-farm uses are also major design features. Engineering and cost analysis was performed to formulate a preliminary design for a unique solar ethanol demonstration plant for on-farm use. Energy requirements were calculated for a variety of starches, simple sugars, and cellulose. These requirements, in increasing order of Btu's required per gallon of ethanol produced, were simple sugars (low), grains (moderate), and cellulose (high). A complete listing of all feedstocks examined is presented. Chapter II provides the design requirements and the detailed process plant design information with flow, layout and performance information. Chapter III provides the results of the ethanol feedstock energy requirements study and chapter IV contains supporting details of the solar collector selection process. The three appendixes which follow address the ethanol fermentation process, the range of cellulose-ethanol production processes, and a detailed description of the Solar Collector performance model.

  18. National Geoscience Data Repository System, Phase II. Final report, January 30, 1995--January 28, 1997

    SciTech Connect

    1998-04-01

    The American Geological Institute (AGI) has completed Phase II of a project to establish a National Geoscience Data Repository System (NGDRS). The project`s primary objectives are to preserve geoscience data in jeopardy of being destroyed and to make that data available to those who have a need to use it in future investigations. These data are available for donation to the public as a result of the downsizing that has occurred in the major petroleum and mining companies in the United States for the past decade. In recent years, these companies have consolidated domestic operations, sold many of their domestic properties and relinquished many of their leases. The scientific data associated with those properties are no longer considered to be useful assets and are consequently in danger of being lost forever. The national repository project will make many of these data available to the geoscience community for the first time. To address this opportunity, AGI sought support from the Department of Energy (DOE) in 1994 to initiate the NGDRS Phase I feasibility study to determine the types and quantity of data that companies would be willing to donate. The petroleum and mining companies surveyed indicated that they were willing to donate approximately five million well logs, one hundred million miles of seismic reflection data, millions of linear feet of core and cuttings, and a variety of other types of scientific data. Based on the positive results of the Phase I study, AGI undertook Phase II of the program in 1995. Funded jointly by DOE and industry, Phase II encompasses the establishment of standards for indexing and cataloging of geoscience data and determination of the costs of transferring data from the private sector to public-sector data repositories. Pilot projects evaluated the feasibility of the project for transfer of different data types and creation of a Web-based metadata supercatalog and browser.

  19. Effect of Calendula officinalis Flower Extract on Acute Phase Proteins, Antioxidant Defense Mechanism and Granuloma Formation During Thermal Burns.

    PubMed

    Chandran, Preethi K; Kuttan, Ramadasan

    2008-09-01

    Effect of Calendula officinalis flower extract was investigated against experimentally induced thermal burns in rats. Burn injury was made on the shaven back of the rats under anesthesia and the animals were treated orally with different doses of the flower extract (20 mg, 100 mg and 200 mg/kg body weight). The animals treated with the extract showed significant improvement in healing when compared with the control untreated animals. The indicators of the wound healing such as collagen-hydroxyproline and hexosamine contents were significantly increased in the treated group indicating accelerated wound healing in the treated animals. The acute phase proteins-haptoglobin and orosomucoid which were increased due to burn injury were found to be decreased significantly in 200 mg/kg body weight extract treated animals. The antioxidant defense mechanism, which was decreased in the liver during burn injury, was found to be enhanced in treated animals. The lipid peroxidation was significantly lowered in the treated group when compared to control animals. Tissue damage marker enzymes- alkaline phosphatase, alanine and aspartate transaminases were significantly lowered in the treated groups in a dose dependant manner. The histopathological analyses of skin tissue also give the evidence of the increased healing potential of the extract after burn injury.

  20. Effect of Calendula officinalis Flower Extract on Acute Phase Proteins, Antioxidant Defense Mechanism and Granuloma Formation During Thermal Burns

    PubMed Central

    Chandran, Preethi K.; Kuttan, Ramadasan

    2008-01-01

    Effect of Calendula officinalis flower extract was investigated against experimentally induced thermal burns in rats. Burn injury was made on the shaven back of the rats under anesthesia and the animals were treated orally with different doses of the flower extract (20 mg, 100 mg and 200 mg/kg body weight). The animals treated with the extract showed significant improvement in healing when compared with the control untreated animals. The indicators of the wound healing such as collagen-hydroxyproline and hexosamine contents were significantly increased in the treated group indicating accelerated wound healing in the treated animals. The acute phase proteins—haptoglobin and orosomucoid which were increased due to burn injury were found to be decreased significantly in 200 mg/kg body weight extract treated animals. The antioxidant defense mechanism, which was decreased in the liver during burn injury, was found to be enhanced in treated animals. The lipid peroxidation was significantly lowered in the treated group when compared to control animals. Tissue damage marker enzymes- alkaline phosphatase, alanine and aspartate transaminases were significantly lowered in the treated groups in a dose dependant manner. The histopathological analyses of skin tissue also give the evidence of the increased healing potential of the extract after burn injury. PMID:18818737

  1. Summary - National Dissemination and the Five Target States, Part 3, Final Report for Phase II--Dissemination, Rural Shared Services.

    ERIC Educational Resources Information Center

    Northern Montana Coll., Havre.

    The dissemination phase (Phase II) of the Rural Shared Services Project is reported in this document. Efforts of the dissemination phase were concentrated in 5 target states: Vermont, Georgia, Wyoming, Montana, and New Mexico; national dissemination was limited to attendance at national conferences, the U. S. Office of Education PREP materials for…

  2. Complex formation, thermal behavior and stability competition between Cu(II) ion and Cu(0) nanoparticles with some new azo dyes. Antioxidant and in vitro cytotoxic activity.

    PubMed

    Gaber, M; El-Sayed, Y S; El-Baradie, K Y; Fahmy, R M

    2013-04-15

    Four triazole and thiadiazole-based azo chromophores namely [(E)-4-((1H-1,2,4-triazol-3-yl)diazenyl)benzene-1,3-diol.(HL(1)), (E)-4-((5-(methylthio)-1H-1,2,4-triazol-3-yl)diazenyl)benzene-1,3-diol.(HL(2)), (E)-4-((1,3,4-thiadiazol-2-yl)diazenyl)benzene-1,3-diol.(HL(3)) and (E)-4-((5-mercapto-1,3,4-thiadiazol-2-yl)diazenyl)benzene-1,3-diol.(HL(4))] were synthesized and characterized by elemental analyses, IR, UV-Vis as well as mass spectroscopy. Cu(II) complexes of the investigated azo dyes have been synthesized and characterized by elemental analyses, IR, electronic and ESR spectra, magnetic susceptibility and thermogravimetric analyses. The bond lengths and bond angles have been calculated to confirm the geometry of the ligands and their Cu(II) complexes. The mode of interaction of the azodyes to copper nanoparticles was described as coordination mode of charged dye molecules on the colloidal Cu(0) surface through anchoring OH(-) group. The apparent association constants of the colloidal copper nanoparticles azodye complexes in solution were evaluated using the spectral method and compared with the formation constant of the Cu(II) azo complexes. The antitumor and antioxidant activities of the synthesized azo dyes and their Cu(II) azo complexes have been evaluated.

  3. Hepatic phase I and phase II biotransformations in quail and trout: comparison to other species commonly used in toxicity testing.

    PubMed

    Gregus, Z; Watkins, J B; Thompson, T N; Harvey, M J; Rozman, K; Klaassen, C D

    1983-03-15

    The ability of quail and trout to perform a number of representative phase I and phase II biotransformations was examined. To facilitate interspecies comparisons, metabolism of the same substrates was examined simultaneously under uniform conditions for rat, mouse, rabbit, guinea pig, cat, and dog. Both nonmammalian species can metabolize four representative substrates of phase I mixed-function oxidases and one substrate of epoxide hydrolase, though activity tended to be lower than that of the mammals. Important differences in the conjugative pathways were also noted. Among these differences were the quail's relative deficiency in glutathione conjugation and the trout's low ability to conjugate sulfate compounds. Trout liver UDP-glucuronosyltransferase activity was remarkably high toward testosterone and bilirubin, while quail liver formed glucuronides of naphthol, p-nitrophenol, and digitoxigenin-monodigitoxoside. Also noteworthy was the high N-acetyltransferase activity of both quail and trout toward isoniazid, beta-naphthylamine, and 2-aminofluorene. Differences in substrate specificity for a given enzymatic pathway may be an indication that multiple forms of drug metabolizing systems also occur in these nonmammalian species. Observation of several hundred- or even thousand-fold differences between species in their enzyme activities for certain substrates under uniform conditions re-emphasizes the need for caution in extrapolation of xenobiotic metabolism from one species to another.

  4. Yakima River Basin Fish Passage Phase II Fish Screen Construction, Project Completion Report.

    SciTech Connect

    Hudson, R. Dennis

    2008-01-01

    On December 5, 1980, Congress passed the Pacific Northwest Electric Power Planning and Conservation Act (Public Law 96-501). The Act created the Northwest Power Planning Council (now the Northwest Power and Conservation Council). The Council was charged with the responsibility to prepare a Regional Conservation and Electric Power Plan and to develop a program to protect, mitigate, and enhance fish and wildlife including related spawning grounds and habitat on the Columbia River and its tributaries. The Council adopted its Fish and Wildlife Program on November 15, 1982. Section 800 of the Program addresses measures in the Yakima River Basin. The Yakima measures were intended to help mitigate hydroelectric impacts in the basin and provide off-site mitigation to compensate for fish losses caused by hydroelectric project development and operations throughout the Columbia River Basin. The Bonneville Power Administration (BPA) was designated as a major source of funding for such off-site mitigation measures and was requested to initiate discussions with the appropriate Federal project operators and the Council to determine the most expeditious means for funding and implementing the program. The primary measures proposed for rapid implementation in the Yakima River basin were the installation of fish passage and protective facilities. Sec. 109 of The Hoover Power Plant Act of 1984, authorized the Secretary of the Interior to design, construct, operate, and maintain fish passage facilities within the Yakima River Basin. Under Phase I of the program, improvements to existing fish passage facilities and installation of new fish ladders and fish screens at 16 of the largest existing diversion dams and canals were begun in 1984 and were completed in 1990. The Yakima Phase II fish passage program is an extension of the Phase I program. In 1988, the Yakama Nation (YN) submitted an application to amend Sections 803(b) and 1403(4.5) of the Northwest Power and Conservation Council

  5. PHASE II CALDERON PROCESS TO PRODUCE DIRECT REDUCED IRON RESEARCH AND DEVELOPMENT PROJECT

    SciTech Connect

    Albert Calderon

    2001-07-23

    This project was initially targeted to the making of coke for blast furnaces by using proprietary technology of Calderon in a phased approach, and Phase I was completed. The project was then re-directed to the making of iron units. U.S. Steel teamed up with Calderon for a joint effort which will last 30 months to produce directly reduced iron with the potential of converting it into molten iron (hot metal) consistent with the Roadmap recommendations of 1998 prepared by the Steel Industry in cooperation with the Department of Energy. The work which is labeled as Phase II will take place at two levels; namely, the bench scale level and the process development unit level. During the past quarter approval for the re-direction took place and work was initiated at both levels.

  6. PHASE II CALDERON PROCESS TO PRODUCE DIRECT REDUCED IRON RESEARCH AND DEVELOPMENT PROJECT

    SciTech Connect

    Albert Calderon

    2002-01-22

    This project was initially targeted to the making of coke for blast furnaces by using proprietary technology of Calderon in a phased approach, and Phase I was completed. The project was then re-directed to the making of iron units. U.S. Steel teamed up with Calderon for a joint effort which will last 30 months to produce directly reduced iron with the potential of converting it into molten iron (hot metal) consistent with the Roadmap recommendations of 1998 prepared by the Steel Industry in cooperation with the Department of Energy. The work which is labeled as Phase II will take place at two levels; namely, the bench scale level and the process development unit (PDU) level.

  7. Spatial distribution of phases during gradual magnetostructural transitions in copper(II)-nitroxide based molecular magnets.

    PubMed

    Fedin, Matvey V; Veber, Sergey L; Bagryanskaya, Elena G; Romanenko, Galina V; Ovcharenko, Victor I

    2015-11-21

    Copper(ii)-nitroxide based molecular magnets Cu(hfac)2L(R) exhibit thermally-induced transitions between high- and low-temperature (HT/LT) magnetostructural states. In this work we report the first study on the spatial distribution of HT/LT phases during gradual transitions in these compounds. We explore the possibility of domain formation at intermediate temperatures, which has never been addressed before. For this purpose, we reexamine the available electron paramagnetic resonance (EPR) and X-ray diffraction data, and perform numerical calculations of EPR spectra for different models of exchange-coupled networks. A thorough analysis shows that during gradual transitions, molecular magnets Cu(hfac)2L(R) represent solid solutions of disordered HT and LT phases, and the formation of single-phase domains larger than a few nanometers in size is unlikely.

  8. Analysis of the antioxidant butylated hydroxytoluene (BHT) in water by means of solid phase extraction combined with GC/MS.

    PubMed

    Fries, Elke; Püttmann, Wilhelm

    2002-05-01

    The antioxidant 3,5-di-tert-butyl-4-hydroxy-toluene (BHT) is widely used as an additive to increase the tenability of food and plastics. BHT is degraded to 3,5-di-tert-butyl-4-hydroxybenzaldehyde (BHT-CHO) in mammals, as well as in the natural environment such as in water and soils. BHT-CHO has been studied extensively in terms of their potential toxicities. The present investigation was carried out to quantify BHT and BHT-CHO in river, ground, rain and drinking water obtained from several locations in Germany. Apart from the compounds mentioned above, 1,2-bis-(3,5-di-tert-butyl-4-hydroxyphenyl)ethane (2-BHT), which is a dimer of BHT, was also detected in the extracts of some ground water samples. The applied analytical method is based on solid phase extraction (SPE) to concentrate trace compounds from water samples followed by gas chromatography/mass spectrometry (GC/MS) of the extracts. A total of 51 of the respective water samples were used for extraction purposes and analyte recoveries were all > or = 80%. The determination limit for BHT was 5 ng l(-1) and for BHT-CHO 16 ng l(-1). The standard deviations for the analytical procedure were 6% for BHT and 10% for BHT-CHO. The use of the antioxidant BHT in Germany has resulted in water concentrations of 7-791 ng l(-1) in the rivers Rhine, Elbe, Main, Oder, Nidda and Schwarzbach. The degradation product BHT-CHO was also detected in the river water samples at concentrations between 29 and 223 ng l(-1). The concentrations of BHT measured in German rivers are lower compared to values measured in the USA and Japan 20 years ago. In ground water, levels for BHT varied from non-detectable up to 2156 ng l(-1) and for BHT-CHO from non-detectable up to 674 ng l(-1). Both compounds were also detected in rain water in Frankfurt/Main at a concentration of 1797 ng l(-1) for BHT and 59 ng l(-1) for BHT-CHO. PMID:12108724

  9. Analysis of the antioxidant butylated hydroxytoluene (BHT) in water by means of solid phase extraction combined with GC/MS.

    PubMed

    Fries, Elke; Püttmann, Wilhelm

    2002-05-01

    The antioxidant 3,5-di-tert-butyl-4-hydroxy-toluene (BHT) is widely used as an additive to increase the tenability of food and plastics. BHT is degraded to 3,5-di-tert-butyl-4-hydroxybenzaldehyde (BHT-CHO) in mammals, as well as in the natural environment such as in water and soils. BHT-CHO has been studied extensively in terms of their potential toxicities. The present investigation was carried out to quantify BHT and BHT-CHO in river, ground, rain and drinking water obtained from several locations in Germany. Apart from the compounds mentioned above, 1,2-bis-(3,5-di-tert-butyl-4-hydroxyphenyl)ethane (2-BHT), which is a dimer of BHT, was also detected in the extracts of some ground water samples. The applied analytical method is based on solid phase extraction (SPE) to concentrate trace compounds from water samples followed by gas chromatography/mass spectrometry (GC/MS) of the extracts. A total of 51 of the respective water samples were used for extraction purposes and analyte recoveries were all > or = 80%. The determination limit for BHT was 5 ng l(-1) and for BHT-CHO 16 ng l(-1). The standard deviations for the analytical procedure were 6% for BHT and 10% for BHT-CHO. The use of the antioxidant BHT in Germany has resulted in water concentrations of 7-791 ng l(-1) in the rivers Rhine, Elbe, Main, Oder, Nidda and Schwarzbach. The degradation product BHT-CHO was also detected in the river water samples at concentrations between 29 and 223 ng l(-1). The concentrations of BHT measured in German rivers are lower compared to values measured in the USA and Japan 20 years ago. In ground water, levels for BHT varied from non-detectable up to 2156 ng l(-1) and for BHT-CHO from non-detectable up to 674 ng l(-1). Both compounds were also detected in rain water in Frankfurt/Main at a concentration of 1797 ng l(-1) for BHT and 59 ng l(-1) for BHT-CHO.

  10. Antioxidant effects of green tea

    PubMed Central

    FORESTER, SARAH C.; LAMBERT, JOSHUA D.

    2013-01-01

    Consumption of green tea (Camellia sinensis) may provide protection against chronic diseases, including cancer. Green tea polyphenols are believed to be responsible for this cancer preventive effect, and the antioxidant activity of the green tea polyphenols has been implicated as a potential mechanism. This hypothesis has been difficult to study in vivo due to metabolism of these compounds and poor understanding of the redox environment in vivo. Green tea polyphenols can be direct antioxidants by scavenging reactive oxygen species or chelating transition metals as has been demonstrated in vitro. Alternatively, they may act indirectly by up-regulating phase II antioxidant enzymes. Evidence of this latter effect has been observed in vivo, yet more work is required to determine under which conditions these mechanisms occur. Green tea polyphenols can also be potent pro-oxidants, both in vitro and in vivo, leading to the formation of hydrogen peroxide, the hydroxyl radical, and superoxide anion. The potential role of these pro-oxidant effects in the cancer preventive activity of green tea is not well understood. The evidence for not only the antioxidant, but also pro-oxidant, properties of green tea are discussed in the present review. PMID:21538850

  11. Modeling of fluidized-bed combustion of coal: Phase II, final reports. Volume II. Detailed description of the model

    SciTech Connect

    Louis, J.F.; Tung, S.E.

    1980-10-01

    This document is the second of a seven volume series of our Phase II Final Report. This volume deals with detailed descriptions of the structure of each program member (subroutines and functions), the interrelation between the members of a submodel, and the interrelation between the various submodels as such. The systems model for fluidized bed combustors (FBC-II) consists of a systematic combination of the following interrelated areas: fluid mechanics and bubble growth, char combustion and associated kinetics for particle burnout, sulfur capture, NO/sub x/ formation and reduction, freeboard reactions, and heat transfer. Program outline is shown in Figure 1.1. Input variables (supplied by the user are inspected to check that they lie inside the allowed range of values and are input to the various routines as needed. The necessary physical and fluid mechanical properties are calculated and utilized in estimating char combustion and sulfur capture in the bed and the freeboard. NO/sub x/ and CO emissions are estimated by taking into account all relevant chemical reactions. A material and energy balance is made over the bed. Figure 1.1 shows a block diagram of the systems program. In this diagram, the overall structure of the FBC program is illustrated in terms of the various submodels that together constitute the systems program. A more detailed outline of the systems program is shown in Figure 1.2. In this figure, all important subroutine members of the FBC program are shown, and their linkage to each other, as well as to the main program is indicated. A description of the exact sequence in which these various routines are called at time of program execution is provided in Chapter 8 under the executive routine MAIN.

  12. Zinc(II) oxide solubility and phase behavior in aqueous sodium phosphate solutions at elevated temperatures

    SciTech Connect

    Ziemniak, S.E.; Jones, M.E.; Combs, K.E.S.

    1990-02-01

    A platinum-lined, flowing autoclave facility is used to investigate the solubility/phase behavior of zinc(II) oxide in aqueous sodium phosphate solutions at temperatures between 290 and 560 K. ZnO solubilities are observed to increase continuously with temperature and phosphate concentration. At higher phosphate concentrations, a solid phase transformation to NaZnPO{sub 4} is observed. NaZnPO{sub 4} solubilities are retrograde with temperature. The measured solubility behavior is examined via a Zn(II) ion hydrolysis/complexing model and thermodynamic functions for the hydrolysis/complexing reaction equilibria are obtained from a least-squares analysis of the data. The existence of two new zinc(II) ion complexes is reported for the first time: Zn(OH){sub 2}(HPO{sub 4}){sup 2{minus}} and Zn(OH){sub 3}(H{sub 2}PO{sub 4}){sup 2{minus}}. A summary of thermochemical properties for species in the systems ZnO-H{sub 2}O and ZnO-Na{sub 2}O-P{sub 2}O{sub 5}-H{sub 2}O is also provided. 21 refs., 10 figs., 7 tabs.

  13. 37 GHz METHANOL MASERS : HORSEMEN OF THE APOCALYPSE FOR THE CLASS II METHANOL MASER PHASE?

    SciTech Connect

    Ellingsen, S. P.; Breen, S. L.; Sobolev, A. M.; Voronkov, M. A.; Caswell, J. L.; Lo, N.

    2011-12-01

    We report the results of a search for class II methanol masers at 37.7, 38.3, and 38.5 GHz toward a sample of 70 high-mass star formation regions. We primarily searched toward regions known to show emission either from the 107 GHz class II methanol maser transition, or from the 6.035 GHz excited OH transition. We detected maser emission from 13 sources in the 37.7 GHz transition, eight of these being new detections. We detected maser emission from three sources in the 38 GHz transitions, one of which is a new detection. We find that 37.7 GHz methanol masers are only associated with the most luminous 6.7 and 12.2 GHz methanol maser sources, which in turn are hypothesized to be the oldest class II methanol sources. We suggest that the 37.7 GHz methanol masers are associated with a brief evolutionary phase (of 1000-4000 years) prior to the cessation of class II methanol maser activity in the associated high-mass star formation region.

  14. 37 GHz Methanol Masers : Horsemen of the Apocalypse for the Class II Methanol Maser Phase?

    NASA Astrophysics Data System (ADS)

    Ellingsen, S. P.; Breen, S. L.; Sobolev, A. M.; Voronkov, M. A.; Caswell, J. L.; Lo, N.

    2011-12-01

    We report the results of a search for class II methanol masers at 37.7, 38.3, and 38.5 GHz toward a sample of 70 high-mass star formation regions. We primarily searched toward regions known to show emission either from the 107 GHz class II methanol maser transition, or from the 6.035 GHz excited OH transition. We detected maser emission from 13 sources in the 37.7 GHz transition, eight of these being new detections. We detected maser emission from three sources in the 38 GHz transitions, one of which is a new detection. We find that 37.7 GHz methanol masers are only associated with the most luminous 6.7 and 12.2 GHz methanol maser sources, which in turn are hypothesized to be the oldest class II methanol sources. We suggest that the 37.7 GHz methanol masers are associated with a brief evolutionary phase (of 1000-4000 years) prior to the cessation of class II methanol maser activity in the associated high-mass star formation region.

  15. Turnable Semiconductor Laser Spectroscopy in Hollow Optical Waveguides, Phase II SBIR

    SciTech Connect

    Gregory J. Fetzer, Ph.D.

    2001-12-24

    In this study a novel optical trace gas sensor based on a perforated hollow waveguide (PHW) was proposed. The sensor has been given the acronym ESHOW for Environmental Sensor using Hollow Optical Waveguides. Realizations of the sensor have demonstrated rapid response time (<2s), low minimum detection limits (typically around 3 x 10-5 absorbance). Operation of the PHW technology has been demonstrated in the near-infrared (NIR) and mid0infrared (MIR) regions of the spectrum. Simulation of sensor performance provided in depth understanding of the signals and signal processing required to provide high sensitivity yet retain rapid response to gas changes. A dedicated sensor electronics and software foundation were developed during the course of the Phase II effort. Commercial applications of the sensor are ambient air and continuous emissions monitoring, industrial process control and hazardous waste site monitoring. There are numerous other applications for such a sensor including medical diagnosis and treatment, breath analysis for legal purposes, water quality assessment, combustion diagnostics, and chemical process control. The successful completion of Phase II resulted in additional funding of instrument development by the Nations Institute of Heath through a Phase I SBIR grant and a strategic teaming relationship with a commercial manufacture of medical instrumentation. The purpose of the NIH grant and teaming relationship is to further develop the sensor to monitor NO in exhaled breath for the purposes of asthma diagnosis.

  16. Predicted Geology of the Pahute Mesa-Oasis Valley Phase II Drilling Initiative

    SciTech Connect

    NSTec Environmental Restoration

    2009-04-20

    Pahute Mesa–Oasis Valley (PM-OV) Phase II drilling will occur within an area that encompasses approximately 117 square kilometers (45 square miles) near the center of the Phase I PM-OV hydrostratigraphic framework model area. The majority of the investigation area lies within dissected volcanic terrain between Pahute Mesa on the north and Timber Mountain on the south. This area consists of a complex distribution of volcanic tuff and lava of generally rhyolitic composition erupted from nearby calderas and related vents. Several large buried volcanic structural features control the distribution of volcanic units in the investigation area. The Area 20 caldera, including its structural margin and associated caldera collapse collar, underlies the northeastern portion of the investigation area. The southern half of the investigation area lies within the northwestern portion of the Timber Mountain caldera complex, including portions of the caldera moat and resurgent dome. Another significant structural feature in the area is the west-northwest-trending Northern Timber Mountain moat structural zone, which bisects the northern portion of the investigation area and forms a structural bench. The proposed wells of the UGTA Phase II drilling initiative can be grouped into four generalized volcanic structural domains based on the stratigraphic distribution and structural position of the volcanic rocks in the upper 1,000 meters (3,300 feet) of the crust, a depth that represents the approximate planned total depths of the proposed wells.

  17. Statistical design in phase II clinical trials and its application in breast cancer.

    PubMed

    Perrone, Francesco; Di Maio, Massimo; De Maio, Ermelinda; Maione, Paolo; Ottaiano, Alessandro; Pensabene, Matilde; Di Lorenzo, Giuseppe; Lombardi, Alessandra Vernaglia; Signoriello, Giuseppe; Gallo, Ciro

    2003-05-01

    Several statistical designs for phase II studies have been proposed, but they are frequently misunderstood or not applied at all. In this review we describe the major characteristics of the available designs. To investigate the extent to which statistical designs were used in some recent phase II studies, and which designs were the most common, we did a survey of 145 trials involving treatment of breast cancer. Studies selected for the survey were published between 1995 and 1999 in one of seven specific oncology journals (all with impact factor consistently higher than 2). 94 of the studies (64.8%) did not have an identifiable statistical design. However, among the 51 studies with statistical design there was a notable heterogeneity in the type of design applied. We put together a list of factors associated with use of statistical design at univariate analysis. These factors included: referral to a previous phase I study, recent trial start date, private sponsorship, single-agent treatment, and multicentre organisation. Single-agent treatment (OR 2.35; 95% CI 1.01-5.51) and multicentre organisation (OR 3.24; 95% CI 1.47-7.15) were independently predictive of the presence of statistical design. Publication in journals with high impact factors and short intervals between the start of the study and publication were also correlated with statistical design.

  18. Long-Term Column Leaching of Phase II Mercury Control Technology By-Products

    SciTech Connect

    Schroeder, K.T.; Cardone, C.R.; White, Fredrick; Rohar, P.C.; Kim, A.G

    2007-07-01

    An NETL research, development and demonstration program under DOE/Fossil Energy Innovations for Existing Plants is directed toward the improvement of the performance and economics of mercury control from coal-fired plants. The current Phase II of the RD&D program emphasizes the evaluation of performance and cost of control technologies through slip-stream and full scale field testing while continuing the development of novel concepts. One of the concerns of the NETL program is the fate of the captured flue gas mercury which is transferred to the condensed phase by-product stream. The stability of mercury and any co-captured elements in the by-products could have a large economic impact if it reduced by-product sales or increasing their disposal costs. As part of a greater characterization effort of Phase II facility baseline and control technology sample pairs, NETL in-house laboratories have performed continuous leaching of a select subset of the available sample pairs using four leachants: water (pH=5.7), dilute sulfuric acid (pH=1.2), dilute acetic acid (pH=2.9), and sodium carbonate (pH=11.1). This report describes results obtained for mercury, arsenic, and selenium during the 5-month leaching experiments.

  19. Catalytic conversion of light alkanes phase II. Topical report, January 1990--January 1993

    SciTech Connect

    1998-12-31

    The Topical Report on Phase II of the project entitled, Catalytic Conversion of Light Alkanes reviews work done between January 1, 1990 and September 30, 1992 on the Cooperative Agreement. The mission of this work is to devise a new catalyst which can be used in a simple economic process to convert the light alkanes in natural gas to oxygenate products which can either be used as clean-burning, high octane liquid fuels, as fuel components or as precursors to liquid hydrocarbon transportation fuel. This Topical Report documents our efforts to design, prepare, characterize and test novel catalysts for the mild selective reaction of light hydrocarbons with air or oxygen to produce alcohols directly. These catalysts are designed to form active metal oxo (MO) species and to be uniquely active for the homolytic cleavage of the carbon-hydrogen bonds in light alkanes producing intermediates which can form alcohols. Research on the Cooperative Agreement is divided into three Phases relating to three molecular environments for the active catalytic species that we are trying to generate. In this report we present our work on catalysts which have oxidation-active metals in polyoxoanions (PHASE II).

  20. High-intensity-discharger 400-W sodium ballast. Phase II. Final report

    SciTech Connect

    Felper, G.

    1981-10-01

    A research and development program directed toward design, test, and evaluation of an energy efficient High Intensity Discharge (HID) Solid-State 400 Watt Ballast lighting system was undertaken. Under Phase I of the project, the existing ballast was modified, performance characteristics were measured, efficiency was compared with a core/coil ballast including energy loss analysis. Six (6) prototype 400 W High Pressure Sodium Ballasts were built, for verification tests by an independent test facility prior to follow-on performance and life tests. This report covers Phase II of the project which was designed to make test data comparisons on results received from the independent test laboratory, determine methods to increase ballast efficiency, determine the importance of power factors, conduct bulb life tests, perform specification review, performance versus cost analysis, investigate the ballast to determine compliance with new FCC requirement, and determine a line transient specification in respect to solid state ballasting. In addition, Phase II required reliability testing, a manufacturing test plan, a marketing study for solid-state ballast, and the manufacture and delivery of fifteen (15) demonstration ballast units to LBL. These requirements are discussed.

  1. Phase I--II study of N4-behenoyl-1-beta-D-arabinofuranosylcytosine.

    PubMed

    Kimura, K; Yamada, K; Uzuka, Y; Maekawa, T; Takaku, F; Shimoyama, M; Ogawa, M; Amaki, I; Osamura, S; Ito, M; Sakai, Y; Oguro, M; Hattori, K; Hoshino, A; Hirota, Y; Ohta, K; Nakamura, T; Masaoka, T; Kimura, I; Ichimaru, M

    1981-01-01

    A phase I-II study of N4-behenoyl-1-beta-D-arabinofuranosyl-cytosine (BH-AC) was conducted by a cooperative study group. In phase I study, a total of 126 patients, 64 of whom had metastatic solid tumors and 62 of whom had leukemia, were administered BH-AC in a single IV dose at day 1 only or in daily IV doses for 3 to 21 days, with dose ranges of 1.5--10.0 mg/kg. Side effects included nausea and vomiting, which were significantly less in incidence and severity than those observed with ara-C. Myelosuppressive toxicity became severe with doses 3.6--5.0 mg/kg per day x 10 days. In phase II study, a total of 37 adult patients with acute leukemia were entered in the study. Responses were noted, with an overall rate of 35% complete remission. Of th 26 patients with AML, there were 13 CR. The recommended schedule of treatment for BH-AC, based on our data, is daily infusion of 4--5 mg/kg over 3 h for approximately 3 weeks. The results with BH-AC in patients with acute leukemia are superior to those which have been reported for ara-C.

  2. Phase II TPDCV protocol for pediatric low-grade hypothalamic/chiasmatic gliomas: 15-year update

    PubMed Central

    Mishra, Kavita K.; Squire, Sarah; Lamborn, Kathleen; Banerjee, Anuradha; Gupta, Nalin; Wara, William M.; Prados, Michael D.; Berger, Mitchel S.

    2010-01-01

    To report long-term results for children with low-grade hypothalamic/chiasmatic gliomas treated on a phase II chemotherapy protocol. Between 1984 and 1992, 33 children with hypothalamic/chiasmatic LGGs received TPDCV chemotherapy on a phase II prospective trial. Median age was 3.0 years (range 0.3–16.2). Twelve patients (36%) underwent STRs, 14 (42%) biopsy only, and seven (21%) no surgery. Twenty patients (61%) had pathologic JPAs, nine (27%) grade II gliomas, and four (12%) no surgical sampling. Median f/u for surviving patients was 15.2 years (range 5.3–20.7); 20 of the 23 surviving patients had 14 or more years of follow-up. Fifteen-year PFS and OS were 23.4 and 71.2%, respectively. Twenty-five patients progressed, of whom 13 are NED, two are AWD, and 10 have died. All children who died were diagnosed and first treated at age three or younger. Age at diagnosis was significantly associated with relapse and survival (P = 0.004 for PFS and P = 0.037 for OS). No PFS or OS benefit was seen with STR versus biopsy/no sampling (P = 0.58 for PFS, P = 0.59 for OS). For patients with JPAs and WHO grade II tumors, the 15-year PFS was 18.8 and 22.2% (P = 0.95) and 15-year OS was 73.7 and 55.6% (P = 0.17), respectively. Upfront TPDCV for children with hypothalamic/chiasmatic LGGs resulted in 15-year OS of 71.2% and 15-year PFS of 23.4%. No survival benefit is demonstrated for greater extent of resection. Age is a significant prognostic factor for progression and survival. PMID:20221671

  3. A Phase I-II Study of Postoperative Capecitabine-Based Chemoradiotherapy in Gastric Cancer

    SciTech Connect

    Jansen, Edwin; Crosby, Tom D.L.; Dubbelman, Ria; Bartelink, Harry; Verheij, Marcel

    2007-12-01

    Background: The Intergroup 0116 randomized study showed that postoperative 5-fluorouracil-based chemoradiotherapy improved locoregional control and overall survival in patients with gastric cancer. We hypothesized that these results could be improved further by using a more effective, intensified, and convenient chemotherapy schedule. Therefore, this Phase I-II dose-escalation study was performed to determine the maximal tolerated dose and toxicity profile of postoperative radiotherapy combined with concurrent capecitabine. Patients and Methods: After recovery from surgery for adenocarcinoma of the gastroesophageal junction or stomach, all patients were treated with capecitabine monotherapy, 1,000 mg/m{sup 2} twice daily for 2 weeks. After a 1-week treatment-free interval, patients received capecitabine (650-1,000 mg/m{sup 2} orally twice daily 5 days/week) in a dose-escalation schedule combined with radiotherapy on weekdays for 5 weeks. Radiotherapy was delivered to a total dose of 45 Gy in 25 fractions to the gastric bed, anastomoses, and regional lymph nodes. Results: Sixty-six patients were treated accordingly. Two patients went off study before or shortly after the start of chemoradiotherapy because of progressive disease. Therefore, 64 patients completed treatment as planned. During the chemoradiotherapy phase, 4 patients developed four items of Grade III dose-limiting toxicity (3 patients in Dose Level II and 1 patient in Dose Level IV). The predefined highest dose of capecitabine, 1,000 mg/m{sup 2} twice daily orally, was tolerated well and, therefore, considered safe for further clinical evaluation. Conclusions: This Phase I-II study shows that intensified chemoradiotherapy with daily capecitabine is feasible in postoperative patients with gastroesophageal junction and gastric cancer.

  4. A design of phase II cancer trials using total and complete response endpoints.

    PubMed

    Lu, Ying; Jin, Hua; Lamborn, Kathleen R

    2005-10-30

    Phase II clinical trials in oncology are used for initial evaluation of the therapeutic efficacy of a new treatment regimen. Simon's two-stage design based on total response (TR) rate is commonly used for such trials. Several authors have proposed alternative strategies to consider either response and toxicity or response and early progression. Because TR consists of both partial response (PR) and complete response (CR) and these two types of responses have different effects on subsequent patient outcome, Lin and Chen proposed a flexible design that is based on a weighted average of PR and CR rates as a way to recognize the differential significance of the two levels of response. Panageas and colleagues, on the other hand, used a trinomial model and direct search to consider a rejection region for PR and CR separately. In this paper, we reformat their hypotheses to assess efficacy based on TR and CR. A new two-stage optimum phase II trial design based on TR and CR is developed. We provide guides on searching the stopping and rejecting regions and on determining sample size. An example of a phase II trial for glioblastomas treatment is presented. In this trial, physicians would be interested in either stable disease (SD), PR, or CR as an indication of efficacy. However, because PR and CR rarely occur, observation of any PR or CR will lean towards acceptance of the treatment. Our design has the advantage of being close to the traditional Simon two-stage design while still having the flexibility to treat responses (PR and CR in this example) differently than SD.

  5. Antioxidant, DNA binding and nuclease activities of heteroleptic copper(II) complexes derived from 2-((2-(piperazin-1-yl)ethylimino)methyl)-4-substituted phenols and diimines

    NASA Astrophysics Data System (ADS)

    Ravichandran, J.; Gurumoorthy, P.; Imran Musthafa, M. A.; Kalilur Rahiman, A.

    2014-12-01

    A series of heteroleptic copper(II) complexes of the type [CuL1-4(diimine)](ClO4)2 (1-8) [L1-4 = 2-((2-(piperazin-1-yl)ethylimino)methyl)-4-substituted phenols, and diimine = 2,2‧-bipyridyl (bpy) or 1,10-phenanthroline (phen)], have been synthesized and characterized by spectroscopic methods. The IR spectra of complexes indicate the presence of uncoordinated perchlorate anions and the electronic spectra revealed the square pyramidal geometry with N4O coordination environment around copper(II) nuclei. Electrochemical studies of the mononuclear complexes evidenced one-electron irreversible reduction wave in the cathodic region. The EPR spectra of complexes with g|| (2.206-2.214) and A|| (154-172 × 10-4 cm-1) values support the square-based CuN3O coordination chromophore and the presence of unpaired electron localized in dx-y ground state. Antioxidant studies against DPPH revealed effective radical scavenging properties of the synthesized complexes. Binding studies suggest that the heteroleptic copper(II) complexes interact with calf thymus DNA (CT-DNA) through minor-groove and electrostatic interaction, and all the complexes display pronounced nuclease activity against supercoiled pBR322 DNA.

  6. Statistical Issues for Design and Analysis of Single-Arm Multi-Stage Phase II Cancer Clinical Trials

    PubMed Central

    Jung, Sin-Ho

    2015-01-01

    Summary Phase II trials have been very widely conducted and published every year for cancer clinical research. In spite of the fast progress in design and analysis methods, single-arm two-stage design is still the most popular for phase II cancer clinical trials. Because of their small sample sizes, statistical methods based on large sample approximation are not appropriate for design and analysis of phase II trials. As a prospective clinical research, the analysis method of a phase II trial is predetermined at the design stage and it is analyzed during and at the end of the trial as planned by the design. The analysis method of a trial should be matched with the design method. For two-stage single arm phase II trials, Simon's method has been the standards for choosing an optimal design, but the resulting data have been analyzed and published ignoring the two-stage design aspect with small sample sizes. In this article, we review analysis methods that exactly get along with the exact two-stage design method. We also discuss some statistical methods to improve the existing design and analysis methods for single-arm two-stage phase II trials. PMID:25749311

  7. Operable Unit 3-13, Group 3, Other Surface Soils (Phase II) Field Sampling Plan

    SciTech Connect

    G. L. Schwendiman

    2006-07-27

    This Field Sampling Plan describes the Operable Unit 3-13, Group 3, Other Surface Soils, Phase II remediation field sampling activities to be performed at the Idaho Nuclear Technology and Engineering Center located within the Idaho National Laboratory Site. Sampling activities described in this plan support characterization sampling of new sites, real-time soil spectroscopy during excavation, and confirmation sampling that verifies that the remedial action objectives and remediation goals presented in the Final Record of Decision for Idaho Nuclear Technology and Engineering Center, Operable Unit 3-13 have been met.

  8. Nine-year change in statistical design, profile, and success rates of Phase II oncology trials.

    PubMed

    Ivanova, Anastasia; Paul, Barry; Marchenko, Olga; Song, Guochen; Patel, Neerali; Moschos, Stergios J

    2016-01-01

    We investigated nine-year trends in statistical design and other features of Phase II oncology clinical trials published in 2005, 2010, and 2014 in five leading oncology journals: Cancer, Clinical Cancer Research, Journal of Clinical Oncology, Annals of Oncology, and Lancet Oncology. The features analyzed included cancer type, multicenter vs. single-institution, statistical design, primary endpoint, number of treatment arms, number of patients per treatment arm, whether or not statistical methods were well described, whether the drug was found effective based on rigorous statistical testing of the null hypothesis, and whether the drug was recommended for future studies.

  9. A Disposable Microfluidic Device with a Screen Printed Electrode for Mimicking Phase II Metabolism

    PubMed Central

    Vasiliadou, Rafaela; Nasr Esfahani, Mohammad Mehdi; Brown, Nathan J.; Welham, Kevin J.

    2016-01-01

    Human metabolism is investigated using several in vitro methods. However, the current methodologies are often expensive, tedious and complicated. Over the last decade, the combination of electrochemistry (EC) with mass spectrometry (MS) has a simpler and a cheaper alternative to mimic the human metabolism. This paper describes the development of a disposable microfluidic device with a screen-printed electrode (SPE) for monitoring phase II GSH reactions. The proposed chip has the potential to be used as a primary screening tool, thus complementing the current in vitro methods. PMID:27598162

  10. Subsonic Ultra Green Aircraft Research Phase II: N+4 Advanced Concept Development

    NASA Technical Reports Server (NTRS)

    Bradley, Marty K.; Droney, Christopher K.

    2012-01-01

    This final report documents the work of the Boeing Subsonic Ultra Green Aircraft Research (SUGAR) team on Task 1 of the Phase II effort. The team consisted of Boeing Research and Technology, Boeing Commercial Airplanes, General Electric, and Georgia Tech. Using a quantitative workshop process, the following technologies, appropriate to aircraft operational in the N+4 2040 timeframe, were identified: Liquefied Natural Gas (LNG), Hydrogen, fuel cell hybrids, battery electric hybrids, Low Energy Nuclear (LENR), boundary layer ingestion propulsion (BLI), unducted fans and advanced propellers, and combinations. Technology development plans were developed.

  11. Summary of WPT FOA phase II demonstration performed on July 21, 2015

    SciTech Connect

    Jones, Perry T.; Onar, Omer C.

    2015-08-01

    This summary provides details of the activities, presentations and hardware demonstrations performed at the International Transportation Innovation Center (iTiC) in Greenville, South Carolina as deliverables for the wireless power transfer (WPT) FOA #000667 phase II gateway. This report does not attempt to identify all encompassing efforts from each of the partners leading up to the demonstration, but will attempt to provide a record which briefly describes the project deliverables met and expectations from the Department of Energy (DOE) as action items agreed to during the wrap-up session on July 21, 2015.

  12. A Disposable Microfluidic Device with a Screen Printed Electrode for Mimicking Phase II Metabolism.

    PubMed

    Vasiliadou, Rafaela; Nasr Esfahani, Mohammad Mehdi; Brown, Nathan J; Welham, Kevin J

    2016-01-01

    Human metabolism is investigated using several in vitro methods. However, the current methodologies are often expensive, tedious and complicated. Over the last decade, the combination of electrochemistry (EC) with mass spectrometry (MS) has a simpler and a cheaper alternative to mimic the human metabolism. This paper describes the development of a disposable microfluidic device with a screen-printed electrode (SPE) for monitoring phase II GSH reactions. The proposed chip has the potential to be used as a primary screening tool, thus complementing the current in vitro methods. PMID:27598162

  13. The multifaceted Type II-L supernova 2014G from pre-maximum to nebular phase

    NASA Astrophysics Data System (ADS)

    Terreran, G.; Jerkstrand, A.; Benetti, S.; Smartt, S. J.; Ochner, P.; Tomasella, L.; Howell, D. A.; Morales-Garoffolo, A.; Harutyunyan, A.; Kankare, E.; Arcavi, I.; Cappellaro, E.; Elias-Rosa, N.; Hosseinzadeh, G.; Kangas, T.; Pastorello, A.; Tartaglia, L.; Turatto, M.; Valenti, S.; Wiggins, P.; Yuan, F.

    2016-10-01

    We present multiband ultraviolet, optical, and near-infrared photometry, along with visual-wavelength spectroscopy, of supernova (SN) 2014G in the nearby galaxy NGC 3448 (25 Mpc). The early-phase spectra show strong emission lines of the high ionization species He II/N IV/C IV during the first 2-3 d after explosion, traces of a metal-rich circumstellar material (CSM) probably due to pre-explosion mass-loss events. These disappear by day 9 and the spectral evolution then continues matching that of normal Type II SNe. The post-maximum light curve declines at a rate typical of Type II-L class. The extensive photometric coverage tracks the drop from the photospheric stage and constrains the radioactive tail, with a steeper decline rate than that expected from the 56Co decay if γ-rays are fully trapped by the ejecta. We report the appearance of an unusual feature on the blue side of H α after 100 d, which evolves to appear as a flat spectral feature linking H α and the [O I] doublet. This may be due to interaction of the ejecta with a strongly asymmetric, and possibly bipolar CSM. Finally, we report two deep spectra at ˜190 and 340 d after explosion, the latter being arguably one of the latest spectra for a Type II-L SN. By modelling the spectral region around the [Ca II], we find a supersolar Ni/Fe production. The strength of the [O I] λλ6300,6363 doublet, compared with synthetic nebular spectra, suggests a progenitor with a zero-age main-sequence mass between 15 and 19 M⊙.

  14. Evaluation of DNA-binding, DNA cleavage, antioxidant and cytotoxic activity of mononuclear ruthenium(II) carbonyl complexes of benzaldehyde 4-phenyl-3-thiosemicarbazones

    NASA Astrophysics Data System (ADS)

    Sampath, Krishnan; Sathiyaraj, Subbaiyan; Jayabalakrishnan, Chinnasamy

    2013-11-01

    Two 4-phenyl-3-thiosemicarbazone ligands, (E)-2-(2-chlorobenzylidene)-N-phenylhydrazinecarbothioamide (HL1) and (E)-2-(2-nitrobenzylidene)-N-phenylhydrazinecarbothioamide (HL2), and its ruthenium(II) complexes were synthesized and characterized by physico-chemical and spectroscopic methods. The Schiff bases act as bidentate, monobasic chelating ligands with S and N as the donor sites and are preferably found in the thiol form in all the complexes studied. The molecular structure of HL1 and HL2 were determined by single crystal X-ray diffraction method. DNA binding of the compounds was investigated by absorption spectroscopy which indicated that the compounds bind to DNA via intercalation. The oxidative cleavage of the complexes with CT-DNA inferred that the effects of cleavage are dose dependent. Antioxidant study of the ligands and complexes showed significant antioxidant activity against DPPH radical. In addition, the in vitro cytotoxicity of the ligands and complexes assayed against HeLa and MCF-7 cell lines showed higher cytotoxic activity with the lower IC50 values indicating their efficiency in killing the cancer cells even at low concentrations.

  15. Effect of substituent of terpyridines on the in vitro antioxidant, antitubercular, biocidal and fluorescence studies of copper(II) complexes with clioquinol

    NASA Astrophysics Data System (ADS)

    Kharadi, G. J.

    2014-01-01

    An octahedral complexes of copper with clioquinol(CQ) and substituted terpyridine have been synthesized. The Cu(II) complexes have been characterized by elemental analyses, thermogravimetric analyses, magnetic moment measurements, FT-IR, electronic, 1H NMR and FAB mass spectra. Antimycobacterial screening of ligand and its copper compound against Mycobacterium tuberculosis shows clear enhancement in the antitubercular activity upon copper complexation. Ferric-reducing anti-oxidant power of all complexes were measured. The fluorescence spectra of complexes show red shift, which may be due to the chelation by the ligands to the metal ion. It enhances ligand ability to accept electrons and decreases the electron transition energy. The antimicrobial efficiency of the complexes were tested on five different microorganisms and showed good biological activity.

  16. Fireside corrosion testing of candidate superheater tube alloys, coatings, and claddings - phase II

    SciTech Connect

    Blough, J.L.; Stanko, G.J.

    1996-08-01

    In Phase I a variety of developmental and commercial tubing alloys and claddings were exposed to laboratory fireside corrosion testing simulating a superheater or reheater in a coal-fired boiler. Phase II (in situ testing) has exposed samples of 347, RA-8511, HR3C, 253MA, Fe{sub 3}Al + 5Cr, 310 modified, 800HT, NF 709, 690 clad, and 671 clad for over 10,000 hours to the actual operating conditions of a 250-MW coal-fired boiler. The samples were installed on an air-cooled, retractable corrosion probe, installed in the reheater cavity, and controlled to the operating metal temperatures of an existing and advanced-cycle coal-fired boiler. Samples of each alloy will be exposed for 4000, 12,000, and 16,000 hours of operation. The results will be presented for the metallurgical examination of the corrosion probe samples after 4000 hours of exposure.

  17. Differential Acclimation of Enzymatic Antioxidant Metabolism and Photosystem II Photochemistry in Tall Fescue under Drought and Heat and the Combined Stresses

    PubMed Central

    Bi, Aoyue; Fan, Jibiao; Hu, Zhengrong; Wang, Guangyang; Amombo, Erick; Fu, Jinmin; Hu, Tao

    2016-01-01

    Quality inferiority in cool-season turfgrass due to drought, heat, and a combination of both stresses is predicted to be more prevalent in the future. Understanding the various response to heat and drought stress will assist in the selection and breeding of tolerant grass varieties. The objective of this study was to investigate the behavior of antioxidant metabolism and photosystem II (PSII) photochemistry in two tall fescue genotypes (PI 234881 and PI 578718) with various thermotolerance capacities. Wide variations were found between heat-tolerant PI 578718 and heat-sensitive PI 234881 for leaf relative water content, malondialdehyde and electrolyte leakage under drought, high-temperature or a combination of both stresses. The sensitivity of PI 234881 exposed to combined stresses was associated with lower superoxide dismutase activity and higher H2O2 accumulation than that in PI 578718. Various antioxidant enzymes displayed positive correlation with chlorophyll content, but negative with membrane injury index at most of the stages in both tall fescue genotypes. The JIP-test analysis in PI 578718 indicated a significant improvement in ABS/RC, TR0/RC, RE0/RC, RE0/ABS values as compared to the control regime, which indicated that PI 578718 had a high potential to protect the PSII system under drought and high temperature stress. And the PS II photochemistry in PI 234881 was damaged significantly compared with PI578718. Moreover, quantitative RT-PCR revealed that heat and drought stresses deduced the gene expression of psbB and psbC, but induced the expression of psbA. These findings to some extent confirmed that the various adaptations of physiological traits may contribute to breeding in cold-season turfgrass in response to drought, high-temperature, and a combination of both stresses. PMID:27148288

  18. Differential Acclimation of Enzymatic Antioxidant Metabolism and Photosystem II Photochemistry in Tall Fescue under Drought and Heat and the Combined Stresses.

    PubMed

    Bi, Aoyue; Fan, Jibiao; Hu, Zhengrong; Wang, Guangyang; Amombo, Erick; Fu, Jinmin; Hu, Tao

    2016-01-01

    Quality inferiority in cool-season turfgrass due to drought, heat, and a combination of both stresses is predicted to be more prevalent in the future. Understanding the various response to heat and drought stress will assist in the selection and breeding of tolerant grass varieties. The objective of this study was to investigate the behavior of antioxidant metabolism and photosystem II (PSII) photochemistry in two tall fescue genotypes (PI 234881 and PI 578718) with various thermotolerance capacities. Wide variations were found between heat-tolerant PI 578718 and heat-sensitive PI 234881 for leaf relative water content, malondialdehyde and electrolyte leakage under drought, high-temperature or a combination of both stresses. The sensitivity of PI 234881 exposed to combined stresses was associated with lower superoxide dismutase activity and higher H2O2 accumulation than that in PI 578718. Various antioxidant enzymes displayed positive correlation with chlorophyll content, but negative with membrane injury index at most of the stages in both tall fescue genotypes. The JIP-test analysis in PI 578718 indicated a significant improvement in ABS/RC, TR0/RC, RE0/RC, RE0/ABS values as compared to the control regime, which indicated that PI 578718 had a high potential to protect the PSII system under drought and high temperature stress. And the PS II photochemistry in PI 234881 was damaged significantly compared with PI578718. Moreover, quantitative RT-PCR revealed that heat and drought stresses deduced the gene expression of psbB and psbC, but induced the expression of psbA. These findings to some extent confirmed that the various adaptations of physiological traits may contribute to breeding in cold-season turfgrass in response to drought, high-temperature, and a combination of both stresses.

  19. Differential Acclimation of Enzymatic Antioxidant Metabolism and Photosystem II Photochemistry in Tall Fescue under Drought and Heat and the Combined Stresses.

    PubMed

    Bi, Aoyue; Fan, Jibiao; Hu, Zhengrong; Wang, Guangyang; Amombo, Erick; Fu, Jinmin; Hu, Tao

    2016-01-01

    Quality inferiority in cool-season turfgrass due to drought, heat, and a combination of both stresses is predicted to be more prevalent in the future. Understanding the various response to heat and drought stress will assist in the selection and breeding of tolerant grass varieties. The objective of this study was to investigate the behavior of antioxidant metabolism and photosystem II (PSII) photochemistry in two tall fescue genotypes (PI 234881 and PI 578718) with various thermotolerance capacities. Wide variations were found between heat-tolerant PI 578718 and heat-sensitive PI 234881 for leaf relative water content, malondialdehyde and electrolyte leakage under drought, high-temperature or a combination of both stresses. The sensitivity of PI 234881 exposed to combined stresses was associated with lower superoxide dismutase activity and higher H2O2 accumulation than that in PI 578718. Various antioxidant enzymes displayed positive correlation with chlorophyll content, but negative with membrane injury index at most of the stages in both tall fescue genotypes. The JIP-test analysis in PI 578718 indicated a significant improvement in ABS/RC, TR0/RC, RE0/RC, RE0/ABS values as compared to the control regime, which indicated that PI 578718 had a high potential to protect the PSII system under drought and high temperature stress. And the PS II photochemistry in PI 234881 was damaged significantly compared with PI578718. Moreover, quantitative RT-PCR revealed that heat and drought stresses deduced the gene expression of psbB and psbC, but induced the expression of psbA. These findings to some extent confirmed that the various adaptations of physiological traits may contribute to breeding in cold-season turfgrass in response to drought, high-temperature, and a combination of both stresses. PMID:27148288

  20. Quality of outcome reporting in phase II studies in pulmonary tuberculosis.

    PubMed

    Bonnett, Laura Jayne; Davies, Geraint Rhys

    2015-01-01

    Tuberculosis (TB) remains a major killer amongst the infectious diseases. Current treatment involves a four-drug regimen for at least 6 months. New drugs and regimens are required to shorten treatment duration, reduce toxicity and combat drug resistance, but the optimal methodology to define the critical path for novel regimens is not well defined. We undertook a systematic review to summarise outcomes reported in Phase II trials of patients with newly diagnosed pulmonary TB to assess the need for a core outcome set. A systematic search of databases (PubMed, MEDLINE, EMBASE and LILACs) was conducted on 1 May 2015 to retrieve relevant peer-reviewed articles. Reference lists of included studies were also searched. This systematic review considered all reported outcomes. Risk of bias was considered via sequence generation, allocation concealment, blinding, reasons for exclusions, and selective reporting. Of 55 included studies, 20 were Phase IIB studies based on culture conversion, 32 were Phase IIA studies based on quantitative bacteriology, and three considered alternative outcomes. Large variation in reported outcomes and trial characteristics was observed across the included studies. Bacteriological results were as often expressed in terms of positivity as negativity, with varying definitions of culture conversion. Variation in reporting was particularly marked for Phase IIA studies, where multiple time intervals were typically selected for analysis and sometimes resulted in differing interpretations of the efficacy of drugs or regimens. Within both Phase IIA and IIB studies, there was variation in the time points at which the study participants were sampled, as well as in the bacteriological media and methods used. For successful future meta-analysis of early-phase studies, the findings of this review suggest that development of a core outcome set would be desirable. This would enable trial results to be more easily compared and combined, potentially leading to

  1. A comparative study of in vitro cytotoxic, antioxidant, and antimicrobial activity of Pt(II), Zn(II), Cu(II), and Co(III) complexes with N-heteroaromatic Schiff base (E)-2-[N'-(1-pyridin-2-yl-ethylidene)hydrazino]acetate.

    PubMed

    Filipović, Nenad R; Marković, Ivanka; Mitić, Dragana; Polović, Natalija; Milčić, Miloš; Dulović, Marija; Jovanović, Maja; Savić, Milena; Nikšić, Miomir; Anđelković, Katarina; Todorović, Tamara

    2014-03-01

    In search for novel biologically active metal based compounds, an evaluation of in vitro cytotoxic, antioxidant, and antimicrobial activity of new Pt(II) complex and its Zn(II), Cu(II), and Co(III) analogues, with NNO tridentately coordinated N-heteroaromatic Schiff base ligand (E)-2-[N'-(1-pyridin-2-yl-ethylidene)hydrazino]acetate, was performed. Investigation of antioxidative properties showed that all of the compounds have strong radical scavenging potencies. The Zn(II) complex showed potent inhibition of DNA cleavage by hydroxyl radical. A cytotoxic action of investigated compounds was evaluated on cultures of human promyelocitic leukaemia (HL-60), human glioma (U251), rat glioma (C6), and mouse melanoma (B16) cell lines. It was shown that binuclear pentacoordinated Zn(II) complex possesses a strong dose-dependent cytotoxic activity, of the same order of magnitude as cisplatin on B16, C6, and U251 cells. Furthermore, Zn(II) complex causes oxidative stress-induced apoptotic death of HL-60 leukemic cells, associated with caspase activation, phosphatidylserine externalization, and DNA fragmentation.

  2. Phase II Trial of Concurrent Sunitinib and Image-Guided Radiotherapy for Oligometastases

    PubMed Central

    Tong, Charles C. L.; Ko, Eric C.; Sung, Max W.; Cesaretti, Jamie A.; Stock, Richard G.; Packer, Stuart H.; Forsythe, Kevin; Genden, Eric M.; Schwartz, Myron; Lau, K. H. Vincent; Galsky, Matthew; Ozao-Choy, Junko; Chen, Shu-hsia; Kao, Johnny

    2012-01-01

    Background Preclinical data suggest that sunitinib enhances the efficacy of radiotherapy. We tested the combination of sunitinib and hypofractionated image-guided radiotherapy (IGRT) in a cohort of patients with historically incurable distant metastases. Methods Twenty five patients with oligometastases, defined as 1–5 sites of active disease on whole body imaging, were enrolled in a phase II trial from 2/08 to 9/10. The most common tumor types treated were head and neck, liver, lung, kidney and prostate cancers. Patients were treated with the recommended phase II dose of 37.5 mg daily sunitinib (days 1–28) and IGRT 50 Gy (days 8–12 and 15–19). Maintenance sunitinib was used in 33% of patients. Median follow up was 17.5 months (range, 0.7 to 37.4 months). Results The 18-month local control, distant control, progression-free survival (PFS) and overall survival (OS) were 75%, 52%, 56% and 71%, respectively. At last follow-up, 11 (44%) patients were alive without evidence of disease, 7 (28%) were alive with distant metastases, 3 (12%) were dead from distant metastases, 3 (12%) were dead from comorbid illness, and 1 (4%) was dead from treatment-related toxicities. The incidence of acute grade ≥ 3 toxicities was 28%, most commonly myelosuppression, bleeding and abnormal liver function tests. Conclusions Concurrent sunitinib and IGRT achieves major clinical responses in a subset of patients with oligometastases. Trial Registration ClinicalTrials.gov NCT00463060 PMID:22761653

  3. Prevalence and impact of correlative science in breast cancer phase II trials.

    PubMed

    Zhang, Tian; Schneider, Andrew; Hamilton, Erika P; Patel, Krish; Kamal, Arif H; Lyman, Gary H; Peppercorn, Jeffrey M

    2013-06-01

    Correlative science (CS) can potentially augment clinical trial results by identifying biomarkers of response and resistance to a novel intervention. We evaluated recently published breast cancer phase II trials (BP2T) to determine prevalence, characteristics, and outcomes of CS. Through Pubmed, we identified BP2T of systemic therapy published between June 2005 and June 2010. A study-specific abstraction tool recorded trial characteristics, CS endpoints, source of tissue, adequacy of samples, biopsy safety, and CS outcomes. BP2T authors were contacted to verify abstraction results. Results were abstracted from 298 eligible trials enrolling 18,782 patients, of which 81 (27.2 %) involved CS. Of these, 57 (70.4 %) included tissue with 16 (28 %) using optional research biopsies and 17 (30 %) requiring mandatory research biopsies. No trial addressed biopsy safety issues. Trials were more likely to include CS if they were: industry versus non-industry sponsored (33.7 % vs. 17.1 %, p = 0.0017), neoadjuvant versus metastatic setting (47 % vs. 21.2 %, p = 0.0001), or U.S. versus non-U.S. trials (37 % vs. 21 %, p = 0.005). A minority of phase II breast cancer trials include CS representing a missed opportunity to learn more from clinical research. When CS is included, consistent reporting of endpoints, feasibility, outcomes, and safety is needed.

  4. ICFT: An initial closed-loop flow test of the Fenton Hill Phase II HDR reservoir

    SciTech Connect

    Dash, Z.V.; Aguilar, R.G.; Dennis, B.R.; Dreesen, D.S.; Fehler, M.C.; Hendron, R.H.; House, L.S.; Ito, H.; Kelkar, S.M.; Malzahn, M.V.

    1989-02-01

    A 30-day closed-loop circulation test of the Phase II Hot Dry Rock reservoir at Fenton Hill, New Mexico, was conducted to determine the thermal, hydraulic, chemical, and seismic characteristics of the reservoir in preparation for a long-term energy-extraction test. The Phase II heat-extraction loop was successfully tested with the injection of 37,000 m/sup 3/ of cold water and production of 23,300 m/sup 3/ of hot water. Up to 10 MW/sub t/ was extracted when the production flow rate reached 0.0139 m/sup 3//s at 192/degree/C. By the end of the test, the water-loss rate had decreased to 26% and a significant portion of the injected water was recovered; 66% during the test and an additional 20% during subsequent venting. Analysis of thermal, hydraulic, geochemical, tracer, and seismic data suggests the fractured volume of the reservoir was growing throughout the test. 19 refs., 64 figs., 19 tabs.

  5. DOE Phase II SBIR: Spectrally-Assisted Vehicle Tracking - Final Report

    SciTech Connect

    Villeneuve, Pierre V.

    2013-02-28

    The goal of this Phase II SBIR has been to develop a prototype software package to demonstrate spectrally-aided vehicle tracking. The primary application is to show improved target vehicle tracking performance in complex environments where traditional spatial tracker systems may show reduced performance. Examples include scenarios where the target vehicle is obscured by a large structure for an extended period of time, or where the target is engaging in extreme maneuvers amongst other civilian vehicles. The target information derived from spatial processing is unable to differentiate between the green versus the red vehicle. Spectral signature exploitation enables comparison of new candidate targets with existing track signatures. The ambiguity in this confusing scenario is resolved by folding spectral analysis results into each target nomination and association processes. The work performed over the two-year effort was divided into three general areas: algorithm refinement, software prototype development, and prototype performance demonstration. The tasks performed under this Phase II resulted in the completion of a software tool suitable for evaluation and testing of advanced tracking concepts.

  6. A modified varying-stage adaptive phase II/III clinical trial design.

    PubMed

    Dong, Gaohong; Vandemeulebroecke, Marc

    2016-07-01

    Conventionally, adaptive phase II/III clinical trials are carried out with a strict two-stage design. Recently, a varying-stage adaptive phase II/III clinical trial design has been developed. In this design, following the first stage, an intermediate stage can be adaptively added to obtain more data, so that a more informative decision can be made. Therefore, the number of further investigational stages is determined based upon data accumulated to the interim analysis. This design considers two plausible study endpoints, with one of them initially designated as the primary endpoint. Based on interim results, another endpoint can be switched as the primary endpoint. However, in many therapeutic areas, the primary study endpoint is well established. Therefore, we modify this design to consider one study endpoint only so that it may be more readily applicable in real clinical trial designs. Our simulations show that, the same as the original design, this modified design controls the Type I error rate, and the design parameters such as the threshold probability for the two-stage setting and the alpha allocation ratio in the two-stage setting versus the three-stage setting have a great impact on the design characteristics. However, this modified design requires a larger sample size for the initial stage, and the probability of futility becomes much higher when the threshold probability for the two-stage setting gets smaller. Copyright © 2016 John Wiley & Sons, Ltd.

  7. The peculiar type II supernova 1993J in M81: Transition to the nebular phase

    NASA Technical Reports Server (NTRS)

    Filippenko, Alexei V.; Matheson, Thomas; Barth, Aaron J.

    1994-01-01

    We present optical spectra of the bright, peculiar Type II supernova 1993J in M81 spanning the first 14 months of its existence, revealing its transition to the nebular phase. Unlike the case in normal Type II supernovae, during the first 2-10 months the H-alpha emission line gradually becomes less prominent relative to other features such as (O I) lambda lambda 6300, 6364 and (Ca II) lambda lambda 7291, 7324, as we had predicted based on early-time (tau less than or approximately equal to 2 months) spectra. The nebular spectrum resembles those of the Type Ib/Ic supernovae 1985F and 1987M, although weak H-alpha emission is easily visible even at late times in SN 1993J. At tau = 8 months a close similarity is found with the spectrum of SN 1987K, the only other Type II supernova known to have undergone such a metamorphosis. The emission lines are considerably broader than those of normal Type II supernovae at comparable phases, consistent with the progenitor having lost a majority of its hydrogen envelope prior to exploding. Consequently, there is now little doubt that Type Ib, and probably Type Ic, supernovae result from core collapse in stripped, massive stars; models of the chemical evolution of galaxies in which these subtypes are ascribed to exploding white dwarfs must be appropriately modified. Although all of the emission lines in spectra of SN 1993J fade roughly exponentially for a considerable time, the fading of H-alpha begins to slow down at tau approximately = 8 months, and in the interval tau = 10-14 months its flux is constant, or even slightly rising in the wings of the line. This behavior, together with the box-like shape and great breadth (full width at half maximum (FWHM) approximately = 17 000 km/s) of the line profile, suggests that the H-alpha emission is being produced by the high-velocity outer layer of hydrogen ejecta interacting with circumstellar gas released by the progenitor prior to its explosion. A similar phenomenon has previously been

  8. Biological autoxidation. II. Cholesterol esters as inert barrier antioxidants. Self-assembly of porous membrane sacs. An hypothesis.

    PubMed

    Kon, S H

    1978-01-01

    The antioxidation defenses recognized thus far appear too weak. Needed are inert barriers to encapsulate foci of activated oxygen (FAOs) and contain their spreading. These capsules must: 1. self-assemble nonenzymatically and spontaneously in face of adversity; 2. resist oxidation and dissolution in water; and 3. be moderately fluid and elastic enough to withstand flexing by tissues. Evidence shows activated oxygen: a. is produced by common cholesterolester (CE)-raising agents; b. boosts accumulation of CEs; and c. splits low-density lipoproteins (LDL), thus releasing CE-rich coalescence-prone lipid micelles. I am proposing that CEs, combined with polar lipids, are uniquely suited to form inert-lipid antioxidation barriers (ILABs). Porous ILAB capsules self-assemble from lipid micelles released by oxidatively degraded LDL. The capsules are thermodynamically unstable but elastic, durable and capable of self-repair through oxidation of ambient LDL. All capsules tend to contract into spheres. Enclosed needle-like "foreign bodies", such as asbestos, puncture the contracting capsules. Hence the odd bulbous architecture of asbestos bodies. ILABs protect from--and their failure initiates and promotes--carcinogenesis and atherosclerosis. ILABs may be mediators of membrane biogenesis. The loss of arterial flexibility in atherosclerosis protects ILAB capsules from breakage. PMID:748727

  9. A two-step spin crossover mononuclear iron(II) complex with a [HS-LS-LS] intermediate phase.

    PubMed

    Bonnet, Sylvestre; Siegler, Maxime A; Costa, José Sánchez; Molnár, Gábor; Bousseksou, Azzedine; Spek, Anthony L; Gamez, Patrick; Reedijk, Jan

    2008-11-21

    The two-step spin crossover of a new mononuclear iron(ii) complex is studied by magnetic, crystallographic and calorimetric methods revealing two successive first-order phase transitions and an ordered intermediate phase built by the repetition of the unprecedented [HS-LS-LS] motif.

  10. Climatepipes: User-friendly data access, data manipulation, data analysis and visualization of community climate models Phase II

    SciTech Connect

    Chaudhary, Aashish

    2015-09-02

    In Phase I, we successfully developed a web-based tool that provides workflow and form-based interfaces for accessing, querying, and visualizing interesting datasets from one or more sources. For Phase II of the project, we have implemented mechanisms for supporting more elaborate and relevant queries.

  11. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study.

    PubMed

    Dorr, R T; Lines, R; Levine, N; Brooks, C; Xiang, L; Hruby, V J; Hadley, M E

    1996-01-01

    A pilot phase I study was conducted with a cyclic heptapeptide analog of alpha-melanocyte stimulating hormone (alpha-MSH). The lactam-bridged molecule, called Melanotan-II (MT-II), has the structure Ac-Nle4-Asp5-His6-D-Phe7-Arg8-Trp9-Lys10 alpha-MSH4-10-NH2 (MT-II) and has superpotent melanotropic activity in vitro. A single-blind, alternating day (saline or MT-II), placebo-controlled trial was conducted in 3 normal male volunteers at the starting dose of 0.01 mg/kg of MT-II. Subcutaneous injections of MT-II or saline were given daily (Monday-Friday) for 2 consecutive weeks. Two subjects were escalated by 0.005 mg/kg increments to 0.03 mg/kg and one to 0.025 mg/kg. The 0.03 mg/kg dose produced Grade II somnolence and fatigue in one of two subjects (WHO standards). Mild nausea, not requiring antiemetic treatment, was reported at most MT-II dose levels. A stretching and yawning complex appeared to correlate with the onset of spontaneous, penile erections which were intermittently experienced for 1-5 hours after MT-II dosing, depending on the MT-II dose. Two subjects had increased pigmentation in the face, upper body and buttock, as measured by quantitative reflectance and by visual perception 1 week after MT-II dosing ended. These results demonstrate that MT-II has tanning activity in humans given only 5 low doses every other day by subcutaneous injection. The recommended single MT-II dose for future Phase I studies is 0.025 mg/kg/day.

  12. Fe II EMISSION IN ACTIVE GALACTIC NUCLEI: THE ROLE OF TOTAL AND GAS-PHASE IRON ABUNDANCE

    SciTech Connect

    Shields, Gregory A.; Ludwig, Randi R.; Salviander, Sarah E-mail: randi@astro.as.utexas.ed

    2010-10-01

    Active galactic nuclei (AGNs) have Fe II emission from the broad-line region (BLR) that differs greatly in strength from object to object. We examine the role of the total and gas-phase iron abundance in determining Fe II strength. Using AGN spectra from the Sloan Digital Sky Survey (SDSS) in the redshift range of 0.2 < z < 0.35, we measure the Fe/Ne abundance of the narrow-line region (NLR) using the [Fe VII]/[Ne V] line intensity ratio. We find no significant difference in the abundance of Fe relative to Ne in the NLR as a function of Fe II/H{beta}. However, the [N II]/[S II] ratio increases by a factor of 2 with increasing Fe II strength. This indicates a trend in N/S abundance ratio, and by implication in the overall metallicity of the NLR gas, with increasing Fe II strength. We propose that the wide range of Fe II strength in AGN largely results from the selective depletion of Fe into grains in the low ionization portion of the BLR. Photoionization models show that the strength of the optical Fe II lines varies almost linearly with gas-phase Fe abundance, while the ultraviolet Fe II strength varies more weakly. Interstellar depletions of Fe can be as large as 2 orders of magnitude, sufficient to explain the wide range of optical Fe II strength in AGNs. This picture is consistent with the similarity of the BLR radius to the dust sublimation radius and with indications of Fe II emitting gas flowing inward from the dusty torus.

  13. SU-E-J-35: Clinical Performance Evaluation of a Phase II Proton CT Scanner

    SciTech Connect

    Mandapaka, A; Ghebremedhin, A; Farley, D; Giacometti, V; Vence, N; Bashkirov, V; Patyal, B; Schulte, R; Plautz, T; Zatserklyaniy, A; Johnson, R; Sadrozinski, H

    2014-06-01

    Purpose: To develop the methodology to evaluate the clinical performance of a Phase II Proton CT scanner Methods: Range errors on the order of 3%-5% constitute a major uncertainty in current charged particle treatment planning based on Hounsfield Unit (HU)-relative stopping power (RSP) calibration curves. Within our proton CT collaboration, we previously developed and built a Phase I proton CT scanner that provided a sensitive area of 9 cm (axial) × 18 cm (in-plane). This scanner served to get initial experience with this new treatment planning tool and to incorporate lessons learned into the next generation design. A Phase II scanner was recently completed and is now undergoing initial performance testing. It will increase the proton acquisition rate and provide a larger detection area of 9 cm x 36 cm. We are now designing a comprehensive evaluation program to test the image quality, imaging dose, and range uncertainty associated with this scanner. The testing will be performed along the lines of AAPM TG 66. Results: In our discussion of the evaluation protocol we identified the following priorities. The image quality of proton CT images, in particular spatial resolution and low-density contrast discrimination, will be evaluated with the Catphan600 phantom. Initial testing showed that the Catphan uniformity phantom did not provide sufficient uniformity; it was thus replaced by a cylindrical water phantom. The imaging dose will be tested with a Catphan dose module, and compared to a typical cone beam CT dose for comparable image quality. Lastly, we developed a dedicated dosimetry range phantom based on the CIRS pediatric head phantom HN715. Conclusion: A formal evaluation of proton CT as a new tool for proton treatment planning is an important task. The availability of the new Phase II proton CT scanner will allow us to perform this task. This research is supported by the National Institute of Biomedical Imaging and Bioengineering of the NIH under award number R01

  14. Solid phase extraction of Cu(II), Ni(II), Pb(II), Cd(II) and Mn(II) ions with 1-(2-thiazolylazo)-2-naphthol loaded Amberlite XAD-1180.

    PubMed

    Tokalioğlu, Serife; Yilmaz, Vedat; Kartal, Senol

    2009-05-01

    A new method for separation and preconcentration of trace amounts of Cu(II), Ni(II), Pb(II), Cd(II) and Mn(II) ions in various matrices was proposed. The method is based on the adsorption and chelation of the metal ions on a column containing Amberlite XAD-1180 resin impregnated with 1-(2-thiazolylazo)-2-naphthol (TAN) reagent prior to their determination by flame atomic absorption spectrometry (FAAS). The effect of pH, type, concentration and volume of eluent, sample volume, flow rates of sample and elution solutions, and interfering ions have been investigated. The optimum pH for simultaneous retention of all the metal ions was 9. Eluent for quantitative elution was 20 ml of 2 mol l(-1) HNO(3). The optimum sample and eluent flow rates were found as 4 ml min(-1), and also sample volume was 500 ml, except for Mn (87% recovery). The sorption capacity of the resin was found to be 0.77, 0.41, 0.57, and 0.30 mg g(-1) for Cu(II), Ni(II), Cd(II), and Mn(II), respectively. The preconcentration factor of the method was 200 for Cu(II), 150 for Pb(II), 100 for Cd(II) and Ni(II), and 50 for Mn(II). The recovery values for all of the metal ions were > or = 95% and relative standard deviations (RSDs) were < or = 5.1%. The detection limit values were in the range of 0.03 and 1.19 microg l(-1). The accuracy of the method was confirmed by analysing the certified reference materials (TMDA 54.4 fortified lake water and GBW 07605 tea samples) and the recovery studies. This procedure was applied to the determination of Cu(II), Ni(II), Pb(II), Cd(II) and Mn(II) in waste water and lake water samples.

  15. Synthesis and application of surface-imprinted activated carbon sorbent for solid-phase extraction and determination of copper (II)

    NASA Astrophysics Data System (ADS)

    Li, Zhenhua; Li, Jingwen; Wang, Yanbin; Wei, Yajun

    2014-01-01

    A new Cu(II)-imprinted amino-functionalized activated carbon sorbent was prepared by a surface imprinting technique for selective solid-phase extraction (SPE) of Cu(II) prior to its determination by inductively coupled plasma atomic emission spectrometry (ICP-AES). Experimental conditions for effective adsorption of Cu(II) were optimized with respect to different experimental parameters using static and dynamic procedures in detail. Compared with non-imprinted sorbent, the ion-imprinted sorbent had higher selectivity and adsorption capacity for Cu(II). The maximum static adsorption capacity of the ion-imprinted and non-imprinted sorbent for Cu(II) was 26.71 and 6.86 mg g-1, respectively. The relatively selectivity factor values (αr) of Cu(II)/Zn(II), Cu(II)/Ni(II), Cu(II)/Co(II) and Cu(II)/Pb(II) were 166.16, 50.77, 72.26 and 175.77, respectively, which were greater than 1. Complete elution of the adsorbed Cu(II) from Cu(II)-imprinted sorbent was carried out using 2 mL of 0.1 mol L-1 EDTA solution. The relative standard deviation of the method was 2.4% for eleven replicate determinations. The method was validated for the analysis by two certified reference materials (GBW 08301, GBW 08303), the results obtained is in good agreement with standard values. The developed method was also successfully applied to the determination of trace copper in natural water samples with satisfactory results.

  16. DOD USER-NEEDS STUDY, PHASE II -- FLOW OF SCIENTIFIC AND TECHNICAL INFORMATION WITHIN THE DEFENSE INDUSTRY. FINAL REPORT. VOLUME II, A. TECHNICAL DESCRIPTION, B. TECHNICAL APPENDICES.

    ERIC Educational Resources Information Center

    GOODMAN, ARNOLD F.; AND OTHERS

    IN PHASE II OF THE DEPARTMENT OF DEFENSE (DOD) SURVEY TO FIND OUT HOW SCIENTISTS AND ENGINEERS IN GOVERNMENT AND INDUSTRIAL RESEARCH, DEVELOPMENT, AND PRODUCTION ACTIVITIES ACQUIRE INFORMATION, SCIENTIFIC PERSONNEL IN THE DEFENSE INDUSTRY WERE INTERVIEWED TO DETERMINE THEIR INFORMATION NEEDS AND THE FLOW OF INFORMATION INHERENT IN SATISFYING THESE…

  17. ADVANCED SIMULATION CAPABILITY FOR ENVIRONMENTAL MANAGEMENT – CURRENT STATUS AND PHASE II DEMONSTRATION RESULTS

    SciTech Connect

    Seitz, Roger; Freshley, Mark D.; Dixon, Paul; Hubbard, Susan S.; Freedman, Vicky L.; Flach, Gregory P.; Faybishenko, Boris; Gorton, Ian; Finsterle, Stefan A.; Moulton, John D.; Steefel, Carl I.; Marble, Justin

    2013-06-27

    The U.S. Department of Energy (USDOE) Office of Environmental Management (EM), Office of Soil and Groundwater, is supporting development of the Advanced Simulation Capability for Environmental Management (ASCEM). ASCEM is a state-of-the-art scientific tool and approach for understanding and predicting contaminant fate and transport in natural and engineered systems. The modular and open source high-performance computing tool facilitates integrated approaches to modeling and site characterization that enable robust and standardized assessments of performance and risk for EM cleanup and closure activities. The ASCEM project continues to make significant progress in development of computer software capabilities with an emphasis on integration of capabilities in FY12. Capability development is occurring for both the Platform and Integrated Toolsets and High-Performance Computing (HPC) Multiprocess Simulator. The Platform capabilities provide the user interface and tools for end-to-end model development, starting with definition of the conceptual model, management of data for model input, model calibration and uncertainty analysis, and processing of model output, including visualization. The HPC capabilities target increased functionality of process model representations, toolsets for interaction with Platform, and verification and model confidence testing. The Platform and HPC capabilities are being tested and evaluated for EM applications in a set of demonstrations as part of Site Applications Thrust Area activities. The Phase I demonstration focusing on individual capabilities of the initial toolsets was completed in 2010. The Phase II demonstration completed in 2012 focused on showcasing integrated ASCEM capabilities. For Phase II, the Hanford Site deep vadose zone (BC Cribs) served as an application site for an end-to-end demonstration of capabilities, with emphasis on integration and linkages between the Platform and HPC components. Other demonstrations

  18. ADVANCED SIMULATION CAPABILITY FOR ENVIRONMENTAL MANAGEMENT- CURRENT STATUS AND PHASE II DEMONSTRATION RESULTS

    SciTech Connect

    Seitz, R.

    2013-02-26

    The U.S. Department of Energy (USDOE) Office of Environmental Management (EM), Office of Soil and Groundwater, is supporting development of the Advanced Simulation Capability for Environmental Management (ASCEM). ASCEM is a state-of-the-art scientific tool and approach for understanding and predicting contaminant fate and transport in natural and engineered systems. The modular and open source high-performance computing tool facilitates integrated approaches to modeling and site characterization that enable robust and standardized assessments of performance and risk for EM cleanup and closure activities. The ASCEM project continues to make significant progress in development of computer software capabilities with an emphasis on integration of capabilities in FY12. Capability development is occurring for both the Platform and Integrated Toolsets and High-Performance Computing (HPC) Multiprocess Simulator. The Platform capabilities provide the user interface and tools for end-to-end model development, starting with definition of the conceptual model, management of data for model input, model calibration and uncertainty analysis, and processing of model output, including visualization. The HPC capabilities target increased functionality of process model representations, toolsets for interaction with Platform, and verification and model confidence testing. The Platform and HPC capabilities are being tested and evaluated for EM applications in a set of demonstrations as part of Site Applications Thrust Area activities. The Phase I demonstration focusing on individual capabilities of the initial toolsets was completed in 2010. The Phase II demonstration completed in 2012 focused on showcasing integrated ASCEM capabilities. For Phase II, the Hanford Site deep vadose zone (BC Cribs) served as an application site for an end-to-end demonstration of capabilities, with emphasis on integration and linkages between the Platform and HPC components. Other demonstrations

  19. Analytical strategies for the direct mass spectrometric analysis of steroid and corticosteroid phase II metabolites.

    PubMed

    Antignac, Jean-Philippe; Brosseaud, Aline; Gaudin-Hirret, Isabelle; André, François; Bizec, Bruno Le

    2005-03-01

    The use of steroid hormones as growth promoters remains illegal in Europe. A classical approach used to control their utilization consists to measure the parent drug in target biological matrices. However, this strategy may fail when the parent drug is submitted to extensive metabolism reactions. For urine and tissue samples, chemical or enzymatic hydrolysis is usually applied in order to deconjugate glucuronide and sulfate phase II metabolites. But this treatment lead to the loss of information such as nature and relative proportions of the different conjugated forms, which can be useful, for example, to discriminate an endogenous production from an exogenous administration for natural hormones, or for other clinical or biochemical specific applications. For these purposes, direct measurement of conjugated metabolites using liquid chromatography-tandem mass spectrometry may represent a solution of choice. In this context, the mass spectrometric behavior of 14 steroid and corticosteroid phase II metabolites after electrospray ionization was investigated. Their fragmentation pathways in tandem mass spectrometry revealed some specificities within the different group of conjugates. A specific acquisition program (MRM mode) was developed for the unambiguous identification of the studied reference compounds. A more generic method (Parent Scan mode) was also developed for fishing approaches consisting to monitor several fragment ions typical of each conjugate class. A reverse phase HPLC procedure was also proposed for efficient retention and separation of the studied compounds. Finally, a protocol based on quaternary amine SPE was developed, permitting the separation of free, glucuronide, and sulfate fractions. Preliminary results on biological samples demonstrated the suitability of this analytical strategy for direct measurement of dexamethasone glucuronide and sulfate residues in bovine urine.

  20. Binding of HgII to high-affinity sites on bacteria inhibits reduction to Hg0 by mixed FeII/III phases.

    PubMed

    Mishra, Bhoopesh; O'Loughlin, Edward J; Boyanov, Maxim I; Kemner, Kenneth M

    2011-11-15

    Magnetite and green rust have been shown to reduce aqueous Hg(II) to Hg(0). In this study, we tested the ability of magnetite and green rust to reduce Hg(II) sorbed to 2 g · L(-1) of biomass (Bacillus subtilis), at high (50 μM) and low (5 μM) Hg loadings and at pH 6.5 and 5.0. At high Hg:biomass loading, where Hg(II) binding to biomass is predominantly through carboxyl functional groups, Hg L(III)-edge X-ray absorption spectroscopy showed reduction of Hg(II) to Hg(0) by magnetite. Reduction occurred within 2 h and 2 d at pH 6.5 and 5.0, respectively. At low Hg:biomass loading, where Hg(II) binds to biomass via sulfhydryl functional groups, Hg(II) was not reduced by magnetite at pH 6.5 or 5.0 after 2 months of reaction. Green rust, which is generally a stronger reductant than magnetite, reduced about 20% of the total Hg(II) bound to biomass via sulfhydryl groups to Hg(0) in 2 d. These results suggest that Hg(II) binding to carboxyl groups does not significantly inhibit the reduction of Hg(II) by magnetite. However, the binding of Hg(II) to biomass via sulfhydryl groups severely inhibits the ability of mixed Fe(II/III) phases like magnetite and green rust to reduce Hg(II) to Hg(0). The mobility of heavy metal contaminants in aquatic and terrestrial environments is greatly influenced by their speciation, especially their oxidation state. In the case of Hg, reduction of Hg(II) to Hg(0) can increase Hg mobility because of the volatility of Hg(0). Since Hg is typically present in aquatic and terrestrial systems at low concentrations, binding of Hg(II) to high-affinity sites on bacteria could have important implications for the potential reduction of Hg(II) to Hg(0) and the overall mobility of Hg in biostimulated subsurface environments. PMID:21913727

  1. Binding of HgII to high-affinity sites on bacteria inhibits reduction to Hg0 by mixed FeII/III phases.

    PubMed

    Mishra, Bhoopesh; O'Loughlin, Edward J; Boyanov, Maxim I; Kemner, Kenneth M

    2011-11-15

    Magnetite and green rust have been shown to reduce aqueous Hg(II) to Hg(0). In this study, we tested the ability of magnetite and green rust to reduce Hg(II) sorbed to 2 g · L(-1) of biomass (Bacillus subtilis), at high (50 μM) and low (5 μM) Hg loadings and at pH 6.5 and 5.0. At high Hg:biomass loading, where Hg(II) binding to biomass is predominantly through carboxyl functional groups, Hg L(III)-edge X-ray absorption spectroscopy showed reduction of Hg(II) to Hg(0) by magnetite. Reduction occurred within 2 h and 2 d at pH 6.5 and 5.0, respectively. At low Hg:biomass loading, where Hg(II) binds to biomass via sulfhydryl functional groups, Hg(II) was not reduced by magnetite at pH 6.5 or 5.0 after 2 months of reaction. Green rust, which is generally a stronger reductant than magnetite, reduced about 20% of the total Hg(II) bound to biomass via sulfhydryl groups to Hg(0) in 2 d. These results suggest that Hg(II) binding to carboxyl groups does not significantly inhibit the reduction of Hg(II) by magnetite. However, the binding of Hg(II) to biomass via sulfhydryl groups severely inhibits the ability of mixed Fe(II/III) phases like magnetite and green rust to reduce Hg(II) to Hg(0). The mobility of heavy metal contaminants in aquatic and terrestrial environments is greatly influenced by their speciation, especially their oxidation state. In the case of Hg, reduction of Hg(II) to Hg(0) can increase Hg mobility because of the volatility of Hg(0). Since Hg is typically present in aquatic and terrestrial systems at low concentrations, binding of Hg(II) to high-affinity sites on bacteria could have important implications for the potential reduction of Hg(II) to Hg(0) and the overall mobility of Hg in biostimulated subsurface environments.

  2. Flavonoid content in ethanolic extracts of selected raw and traditionally processed indigenous foods consumed by vulnerable groups of Kenya: antioxidant and type II diabetes-related functional properties.

    PubMed

    Kunyanga, Catherine N; Imungi, Jasper K; Okoth, Michael W; Biesalski, Hans K; Vadivel, Vellingiri

    2011-08-01

    The present study evaluated the flavonoid content, antioxidant as well as type II diabetes-related enzyme inhibition activities of ethanolic extract of certain raw and traditionally processed indigenous food ingredients including cereals, legumes, oil seeds, tubers, vegetables and leafy vegetables, which are commonly consumed by vulnerable groups in Kenya. The vegetables exhibited higher flavonoid content (50-703 mg/100 g) when compared with the grains (47-343 mg/100 g). The ethanolic extract of presently studied food ingredients revealed 33-93% DPPH radical scavenging capacity, 486-6,389 mmol Fe(II)/g reducing power, 19-43% α-amylase inhibition activity and 14-68% α-glucosidase inhibition activity. Among the different food-stuffs, the drumstick and amaranth leaves exhibited significantly higher flavonoid content with excellent functional properties. Roasting of grains and cooking of vegetables were found to be suitable processing methods in preserving the functional properties. Hence, such viable processing techniques for respective food samples will be considered in the formulation of functional supplementary foods for vulnerable groups in Kenya.

  3. Site Characterization of the Source Physics Experiment Phase II Location Using Seismic Reflection Data

    NASA Astrophysics Data System (ADS)

    Sexton, E. A.; Snelson, C. M.; Chipman, V.; Emer, D. F.; White, R. L.; Emmitt, R.; Wright, A. A.; Drellack, S.; Huckins-Gang, H.; Mercadante, J.; Floyd, M.; McGowin, C.; Cothrun, C.; Bonal, N.

    2013-12-01

    An objective of the Source Physics Experiment (SPE) is to identify low-yield nuclear explosions from a regional distance. Low-yield nuclear explosions can often be difficult to discriminate among the clutter of natural and man-made explosive events (e.g., earthquakes and mine blasts). The SPE is broken into three phases. Phase I has provided the first of the physics-based data to test the empirical models that have been used to discriminate nuclear events. The Phase I series of tests were placed within a highly fractured granite body. The evolution of the project has led to development of Phase II, to be placed within the opposite end member of geology, an alluvium environment, thereby increasing the database of waveforms to build upon in the discrimination models. Both the granite and alluvium sites have hosted nearby nuclear tests, which provide comparisons for the chemical test data. Phase III of the SPE is yet to be determined. For Phase II of the experiment, characterization of the location is required to develop the geologic/geophysical models for the execution of the experiment. Criteria for the location are alluvium thickness of approximately 170 m and a water table below 170 m; minimal fracturing would be ideal. A P-wave mini-vibroseis survey was conducted at a potential site in alluvium to map out the subsurface geology. The seismic reflection profile consisted of 168 geophone stations, spaced 5 m apart. The mini-vibe was a 7,000-lb peak-force source, starting 57.5 m off the north end of the profile and ending 57.5 m past the southern-most geophone. The length of the profile was 835 m. The source points were placed every 5 m, equally spaced between geophones to reduce clipping. The vibroseis sweep was from 20 Hz down to 180 Hz over 8 seconds, and four sweeps were stacked at each shot location. The shot gathers show high signal-to-noise ratios with clear first arrivals across the entire spread and the suggestion of some shallow reflectors. The data were

  4. Membrane/distillation hybrid process research and development. Final report, phase II

    SciTech Connect

    Mazanec, T.J.

    1997-07-01

    This report covers work conducted under the grant awarded to BP by DOE in late 1991 entitled {open_quotes}Membrane/Distillation Hybrid Process Research and Development.{close_quotes} The program was directed towards development and commercialization of the BP process for separation of vapor phase olefins from non-olefins via facilitated transport using an aqueous facilitator. The program has come to a very successful conclusion, with formation of a partnership between BP and Stone and Webster Engineering Corporation (SWEC) to market and commercialize the technology. The focus of this report is the final portion of the program, during which engineering re-design, facilitator optimization, economic analysis, and marketing have been the primary activities. At the end of Phase II BP was looking to partner with an engineering firm to advance the selective olefin recovery (SOR) technology from the lab/demo stage to full commercialization. In August 1995 BP and SWEC reached an agreement to advance the technology by completing additional Phase III work with DOE and beginning marketing activities.

  5. Orbit Design for Phase I and II of the Magnetospheric Multiscale Mission (MMS)

    NASA Technical Reports Server (NTRS)

    Hughes, Steve P.

    2003-01-01

    The Magnetospheric Multiscale Mission (MMS) is a NASA mission intended to make fundamental advancements in our understanding of the Earth's Magnetosphere. There are three processes that MMS is intended to study including magnetic recon- nection, charged particle acceleration, and turbulence. There are four phases of the MMS mission and each phase is designed to study a particular region of the Earth's magnetosphere. The mission is composed of a formation of four spacecraft that are nominally in a regular tetrahedron formation. In this work, we present optimal orbit designs for Phase I and II. This entails designing optimal reference orbits so that the spacecraft dwell-time in the region of interest is a maximum. This is non-trivial because the Earth's magnetosphere is dynamic and its shape and position are not constant in inertial space. Optimal orbit design for MMS also entails designing the formation so that the relative motion of the four spacecraft yields the greatest science return. We develop performance metrics that are related to the science return, and use Sequential Quadratic Programming (SQP) to determine optimal relative motion solutions. We also ensure that practical constraints such as maximum eclipse time and minimum inter-spacecraft separation distances are not violated.

  6. Phase II Water Rental Pilot Project: Snake River Resident Fish and Wildlife Resources and Management Recommendations.

    SciTech Connect

    Stovall, Stacey H.

    1994-08-01

    The Idaho Water Rental Pilot Project was implemented in 1991 as part of the Non-Treaty Storage Fish and Wildlife Agreement between Bonneville Power Administration and the Columbia Basin Fish and Wildlife Authority. The goal of the project is to quantify resident fish and wildlife impacts resulting from salmon flow augmentation releases made from the upper Snake River Basin. Phase I summarized existing resource information and provided management recommendations to protect and enhance resident fish and wildlife habitat resulting from storage releases for the I improvement of an adromous fish migration. Phase II includes the following: (1) a summary of recent biological, legal, and political developments within the basin as they relate to water management issues, (2) a biological appraisal of the Snake River between American Falls Reservoir and the city of Blackfoot to examine the effects of flow fluctuation on fish and wildlife habitat, and (3) a preliminary accounting of 1993--1994 flow augmentation releases out of the upper Snake, Boise, and Payette river systems. Phase III will include the development of a model in which annual flow requests and resident fish and wildlife suitability information are interfaced with habitat time series analysis to provide an estimate of resident fish and wildlife resources.

  7. Geothermal Evaluation of The Hosston Formation Lackland Air Force Base, San Antonio, Texas Phase II Report

    SciTech Connect

    Zeisloft, Jon; Foley, Duncan

    1984-05-30

    This report summarizes the results of a phased program to test the geothermal characteristics of the Hosston Formation at Lackland Air Force Base, San Antonio, Texas. The geothermal resource evaluation was made possible through drilling and preliminary testing of a large diameter well, Lackland AFB No.1, at the south portion of the base. Phase I of the program had 3 major components: (1) compilation and interpretation of surface and subsurface geologic data to site the well; (2) design of the well; and (3) permitting the well. Phase II consisted of well drilling and preliminary development. The goal of the program was to identify water temperature, water quality, and productivity characteristics of the Hosston aquifer, which preliminary studies suggested might be favorable for direct applications on the base. Results reported herein suggest that heat pumps or other engineering alternatives might be needed for such applications. Results of the well drilling give data on water productivity, quality and temperature. Air-lift testing shows that, although the well does not flow to surface, good artesian pressure exists. Water quality appears acceptable, with about 2200 parts per million total dissolved solids. Equilibrated reservoir temperatures appear to be slightly less than 108 F (42 C).

  8. Granular bed filter development program, Phase II. Quarterly report, January-March 1981

    SciTech Connect

    Moresco, L. L.; Ferguson, J.

    1981-08-01

    Phase I included the development of a mathematical model, a cold flow parametric test series in a 0.746 Nm/sup 3//s GBF, and investigations of potential dust plugging problems at the inlet screen. Collection efficiencies of 99% and filter outlet loadings less than 0.0074 g/m/sup 3/ were demonstrated. The objectives of Phase II are to investigate the effects of elevated temperature and coal combustion particulate on GBF filtration performance; to update the analytical model developed in Phase I to reflect high temperature effects; to optimize filter internal configuration; to perform parametric and long duration tests to characterize the effects of filter design improvements on filtration efficiencies. Hot flow testing to date has confirmed that the GBF configured with inlet and outlet screens has exhibited a tendency for extensive and irreversible ash plugging. The potential advantages of a screenless configuration, having higher filtration efficiency, has been confirmed. This report describes the continuation of work pertinent to the development and design improvement of the GBF system, specifically addressing: (1) the development of governing equations derived for the 3-dimensional GBF mathematical model; (2) the initial results of subcontracted experiments to establish correlations of particulate capture mechanisms for use in the numerical 3-dimensional model; and (3) the design and physical modifications incorporated into the Model 4 GBF hot test setup for the final series of hot gas tests.

  9. Final Phase II report : QuickSite(R) investigation, Everest, Kansas.

    SciTech Connect

    LaFreniere, L. M.

    2003-11-01

    this reason, the CCC/USDA is conducting an environmental site investigation to determine the source(s) and extent of the carbon tetrachloride contamination at Everest and to assess whether the contamination requires remedial action. The investigation at Everest is being performed by the Environmental Research Division of Argonne National Laboratory. Argonne is a nonprofit, multidisciplinary research center operated by the University of Chicago for the U.S. Department of Energy (DOE). The CCC/USDA has entered into an interagency agreement with DOE, under which Argonne provides technical assistance to the CCC/USDA with environmental site characterization and remediation at its former grain storage facilities. At these facilities, Argonne is applying its QuickSite{reg_sign} environmental site characterization methodology. This methodology has been applied successfully at a number of former CCC/USDA facilities in Kansas and Nebraska and has been adopted by the American Society for Testing and Materials (ASTM 1998) as standard practice for environmental site characterization. Phase I of the QuickSite{reg_sign} investigation examined the key geologic, hydrogeologic, and hydrogeochemical relationships that define potential contaminant migration pathways at Everest (Argonne 2001). Phase II of the QuickSite{reg_sign} investigation at Everest was undertaken with the primary goal of delineating and improving understanding of the distribution of carbon tetrachloride contamination in groundwater at this site and the potential source area(s) that might have contributed to this contamination. To address this goal, four specific technical objectives were developed to guide the Phase II field studies. Sampling of near-surface soils at the former Everest CCC/USDA facility that was originally planned for Phase I had to be postponed until October 2000 because of access restrictions. Viable vegetation was not available for sampling then. This period is termed the first session of Phase II

  10. Theory of helium under heat flow near the lambda point. II. Dynamics of phase change

    SciTech Connect

    Onuki, A.

    1984-05-01

    The HeI-He II interface is a crucial aspect in the transformation processes between the superfluid and normal fluid phases. Its motion is investigated when temperatures and heat flows at boundaries deviate from those of a stationary coexistence state. As a unique feature, the heat flow to the interface from the He I side can be mostly transmitted to the He II side by thermal counterflow, and the latent heat generation (or absorption) at the interface becomes negligibly small. In any case the interfacial motion is so slow that the temperature on the He II side T/sub infinity/ is still given by the stationary relation T/sub lambda/-T/sub infinity/proportionalQ/sup 3/4/, where T/sub lambda/ is the critical temperatue and Q is the heat flow. The temperature profile and the interfacial position are calculated in some nonstationary cases. To this end a simple approximation scheme is developed. First, the interface can propagate with a constant velocity and the superfluid region can expand as a shock wave. Second, if the heat flow at the warmer boundary Q/sub w/ and that in the He II region Q/sub -/ are fixed at different values, the length of the He I region y/sub i/ changes in time as (d/dt)y/sup 1+p//sub i/ = constproportional Q/sub w/-Q/sub -/, where p = 1/(1-x/sub lambda/), and x/sub lambda/ is the critical exponent of the thermal conductivity. In particular, if y/sub i/ = 0 at t = 0 and Q/sub w/>Q/sub -/, the normal fluid region emerges as y/sub i/proportionalt/sup() 1/1+P/ at the warmer boundary. Third, if Q/sub -/ and the temperature at the warmer boundary are fixed, the interfacial position approaches an equilibrium position exponentially in time. The uniqueness of the problem arises from the superfluidity on the He II side and the strong critical singularity of the thermal conductivity on the He I side.

  11. Identification of the anti-oxidant components in a two-step solvent extract of bovine bile lipid: Application of reverse phase HPLC, mass spectrometry and fluorimetric assays.

    PubMed

    Singh, Namrata; Bhattacharyya, Debasish

    2016-04-15

    An ether extract of nine different bacterial metabolites in combination with two solvent extract (ether followed by ethanol) of bile lipids from ox gall bladder is used as an immune stimulator drug. Over the years bile acids are discussed regarding their anti-oxidant and lipid peroxidation properties. Since some of the bile acids are known to be potent antioxidants, presence of similar activity in the solvent extract of ox bile lipid was investigated using TLC and reverse phase HPLC systems. Fractions from HPLC were analyzed with mass spectrometry using electrospray ionization. The presence of twelve different bile acids along with other substances in small proportions including fatty acids, sulfate conjugates and bile pigments were confirmed. The twelve separated peaks had similar retention times as those of tauroursodeoxycholic acid, glycoursodeoxycholic acid, taurocholic acid, glycocholic acid, glycochenodeoxycholic acid, taurochenodeoxycholic acid, taurodeoxycholic acid, cholic acid, ursodeoxycholic acid, chenodeoxycholic acid, deoxycholic acid, and lithocholic acid. Subsequently, all fractions were tested for their anti-oxidative property on HepG2 cells exposed to H2O2 that served as an oxidative injury model. Four fluorescent dyes H2DCF DA, MitoSOX red, Amplex red and DAF-2 DA were used for estimation of reactive radicals in the HepG2 cells. Among the separated bile acids, tauroursodeoxycholic acid, glycoursodeoxycholic acid and ursodeoxycholic acid prevented the HepG2 cells from H2O2-induced oxidative stress. PMID:26639449

  12. North Atlantic simulations in Coordinated Ocean-ice Reference Experiments phase II (CORE-II). Part II: Inter-annual to decadal variability

    NASA Astrophysics Data System (ADS)

    Danabasoglu, Gokhan; Yeager, Steve G.; Kim, Who M.; Behrens, Erik; Bentsen, Mats; Bi, Daohua; Biastoch, Arne; Bleck, Rainer; Böning, Claus; Bozec, Alexandra; Canuto, Vittorio M.; Cassou, Christophe; Chassignet, Eric; Coward, Andrew C.; Danilov, Sergey; Diansky, Nikolay; Drange, Helge; Farneti, Riccardo; Fernandez, Elodie; Fogli, Pier Giuseppe; Forget, Gael; Fujii, Yosuke; Griffies, Stephen M.; Gusev, Anatoly; Heimbach, Patrick; Howard, Armando; Ilicak, Mehmet; Jung, Thomas; Karspeck, Alicia R.; Kelley, Maxwell; Large, William G.; Leboissetier, Anthony; Lu, Jianhua; Madec, Gurvan; Marsland, Simon J.; Masina, Simona; Navarra, Antonio; Nurser, A. J. George; Pirani, Anna; Romanou, Anastasia; Salas y Mélia, David; Samuels, Bonita L.; Scheinert, Markus; Sidorenko, Dmitry; Sun, Shan; Treguier, Anne-Marie; Tsujino, Hiroyuki; Uotila, Petteri; Valcke, Sophie; Voldoire, Aurore; Wang, Qiang; Yashayaev, Igor

    2016-01-01

    Simulated inter-annual to decadal variability and trends in the North Atlantic for the 1958-2007 period from twenty global ocean - sea-ice coupled models are presented. These simulations are performed as contributions to the second phase of the Coordinated Ocean-ice Reference Experiments (CORE-II). The study is Part II of our companion paper (Danabasoglu et al., 2014) which documented the mean states in the North Atlantic from the same models. A major focus of the present study is the representation of Atlantic meridional overturning circulation (AMOC) variability in the participating models. Relationships between AMOC variability and those of some other related variables, such as subpolar mixed layer depths, the North Atlantic Oscillation (NAO), and the Labrador Sea upper-ocean hydrographic properties, are also investigated. In general, AMOC variability shows three distinct stages. During the first stage that lasts until the mid- to late-1970s, AMOC is relatively steady, remaining lower than its long-term (1958-2007) mean. Thereafter, AMOC intensifies with maximum transports achieved in the mid- to late-1990s. This enhancement is then followed by a weakening trend until the end of our integration period. This sequence of low frequency AMOC variability is consistent with previous studies. Regarding strengthening of AMOC between about the mid-1970s and the mid-1990s, our results support a previously identified variability mechanism where AMOC intensification is connected to increased deep water formation in the subpolar North Atlantic, driven by NAO-related surface fluxes. The simulations tend to show general agreement in their temporal representations of, for example, AMOC, sea surface temperature (SST), and subpolar mixed layer depth variabilities. In particular, the observed variability of the North Atlantic SSTs is captured well by all models. These findings indicate that simulated variability and trends are primarily dictated by the atmospheric datasets which

  13. Neutron background signal in superheated droplet detectors of the Phase II SIMPLE dark matter search

    NASA Astrophysics Data System (ADS)

    Fernandes, A. C.; Kling, A.; Felizardo, M.; Girard, T. A.; Ramos, A. R.; Marques, J. G.; Prudêncio, M. I.; Marques, R.; Carvalho, F. P.; Roche, I. L.

    2016-03-01

    The simulation of the neutron background for Phase II of the SIMPLE direct dark matter search experiment is fully reported with various improvements relative to previous estimates. The model employs the Monte Carlo MCNP neutron transport code, using as input a realistic geometry description, measured radioassays and material compositions, and tabulated (α,n) yields and spectra. Developments include the accounting of recoil energy distributions, consideration of additional reactions and materials and examination of the relevant (α,n) data. A thorough analysis of the simulation results is performed that addresses an increased number of non-statistical uncertainties. The referred omissions are seen to provide a net increase of 13% in the previously-reported background estimates whereas the non-statistical uncertainty rises to 25%. The final estimated recoil event rate is 0.372 ± 0.002 (stat.) ± 0.097 (non-stat.) evt/kgd resulting in insignificant changes over the results of the experiment.

  14. Evaluation of hydrothermal resources of North Dakota. Phase II. Final report

    SciTech Connect

    Harris, K.L.; Howell, F.L.; Winczewski, L.M.; Wartman, B.L.; Umphrey, H.R.; Anderson, S.B.

    1981-06-01

    The Phase II activities dealt with three main topical areas: geothermal gradient and heat-flow studies, stratigraphic studies, and water quality studies. Efforts were concentrated on Mesozoic and Cenozoic rocks. The geothermal gradient and heat-flow studies involved running temperature logs in groundwater observation holes in areas of interest, and locating, obtaining access to, and casing holes of convenience to be used as heat-flow determination sites. The stratigraphic and water quality studies involved two main efforts: updating and expanding WELLFILE and assembling a computer library system (WELLCAT) for all water wells drilled in the state. WATERCAT combines data from the United States Geological Survey Water Resources Division's WATSTOR and GWST computer libraries; and includes physical, stratigraphic, and water quality data. Goals, methods, and results are presented.

  15. 3F8 monoclonal antibody treatment of patients with stage 4 neuroblastoma: a phase II study.

    PubMed

    Cheung, N K; Kushner, B H; Yeh, S D; Larson, S M

    1998-06-01

    3F8 is an IgG3 murine monoclonal antibody directed against the ganglioside GD2. In a phase II study, 3F8 was administered i.v. to 16 patients (pts) who had stage 4 neuroblastoma. Response was seen in bony lesions (2 of 7 pts) and marrow (3 of 8 pts). Acute toxicities of pain, fever, urticaria, hypertension, hypotension and anaphylactoid reactions were self-limited and manageable. Three pts are long-term survivors between 79-130+ months after 3F8 treatment without additional systemic therapy and no delayed neurological complications. The potential benefits of 3F8 when added to chemoradio-therapy warrant further investigation.

  16. Spectroscopic, thermodynamic, kinetic studies and oxidase/antioxidant biomimetic catalytic activities of tris(3,5-dimethylpyrazolyl)borate Cu(II) complexes.

    PubMed

    Shaban, Shaban Y; Ramadan, Abd El-Motaleb M; Ibrahim, Mohamed M; Mohamed, Mahmoud A; van Eldik, Rudi

    2015-08-21

    A series of copper(ii) complexes, viz. [Tp(MeMe)Cu(Cl)(H2O)] (), [Tp(MeMe)Cu(OAc)(H2O)] (), [Tp(MeMe)Cu(NO3)] () and [Tp(MeMe)Cu(ClO4)] () containing tris(3,5-dimethylpyrazolyl)borate (KTp(MeMe)), have been synthesized and fully characterized. The substitution reaction of with thiourea was studied under pseudo-first-order conditions as a function of concentration, temperature and pressure in methanol and acetonitrile as solvents. Two reaction steps that both depended on the nucleophile concentration were observed for both solvents. Substitution of coordinated methanol is about 40 times faster than the substitution of chloride. In acetonitrile, the rate constant for the displacement of coordinated acetonitrile was more than 20 times faster than the substitution of chloride. The reported activation parameters indicate that both reaction steps follow a dissociative mechanism in both solvents. On going from methanol to acetonitrile, the rate constant for the displacement of the solvent becomes more than 200 times faster due to the more labile acetonitrile, but the substitution mechanism remained to have a dissociative character. The antioxidant activities of were evaluated for superoxide dismutase (SOD), glutathione-s-transferase (GST0 and glutathione reduced (GSH-Rd) activity. and were found to show (p < 0.05) the highest antioxidant activity in comparison to and , which can be ascribed to the geometric configuration as well as the nature of the co-ligand. showed catechol oxidase activity with turnover numbers of 20 min(-1) and a coordination affinity for 3,5-DTBC of K1, = 31 mM(-1). K1 is rather large and seems to be typical for faster biomimetic models, and also for the enzyme itself (25 mM(-1)). The reaction rate depended linearly on the complex concentration, indicating a first-order dependence on the catalyst concentration. PMID:26172408

  17. Cu(II)-dipeptide complexes of 2-(4'-thiazolyl)benzimidazole: synthesis, DNA oxidative damage, antioxidant and in vitro antitumor activity.

    PubMed

    Fu, Xia-Bing; Zhang, Jia-Jia; Liu, Dan-Dan; Gan, Qian; Gao, Hong-Wei; Mao, Zong-Wan; Le, Xue-Yi

    2015-02-01

    Two new Cu(II)-dipeptide complexes of 2-(4'-thiazolyl)benzimidazole, [Cu(Gly-Gly)(TBZ)(Cl)]·4H2O (1) and [Cu(Gly-l-Leu)(TBZ)(Cl)]·H2O (2) (Gly-Gly=glycyl-glycine anion, Gly-l-Leu=glycyl-l-leucine anion and TBZ=2-(4'-thiazolyl)benzimidazole) have been synthesized and characterized by elemental analyses, molar conductance measurements and spectroscopy methods (IR, UV-visible, electrospray ionization mass spectra (ESI-MS) and EPR). The DNA binding and cleavage properties of the complexes monitored by multi-spectroscopic techniques (UV absorption, fluorescence and circular dichroism), viscosity determination and agarose gel electrophoresis indicated that the complexes bound to calf thymus (CT)-DNA via a partial intercalative mode with considerable intrinsic binding constants (Kb=1.64×10(5)M(-1) for 1 and 2.59×10(5)M(-1) for 2), and cleaved pBR322 DNA efficiently in the mediation of ascorbic acid (AA), probably via an oxidative damage mechanism induced by OH. The antioxidant activities of the complexes have been evaluated by means of modified nitroblue tetrazolium (NBT) photoreduction and cellular antioxidant activity (CAA) assays using HepG2 cells as a model, and it was found that IC50 values of 1 and 2 for dismutation of O2(-) were 0.172 and 0.247μM, respectively, and the CAA50 values were 10.57 and 10.74μM. In addition, the complexes were subjected to in vitro cytotoxicity against three human carcinoma cell lines (HeLa, A549 and HepG2), which revealed that the complexes exhibited effective cytotoxicity (IC50 values varying from 33.17 to 100μM) and selective inhibition toward HeLa cell lines. These findings indicate that the complexes have the potential to act as effective metallopeptide chemotherapeutic agents.

  18. Astaxanthin protects ARPE-19 cells from oxidative stress via upregulation of Nrf2-regulated phase II enzymes through activation of PI3K/Akt

    PubMed Central

    Li, Zhongrui; Dong, Xin; Liu, Hongling; Chen, Xi; Shi, Huanqi; Fan, Yan; Hou, Dingshan

    2013-01-01

    Purpose Oxidative stress on retinal pigment epithelial (RPE) cells is thought to play a crucial role in the development and progression of age-related macular degeneration. Astaxanthin (AST) is a carotenoid that shows significant antioxidant properties. This study was designed to investigate the protective effect of AST on ARPE-19 cells against oxidative stress and the possible underlying mechanism. Methods ARPE-19 cells exposed to different doses of H2O2 were incubated with various concentrations of AST and cell viability subsequently detected with the (4-[3-[4-iodophenyl]-2–4(4-nitrophenyl)-2H-5- tetrazolio-1,3-benzene disulfonate]; WST-1) assay. The apoptosis rate and intracellular levels of reactive oxygen species (ROS) were measured with flow cytometry. NAD(P)H quinine oxidoreductase 1 (NQO1), hemeoxygenase-1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and glutamate-cysteine ligase catalytic subunit (GCLC) expression were examined with real-time PCR and western blotting. The nuclear localization of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protein and the expression levels of cleaved caspase-3 and protein kinase B proteins were evaluated with western blotting. Results AST clearly reduced H2O2-induced cell viability loss, cell apoptosis, and intracellular generation of ROS. Furthermore, treatment with AST activated the Nrf2-ARE pathway by inducing Nrf2 nuclear localization. Consequently, Phase II enzymes NQO1, HO-1, GCLM, and GCLC mRNA and proteins were increased. AST inhibited expression of H2O2-induced cleaved caspase-3 protein. Activation of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway was involved in the protective effect of AST on the ARPE-19 cells. Conclusions AST protected ARPE-19 cells against H2O2-induced oxidative stress via Nrf2-mediated upregulation of the expression of Phase II enzymes involving the PI3K/Akt pathway. PMID:23901249

  19. SRNL PHASE II SHELF LIFE STUDIES - SERIES 1 ROOM TEMPERATURE AND HIGH RELATIVE HUMIDITY

    SciTech Connect

    Mickalonis, J.; Duffey, J.

    2012-09-12

    The Savannah River National Laboratory (SRNL) Phase II, Series 1 shelf-life corrosion testing for the Department of Energy Standard 3013 container is presented and discussed in terms of the localized corrosion behavior of Type 304 stainless steel in contact with moist plutonium oxide and chloride salt mixtures and the potential impact to the 3013 inner container. This testing was designed to address the influence of temperature, salt composition, initial salt moisture, residual stress and type of oxide/salt contact on the relative humidity inside a 3013 container and the initiation and propagation of localized corrosion, especially stress corrosion cracking. The integrated plan is being conducted by Los Alamos National Laboratory and SRNL. SRNL is responsible for conducting a corrosion study in small scale vessels containing plutonium oxide and chloride salts under conditions of humidity, temperature and oxide/salt compositions both within the limits of 3013 storage conditions as well as beyond the 3013 storage requirements to identify margins for minimizing the initiation of stress corrosion cracking. These worst case conditions provide data that bound the material packaged in 3013 containers. Phase I of this testing was completed in 2010. The Phase II, Series 1 testing was performed to verify previous results from Phase I testing and extend our understanding about the initiation of stress corrosion cracking and pitting that occur in 304L under conditions of room temperature, high humidity, and a specific plutonium oxide/salt chemistry. These results will aid in bounding the safe storage conditions of plutonium oxides in 3013 containers. A substantial change in the testing was the addition of the capability to monitor relative humidity during test exposure. The results show that under conditions of high initial moisture ({approx}0.5 wt%) and room temperature stress corrosion cracking occurred in 304L teardrop coupons in contact with the oxide/salt mixture at times

  20. Inhibition of ROS-induced apoptosis in endothelial cells by nitrone spin traps via induction of phase II enzymes and suppression of mitochondria-dependent pro-apoptotic signaling.

    PubMed

    Das, Amlan; Gopalakrishnan, Bhavani; Voss, Oliver H; Doseff, Andrea I; Villamena, Frederick A

    2012-08-15

    Oxidative stress is the main etiological factor behind the pathogenesis of various diseases including inflammation, cancer, cardiovascular and neurodegenerative disorders. Due to the spin trapping abilities and various pharmacological properties of nitrones, their application as therapeutic agent has been gaining attention. Though the antioxidant properties of the nitrones are well known, the mechanism by which they modulate the cellular defense machinery against oxidative stress is not well investigated and requires further elucidation. Here, we have investigated the mechanisms of cytoprotection of the nitrone spin traps against oxidative stress in bovine aortic endothelial cells (BAEC). Cytoprotective properties of both the cyclic nitrone 5,5-dimethyl-pyrroline N-oxide (DMPO) and linear nitrone α-phenyl N-tert-butyl nitrone (PBN) against H₂O₂-induced cytotoxicity were investigated. Preincubation of BAEC with PBN or DMPO resulted in the inhibition of H₂O₂-mediated cytotoxicity and apoptosis. Nitrone-treatment resulted in the induction and restoration of phase II antioxidant enzymes via nuclear translocation of NF-E2-related factor 2 (Nrf-2) in oxidatively-challenged cells. Furthermore, the nitrones were found to inhibit the mitochondrial depolarization and subsequent activation of caspase-3 induced by H₂O₂. Significant down-regulation of the pro-apoptotic proteins p53 and Bax, and up-regulation of the anti-apoptotic proteins Bcl-2 and p-Bad were observed when the cells were preincubated with the nitrones prior to H₂O₂-treatment. It was also observed that Nrf-2 silencing completely abolished the protective effects of nitrones. Hence, these findings suggest that nitrones confer protection to the endothelial cells against oxidative stress by modulating phase II antioxidant enzymes and subsequently inhibiting mitochondria-dependent apoptotic cascade. PMID:22580046

  1. Inhibition of ROS-induced apoptosis in endothelial cells by nitrone spin traps via induction of phase II enzymes and suppression of mitochondria-dependent pro-apoptotic signaling

    PubMed Central

    Das, Amlan; Gopalakrishnan, Bhavani; Voss, Oliver H.; Doseff, Andrea I.; Villamena, Frederick A.

    2012-01-01

    Oxidative stress is the main etiological factor behind the pathogenesis of various diseases including inflammation, cancer, cardiovascular and neurodegenerative disorders. Due to the spin trapping abilities and various pharmacological properties of nitrones, their application as therapeutic agent has been gaining attention. Though the antioxidant properties of the nitrones are well known, the mechanisms by which they modulate the cellular defense machinery against oxidative stress is not well investigated and requires further elucidation. Here, we have investigated the mechanisms of cytoprotection of the nitrone spin traps against oxidative stress in bovine aortic endothelial cells (BAEC). Cytoprotective properties of both the cyclic nitrone 5,5-dimethyl-pyrroline N-oxide (DMPO) and linear nitrone alpha-phenyl N-tert-butyl nitrone (PBN) against H2O2-induced cytoxicity were investigated. Preincubation of BAEC with PBN or DMPO resulted in the inhibition of H2O2–mediated cytotoxicity and apoptosis. Nitrone-treatment resulted in the induction and restoration of phase II antioxidant enzymes via nuclear translocation of NF-E2-related factor 2 (Nrf-2) in oxidatively-challenged cells. Furthermore, the nitrones were found to inhibit the mitochondrial depolarization and subsequent activation of caspase-3 induced by H2O2. Significant down-regulation of the pro-apoptotic proteins p53 and Bax, and up-regulation of the anti-apoptotic proteins Bcl-2 and p-Bad were observed when the cells were preincubated with the nitrones prior to H2O2–treatment. It was also observed that Nrf-2 silencing completely abolished the protective effects of nitrones. Hence, these findings suggest that nitrones confer protection to the endothelial cells against oxidative stress by modulating phase II antioxidant enzymes and subsequently inhibiting mitochondria-dependent apoptotic cascade. PMID:22580046

  2. Solid phase extraction of trace amount of Cu(II) using functionalized-graphene

    NASA Astrophysics Data System (ADS)

    Moghimi, Ali

    2013-11-01

    A novel and selective method for the fast determination of trace amounts of Cu(II) ions in water samples has been developed. The first organic-solution-processable functionalized-graphene (SPF-Graphene) hybrid material with porphyrins, porphyrin-graphene nanohybrid, 5-(4-aminophenyl)-10, 15, 20-triphenyl porphyrin and its photophysical properties including optical (TPP) and grapheme oxide molecules covalently bonded together via an amide bond (TPP-NHCO-SPFGraphene) were used as absorbent for extraction of Cu(II) ions by solid phase extraction method. The complexes were eluted with HNO3 (2 M) 10% (vol/vol) methanol in acetone and determined the analyte by flame atomic absorption spectrometry. The procedure is based on the selective formation of Cu(II) at optimum pH by elution with organic eluents and determination by flame atomic absorption spectrometry. The method is based on complex formation on the surface of the ENVI-18 DISK™ disks modified porphyrin-graphene nanohybrid, 5-(4-aminophenyl)-10,15,20-triphenyl porphyrin (TPP) and grapheme oxide molecules covalently bonded together via an amide bond (TPP-NHCO-SPFGraphene) followed by stripping of the retained species by minimum amounts of appropriate organic solvents. The elution is efficient and quantitative. The effect of potential interfering ions, pH, TPP-NHCO-SPFGraphene, amount, stripping solvent, and sample flow rate were also investigated. Under the optimal experimental conditions, the break-through volume was found to about 1000 mL providing a preconcentration factor of 600. The maximum capacity of the disks was found to be 398 ± 3 μg for Cu2+. The limit of detection of the proposed method is 5 ng per 1000 mL. The method was applied to the extraction and recovery of copper in different water samples.

  3. Time-dependence Effects in Photospheric-Phase Type II Supernova Spectra

    NASA Astrophysics Data System (ADS)

    Dessart, Luc; Hillier, D. John

    2007-08-01

    We have incorporated time-dependent terms into the statistical and radiative equilibrium calculations of the non-LTE line-blanketed radiative transfer code CMFGEN. To illustrate the significant improvements in spectral fitting achieved for photospheric phase Type II SN, and to document the effects associated with time dependence, we model the outer 6.1 Msolar of ejecta of a BSG/RSG progenitor star. Hopping by 3-day increments, we compute the UV to near-IR spectral evolution for both continuum and lines, from the fully ionized conditions at one week to the partially recombined conditions at 6 weeks after the explosion. We confirm the importance of allowing for time-dependence in the modeling of Type-II SN, as recently discussed by Utrobin & Chugai for SN1987A. However unlike Utrobin & Chugai, who treated the radiation field in a core-halo approximation and assumed the Sobolev approximation for line formation, we allow for the full interaction between the radiation field and level populations, and study the effects on the full spectrum. At the hydrogen-recombination epoch, HI lines and NaD are considerably stronger and broader than in equivalent steady-state models, while CaII is weakened. Former successes of steady-state CMFGEN models are unaffected, while former discrepancies are cured. Time dependence affects all lines, while the continuum, from the UV to the optical, changes only moderately. We identify two key effects: First, time dependence together with the energy gain through changes in ionization and excitation lead to an over-ionization in the vicinity of the photosphere, dramatically affecting line optical depths and profiles. Second, the ionization is frozen-in at large radii/velocities. This stems solely from the time-scale contrast between recombination and expansion and will occur, modulo non-thermal excitation effects, in all SN types. The importance of this effect on spectral analyses, across SN types and epochs, remains to be determined.

  4. Robust Type-II Weyl Semimetal Phase in Transition Metal Diphosphides XP_{2} (X=Mo, W).

    PubMed

    Autès, G; Gresch, D; Troyer, M; Soluyanov, A A; Yazyev, O V

    2016-08-01

    The recently discovered type-II Weyl points appear at the boundary between electron and hole pockets. Type-II Weyl semimetals that host such points are predicted to exhibit a new type of chiral anomaly and possess thermodynamic properties very different from their type-I counterparts. In this Letter, we describe the prediction of a type-II Weyl semimetal phase in the transition metal diphosphides MoP_{2} and WP_{2}. These materials are characterized by relatively simple band structures with four pairs of type-II Weyl points. Neighboring Weyl points have the same chirality, which makes the predicted topological phase robust with respect to small perturbations of the crystalline lattice. In addition, this peculiar arrangement of the Weyl points results in long topological Fermi arcs, thus making them readily accessible in angle-resolved photoemission spectroscopy. PMID:27541470

  5. Robust Type-II Weyl Semimetal Phase in Transition Metal Diphosphides X P2 (X =Mo , W)

    NASA Astrophysics Data System (ADS)

    Autès, G.; Gresch, D.; Troyer, M.; Soluyanov, A. A.; Yazyev, O. V.

    2016-08-01

    The recently discovered type-II Weyl points appear at the boundary between electron and hole pockets. Type-II Weyl semimetals that host such points are predicted to exhibit a new type of chiral anomaly and possess thermodynamic properties very different from their type-I counterparts. In this Letter, we describe the prediction of a type-II Weyl semimetal phase in the transition metal diphosphides MoP2 and WP2 . These materials are characterized by relatively simple band structures with four pairs of type-II Weyl points. Neighboring Weyl points have the same chirality, which makes the predicted topological phase robust with respect to small perturbations of the crystalline lattice. In addition, this peculiar arrangement of the Weyl points results in long topological Fermi arcs, thus making them readily accessible in angle-resolved photoemission spectroscopy.

  6. Phase II trial of weekly Docetaxel, Zoledronic acid, and Celecoxib for castration-resistant prostate cancer.

    PubMed

    Kattan, Joseph; Bachour, Marwan; Farhat, Fadi; El Rassy, Elie; Assi, Tarek; Ghosn, Marwan

    2016-08-01

    Background Treatment options for patients with metastatic castration-resistance prostate cancer are unsatisfactory. Docetaxel monotherapy offers promising results with a tolerable toxicity profile. However, enhancing the clinical index of Docetaxel-based therapy remains the ultimate goal. Methods We conducted a phase II, open label, multinational prospective trial to evaluate the efficacy of weekly Docetaxel combined with Zoledronic acid and Celecoxib. Eligible patients received 25 mg/m(2) Docetaxel weekly for 3 consecutive weeks every 4 weeks, 4 mg Zoledronic acid every 4 weeks, and 200 mg oral Celecoxib twice daily. Enrollment was terminated prematurely upon the publication of reports of cardiac toxicity associated with cyclooxygenase (COX) 2 inhibitors. Results Our study enrolled 22 patients with a median of 4.7 cycles per patient. The median overall survival (OS) was 9.8 months (range 0.7 to 24.1 months) with 36 % and 4.5 % survival rates at 1 and 2 years, respectively. Our patients had a biologic response in 40.1 % of cases and a palliative response in 72.7 %. Among the eight patients with measurable disease, three had partial responses, two had stable disease, and three had progressive disease, leading to a response rate (RR) of 62.5 %. The observed toxicities were mild and limited to grade 3 events. Nine patients had anemia (40.1 %), 5 had sensory neuropathy (22.7 %) and 2 had stomatitis (9.1 %). Conclusion The combination of Docetaxel, Celecoxib, and Zoledronic acid failed to improve OS or to offer an acceptable biologic response. We do not believe that there is compelling evidence to include either Celecoxib or Zoledronic acid in further phase II/III trials. PMID:27159981

  7. Phase II screening trial of lithium carbonate in amyotrophic lateral sclerosis

    PubMed Central

    Moore, D.H.; Forshew, D.A.; Katz, J.S.; Barohn, R.J.; Valan, M.; Bromberg, M.B.; Goslin, K.L.; Graves, M.C.; McCluskey, L.F.; McVey, A.L.; Mozaffar, T.; Florence, J.M.; Pestronk, A.; Ross, M.; Simpson, E.P.; Appel, S.H.

    2011-01-01

    Objective: To use a historical placebo control design to determine whether lithium carbonate slows progression of amyotrophic lateral sclerosis (ALS). Methods: A phase II trial was conducted at 10 sites in the Western ALS Study Group using similar dosages (300–450 mg/day), target blood levels (0.3–0.8 mEq/L), outcome measures, and trial duration (13 months) as the positive trial. However, taking riluzole was not a requirement for study entry. Placebo outcomes in patients matched for baseline features from a large database of recent clinical trials, showing stable rates of decline over the past 9 years, were used as historical controls. Results: The mean rate of decline of the ALS Functional Rating Scale–Revised was greater in 107 patients taking lithium carbonate (−1.20/month, 95% confidence interval [CI] −1.41 to −0.98) than that in 249 control patients (−1.01/month, 95% CI −1.11 to −0.92, p = 0.04). There were no differences in secondary outcome measures (forced vital capacity, time to failure, and quality of life), but there were more adverse events in the treated group. Conclusions: The lack of therapeutic benefit and safety concerns, taken together with similar results from 2 other recent trials, weighs against the use of lithium carbonate in patients with ALS. The absence of drift over time and the availability of a large database of patients for selecting a matched historical control group suggest that use of historical controls may result in more efficient phase II trials for screening putative ALS therapeutic agents. Classification of evidence: This study provided Class IV evidence that lithium carbonate does not slow the rate of decline of function in patients with ALS over 13 months. Neurology® 2011;77:973–979 PMID:21813790

  8. A phase II study of tamoxifen plus melatonin in metastatic solid tumour patients.

    PubMed

    Lissoni, P; Paolorossi, F; Tancini, G; Ardizzoia, A; Barni, S; Brivio, F; Maestroni, G J; Chilelli, M

    1996-11-01

    Preliminary data would suggest that the pineal hormone, melatonin (MLT), may enhance tamoxifen (TMX) anti-tumour efficacy. Both MLT and TMX have been used as single agents in the palliative treatment of metastatic neoplasms, other than the classical hormone-dependent tumours, without, however, any clear efficacy. On this basis, a phase II study with TMX plus MLT has been performed in untreatable metastatic solid tumour patients. The study included 25 metastatic solid tumour patients other than breast cancer and prostate cancer (six unknown primary tumour; four melanoma; four uterine cervix carcinoma; five pancreatic cancer; three hepatocarcinoma; two ovarian cancer; one non-small-cell lung cancer), for whom no other effective standard therapy was available, because of poor clinical conditions, no response to previous chemotherapies and/or chemotherapy-resistant tumours. Both drugs were given orally every day until disease progression (TMX, 20 mg day-1 at noon; MLT, 20 mg day-1 in the evening). Three patients had a partial response (PR) (12%; 95% confidence limits 2-24%) (one cervix carcinoma; one melanoma; one unknown primary tumour). A stable disease (SD) was achieved in 13 other patients, whereas the remaining nine patients progressed. Performance status (PS) improved in 9/25 patients, whose median score increased from 50% to 70%. Finally, a survival longer than 1 year was observed in 7/25 (28%) patients. This phase II study would suggest that the neuroendocrine combination with TMX plus MLT may have some benefit in untreatable metastatic solid tumour patients, either in controlling cancer cell proliferation or improving the PS.

  9. A phase II study of tamoxifen plus melatonin in metastatic solid tumour patients.

    PubMed Central

    Lissoni, P.; Paolorossi, F.; Tancini, G.; Ardizzoia, A.; Barni, S.; Brivio, F.; Maestroni, G. J.; Chilelli, M.

    1996-01-01

    Preliminary data would suggest that the pineal hormone, melatonin (MLT), may enhance tamoxifen (TMX) anti-tumour efficacy. Both MLT and TMX have been used as single agents in the palliative treatment of metastatic neoplasms, other than the classical hormone-dependent tumours, without, however, any clear efficacy. On this basis, a phase II study with TMX plus MLT has been performed in untreatable metastatic solid tumour patients. The study included 25 metastatic solid tumour patients other than breast cancer and prostate cancer (six unknown primary tumour; four melanoma; four uterine cervix carcinoma; five pancreatic cancer; three hepatocarcinoma; two ovarian cancer; one non-small-cell lung cancer), for whom no other effective standard therapy was available, because of poor clinical conditions, no response to previous chemotherapies and/or chemotherapy-resistant tumours. Both drugs were given orally every day until disease progression (TMX, 20 mg day-1 at noon; MLT, 20 mg day-1 in the evening). Three patients had a partial response (PR) (12%; 95% confidence limits 2-24%) (one cervix carcinoma; one melanoma; one unknown primary tumour). A stable disease (SD) was achieved in 13 other patients, whereas the remaining nine patients progressed. Performance status (PS) improved in 9/25 patients, whose median score increased from 50% to 70%. Finally, a survival longer than 1 year was observed in 7/25 (28%) patients. This phase II study would suggest that the neuroendocrine combination with TMX plus MLT may have some benefit in untreatable metastatic solid tumour patients, either in controlling cancer cell proliferation or improving the PS. PMID:8912546

  10. The sROD module for the ATLAS Tile Calorimeter Phase-II Upgrade Demonstrator

    NASA Astrophysics Data System (ADS)

    Carrió, F.; Castillo, V.; Ferrer, A.; Fiorini, L.; Hernández, Y.; Higón, E.; Mellado, B.; March, L.; Moreno, P.; Reed, R.; Solans, C.; Valero, A.; Valls, J. A.

    2014-02-01

    TileCal is the central hadronic calorimeter of the ATLAS experiment at the Large Hadron Collider (LHC) at CERN. The main upgrade of the LHC to increase the instantaneous luminosity is scheduled for 2022. The High Luminosity LHC, also called upgrade Phase-II, will imply a complete redesign of the read-out electronics in TileCal. In the new read-out architecture, the front-end electronics aims to transmit full digitized information to the back-end system in the counting rooms. Thus, the back-end system will also provide digital calibrated information with enhanced precision and granularity to the first level trigger to improve the trigger efficiencies. The demonstrator project is envisaged to qualify this new proposed architecture. A reduced part of the detector, 1/256 of the total, will be equipped with the new electronics during 2014 to evaluate the proposed architecture in real conditions. The upgraded Read-Out Driver (sROD) will be the core element of the back-end electronics in Phase-II. The sROD module is designed on a double mid-size AMC format and will operate under an AdvancedTCA framework. The module includes two Xilinx Series 7 Field Programmable Gate Arrays (FPGAs) for data receiving and processing, as well as the implementation of embedded systems. Related to optical connectors, the sROD uses 4 QSFPs to receive and transmit data from the front-end electronics and 1 Avago MiniPOD to send preprocessed data to the first level trigger system. An SFP module maintains the compatibility with the existing hardware. A complete description of the sROD module for the demonstrator including the main functionalities, circuit design and the control software and firmware will be presented.

  11. Environmentally benign manufacturing of compact disc stampers [Final Phase II report

    SciTech Connect

    1999-07-08

    Optical data storage is currently a $10B/yr. business. With the introduction of the high capacity Digital Versatile Disc (D/D) as well as the continued growth of CD-Audio and CD-ROM worldwide sales of optical data products as a whole are growing at rate of more than 10% per year. In North America, more than 2.5 billion optical discs will be sold in 1998. By 1999, the numbers of optical discs produced for the North American market will grow to almost three billion. The optical disc manufacturing industry is dominated by Asian and European companies (e.g. Sony of Japan and Philips of Netherlands). Prism Corporation has created a process that could significantly improve US competitiveness in the business of optical disc production. The objectives of the Phase II STTR project were to build and test an ion machining system (IMS) for stamper fabrication, prove overall manufacturing system feasibility by fabrication stampers and replicas, and evaluate alternative materials and alternative process parameters to optimize the process. During tie period of the Phase II project Prism Corporation was able to meet these objectives. In the course of doing so, adjustments had been made to better the project and in turn the final product. An ion machining system was designed and built that produced stampers ready for the molding process. Also, many control steps in the manufacturing process were studied to improve the current process and make it even more compatible with the industry standards, fitting seamlessly into current manufacturing lines.

  12. Suggested response criteria for phase II antitumor drug studies for neurofibromatosis type 2 related vestibular schwannoma

    PubMed Central

    Plotkin, Scott R.; Halpin, Chris; Blakeley, Jaishri O.; Slattery, William H.; Welling, D. Bradley; Chang, Susan M.; Loeffler, Jay S.; Harris, Gordon J.; Sorensen, A. Gregory; McKenna, Michael J.

    2014-01-01

    Neurofibromatosis type 2 (NF2) is a tumor suppressor gene syndrome characterized by multiple schwannomas, especially vestibular schwannomas (VS), and meningiomas. Anticancer drug trials are now being explored, but there are no standardized endpoints in NF2. We review the challenges of NF2 clinical trials and suggest possible response criteria for use in initial phase II studies. We suggest two main response criteria in such trials. Objective radiographic response is defined as a durable 20% or greater reduction in VS volume based on postcontrast T1-weighted MRI images collected with 3 mm or finer cuts through the internal auditory canal. Hearing response is defined as a statistically significant improvement in word recognition scores using 50-word recorded lists in audiology. A possible composite endpoint incorporating both radiographic response and hearing response is outlined. We emphasize pitfalls in response assessment and suggest guidelines to minimize misinterpretations of response. We also identify research goals in NF2 to facilitate future trial conduct, such as identifying the expectations for time to tumor progression and time to measurable hearing loss in untreated NF2-related VS, and the relation of both endpoints to patient prognostic factors (such as age, baseline tumor volume, and measures of disease severity). These data would facilitate future use of endpoints based on stability of tumor size and hearing, which might be more appropriate for testing certain drugs. We encourage adoption of standardized endpoints early in the development of phase II trials for this population to facilitate comparison of results across trials of different agents. PMID:19430883

  13. PAH biotransformation in terrestrial invertebrates--a new phase II metabolite in isopods and springtails.

    PubMed

    Stroomberg, Gerard J; Zappey, Herman; Steen, Ruud J C A; van Gestel, Cornelis A M; Ariese, Freek; Velthorst, Nel H; van Straalen, Nico M

    2004-06-01

    Soil-living invertebrates are exposed to high concentrations of contaminants accumulating in dead organic matter, such as polycyclic aromatic hydrocarbons (PAHs). The capacity for PAH biotransformation is not equally developed in all invertebrates. In this paper, we compare three species of invertebrates, Porcellio scaber (Isopoda), Eisenia andrei (Lumbricidae) and Folsomia candida (Collembola), for the metabolites formed upon exposure to pyrene. Metabolic products of pyrene biotransformation in extracts from whole animals or isopod hepatopancreas were compared to those found in fish bile (flounder and plaice). An optimized HPLC method was used with fluorescence detection; excitation/emission spectra were compared to reference samples of 1-hydroxypyrene and enzymatically synthesized conjugates. Enzymatic hydrolysis after fractionation was used to demonstrate that the conjugates originated from 1-hydroxypyrene. All three invertebrates were able to oxidize pyrene to 1-hydroxypyrene, however, isopods and collembolans stood out as more efficient metabolizers compared to earthworms. In contrast to fish, none of the invertebrates produced pyrene-1-glucuronide as a phase II conjugate. Both Collembola and Isopoda produced significant amounts of pyrene-1-glucoside, whereas isopods also produced pyrene-1-sulfate. A third, previously unknown, conjugate was found in both isopods and springtails, and was analysed further using electrospray and atmospheric pressure chemical ionisation mass spectrometry. Based on the obtained mass spectra, a new conjugate is proposed: pyrene-1-O-(6"-O-malonyl)glucoside. The use of glucose-malonate as a conjugant in animal phase II biotransformation has not been described before, but is understandable in the microenvironment of soil-living invertebrates. In the earthworm, three other pyrene metabolites were observed, none of which was shared with the arthropods, although two were conjugates of 1-hydroxypyrene. Our study illustrates the great

  14. Low energy threshold analysis of the phase I and phase II data sets of the Sudbury neutrino observatory

    SciTech Connect

    Seibert, S R; Hime, A; Elliott, S R; Rielage, K

    2009-01-01

    Results are reported from a joint analysis of Phase I and Phase II data from the Sudbury Neutrino Observatory. The effective electron kinetic energy threshold used is T{sub eff} = 3.5 MeV, the lowest analysis threshold yet achieved with water Cherenkov detector data. In units of 10{sup 6} cm{sup -2} s{sup =1}, the total flux of active-flavor neutrinos from {sup 8}B decay in the Sun measured using the neutral current (NC) reaction of neutrinos on deuterons, with no constraint on the {sup 8}B neutrino energy spectrum, is found to be {Phi}{sub NC} = 5.140{sub -0.158}{sup +0.160}(stat){sub -0.117}{sup +0.132}(syst). These uncertainties are more than a factor of two smaller than previously published results. Also presented are the spectra of recoil electrons from the charged current reaction of neutrinos on deuterons and the elastic scattering of electrons. A fit to the SNO data in which the free parameters directly describe the total {sup 8}B neutrino flux and the energy-dependent Ve survival probability provides a measure of the total {sup 8}B neutrino flux {Phi}{sub 8{sub B}} = 5.046{sub -0.152}{sup +0.159}(stat){sub -0.123}{sup +0.107}(syst). Combining these new results with results of all other solar experiments and the KamLAND reactor experiment yields best-fit values of the mixing parameters of {theta}{sub 12} = 34.06{sub -0.84}{sup +1.16} degrees and {Delta}m{sub 21}{sup 2} = 7.59{sub -0.21}{sup +0.20} x 10{sup -5} eV{sup 2}. The global value of {Phi}{sub 8{sub B}} is extracted to a precision of {sub -2.95}{sup +2.38}%. In a three-flavor analysis the best fit value of sin{sup 2} {theta}{sub 13} is 2.00{sub -1.63}{sup +2.09} x 10{sup -2}. Interpreting this as a limit implies an upper bound of sin{sup 2} {theta}{sub 13} < 0.057 (95% C. L.).

  15. In vivo phase II-enzymes inducers, as potential chemopreventive agents, based on the chalcone and furoxan skeletons.

    PubMed

    Cabrera, Mauricio; Mastandrea, Ignacio; Otero, Gabriel; Cerecetto, Hugo; González, Mercedes

    2016-04-15

    Cancer chemoprevention involves prevention/delay/reverse of the carcinogenic process through administration of cancer chemopreventive agents (CCA). Compounds which are able to induce detoxification-enzymes, especially monofunctional phase II enzymes, have become in excellent approaches for new CCA. Herein, we report the synthesis of new furoxanyl chalcone-like hybrid compounds as CCA. In vitro studies showed that phenylfuroxanyl derivatives 6 and 9 displayed the best activities being 9 the greatest monofunctional-inducer. Additionally, compounds were non-mutagenic against TA98 Salmonella typhimurium strain (Ames test) and could be used in the prevention of the progression of pre-malignant lesions for their cytotoxic activity against tumoral cells. In vivo proof of concept showed increment on phase II-enzymes activities in liver, colon and mammary gland having derivative 9 the best induction profiles. We probed Nrf2 nuclear translocation is operative for both compounds allowing to exert protective effects via expression of downstream phase-II enzymes.

  16. Phenolic profile and antioxidant activities of olive mill wastewater.

    PubMed

    El-Abbassi, Abdelilah; Kiai, Hajar; Hafidi, Abdellatif

    2012-05-01

    Olive trees play an important role in the Moroccan agro-economy, providing both employment and export revenue. However, the olive oil industry generates large amounts of wastes and wastewaters. The disposal of these polluting by-products is a significant environmental problem that needs an adequate solution. On one hand, the phytotoxic and antimicrobial effects of olive mill wastewaters are mainly due to their phenolic content. The hydrophilic character of the polyphenols results in the major proportion of natural phenols being separated into the water phase during the olive processing. On other hand, the health benefits arising from a diet containing olive oil have been attributed to its richness in phenolic compounds that act as natural antioxidants and are thought to contribute to the prevention of heart diseases and cancers. Olive mill wastewater (OMW) samples have been analysed in terms of their phenolic constituents and antioxidant activities. The total phenolic content, flavonoids, flavanols, and proanthocyanidins were determined. The antioxidant and radical scavenging activity of phenolic extracts and microfiltred samples was evaluated using different tests (iron(II) chelating activity, total antioxidant capacity, DPPH assays and lipid peroxidation test). The obtained results reveal the considerable antioxidant capacity of the OMW, that can be considered as an inexpensive potential source of high added value powerful natural antioxidants comparable to some synthetic antioxidants commonly used in the food industry.

  17. Final Phase II Report : QuickSite{reg_sign} investigation, Centralia, Kansas.

    SciTech Connect

    LaFreniere, L.

    2004-04-01

    District No.3. Therefore, local residents are not drinking or using the contaminated groundwater detected at the former facility. The Environmental Research Division of Argonne National Laboratory is performing the investigation at Centralia on behalf of the CCC/USDA. Argonne is a nonprofit, multidisciplinary research center operated by the University of Chicago for the U.S. Department of Energy (DOE). The CCC/USDA has entered into an interagency agreement with DOE, under which Argonne provides technical assistance to the CCC/USDA with environmental site characterization and remediation at its former grain storage facilities. At these former facilities, Argonne is applying its QuickSite{reg_sign} environmental site characterization methodology. QuickSite is Argonne's proprietary implementation system for the expedited site characterization process. This methodology has been applied successfully at a number of former CCC/USDA facilities in Nebraska and Kansas and has been adopted by the American Society for Testing and Materials (ASTM 1998) as standard practice for environmental site characterization. Argonne's investigations are conducted with a phased approach. Phase I focuses primarily on the investigation and evaluation of geology, hydrogeology, and hydrogeochemistry to identify potential contaminant pathways at a site. Phase II focuses on delineating the contamination present in both soil and aquifers along the potential migration pathways. Phase I of Argonne's investigation was conducted in March-April 2002. The results and findings of the Phase I investigation at Centralia were reported previously (Argonne 2003). This report documents the findings of the Phase II activities at Centralia. Section 1 provides a brief history of the area, a review of the Phase I results and conclusions, technical objectives for the Phase II investigation, and a brief description of the sections contained in this report. Section 2 describes the investigative methods used during the Phase

  18. Sodium 2-propenyl thiosulfate derived from garlic induces phase II detoxification enzymes in rat hepatoma H4IIE cells.

    PubMed

    Chang, Hye-Sook; Ko, Miyan; Ishizuka, Mayumi; Fujita, Shoichi; Yabuki, Akira; Hossain, Mohammad Alamgir; Yamato, Osamu

    2010-06-01

    There is evidence that onions and garlic protect against cancer in humans. It has been suggested that this effect is partly due to the organosulfur compounds in Allium vegetables and that these substances act through induction of phase II detoxification enzymes. Here, we hypothesized that alk(en)yl thiosulfates, sodium n-propyl thiosulfate (NPTS), and sodium 2-propenyl thiosulfate (2PTS), which were identified in onions and garlic, respectively, may induce phase II enzymes. Therefore, rat hepatoma cells (H4IIE) were cultured with 1 to 100 micromol/L of NPTS or 2PTS for 48 hours at 37 degrees C; and the activities and messenger RNA (mRNA) expression levels of phase II enzymes in H4IIE cells were investigated. The effects of diallyl trisulfide and tert-butylhydroquinone, known as phase II inducers, were also examined as positive controls and compared with the responses of NPTS and 2PTS. Quinone reductase (QR) activity and mRNA expression levels of QR and epoxide hydrolase 1 were significantly increased by 2PTS (P < .05-.005). In particular, QR activity was increased at a relatively low concentration of 2PTS (10 micromol/L). However, glutathione S-transferase activity and mRNA expression levels of glutathione S-transferase A5 and uridine diphosphate glucuronosyl transferase 1A1 were not changed by 2PTS. In contrast, NPTS did not affect the activities and mRNA expression levels of these phase II enzymes. These results show that 2PTS can induce phase II enzymes, and its inductive effect is comparable or superior to that of diallyl trisulfide and tert-butylhydroquinone. PMID:20650352

  19. ART CCIM Phase II-A Off-Gas System Evaluation Test Plan

    SciTech Connect

    Nick Soelberg; Jay Roach

    2009-01-01

    This test plan defines testing to be performed using the Idaho National Laboratory (INL) engineering-scale cold crucible induction melter (CCIM) test system for Phase II-A of the Advanced Remediation Technologies (ART) CCIM Project. The multi-phase ART-CCIM Project is developing a conceptual design for replacing the joule-heated melter (JHM) used to treat high level waste (HLW) in the Defense Waste Processing Facility (DWPF) at the Savannah River Site (SRS) with a cold crucible induction melter. The INL CCIM test system includes all feed, melter off-gas control, and process control subsystems needed for fully integrated operation and testing. Testing will include operation of the melter system while feeding a non-radioactive slurry mixture prepared to simulate the same type of waste feed presently being processed in the DWPF. Process monitoring and sample collection and analysis will be used to characterize the off-gas composition and properties, and to show the fate of feed constituents, to provide data that shows how the CCIM retrofit conceptual design can operate with the existing DWPF off-gas control system.

  20. Phase II randomised trial of chemoradiotherapy with FOLFOX4 or cisplatin plus fluorouracil in oesophageal cancer

    PubMed Central

    Conroy, T; Yataghène, Y; Etienne, P L; Michel, P; Senellart, H; Raoul, J L; Mineur, L; Rives, M; Mirabel, X; Lamezec, B; Rio, E; Le Prisé, E; Peiffert, D; Adenis, A

    2010-01-01

    Background: Concurrent chemoradiotherapy is a valuable treatment option for localised oesophageal cancer (EC), but improvement is still needed. A randomised phase II trial was initiated to assess the feasibility and efficacy in terms of the endoscopic complete response rate (ECRR) of radiotherapy with oxaliplatin, leucovorin and fluorouracil (FOLFOX4) or cisplatin/fluorouracil. Methods: Patients with unresectable EC (any T, any N, M0 or M1a), or medically unfit for surgery, were randomly assigned to receive either six cycles (three concomitant and three post-radiotherapy) of FOLFOX4 (arm A) or four cycles (two concomitant and two post-radiotherapy) of cisplatin/fluorouracil (arm B) along with radiotherapy 50 Gy in both arms. Responses were reviewed by independent experts. Results: A total of 97 patients were randomised (arm A/B, 53/44) and 95 were assessable. The majority had squamous cell carcinoma (82% arm A/B, 42/38). Chemoradiotherapy was completed in 74 and 66%. The ECRR was 45 and 29% in arms A and B, respectively. Median times to progression were 15.2 and 9.2 months and the median overall survival was 22.7 and 15.1 months in arms A and B, respectively. Conclusion: Chemoradiotherapy with FOLFOX4, a well-tolerated and convenient combination with promising efficacy, is now being tested in a phase III trial. PMID:20940718

  1. Optimal adaptive two-stage designs for early phase II clinical trials.

    PubMed

    Shan, Guogen; Wilding, Gregory E; Hutson, Alan D; Gerstenberger, Shawn

    2016-04-15

    Simon's optimal two-stage design has been widely used in early phase clinical trials for Oncology and AIDS studies with binary endpoints. With this approach, the second-stage sample size is fixed when the trial passes the first stage with sufficient activity. Adaptive designs, such as those due to Banerjee and Tsiatis (2006) and Englert and Kieser (2013), are flexible in the sense that the second-stage sample size depends on the response from the first stage, and these designs are often seen to reduce the expected sample size under the null hypothesis as compared with Simon's approach. An unappealing trait of the existing designs is that they are not associated with a second-stage sample size, which is a non-increasing function of the first-stage response rate. In this paper, an efficient intelligent process, the branch-and-bound algorithm, is used in extensively searching for the optimal adaptive design with the smallest expected sample size under the null, while the type I and II error rates are maintained and the aforementioned monotonicity characteristic is respected. The proposed optimal design is observed to have smaller expected sample sizes compared to Simon's optimal design, and the maximum total sample size of the proposed adaptive design is very close to that from Simon's method. The proposed optimal adaptive two-stage design is recommended for use in practice to improve the flexibility and efficiency of early phase therapeutic development. PMID:26526165

  2. An investigation of long-distance propagation of gravity waves under CAWSES India Phase II Programme

    NASA Astrophysics Data System (ADS)

    Parihar, N.; Taori, A.

    2015-05-01

    Coordinated measurements of airglow features from the mesosphere-lower thermosphere (MLT) region were performed at Allahabad (25.5° N, 81.9° E) and Gadanki (13.5° N, 79.2° E), India to study the propagation of gravity waves in 13-27° N latitude range during the period June 2009 to May 2010 under CAWSES (Climate And Weather of Sun Earth System) India Phase II Programme. At Allahabad, imaging observations of OH broadband emissions and OI 557.7 nm emission were made using an all-sky imager, while at Gadanki photometric measurements of OH (6, 2) Meinel band and O2 (0, 1) Atmospheric band emissions were carried out. On many occasions, the nightly observations reveal the presence of similar waves at both locations. Typically, the period of observed similar waves lay in the 2.2-4.5 h range, had large phase speeds (~ 77-331 m s-1) and large wavelengths (~ 1194-2746 km). The images of outgoing long-wave radiation activity of the National Oceanic and Atmospheric Administration (NOAA) and the high-resolution infrared images of KALPANA-1 satellite suggest that such waves possibly originated from some nearby convective sources. An analysis of their propagation characteristics in conjunction with SABER/TIMED temperature profiles and Horizontal Wind Model (HWM 2007) wind estimates suggest that the waves propagated over long distances (~ 1200-2000 km) in atmospheric ducts.

  3. Phase II: Field Detector Development For Undeclared/Declared Nuclear Testing For Treaty Verfiation Monitoring

    SciTech Connect

    Kriz, M.; Hunter, D.; Riley, T.

    2015-10-02

    Radioactive xenon isotopes are a critical part of the Comprehensive Nuclear Test Ban Treaty (CTBT) for the detection or confirmation of nuclear weapons tests as well as on-site treaty verification monitoring. On-site monitoring is not currently conducted because there are no commercially available small/robust field detector devices to measure the radioactive xenon isotopes. Xenon is an ideal signature to detect clandestine nuclear events since they are difficult to contain and can diffuse and migrate through soils due to their inert nature. There are four key radioxenon isotopes used in monitoring: 135Xe (9 hour half-life), 133mXe (2 day half-life), 133Xe (5 day half-life) and 131mXe (12 day half-life) that decay through beta emission and gamma emission. Savannah River National Laboratory (SRNL) is a leader in the field of gas collections and has developed highly selective molecular sieves that allow for the collection of xenon gas directly from air. Phase I assessed the development of a small, robust beta-gamma coincidence counting system, that combines collection and in situ detection methodologies. Phase II of the project began development of the custom electronics enabling 2D beta-gamma coincidence analysis in a field portable system. This will be a significant advancement for field detection/quantification of short-lived xenon isotopes that would not survive transport time for laboratory analysis.

  4. A phase II trial of bryostatin 1 in patients with non-Hodgkin's lymphoma

    PubMed Central

    Blackhall, F H; Ranson, M; Radford, J A; Hancock, B W; Soukop, M; McGown, A T; Robbins, A; Halbert, G

    2001-01-01

    Bryostatin 1 is a naturally occurring macrocyclic lactone with promising antitumour and immunomodulatory function in preclinical and phase I clinical investigations. In this phase II study, 17 patients with progressive non-Hodgkin's lymphoma of indolent type (NHL), previously treated with chemotherapy, received a median of 6 (range 1–9) intravenous infusions of 25 μg/m2bryostatin 1 given once weekly over 24 hours. In 14 evaluable patients no responses were seen. Stable disease was attained in one patient for 9 months. The principal toxicities were myalgia and phlebitis. Treatment was discontinued early because of toxicity alone (phlebitis) in 2 patients, toxicity in addition to progressive disease in 3 patients (myalgia and phlebitis n = 2; thrombocytopenia n = 1) and progressive disease in 5 patients. The results fail to demonstrate efficacy of this regimen of bryostatin 1 in the treatment of NHL. In light of preclinical data that demonstrate synergy between bryostatin 1 and several cytotoxic agents and cytokines, clinical studies to investigate bryostatin 1 in combination are warranted. We also present data to demonstrate that central venous lines may be used in future studies to avoid phlebitis. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11263437

  5. A review of statistical designs for improving the efficiency of phase II studies in oncology.

    PubMed

    Wason, James Ms; Jaki, Thomas

    2016-06-01

    Phase II oncology trials are carried out to assess whether an experimental anti-cancer treatment shows sufficient signs of effectiveness to justify being tested in a phase III trial. Traditionally such trials are conducted as single-arm studies using a binary response rate as the primary endpoint. In this article, we review and contrast alternative approaches for such studies. Each approach uses only data that are necessary for the traditional analysis. We consider two broad classes of methods: ones that aim to improve the efficiency using novel design ideas, such as multi-stage and multi-arm multi-stage designs; and ones that aim to improve the analysis, by making better use of the richness of the data that is ignored in the traditional analysis. The former class of methods provides considerable gains in efficiency but also increases the administrative and logistical issues in running the trial. The second class consists of viable alternatives to the standard analysis that come with little additional requirements and provide considerable gains in efficiency. PMID:26031358

  6. GERDA phase II detectors: Behind the production and characterisation at low background conditions

    SciTech Connect

    Maneschg, Werner; Collaboration: GERDA Collaboration; and others

    2013-08-08

    The low background GERmanium Detector Array (GERDA) at Laboratori Nazionali del Gran Sasso (LNGS) is designed to search for the rare neutrinoless double beta decay (0νββ) in {sup 76}Ge. Bare germanium diodes are operated in liquid argon which is used as coolant, as passive and soon active as well shield against external radiation. Currently, Phase I of the experiment is running using ∼15 kg of co-axial High Purity Germanium diodes. In order to increase the sensitivity of the experiment 30 Broad Energy Germanium (BEGe) diodes will be added within 2013. This presentation reviews the production chain of the new BEGe detectors from isotopic enrichment to diode production and testing. As demonstrated all steps were carefully planned in order to minimize the exposure of the enriched germanium to cosmic radiation. Following this premise, acceptance and characterisation measurement of the newly produced diodes have been performed within the HEROICA project in the Belgian underground laboratory HADES close to the diode manufacturer. The test program and the results from a subset of the recently terminated GERDA Phase II BEGe survey will be presented.

  7. A phase II trial of sequential ribonucleotide reductase inhibition in aggressive myeloproliferative neoplasms

    PubMed Central

    Zeidner, Joshua F.; Karp, Judith E.; Blackford, Amanda L.; Smith, B. Douglas; Gojo, Ivana; Gore, Steven D.; Levis, Mark J.; Carraway, Hetty E.; Greer, Jacqueline M.; Ivy, S. Percy; Pratz, Keith W.; McDevitt, Michael A.

    2014-01-01

    Myeloproliferative neoplasms are a varied group of disorders that can have prolonged chronic phases, but eventually accelerate and can transform into a secondary acute myeloid leukemia that is ultimately fatal. Triapine is a novel inhibitor of the M2 subunit of ribonucleotide reductase. Sequential inhibition of ribonucleotide reductase with triapine and an M1 ribonucleotide reductase inhibitor (fludarabine) was noted to be safe, and led to a 29% complete plus partial response rate in myeloproliferative neoplasms. This article reports the findings of a phase II trial of triapine (105 mg/m2/day) followed by fludarabine (30 mg/m2/day) daily for 5 consecutive days in 37 patients with accelerated myeloproliferative neoplasms and secondary acute myeloid leukemia. The overall response rate was 49% (18/37), with a complete remission rate of 24% (9/37). Overall response rates and complete remissions were seen in all disease subsets, including secondary acute myeloid leukemia, in which the overall response rate and complete remission rate were 48% and 33%, respectively. All patients with known JAK2 V617F mutations (6/6) responded. The median overall survival of the entire cohort was 6.9 months, with a median overall survival of both overall responders and complete responders of 10.6 months. These data further demonstrate the promise of sequential inhibition of ribonucleotide reductase in patients with accelerated myeloproliferative neoplasms and secondary acute myeloid leukemia. This study was registered with clinicaltrials.gov (NCT00381550). PMID:24362550

  8. Kinetics of hepatic phase I and II biotransformation reactions in eight finfish species.

    PubMed

    González, Jaime Fernando; Reimschuessel, Renate; Shaikh, Badar; Kane, Andrew S

    2009-01-01

    Hepatic microsomes and cytosols of channel catfish (Ictalurus punctatus), rainbow trout (Oncorhynchus mykiss), Atlantic salmon (Salmo salar), red tilapia (Oreochromis sp.), largemouth bass (Micropterussalmoides), striped bass (Morone saxatilis), hybrid striped bass (M. saxatilis x M. crysops), and bluegill (Lepomis macrochuris) (n=8) were used to study the kinetics of phase I (ECOD, EROD, PROD, BROD) and phase II (UDP-glucuronosyltransferase (UDPGT)-, sulfotransferase (ST)- and glutathione-s-transferase (GST)-mediated) reactions. The best catalytic efficiency for ECOD and GST activities was performed by channel catfish, Atlantic salmon, rainbow trout and tilapia. The highest EROD catalytic efficiency was for Atlantic salmon. None of the species had either PROD or BROD activities. Rainbow trout had very similar UDPGT catalytic efficiency to tilapia, channel catfish, Atlantic salmon, largemouth bass and bluegill. Sulfotransferase conjugation had no significant differences among the species. In summary, tilapia, channel catfish, Atlantic salmon and rainbow trout had the best biotransforming capabilities; striped bass, hybrid striped bass and bluegill were low metabolizers and largemouth bass shared some capabilities with both groups.

  9. Silicon strip tracking detector development and prototyping for the Phase-II upgrade of the ATLAS experiment

    NASA Astrophysics Data System (ADS)

    Kuehn, S.

    2016-07-01

    In about ten years from now, the Phase-II upgrade of the LHC will be carried out. Due to increased luminosity, a severe radiation dose and high particle rates will occur for the experiments. In consequence, several detector components will have to be upgraded. In the ATLAS experiment, the current inner detector will be replaced by an all-silicon tracking detector with the goal of at least delivering the present detector performance also in the harsh Phase-II LHC conditions. This report presents the current planning and results from first prototype measurements of the upgrade silicon strip tracking detector.

  10. Advanced Simulation Capability for Environmental Management - Current Status and Phase II Demonstration Results - 13161

    SciTech Connect

    Seitz, Roger R.; Flach, Greg; Freshley, Mark D.; Freedman, Vicky; Gorton, Ian; Dixon, Paul; Moulton, J. David; Hubbard, Susan S.; Faybishenko, Boris; Steefel, Carl I.; Finsterle, Stefan; Marble, Justin

    2013-07-01

    The U.S. Department of Energy (US DOE) Office of Environmental Management (EM), Office of Soil and Groundwater, is supporting development of the Advanced Simulation Capability for Environmental Management (ASCEM). ASCEM is a state-of-the-art scientific tool and approach for understanding and predicting contaminant fate and transport in natural and engineered systems. The modular and open source high-performance computing tool facilitates integrated approaches to modeling and site characterization that enable robust and standardized assessments of performance and risk for EM cleanup and closure activities. The ASCEM project continues to make significant progress in development of computer software capabilities with an emphasis on integration of capabilities in FY12. Capability development is occurring for both the Platform and Integrated Tool-sets and High-Performance Computing (HPC) Multi-process Simulator. The Platform capabilities provide the user interface and tools for end-to-end model development, starting with definition of the conceptual model, management of data for model input, model calibration and uncertainty analysis, and processing of model output, including visualization. The HPC capabilities target increased functionality of process model representations, tool-sets for interaction with Platform, and verification and model confidence testing. The Platform and HPC capabilities are being tested and evaluated for EM applications in a set of demonstrations as part of Site Applications Thrust Area activities. The Phase I demonstration focusing on individual capabilities of the initial tool-sets was completed in 2010. The Phase II demonstration completed in 2012 focused on showcasing integrated ASCEM capabilities. For Phase II, the Hanford Site deep vadose zone (BC Cribs) served as an application site for an end-to-end demonstration of capabilities, with emphasis on integration and linkages between the Platform and HPC components. Other demonstrations

  11. The Potential Economic Impact of Electricity Restructuring in the State of Oklahoma: Phase II Report

    SciTech Connect

    Hadley, SW

    2001-10-30

    Because of the recent experiences of several states undergoing restructuring (e.g., higher prices, greater volatility, lower reliability), concerns have been raised in states currently considering restructuring as to whether their systems are equally vulnerable. Factors such as local generation costs, transmission constraints, market concentration, and market design can all play a role in the success or failure of the market. These factors along with the mix of generation capacity supplying the state will influence the relative prices paid by consumers. The purpose of this project is to provide a model and process to evaluate the potential price and economic impacts of restructuring the Oklahoma electric industry. The Phase I report concentrated on providing an analysis of the Oklahoma system in the near-term, using only present generation resources and customer demands. This Phase II study analyzed the Oklahoma power market in 2010, incorporating the potential of new generation resources and customer responses. Five key findings of this Phase II were made: (1) Projected expansion in generating capacity exceeds by over 3,000 MW the demands within the state plus the amount that could be exported with the current transmission system. (2) Even with reduced new plant construction, most new plants could lose money (although residential consumers would see lower rates) unless they have sufficient market power to raise their prices without losing significant market share (Figure S-1). (3) If new plants can raise prices to stay profitable, existing low-cost coal and hydro plants will have very high profits. Average prices to customers could be 5% to 25% higher than regulated rates (Figure S-1). If the coal and hydro plants are priced at cost-based rates (through long-term contracts or continued regulation) while all other plants use market-based rates then prices are lower. (4) Customer response to real-time prices can lower the peak capacity requirements by around 9

  12. Spin Forming Aluminum Crew Module (CM) Metallic Aft Pressure Vessel Bulkhead (APVBH) - Phase II

    NASA Technical Reports Server (NTRS)

    Hoffman, Eric K.; Domack, Marcia S.; Torres, Pablo D.; McGill, Preston B.; Tayon, Wesley A.; Bennett, Jay E.; Murphy, Joseph T.

    2015-01-01

    The principal focus of this project was to assist the Multi-Purpose Crew Vehicle (MPCV) program in developing a spin forming fabrication process for manufacture of the Orion crew module (CM) aft pressure vessel bulkhead. The spin forming process will enable a single piece aluminum (Al) alloy 2219 aft bulkhead resulting in the elimination of the current multiple piece welded construction, simplify CM fabrication, and lead to an enhanced design. Phase I (NASA TM-2014-218163, (1)) of this assessment explored spin forming the single-piece CM forward pressure vessel bulkhead. The MPCV Program and Lockheed Martin (LM) recently made two critical decisions relative to the NESC Phase I work scope: (1) LM selected the spin forming process to manufacture a singlepiece aft bulkhead for the Orion CM, and (2) the aft bulkhead will be manufactured from Al 2219. Based on the Program's new emphasis related to the spin forming process, the NESC was asked to conduct a Phase II assessment to assist in the LM manufacture of the aft bulkhead and to conduct a feasibility study into spin forming the Orion CM cone. This activity was approved on June 19, 2013. Dr. Robert Piascik, NASA Technical Fellow for Materials at the Langley Research Center (LaRC), was selected to lead this assessment. The project plan was approved by the NASA Engineering and Safety Center (NESC) Review Board (NRB) on July 18, 2013. The primary stakeholders for this assessment are the NASA and LM MPCV Program offices. Additional benefactors are commercial launch providers developing CM concepts.

  13. Spin Forming Aluminum Crew Module (CM) Metallic Aft Pressure Vessel Bulkhead (APVBH) - Phase II

    NASA Technical Reports Server (NTRS)

    Hoffman, Eric K.; Domack, Marcia S.; Torres, Pablo D.; McGill, Preston B.; Tayon, Wesley A.; Bennett, Jay E.; Murphy, Joseph T.

    2015-01-01

    The principal focus of this project was to assist the Multi-Purpose Crew Vehicle (MPCV) Program in developing a spin forming fabrication process for manufacture of the Orion crew module (CM) aft pressure vessel bulkhead. The spin forming process will enable a single piece aluminum (Al) alloy 2219 aft bulkhead resulting in the elimination of the current multiple piece welded construction, simplify CM fabrication, and lead to an enhanced design. Phase I (NASA TM-2014-218163 (1)) of this assessment explored spin forming the single-piece CM forward pressure vessel bulkhead. The Orion MPCV Program and Lockheed Martin (LM) recently made two critical decisions relative to the NESC Phase I work scope: (1) LM selected the spin forming process to manufacture a single-piece aft bulkhead for the Orion CM, and (2) the aft bulkhead will be manufactured from Al 2219. Based on the Program's new emphasis related to the spin forming process, the NESC was asked to conduct a Phase II assessment to assist in the LM manufacture of the aft bulkhead and to conduct a feasibility study into spin forming the Orion CM cone. This activity was approved on June 19, 2013. Dr. Robert Piascik, NASA Technical Fellow for Materials at the Langley Research Center (LaRC), was selected to lead this assessment. The project plan was approved by the NASA Engineering and Safety Center (NESC) Review Board (NRB) on July 18, 2013. The primary stakeholders for this assessment were the NASA and LM MPCV Program offices. Additional benefactors are commercial launch providers developing CM concepts.

  14. Synthesis, structural characterization and antioxidant/anti-inflammatory activity of pentacoordinated bis(isoselenocyanato) and bis(isothiocyanato) Cu II and Ni II complexes with Me 5dien: Crystal structure of [Cu(Me 5dien)(NCSe) 2

    NASA Astrophysics Data System (ADS)

    Georgousis, Zacharias D.; Christidis, Panayiotis C.; Hadjipavlou-Litina, Dimitra; Bolos, Christos A.

    2007-06-01

    Complexes of the general formula [M(Me 5dien)X 2] [where M = Cu II and Ni II, Me 5dien = N, N, N', N″, N″- pentamethyldiethylenetriamine and X = (SCN -) or (SeCN -)] have been synthesized and characterized by elemental analyses, infrared and electronic spectroscopy, magnetic moment and molar conductivity measurements and X-ray crystallography. The crystal structure of [Cu(Me 5dien)(NCSe) 2] revealed the tridentate coordination of Me 5dien and the N-terminal coordination of two SeCN ligands to the Cu II ion. The latter adopts a distorted square pyramidal geometry, with the basal positions occupied by the three nitrogen atoms of Me 5dien and by the nitrogen atom of one isoselenocyanate ligand. The apical position is occupied by the nitrogen atom of the second isoselenocyanate ligand. Infrared spectra of the complexes confirmed the N-terminal coordination of the pseudohalides and the tridentate coordination of the triamine. Electronic spectra were all consistent with five-coordinate square pyramidal geometries. The complexes are monomeric, paramagnetic and non-electrolytes in MeOH, but 1:1 electrolytes in DMSO. The complexes were tested for antioxidant/anti-inflammatory activity. The presence of a isoselenocyanato (NCSe) group leads to higher reducing activity in comparison to the isothiocyanato (NCS) group. The nature of the metal plays also an important role to this activity. Complex [Ni(Me 5dien)(NCSe) 2] is more potent than the corresponding copper complex and offers 44.7% protection against the carrageenin-induced rat paw edema.

  15. Phase I/randomized phase II study of afatinib, an irreversible ErbB family blocker, with or without protracted temozolomide in adults with recurrent glioblastoma

    PubMed Central

    Reardon, David A.; Nabors, Louis B.; Mason, Warren P.; Perry, James R.; Shapiro, William; Kavan, Petr; Mathieu, David; Phuphanich, Surasak; Cseh, Agnieszka; Fu, Yali; Cong, Julie; Wind, Sven; Eisenstat, David D.

    2015-01-01

    Background This phase I/II trial evaluated the maximum tolerated dose (MTD) and pharmacokinetics of afatinib plus temozolomide as well as the efficacy and safety of afatinib as monotherapy (A) or with temozolomide (AT) vs temozolomide monotherapy (T) in patients with recurrent glioblastoma (GBM). Methods Phase I followed a traditional 3 + 3 dose-escalation design to determine MTD. Treatment cohorts were: afatinib 20, 40, and 50 mg/day (plus temozolomide 75 mg/m2/day for 21 days per 28-day cycle). In phase II, participants were randomized (stratified by age and KPS) to receive A, T or AT; A was dosed at 40 mg/day and T at 75 mg/m2 for 21 of 28 days. Primary endpoint was progression-free survival rate at 6 months (PFS-6). Participants were treated until intolerable adverse events (AEs) or disease progression. Results Recommended phase II dose was 40 mg/day (A) + T based on safety data from phase I (n = 32). Most frequent AEs in phase II (n = 119) were diarrhea (71% [A], 82% [AT]) and rash (71% [A] and 69% [AT]). Afatinib and temozolomide pharmacokinetics were unaffected by coadministration. Independently assessed PFS-6 rate was 3% (A), 10% (AT), and 23% (T). Median PFS was longer in afatinib-treated participants with epidermal growth factor receptor (EFGR) vIII-positive tumors versus EGFRvIII-negative tumors. Best overall response included partial response in 1 (A), 2 (AT), and 4 (T) participants and stable disease in 14 (A), 14 (AT), and 21 (T) participants. Conclusions Afatinib has a manageable safety profile but limited single-agent activity in unselected recurrent GBM patients. PMID:25140039

  16. Lamellar-to-hexagonal/sub II/ phase transitions in the plasma membrane of isolated protoplasts after freeze-induced dehydration

    SciTech Connect

    Gordon-Kamm, W.J.; Steponkus, P.L.

    1984-10-01

    In protoplasts isolated from nonacclimated rye leaves (Secale cereale L. cultivar Puma), cooling to -10/sup 0/C at a rate of 1/sup 0/C/min results in extensive freeze-induced dehydration (osmotic contraction), and injury is manifested as the loss of osmotic responsiveness during warming. Under these conditions, several changes were observed in the freeze-fracture morphology of the plasma membrane. These included (i) lateral phase separations in the plasma membrane, (ii) aparticulate lamellae lying next to the plasma membrane, and (iii) regions of the plasma membrane and associated lamellae in various stages of lamellar-to-hexagonal/sub II/ transition. These morphological changes also were observed after equilibration in 5.37 osmolal sorbitol at 0/sup 0/C, which produced a similar extent of dehydration as did freezing to -10/sup 0/C. In contrast, only small areas of lateral phase separation in the plasma membrane, with no observable aparticulate lamellae or hexagonal/sub II/ configurations, were observed in protoplasts supercooled to -10/sup 0/C. Therefore, freeze-induced lamellar-to-hexagonal/sub II/ phase transitions in the plasma membrane are a consequence of dehydration rather than subzero temperature per se. When suspensions of protoplasts isolated from cold-acclimated leaves were frozen to -10/sup 0/C, no injury was incurred, and hexagonal/sub II/ phase transitions were not observed. No hexagonal/sub II/ phase was observed even at -35/sup 0/C, though acclimated protoplasts are injured at this temperature. 34 references, 2 figures.

  17. Alterations in oxidant/antioxidant balance, high-mobility group box 1 protein and acute phase response in cross-bred suckling piglets suffering from rotaviral enteritis.

    PubMed

    Kumar De, Ujjwal; Mukherjee, Reena; Nandi, Sukdeb; Patel, Bhimnere Hanumatnagouda Manjunatha; Dimri, Umesh; Ravishankar, Chintu; Verma, Ashok Kumar

    2014-10-01

    Rotaviral enteritis has emerged as a major cause of morbidity and mortality in piglets during their post-natal life. The present study was carried out to examine high-mobility group box 1 (HMGB1) protein, acute phase response and oxidative stress indices in the serum of suckling piglets suffering from enteritis with or without association of porcine group A rotavirus infection. The present investigation utilized 23 clinical cases with signs of acute enteritis and 12 more healthy piglets of a similar age group as control animals. Out of 23 enteritis cases, 12 cases were found to be positive for porcine group A rotavirus infection as confirmed by reverse transcription-polymerase chain reaction (RT-PCR) using specific primers for group A rotavirus, and the rest were found negative. The acute enteritis cases in piglets were associated with an elevated level of HMGB1 protein and serum haptoglobin and ceruloplasmin suggestive of an acute phase response. Among the oxidative stress indices, the concentrations of malondialdehyde (MDA) and nitric oxide (NO) in serum were significantly increased. A pronounced drop of total antioxidant capacity and the activity of antioxidant enzymes such as catalase and superoxide dismutase in the serum of piglets suffering from acute enteritis compared to healthy ones were also noticed. The alterations in HMGB1 protein, acute phase response and oxidative stress indices were more pronounced in cases with the involvement of porcine rotavirus as compared to rotavirus-negative cases. It is concluded that HMGB1 protein, markers of oxidative stress and acute phase proteins might play an important role in the aetiopathogenesis of porcine diarrhoea caused by rotavirus and might be true markers in diagnosing the conditions leading to the extension of the prompt and effective therapeutic care.

  18. Demonstration Assessment of Light-Emitting Diode (LED) Roadway Lighting, I-35W Bridge, Minneapolis, Minnesota, Phase II Report

    SciTech Connect

    Kinzey, B. R.; Davis, R. G.

    2014-09-30

    On the I-35W Bridge in Minneapolis, Minnesota, the GATEWAY program conducted a two-phase demonstration of LED roadway lighting on the main span, which is one of the country's oldest continuously operated exterior LED lighting installations. The Phase II report documents longer-term performance of the LED lighting system that was installed in 2008, and is the first report on the longer-term performance of LED lighting in the field.

  19. Phase I/II Study of Nilotinib/Ruxolitinb Therapy for TKI Resistant Ph-Leukemia

    ClinicalTrials.gov

    2016-03-04

    Chronic Phase Chronic Myeloid Leukemia; Accelerated Phase Chronic Myeloid Leukemia; Blastic Phase Chronic Myeloid Leukemia; Philadelphia Positive Acute Lymphoblastic Leukemia; Resistant to Tyrosine Kinase Inhibitor Therapy

  20. A new ternary copper(II) complex derived from 2-(2";-pyridyl)benzimidazole and glycylglycine: Synthesis, characterization, DNA binding and cleavage, antioxidation and HSA interaction

    NASA Astrophysics Data System (ADS)

    Fu, Xia-Bing; Lin, Zi-Hua; Liu, Hai-Feng; Le, Xue-Yi

    2014-03-01

    A new ternary copper(II)-dipeptide complex [Cu(glygly)(HPB)(Cl)]ṡ2H2O (glygly = glycylglycine anion, HPB = 2-(2";-pyridyl)benzimidazole) has been synthesized and characterized. The DNA interaction of the complex was studied by spectroscopic methods, viscosity, and electrophoresis measurements. The antioxidant activity was also investigated using the pyrogallol autoxidation assay. Besides, the interaction of the complex with human serum albumin (HSA) in vitro was examined by multispectroscopic techniques. The complex partially intercalated to CT-DNA with a high binding constant (Kb = 7.28 × 105 M-1), and cleaved pBR322 DNA efficiently via an oxidative mechanism in the presence of Vc, with the HO· and O2-rad as the active species, and the SOD as a promoter. Furthermore, the complex shows a considerable SOD-like activity with the IC50 value of 3.8386 μM. The complex exhibits desired binding affinity to HSA, in which hydrogen bond or vander Waals force played a major role. The alterations of HSA secondary structure induced by the complex were confirmed by UV-visible, CD, synchronous fluorescence and 3D fluorescence spectroscopy.

  1. Change of Mandibular Position during Two-Phase Orthodontic Treatment of Skeletal Class II in the Chinese Population

    PubMed Central

    Hägg, Urban; Wong, Ricky Wing Kit; Liao, Chongshan; Yang, Yanqi

    2015-01-01

    The aim of this study was to evaluate the change in mandibular position during a two-phase orthodontic treatment of skeletal Class II malocclusion. Thirty consecutively treated Chinese male adolescents who had undergone two-phase treatment with Herbst appliance and fixed appliance and fulfilled the specific selection criteria were sampled. Cephalograms taken at T0 (before treatment), T1 (at the end of functional appliance treatment), and T2 (at the end of fixed appliance treatment) were analyzed. The change in sagittal positioning of the mandible was 6.8±3.44 mm in phase I (T0-T1), 0.4±2.79 mm in phase II (T1-T2), and 7.2±4.61 mm in total. The mandible came forward in 100% of the patients at T1. In phase II, it came forward in one-third (positive group) remained unchanged in one-third (stable group) and went backward in one-third (negative group) of the patients. At T2, it came forward twice as much in the positive group compared to the negative group. Mandibular length was significantly increased in 100% of the patients in both phases. In conclusion, during the treatment with functional appliance, the mandibular prognathism increases in all patients, whereas during the treatment with fixed appliance there is no significant change in mandibular prognathism. PMID:25695103

  2. Resampling the N9741 Trial to Compare Tumor Dynamic Versus Conventional End Points in Randomized Phase II Trials

    PubMed Central

    Sharma, Manish R.; Gray, Elizabeth; Goldberg, Richard M.; Sargent, Daniel J.; Karrison, Theodore G.

    2015-01-01

    Purpose The optimal end point for randomized phase II trials of anticancer therapies remains controversial. We simulated phase II trials by resampling patients from N9741, a randomized phase III trial of chemotherapy regimens for metastatic colorectal cancer, and compared the power of various end points to detect the superior therapy (FOLFOX [infusional fluorouracil, leucovorin, and oxaliplatin] had longer overall survival than both IROX [irinotecan plus oxaliplatin] and IFL [irinotecan and bolus fluorouracil plus leucovorin]). Methods Tumor measurements and progression-free survival (PFS) data were obtained for 1,471 patients; 1,002 had consistently measured tumors and were resampled (5,000 replicates) to simulate two-arm, randomized phase II trials with α = 0.10 (one sided) and 20 to 80 patients per arm. End points included log ratio of tumor size at 6, 12, and 18 weeks relative to baseline; time to tumor growth (TTG), estimated using a nonlinear mixed-effects model; and PFS. Arms were compared using rank sum tests for log ratio and TTG and a log-rank test for PFS. Results For FOLFOX versus IFL, TTG and PFS had similar power, with both exceeding the power of log ratio at 18 weeks; for FOLFOX versus IROX, TTG and log ratio at 18 weeks had similar power, with both exceeding the power of PFS. The best end points exhibited > 80% power with 60 to 80 patients per arm. Conclusion TTG is a powerful end point for randomized phase II trials of cytotoxic therapies in metastatic colorectal cancer; it was either comparable or superior to PFS and log ratio at 18 weeks. Additional studies will be needed to clarify the potential of TTG as a phase II end point. PMID:25349295

  3. Advanced Start of Combustion Sensor Phases I and II-A: Feasibility Demonstration, Design and Optimization

    SciTech Connect

    Chad Smutzer

    2010-01-31

    Homogeneous Compressed Charge Ignition (HCCI) has elevated the need for Start of Combustion (SOC) sensors. HCCI engines have been the exciting focus of engine research recently, primarily because HCCI offers higher thermal efficiency than the conventional Spark Ignition (SI) engines and significantly lower NOx and soot emissions than conventional Compression Ignition (CI) engines, and could be fuel neutral. HCCI has the potential to unify all the internal combustion engine technology to achieve the high-efficiency, low-emission goal. However, these advantages do not come easy. It is well known that the problems encountered with HCCI combustion center on the difficulty of controlling the Start of Combustion. TIAX has an SOC sensor under development which has shown promise. In previous work, including a DOE-sponsored SBIR project, TIAX has developed an accelerometer-based method which was able to determine SOC within a few degrees crank angle for a range of operating conditions. A signal processing protocol allows reconstruction of the combustion pressure event signal imbedded in the background engine vibration recorded by the accelerometer. From this reconstructed pressure trace, an algorithm locates the SOC. This SOC sensor approach is nonintrusive, rugged, and is particularly robust when the pressure event is strong relative to background engine vibration (at medium to high engine load). Phase I of this project refined the previously developed technology with an engine-generic and robust algorithm. The objective of the Phase I research was to answer two fundamental questions: Can the accelerometer-based SOC sensor provide adequate SOC event capture to control an HCCI engine in a feedback loop? And, will the sensor system meet cost, durability, and software efficiency (speed) targets? Based upon the results, the answer to both questions was 'YES'. The objective of Phase II-A was to complete the parameter optimization of the SOC sensor prototype in order to reach a

  4. Nimotuzumab combined with radiotherapy for esophageal cancer: preliminary study of a Phase II clinical trial

    PubMed Central

    Liang, Jun; E, Mingyan; Wu, Gang; Zhao, Lujun; Li, Xia; Xiu, Xia; Li, Ning; Chen, Bo; Hui, Zhouguang; Lv, Jima; Fang, Hui; Tang, Yu; Bi, Nan; Wang, Wenqing; Zhai, Yirui; Li, Tao; Chen, Dongfu; Zou, Shuangmei; Lu, Ning; Perez-Rodríguez, Rolando; Zheng, Junqi; Wang, Luhua

    2013-01-01

    Objective To determine the safety and therapeutic effects of nimotuzumab (h-R3) combined with radiotherapy in esophageal cancer. Methods This Phase II clinical trial involved 42 patients with stage II (inoperable or refused surgery) to stage IV (supraclavicular lymph node metastasis only) esophageal cancers treated between November 2008 and July 2010. All patients had squamous cell carcinomas, and all received three-dimensional conformal radiotherapy and 200 mg nimotuzumab per week during radiotherapy. Results There were 9, 25, and 8 patients with stage II, III and IV disease, respectively. All except two patients received 50–70 Gy radiation; 37 patients (88.1%) received more than five nimotuzumab doses. Grade III toxicities (21.4% of all adverse events) included esophagitis and gastrointestinal, dermatological and hematological toxicities. Complete response, partial response, stable disease, and progressive disease were observed in 0, 22 (52.4%), 17 (40.5%) and 3 (7.1%) patients at 1 month after the treatment. The epidermal growth factor receptor (EGFR) overexpression rate was 95.2%. After a median follow-up of 37 months, the median survival time (MST) was 14 months. The 2 year and 3 year overall survival (OS) rates were 33.3% and 26.2%, respectively. The median progression-free survival (PFS) time was 10 months. The 2 year and 3 year PFS rates were 24.5% and 22.1%, respectively. The MST in the 13 patients with (+++) EGFR expression (group A) and 7 patients with (++) EGFR expression (group B) was 15 and 11 months, respectively. The 2 year and 3 year OS rates were 46.2% and 38.5% in group A and 28.6% and 28.6% in group B, respectively (P = 0.405). Conclusion Although concurrent chemoradiotherapy was the standard care for locally advanced esophageal cancer, radiotherapy was the choice for those who were refused or could not tolerate chemoradiotherapy. Our study shows that nimotuzumab combined with radiotherapy was well tolerated in patients with esophageal cancer

  5. Reversed-phase high-performance liquid chromatography of the stereoisomers of some sweetener peptides with a helical nickel(II) chelate in the mobile phase.

    PubMed

    Bazylak, G

    1994-05-13

    The use of a chiral mobile phase additive in the form of the helically distorted, square-planar, chiral nickel(II) chelate dl-[4,4'-(1-methyl-2-propylethane-1,2-diyldiimino)bis(pent-3 -en-2- onato)]nickel(II) was investigated for the resolution of optical isomers of dipeptide-type sweeteners, viz., aspartame, alitame and antiaspartame, and some of their decomposition products, e.g., diketopiperazines. The chiral discrimination mechanism for the solutes was elucidated. The proposed chiral RP-HPLC system was applied to the stereoselective determination of aspartame impurities in samples of its commercial dietetic and pharmaceutical formulations.

  6. DOE SBIR Phase II Final Report: Distributed Relevance Ranking in Heterogeneous Document Collections

    SciTech Connect

    Abe Lederman

    2007-01-08

    This report contains the comprehensive summary of the work performed on the SBIR Phase II project (“Distributed Relevance Ranking in Heterogeneous Document Collections”) at Deep Web Technologies (http://www.deepwebtech.com). We have successfully completed all of the tasks defined in our SBIR Proposal work plan (See Table 1 - Phase II Tasks Status). The project was completed on schedule and we have successfully deployed an initial production release of the software architecture at DOE-OSTI for the Science.gov Alliance's search portal (http://www.science.gov). We have implemented a set of grid services that supports the extraction, filtering, aggregation, and presentation of search results from numerous heterogeneous document collections. Illustration 3 depicts the services required to perform QuickRank™ filtering of content as defined in our architecture documentation. Functionality that has been implemented is indicated by the services highlighted in green. We have successfully tested our implementation in a multi-node grid deployment both within the Deep Web Technologies offices, and in a heterogeneous geographically distributed grid environment. We have performed a series of load tests in which we successfully simulated 100 concurrent users submitting search requests to the system. This testing was performed on deployments of one, two, and three node grids with services distributed in a number of different configurations. The preliminary results from these tests indicate that our architecture will scale well across multi-node grid deployments, but more work will be needed, beyond the scope of this project, to perform testing and experimentation to determine scalability and resiliency requirements. We are pleased to report that a production quality version (1.4) of the science.gov Alliance's search portal based on our grid architecture was released in June of 2006. This demonstration portal is currently available at http://science.gov/search30 . The portal

  7. Anti-IP-10 antibody (BMS-936557) for ulcerative colitis: a phase II randomised study

    PubMed Central

    Mayer, Lloyd; Sandborn, William J; Stepanov, Yuriy; Geboes, Karel; Hardi, Robert; Yellin, Michael; Tao, Xiaolu; Xu, Li An; Salter-Cid, Luisa; Gujrathi, Sheila; Aranda, Richard; Luo, Allison Y

    2014-01-01

    Objective Interferon-γ-inducible protein-10 (IP-10 or CXCL10) plays a role in inflammatory cell migration and epithelial cell survival and migration. It is expressed in higher levels in the colonic tissue and plasma of patients with ulcerative colitis (UC). This phase II study assessed the efficacy and safety of BMS-936557, a fully human, monoclonal antibody to IP-10, in the treatment of moderately-to-severely active UC. Design In this 8-week, phase II, double-blind, multicentre, randomised study, patients with active UC received placebo or BMS-936557 (10 mg/kg) intravenously every other week. The primary endpoint was the rate of clinical response at Day 57; clinical remission and mucosal healing rates were secondary endpoints. Post hoc analyses evaluated the drug exposure–response relationship and histological improvement. Results 109 patients were included (BMS-936557: n=55; placebo: n=54). Prespecified primary and secondary endpoints were not met; clinical response rate at Day 57 was 52.7% versus 35.2% for BMS-936557 versus placebo (p=0.083), and clinical remission and mucosal healing rates were 18.2% versus 16.7% (p=1.00) and 41.8% versus 35.2% (p=0.556), respectively. However, higher BMS-936557 steady-state trough concentration (Cminss) was associated with increased clinical response (87.5% vs 37.0% (p<0.001) for patients with Cminss 108–235 μg/ml vs placebo) and histological improvements (73.0% vs 41.0%; p=0.004). Infections occurred in 7 (12.7%) BMS-936557-treated patients and 3 (5.8%) placebo-treated patients. 2 (3.6%) BMS-936557 patients discontinued due to adverse events. Conclusions Anti-IP-10 antibody, BMS-936557, is a potentially effective therapy for moderately-to-severely active UC. Higher drug exposure correlated with increasing clinical response and histological improvement. Further dose–response studies are warranted. Clinical Trial Registration Number: ClinicalTrials.gov NCT00656890. PMID:23461895

  8. Ultra-secure RF Tags for Safeguards and Security - SBIR Phase II Final Report

    SciTech Connect

    Twogood, Richard E

    2015-01-27

    This is the Final Report for the DOE Phase II SBIR project “Ultra-secure RF Tags for Safeguards and Security.” The topics covered herein include technical progress made, progress against the planned milestones and deliverables, project outcomes (results, collaborations, intellectual property, etc.), and a discussion on future expectations of deployment and impacts of the results of this work. In brief, all planned work for the project was successfully completed, on or ahead of schedule and on budget. The major accomplishment was the successful development of a very advanced passive ultra-secure RFID tag system with combined security features unmatched by any commercially available ones. These tags have high-level dynamic encrypted authentication, a novel tamper-proofing mechanism, system software including graphical user interfaces and networking, and integration with a fiber-optic seal mechanism. This is all accomplished passively (with no battery) by incorporating sophisticated hardware in the tag which harvests the energy from the RFID readers that are interrogating the tag. Based on initial feedback (and deployments) at DOE’s Lawrence Livermore National Laboratory (LLNL), it is anticipated these tags and their offspring will meet DOE and international community needs for highly secure RFID systems. Beyond the accomplishment of those original objectives for the ultra-secure RF tags, major new spin-off thrusts from the original work were identified and successfully pursued with the cognizance of the DOE sponsor office. In particular, new classes of less sophisticated RFID tags were developed whose lineage derives from the core R&D thrusts of this SBIR. These RF “tag variants” have some, but not necessarily all, of the advanced characteristics described above and can therefore be less expensive and meet far wider markets. With customer pull from the DOE and its national laboratories, new RFID tags and systems (including custom readers and software) for

  9. EXPERIMENTAL EVALUATION OF CHEMICAL SEQUESTRATION OF CARBON DIOXIDE IN DEEP AQUIFER MEDIA - PHASE II

    SciTech Connect

    Neeraj Gupta; Bruce Sass; Jennifer Ickes

    2000-11-28

    In 1998 Battelle was selected by the U.S. Department of Energy's (DOE) National Energy Technology Laboratory (NETL) under a Novel Concepts project grant to continue Phase II research on the feasibility of carbon dioxide (CO{sub 2}) sequestration in deep saline formations. The focus of this investigation is to conduct detailed laboratory experiments to examine factors that may affect chemical sequestration of CO{sub 2} in deep saline formations. Reactions between sandstone and other geologic media from potential host reservoirs, brine solutions, and CO{sub 2} are being investigated under high-pressure conditions. Some experiments also include sulfur dioxide (SO{sub 2}) gases to evaluate the potential for co-injection of CO{sub 2} and SO{sub 2} related gases in the deep formations. In addition, an assessment of engineering and economic aspects is being conducted. This current Technical Progress Report describes the status of the project as of September 2000. The major activities undertaken during the quarter included several experiments conducted to investigate the effects of pressure, temperature, time, and brine composition on rock samples from potential host reservoirs. Samples (both powder and slab) were taken from the Mt. Simon Sandstone, a potential CO{sub 2} host formation in the Ohio, the Eau Claire Shale, and Rome Dolomite samples that form the caprock for Mt. Simon Sandstone. Also, a sample with high calcium plagioclase content from Frio Formation in Texas was used. In addition, mineral samples for relatively pure Anorthite and glauconite were experimented on with and without the presence of additional clay minerals such as kaolinite and montmorillonite. The experiments were run for one to two months at pressures similar to deep reservoirs and temperatures set at 50 C or 150 C. Several enhancements were made to the experimental equipment to allow for mixing of reactants and to improve sample collection methods. The resulting fluids (gases and liquids) as

  10. Determination of antioxidants by a novel on-line HPLC-cupric reducing antioxidant capacity (CUPRAC) assay with post-column detection.

    PubMed

    Celik, Saliha Esin; Ozyürek, Mustafa; Güçlü, Kubilay; Apak, Reşat

    2010-07-26

    A novel on-line HPLC-cupric reducing antioxidant capacity (CUPRAC) method was developed for the selective determination of polyphenols (flavonoids, simple phenolic and hydroxycinnamic acids) in complex plant matrices. The method combines chromatographic separation, constituent analysis, and post-column identification of antioxidants in plant extracts. The separation of polyphenols was performed on a C18 column using gradient elution with two different mobile phase solutions, i.e., MeOH and 0.2% o-phosphoric acid. The HPLC-separated antioxidant polyphenols in the extracts react with copper(II)-neocuproine (Cu(II)-Nc) reagent in a post-column reaction coil to form a derivative. The reagent is reduced by antioxidants to the copper(I)-neocuproine (Cu(I)-Nc) chelate having maximum absorption at 450 nm. The negative peaks of antioxidant constituents were monitored by measuring the increase in absorbance due to Cu(I)-Nc. The detection limits of polyphenols at 450 nm (in the range of 0.17-3.46 microM) after post-column derivatization were comparable to those at 280 nm UV detection without derivatization. The developed method was successfully applied to the identification of antioxidant compounds in crude extracts of Camellia sinensis, Origanum marjorana and Mentha. The method is rapid, inexpensive, versatile, non-laborious, uses stable reagents, and enables the on-line qualitative and quantitative estimation of antioxidant constituents of complex plant samples.

  11. Synthesis, Characterization, Antioxidant, and Antibacterial Studies of Some Metal(II) Complexes of Tetradentate Schiff Base Ligand: (4E)-4-[(2-{(E)-[1-(2,4-Dihydroxyphenyl)ethylidene]amino}ethyl)imino]pentan-2-one

    PubMed Central

    Ejidike, Ikechukwu P.; Ajibade, Peter A.

    2015-01-01

    Co(II), Ni(II), Cu(II), and Zn(II) complexes of (4E)-4-[(2-{(E)-[1-(2,4-dihydroxyphenyl)ethylidene]amino}ethyl)imino]pentan-2-one have been synthesized and characterized by elemental analyses, molar conductance, electronic and IR spectral studies, and XRD. FTIR confirmed the ligand coordinates the metal ion to form mononuclear complex via the oxygen and nitrogen atoms of the phenolic group and azomethine group, respectively. Tetrahedral geometry is proposed for Co(II) complex and square-planar geometry for Ni(II) and Cu(II) complexes. The antibacterial studies of the compounds were determined and they show that the metal complexes are more active than the free ligands. The antioxidant activity by DPPH and ABTS method was examined and it shows Cu(II); IC50 = 2.31 ± 1.54 µM for DPPH and Co(II); IC50 = 1.83 ± 1.08 µM for ABTS were the most active. PMID:26074738

  12. Toxicity Screening of the ToxCast Phase II Chemical Library Using a Zebrafish Developmental Assay (SOT)

    EPA Science Inventory

    As part of the chemical screening and prioritization research program of the US EPA, the ToxCast Phase II chemicals were assessed using a vertebrate screen for developmental toxicity. Zebrafish embryos (Danio rerio) were exposed in 96-well plates from late-blastula stage (6hr pos...

  13. 75 FR 5279 - Sucker Creek Channel and Floodplain Restoration Project (Phase II), Rogue River-Siskiyou National...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-02

    ...; ] DEPARTMENT OF AGRICULTURE Forest Service Sucker Creek Channel and Floodplain Restoration Project (Phase II..., Oregon. Purpose and Need for Action The purpose of the Sucker Creek Channel and Floodplain Restoration... show that the stream channel was more sinuous and contained a larger floodplain, characteristic of...

  14. 75 FR 56533 - Wireless Telecommunications Bureau Postpones Auction of 218-219 MHz Service and Phase II 220 MHz...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-16

    ... COMMISSION Wireless Telecommunications Bureau Postpones Auction of 218-219 MHz Service and Phase II 220 MHz... document announces the postponement of Auction 89. FOR FURTHER INFORMATION CONTACT: Wireless... related documents are also available on the Internet at the Commission's Web site:...

  15. An Evaluation of the Local Initiatives Support Corporation: Findings from Phase II. Discussion Paper D86-1.

    ERIC Educational Resources Information Center

    Vidal, Avis C.; And Others

    This report summarizes the preliminary results of Phase II of an evaluation of the Local Initiatives Support Corporation (LISC), a national nonprofit lending and grantmaking institution founded in 1980 to draw private sector financial and technical resources into the development of deteriorated communities and neighborhoods. In this second phase…

  16. Interaction-Point Phase-Space Characterization using Single-Beam and Luminous-Region Measurements at PEP-II

    SciTech Connect

    Kozanecki, W; Bevan, A.J.; Viaud, B.F.; Cai, Y.; Fisher, A.S.; O'Grady, C.; Lindquist, B.; Roodman, A.; J.M.Thompson, M.Weaver; /SLAC

    2008-09-09

    We present an extensive experimental characterization of the e{sup {+-}} phase space at the interaction point of the SLAC PEP-II B-Factory, that combines a detailed mapping of luminous-region observables using the BABAR detector, with stored-beam measurements by accelerator techniques.

  17. Clinical phase I/II research on ultrasound thermo-chemotherapy in oral and maxillofacial-head and neck carcinoma

    NASA Astrophysics Data System (ADS)

    Shen, Guofeng; Ren, Guoxin; Guo, Wei; Chen, Yazhu

    2012-11-01

    The principle of a ultrasound thermo-chemotherapy instrument and the clinical phase I/II research on short-term and long-term therapeutic effect and main side-effect of ultrasound hyperthermia combined with chemotherapy in oral and maxillofacial-head & neck carcinoma by the instrument will be presented in this paper.

  18. Pediatric Phase II Trials of Poly-ICLC in the Management of Newly Diagnosed and Recurrent Brain Tumors

    PubMed Central

    Hartman, Lisa L.R.; Crawford, John R.; Makale, Milan T.; Milburn, Mehrzad; Joshi, Shweta; Salazar, Andres M.; Hasenauer, Beth; VandenBerg, Scott R.; MacDonald, Tobey J.; Durden, Donald L.

    2015-01-01

    Summary Brain tumors are the most common solid tumor diagnosed in childhood that account for significant morbidity and mortality. New therapies are urgently needed; hence, we conducted the first ever prospective open-label phase II trials of the biological response modifier, poly-ICLC, in children with brain tumors. Poly-ICLC is a synthetic double-stranded RNA that has direct antiviral, antineoplastic, and immune adjuvant effects. A total of 47 children representing a variety of brain tumor histopathologic subtypes were treated with poly-ICLC. On the basis of the results of the initial phase II trial, an expanded prospective phase II trial in low-grade glioma (LGG) has been initiated. MRI was used to acquire volume-based measures of tumor response. No dose-limiting toxicities have been observed. In the initial study 3 of 12 subjects with progressive high-grade gliomas (HGGs) responded, and 2 of 4 children with progressive LGG experienced stable disease for 18 to 24 months. In the follow-up LGG phase II study, 2 of 5 LGG patients were stable over 18 months, with 1 stable for 6 months. Overall 5 of 10 LGG patients have responded. On the basis of low toxicity and the promising LGG response, poly-ICLC may be effective for childhood LGG, and the results justify biomarker studies for personalization of poly-ICLC as a single agent or adjuvant. PMID:24309609

  19. ENVIRONMENTAL TECHNOLOGY VERIFICATION REPORT, C. LEE COOK DIVISION, DOVER CORPORATION, STATIC PAC (TM) SYSTEM, PHASE II REPORT

    EPA Science Inventory

    The Environmental Technology Verification report discusses the technology and performance of the Static Pac System, Phase II, natural gas reciprocating compressor rod packing manufactured by the C. Lee Cook Division, Dover Corporation. The Static Pac System is designed to seal th...

  20. Intracerebral administration of CpG oligonucleotide for patients with recurrent glioblastoma: a phase II study.

    PubMed

    Carpentier, Alexandre; Metellus, Philippe; Ursu, Renata; Zohar, Sarah; Lafitte, Francois; Barrié, Maryline; Meng, Yuxia; Richard, Margaretha; Parizot, Christophe; Laigle-Donadey, Florence; Gorochov, Guy; Psimaras, Dimitri; Sanson, Marc; Tibi, Annick; Chinot, Olivier; Carpentier, Antoine F

    2010-04-01

    Immunostimulating oligodeoxynucleotides containing CpG motifs (CpG-ODN) have shown promising efficacy in cancer models when injected locally. In a phase I clinical trial, intratumoral infusions of CpG-ODN in glioblastoma (GBM) patients were well tolerated at doses up to 20 mg. This phase II trial was designed to study the efficacy of a local treatment by CpG-ODN in patients with recurrent GBMs. Patients with recurrent GBM occurring at least 3 months after radiotherapy, and previously treated with 1 or 2 regimens of chemotherapy received 20 mg of CpG-ODN (CpG-28) by convection-enhanced delivery. The primary endpoint was the percentage of patients without tumor progression 6 months after inclusion. Secondary endpoints were tolerance, survival, and radiological response. Thirty-four patients were enrolled in two centers between November 2004 and March 2006. Thirty-one patients received CpG-ODN treatment. The progression-free survival (PFS) at 6 months was 19%. One partial response and 3 minor responses were observed. The median overall survival was 28 weeks. Eight patients (24%) were alive 1 year after inclusion and 5 patients (15%) were alive after 2 years. Treatment was usually well tolerated. As reported previously, the most common toxicities were lymphopenia, mild fever, seizures, and transient neurological worsening. Despite a few cases showing a radiological response, CpG-28 showed modest activity on the 6-month PFS in this patient population. The molecular or clinical characteristics of a subgroup of patients that could potentially benefit from such an approach remain to be defined. PMID:20308317

  1. A Phase II Study of Cixutumumab (IMC-A12, NSC742460) in Advanced Hepatocellular Carcinoma

    PubMed Central

    Abou-Alfa, Ghassan K.; Capanu, Marinela; O’Reilly, Eileen M.; Ma, Jennifer; Chou, Joanne F.; Gansukh, Bolorsukh; Shia, Jinru; Kalin, Marcia; Katz, Seth; Abad, Leslie; Reidy-Lagunes, Diane L.; Kelsen, David P.; Chen, Helen X.; Saltz, Leonard B.

    2014-01-01

    Background and Aims IGF-IR is implicated in hepatic carcinogenesis. This and preliminary evidence of biological activity of anti-IGF-1R monoclonal antibody cixutumumab in phase I trials prompted this phase II study. Methods Patients with advanced HCC, Child-Pugh A-B8, received cixutumumab 6 mg/kg weekly, in a Simon two-stage design study, with the primary endpoints being 4-month PFS and RECIST-defined response rate. Tissue and circulating markers plus different HCC scoring systems were evaluated for correlation with PFS and OS. Results As a result of pre-specified futility criteria, only stage 1 was accrued: N= 24: median age 67.5 years (range 49–83), KPS 80% (70–90%), 20 males (83%), 9 stage III (37%)/15 stage IV (63%), 18 Child-Pugh A (75%), 11 HBV (46%) /10 HCV (42%)/11 alcoholic cirrhosis (46%)/2 NASH (8%), 11 (46%) diabetic. Median number of doses: 7 (range 1–140). Grade 3/4 toxicities > 10% included: diabetes, elevated liver function tests, hyponatremia, and lymphopenia. Four-month PFS was 30% (95% CI 13–48), and there were no objective responses. Median overall survival was 8 months (95%CI 5.8– 14). IGF-R1 staining did not correlate with outcome. Elevated IGFBP-1 correlated with improved PFS (1.2 [95%CI 1–1.4]; p 0.009) and OS (1.2 [95%CI 1.1–1.4]; p 0.003). Conclusions Cixutumumab monotherapy did not have clinically meaningful activity in this unselected HCC population. Grade 3–4 hyperglycemia occurred in 46% of patients. Elevated IGFBP-1 correlated with improved PFS and OS. PMID:24045151

  2. Phase I to II cross-induction of xenobiotic metabolizing enzymes: A feedforward control mechanism for potential hormetic responses

    SciTech Connect

    Zhang Qiang Pi Jingbo; Woods, Courtney G.; Andersen, Melvin E.

    2009-06-15

    Hormetic responses to xenobiotic exposure likely occur as a result of overcompensation by the homeostatic control systems operating in biological organisms. However, the mechanisms underlying overcompensation that leads to hormesis are still unclear. A well-known homeostatic circuit in the cell is the gene induction network comprising phase I, II and III metabolizing enzymes, which are responsible for xenobiotic detoxification, and in many cases, bioactivation. By formulating a differential equation-based computational model, we investigated in this study whether hormesis can arise from the operation of this gene/enzyme network. The model consists of two feedback and one feedforward controls. With the phase I negative feedback control, xenobiotic X activates nuclear receptors to induce cytochrome P450 enzyme, which bioactivates X into a reactive metabolite X'. With the phase II negative feedback control, X' activates transcription factor Nrf2 to induce phase II enzymes such as glutathione S-transferase and glutamate cysteine ligase, etc., which participate in a set of reactions that lead to the metabolism of X' into a less toxic conjugate X''. The feedforward control involves phase I to II cross-induction, in which the parent chemical X can also induce phase II enzymes directly through the nuclear receptor and indirectly through transcriptionally upregulating Nrf2. As a result of the active feedforward control, a steady-state hormetic relationship readily arises between the concentrations of the reactive metabolite X' and the extracellular parent chemical X to which the cell is exposed. The shape of dose-response evolves over time from initially monotonically increasing to J-shaped at the final steady state-a temporal sequence consistent with adaptation-mediated hormesis. The magnitude of the hormetic response is enhanced by increases in the feedforward gain, but attenuated by increases in the bioactivation or phase II feedback loop gains. Our study suggests a

  3. Predicting Pattern Tooling and Casting Dimensions for Investment Casting, Phase II

    SciTech Connect

    Nick Cannell; Adrian S. Sabau

    2005-09-30

    The investment casting process allows the production of complex-shape parts and close dimensional tolerances. One of the most important phases in the investment casting process is the design of the pattern die. Pattern dies are used to create wax patterns by injecting wax into dies. The first part of the project involved preparation of reports on the state of the art at that time for all the areas under consideration (die-wax, wax-shell, and shell-alloy). The primary R&D focus during Phase I was on the wax material since the least was known about it. The main R&D accomplishments during this phase were determination of procedures for obtaining the thermal conductivity and viscoelastic properties of an unfilled wax and validating those procedures. Phase II focused on die-wax and shell-alloy systems. A wax material model was developed based on results obtained during the previous R&D phase, and a die-wax model was successfully incorporated into and used in commercial computer programs. Current computer simulation programs have complementary features. A viscoelastic module was available in ABAQUS but unavailable in ProCAST, while the mold-filling module was available in ProCAST but unavailable in ABAQUS. Thus, the numerical simulation results were only in good qualitative agreement with experimental results, the predicted shrinkage factors being approximately 2.5 times larger than those measured. Significant progress was made, and results showed that the testing and modeling of wax material had great potential for industrial applications. Additional R&D focus was placed on one shell-alloy system. The fused-silica shell mold and A356 aluminum alloy were considered. The experimental part of the program was conducted at ORNL and commercial foundries, where wax patterns were injected, molds were invested, and alloys were poured. It was very important to obtain accurate temperature data from actual castings, and significant effort was made to obtain temperature profiles in

  4. Investigation of HV/HR-CMOS technology for the ATLAS Phase-II Strip Tracker Upgrade

    NASA Astrophysics Data System (ADS)

    Fadeyev, V.; Galloway, Z.; Grabas, H.; Grillo, A. A.; Liang, Z.; Martinez-Mckinney, F.; Seiden, A.; Volk, J.; Affolder, A.; Buckland, M.; Meng, L.; Arndt, K.; Bortoletto, D.; Huffman, T.; John, J.; McMahon, S.; Nickerson, R.; Phillips, P.; Plackett, R.; Shipsey, I.; Vigani, L.; Bates, R.; Blue, A.; Buttar, C.; Kanisauskas, K.; Maneuski, D.; Benoit, M.; Di Bello, F.; Caragiulo, P.; Dragone, A.; Grenier, P.; Kenney, C.; Rubbo, F.; Segal, J.; Su, D.; Tamma, C.; Das, D.; Dopke, J.; Turchetta, R.; Wilson, F.; Worm, S.; Ehrler, F.; Peric, I.; Gregor, I. M.; Stanitzki, M.; Hoeferkamp, M.; Seidel, S.; Hommels, L. B. A.; Kramberger, G.; Mandić, I.; Mikuž, M.; Muenstermann, D.; Wang, R.; Zhang, J.; Warren, M.; Song, W.; Xiu, Q.; Zhu, H.

    2016-09-01

    ATLAS has formed strip CMOS project to study the use of CMOS MAPS devices as silicon strip sensors for the Phase-II Strip Tracker Upgrade. This choice of sensors promises several advantages over the conventional baseline design, such as better resolution, less material in the tracking volume, and faster construction speed. At the same time, many design features of the sensors are driven by the requirement of minimizing the impact on the rest of the detector. Hence the target devices feature long pixels which are grouped to form a virtual strip with binary-encoded z position. The key performance aspects are radiation hardness compatibility with HL-LHC environment, as well as extraction of the full hit position with full-reticle readout architecture. To date, several test chips have been submitted using two different CMOS technologies. The AMS 350 nm is a high voltage CMOS process (HV-CMOS), that features the sensor bias of up to 120 V. The TowerJazz 180 nm high resistivity CMOS process (HR-CMOS) uses a high resistivity epitaxial layer to provide the depletion region on top of the substrate. We have evaluated passive pixel performance, and charge collection projections. The results strongly support the radiation tolerance of these devices to radiation dose of the HL-LHC in the strip tracker region. We also describe design features for the next chip submission that are motivated by our technology evaluation.

  5. Phase-II conjugation ability for PAH metabolism in amphibians: characteristics and inter-species differences.

    PubMed

    Ueda, Haruki; Ikenaka, Yoshinori; Nakayama, Shouta M M; Tanaka-Ueno, Tomoko; Ishizuka, Mayumi

    2011-10-01

    The present study examines amphibian metabolic activity - particularly conjugation - by analysis of pyrene (a four ring, polycyclic aromatic hydrocarbon) metabolites using high-performance liquid chromatography (HPLC) with fluorescence detector (FD), a mass spectrometry detector (MS) system and kinetic analysis of conjugation enzymes. Six amphibian species were exposed to pyrene (dissolved in water): African claw frog (Xenopus laevis); Tago's brown frog (Rana tagoi); Montane brown frog (Rana ornativentris); Wrinkled frog (Rana rugosa); Japanese newt (Cynops pyrrhogaster); and Clouded salamander (Hynobius nebulosus); plus one fish species, medaka (Oryzias latipes); and a fresh water snail (Clithon retropictus), and the resultant metabolites were collected. Identification of pyrene metabolites by HPLC and ion-trap MS system indicated that medaka mainly excreted pyrene-1-glucuronide (PYOG), while pyrene-1-sulfate (PYOS) was the main metabolite in all amphibian species. Pyrene metabolites in amphibians were different from those in invertebrate fresh water snails. Inter-species differences were also observed in pyrene metabolism among amphibians. Metabolite analysis showed that frogs relied more strongly on sulfate conjugation than did Japanese newts and clouded salamanders. Furthermore, urodelan amphibians, newts and salamanders, excreted glucose conjugates of pyrene that were not detected in the anuran amphibians. Kinetic analysis of conjugation by hepatic microsomes and cytosols indicated that differences in excreted metabolites reflected differences in enzymatic activities. Furthermore, pyrenediol (PYDOH) glucoside sulfate was detected in the Japanese newt sample. This novel metabolite has not been reported previously to this report, in which we have identified unique characteristics of amphibians in phase II pyrene metabolism.

  6. Weekly pegylated liposomal doxorubicin and paclitaxel in patients with metastatic breast carcinoma: A phase II study

    PubMed Central

    LEONARDI, VITA; PALMISANO, VALENTINA; PEPE, ALESSIO; USSET, ANTONELLA; MANUGUERRA, GIOVANNA; SAVIO, GIUSEPPINA; DE BELLA, MANUELA TAMBURO; LAUDANI, AGATA; ALÙ, MASSIMO; CUSIMANO, MARIA PIA; SCIANNA, CATERINA; GIRESI, ARMANDO; AGOSTARA, BIAGIO

    2010-01-01

    Pegylated liposomal doxorubicin (PLD) has the advantage of delivering active anthracycline directly to the tumor site, while exposing the patient to a lesser degree of doxorubicin-associated toxicities. Recently, a regimen in which paclitaxel is infused weekly over 1 h produced substantial antitumor activity with little myelosuppression. We designed a phase II trial to study the efficacy and toxicity of 10 mg/m2 PLD on Days 1, 8 and 15, plus 70 mg/m2 paclitaxel weekly in patients with untreated metastatic breast cancer and a high risk of cardiotoxicity. The study included 35 patients, with 31 (88.5%) evaluable for efficacy and 35 (100%) for toxicity. A total of 28 patients (80%) had two or more sites of disease. Overall, 4 complete and 16 partial responses were noted with an overall response rate of 64.5%, with 6 cases of stable and 5 cases of progressive disease. Toxicity was found to be manageable in that the only grade 3–4 side effects recorded were palmar-plantar erythrodysesthesia, 8.5%; mucositis, 2.8%; leucopenia, 12.5%; anemia, 2.8% and AST/ALT, 2.8%. No cardiotoxicity was observed. In conclusion, weekly PLD plus paclitaxel appears to be a well-tolerated and effective approach for metastatic breast cancer patients with a high risk of cardiotoxicity. PMID:22966374

  7. Burnup calculations and chemical analysis of irradiated fuel samples studied in LWR-PROTEUS phase II

    SciTech Connect

    Grimm, P.; Guenther-Leopold, I.; Berger, H. D.

    2006-07-01

    The isotopic compositions of 5 UO{sub 2} samples irradiated in a Swiss PWR power plant, which were investigated in the LWR-PROTEUS Phase II programme, were calculated using the CASMO-4 and BOXER assembly codes. The burnups of the samples range from 50 to 90 MWd/kg. The results for a large number of actinide and fission product nuclides were compared to those of chemical analyses performed using a combination of chromatographic separation and mass spectrometry. A good agreement of calculated and measured concentrations is found for many of the nuclides investigated with both codes. The concentrations of the Pu isotopes are mostly predicted within {+-}10%, the two codes giving quite different results, except for {sup 242}Pu. Relatively significant deviations are found for some isotopes of Cs and Sm, and large discrepancies are observed for Eu and Gd. The overall quality of the predictions by the two codes is comparable, and the deviations from the experimental data do not generally increase with burnup. (authors)

  8. A phase II study of ixabepilone and trastuzumab for metastatic HER2-positive breast cancer

    PubMed Central

    Tolaney, S. M.; Najita, J.; Sperinde, J.; Huang, W.; Chen, W. Y.; Savoie, J.; Fornier, M.; Winer, E. P.; Bunnell, C.; Krop, I. E.

    2013-01-01

    Background A multicenter NCI-sponsored phase II study was conducted to analyze the safety and efficacy of the combination of ixabepilone with trastuzumab in patients with metastatic HER2-positive breast cancer. Patients and methods Two cohorts were enrolled: cohort 1 had received no prior chemotherapy or trastuzumab for metastatic disease and cohort 2 had received 1–2 prior trastuzumab-containing regimens for metastatic disease. Patients in both cohorts received ixabepilone 40 mg/m2 as a 3-h infusion and trastuzumab on day 1 of a 21-day cycle. Tumor biomarkers that may predict response to trastuzumab were explored. Results Thirty-nine women entered the study with 15 patients in cohort 1 and 24 patients in cohort 2. Across both cohorts, the overall RR was 44%, with a clinical benefit rate (CR + PR + SD for at least 24 weeks) of 56%. Treatment-related toxic effects included neuropathy (grade ≥2, 56%), leukopenia (grade ≥2, 26%), myalgias (grade ≥2, 21%), neutropenia (grade ≥2, 23%), and anemia (grade ≥2, 18%). Conclusions This represents the first study of the combination of ixabepilone with trastuzumab for the treatment of metastatic HER2-positive breast cancer. These results suggest that the combination has encouraging activity as first and subsequent line therapy for metastatic breast cancer. PMID:23559151

  9. THE WIDE-AREA ENERGY STORAGE AND MANAGEMENT SYSTEM PHASE II Final Report - Flywheel Field Tests

    SciTech Connect

    Lu, Ning; Makarov, Yuri V.; Weimar, Mark R.; Rudolph, Frank; Murthy, Shashikala; Arseneaux, Jim; Loutan, Clyde; Chowdhury, S.

    2010-08-31

    This research was conducted by Pacific Northwest National Laboratory (PNNL) operated for the U.S. department of Energy (DOE) by Battelle Memorial Institute for Bonneville Power Administration (BPA), California Institute for Energy and Environment (CIEE) and California Energy Commission (CEC). A wide-area energy management system (WAEMS) is a centralized control system that operates energy storage devices (ESDs) located in different places to provide energy and ancillary services that can be shared among balancing authorities (BAs). The goal of this research is to conduct flywheel field tests, investigate the technical characteristics and economics of combined hydro-flywheel regulation services that can be shared between Bonneville Power Administration (BPA) and California Independent System Operator (CAISO) controlled areas. This report is the second interim technical report for Phase II of the WAEMS project. This report presents: 1) the methodology of sharing regulation service between balancing authorities, 2) the algorithm to allocate the regulation signal between the flywheel and hydro power plant to minimize the wear-and-tear of the hydro power plants, 3) field results of the hydro-flywheel regulation service (conducted by the Beacon Power), and 4) the performance metrics and economic analysis of the combined hydro-flywheel regulation service.

  10. Docetaxel for malignant mesothelioma: phase II study of the Eastern Cooperative Oncology Group.

    PubMed

    Belani, Chandra P; Adak, Sudeshna; Aisner, Seena; Stella, Philip J; Levitan, Nathan; Johnson, David H

    2004-07-01

    This Eastern Cooperative Oncology Group phase II trial was conducted to study the effectiveness of docetaxel in patients with malignant mesothelioma. Patients were treated with docetaxel 100 mg/m2 intravenously administered as a 1-hour infusion repeated every 3 weeks. The study accrued a total of 20 patients, 1 of whom was considered ineligible. Of the 19 eligible patients, 1 patient (5%) achieved a partial response, 3 patients (16%) had stable disease, 11 patients (58%) had progressive disease, and 4 patients (21%) were unevaluable. The study was terminated after the first accrual stage because of an insufficient number of complete or partial responses. To date, only 1 patient (with stable disease) has not relapsed. The estimated median survival time is 4 months and the estimated median time to treatment failure is 2.2 months. There were 3 early deaths associated with the treatment regimen: severe gastrointestinal toxicity, hemorrhage, and an acute pulmonary event. Docetaxel as a single agent does not demonstrate evidence of activity in malignant mesothelioma.

  11. Washington Phase II Fish Diversion Screen Evaluations in the Yakima River Basin, 2000.

    SciTech Connect

    Chamness, M. A.

    2001-03-01

    Pacific Northwest National Laboratory (PNNL) evaluated 21 Phase II screen sites in the Yakima River Basin as part of a multi-year study for the Bonneville Power Administration (BPA) on the effectiveness of fish screening devices. The sites were examined in 1997, 1998, 1999, and 2000 to determine if they were being effectively operated and maintained to provide fish a safe, efficient return to the Yakima River. Data were collected to determine if velocities in front of the screens and in the bypass met current National Marine Fisheries Service (NMFS) criteria to promote safe and timely fish bypass and whether bypass outfall conditions allowed fish to safely return to the river. Based on the results of our studies in 2000, we conclude that: in general, water velocity conditions at the screen sites met fish passage criteria set forth by the NMFS; most facilities were efficiently protecting juvenile fish from entrainment, impingement, or migration delay; automated cleaning brushes generally functioned properly; chains and other moving parts were well greased and inoperative; and removal of sediment build-up and accumulated leafy and woody debris are areas that continue to improve.

  12. Phase II Trial of Talampanel, a Glutamate Receptor Inhibitor, for Adults with Recurrent Malignant Gliomas

    PubMed Central

    Iwamoto, Fabio M.; Kreisl, Teri N.; Kim, Lyndon; Duic, J. Paul; Butman, John A.; Albert, Paul S.; Fine, Howard A.

    2010-01-01

    Background: Glioma cells secrete glutamate and also express AMPA glutamate receptors, which contribute to proliferation, migration and neurotoxicity of malignant gliomas. Talampanel is an oral AMPA receptor inhibitor with excellent CNS penetration and good tolerability in clinical trials for epilepsy and other neurological disorders. Methods: We conducted a phase II trial to evaluate the efficacy of talampanel in patients with recurrent malignant glioma as measured by 6-month progression free survival (PFS6). Results: Thirty patients (22 glioblastomas [GBM], 8 anaplastic gliomas [AG]; 63% men) with median age of 51 years (range, 20 to 67) and median KPS of 80 were included. Patients tolerated treatment well and most adverse events were mild and reversible; the most common toxicities were fatigue (27%), dizziness (23%) and ataxia (17%). There was only one partial response (5%) in the GBM stratum and none among AG patients. With a median follow-up of 13 months, 28 patients (93%) had died. The PFS6 was 4.6% for the initial 22 GBM patients and the study was terminated early due to treatment futility; PFS6 was 0% for 8 AG patients. Median PFS was 5.9 weeks for GBM and 8.9 weeks for AG patients. Median overall survival was 13 weeks for GBM and 14 months for AG patients. Conclusion: Talampanel was well tolerated but had no significant activity as a single agent in unselected recurrent malignant gliomas. PMID:20143438

  13. An Overview of Power, Energy Storage, and Conversion Efforts for 2014 SBIR Phases I and II

    NASA Technical Reports Server (NTRS)

    Nguyen, Hung D.; Steele, Gynelle C.

    2016-01-01

    Technological innovation is the overall focus of NASA's Small Business Innovation Research (SBIR) program. The program invests in the development of innovative concepts and technologies to help NASA's mission directorates address critical research and development needs for agency projects. NASA's Small Business Innovation Research (SBIR) program focuses on technological innovation by investing in development of innovative concepts and technologies to help NASA mission directorates address critical research needs for Agency programs. This report highlights 15 of the innovative SBIR 2014 Phase I and II projects that focus on one of NASA Glenn Research Center's six core competencies-Power, Energy Storage and Conversion. The technologies cover a wide spectrum of applications such as high-radiation-tolerant ceramic voltage isolators, development of hermetic sealing glasses for solid oxide fuel cells, rechargeable lithium metal cells, high-efficiency direct methane solid oxide fuel cell systems, Li metal protection for high-energy space batteries, isolated bidirectional direct current converters for distributed battery energy applications, and high-efficiency rad-hard ultrathin Si photovoltaic cell technology for space. Each article describes an innovation and technical objective and highlights NASA commercial and industrial applications. This report provides an opportunity for NASA engineers, researchers, and program managers to learn how NASA SBIR technologies could help their programs and projects, and lead to collaborations and partnerships between the small SBIR companies and NASA that would benefit both.

  14. Silicon sensor prototypes for the Phase II upgrade of the CMS tracker

    NASA Astrophysics Data System (ADS)

    Bergauer, Thomas

    2016-09-01

    The High-Luminosity LHC (HL-LHC) has been identified as the highest priority program in High Energy Physics in the mid-term future. It will provide the experiments an additional integrated luminosity of about 2500 fb-1 over 10 years of operation, starting in 2025. In order to meet the experimental challenges of unprecedented p-p luminosity, especially in terms of radiation levels and occupancy, the CMS collaboration will need to replace its entire strip tracker by a new one. In this paper the baseline layout option for this new Phase-II tracker is shown, together with two variants using a tilted barrel geometry or larger modules from 8-inch silicon wafers. Moreover, the two module concepts are discussed, which consist either of two strip sensors (2S) or of one strip and one pixel sensor (PS). These two designs allow pT discrimination at module level enabling the tracker to contribute to the L1 trigger decision. The paper presents testing results of the macro-pixel-light sensor for the PS module and shows the first electrical characterization of unirradiated, full-scale strip sensor prototypes for the 2S module concept, both on 6- and 8-inch wafers.

  15. Culture and Use of Mesenchymal Stromal Cells in Phase I and II Clinical Trials

    PubMed Central

    Philippe, Bourin; Luc, Sensebé; Valérie, Planat-Bénard; Jérôme, Roncalli; Alessandra, Bura-Rivière; Louis, Casteilla

    2010-01-01

    Present in numerous tissues, mesenchymal stem cells/multipotent stromal cells (MSCs) can differentiate into different cell types from a mesoderm origin. Their potential has been extended to pluripotency, by their possibility of differentiating into tissues and cells of nonmesodermic origin. Through the release of cytokines, growth factors and biologically active molecules, MSCs exert important paracrine effects during tissue repair and inflammation. Moreover, MSCs have immunosuppressive properties related to non-HLA restricted immunosuppressive capacities. All these features lead to an increasing range of possible applications of MSCs, from treating immunological diseases to tissue and organ repair, that should be tested in phase I and II clinical trials. The most widely used MSCs are cultured from bone marrow or adipose tissue. For clinical trial implementation, BM MSCs and ADSCs should be produced according to Good Manufacturing Practices. Safety remains the major concern and must be ensured during culture and validated with relevant controls. We describe some applications of MSCs in clinical trials. PMID:21052537

  16. A phase II study of topotecan in patients with relapsed small-cell lung cancer.

    PubMed

    Takeda, Koji; Negoro, Shunichi; Sawa, Toshiyuki; Nakagawa, Kazuhiko; Kawahara, Masaaki; Isobe, Takeshi; Kudoh, Shinzoh; Masuda, Noriyuki; Niitani, Hisanobu; Fukuoka, Masahiro

    2003-01-01

    An early phase II study of topotecan produced favorable results in a small number of untreated and previously treated patients with small-cell lung cancer (SCLC). This multicenter study was conducted in patients with relapsed SCLC at 19 medical institutions in Japan. Topotecan 1.0 mg/m2/day was administered for 5 consecutive days every 3 weeks. Fifty-three patients were enrolled in the study. One patient was withdrawn before the commencement of study treatment, and 2 patients were unable to continue study treatment due to an interruption in the supply of study medication. The response rate was 26.0% in 13 of the 50 evaluable patients who were eligible and completed protocol-specified treatment and procedures. The median time to progression and overall survival were 133 days and 262 days, respectively. The most frequently reported toxicity was reversible myelosuppression, such as leukopenia, neutropenia, anemia (decreased hemoglobin), and thrombocytopenia. Nonhematological toxicity was also reported but the incidence of grade 3/4 symptoms was low. The results of this study indicate that topotecan is effective against relapsed SCLC with good tolerability.

  17. Phage idiotype vaccination: first phase I/II clinical trial in patients with multiple myeloma

    PubMed Central

    2014-01-01

    Background Multiple myeloma is characterized by clonal expansion of B cells producing monoclonal immunoglobulins or fragments thereof, which can be detected in the serum and/or urine and are ideal target antigens for patient-specific immunotherapies. Methods Using phage particles as immunological carriers, we employed a novel chemically linked idiotype vaccine in a clinical phase I/II trial including 15 patients with advanced multiple myeloma. Vaccines composed of purified paraproteins linked to phage were manufactured successfully for each patient. Patients received six intradermal immunizations with phage idiotype vaccines in three different dose groups. Results Phage idiotype was well tolerated by all study participants. A subset of patients (80% in the middle dose group) displayed a clinical response indicated by decrease or stabilization of paraprotein levels. Patients exhibiting a clinical response to phage vaccines also raised idiotype-specific immunoglobulins. Induction of a cellular immune response was demonstrated by a cytotoxicity assay and delayed type hypersensitivity tests. Conclusion We present a simple, time- and cost-efficient phage idiotype vaccination strategy, which represents a safe and feasible patient-specific therapy for patients with advanced multiple myeloma and produced promising anti-tumor activity in a subset of patients. PMID:24885819

  18. A phase II and pharmacokinetic study with oral piritrexim for metastatic breast cancer.

    PubMed Central

    de Vries, E. G.; Gietema, J. A.; Workman, P.; Scott, J. E.; Crawshaw, A.; Dobbs, H. J.; Dennis, I.; Mulder, N. H.; Sleijfer, D. T.; Willemse, P. H.

    1993-01-01

    Piritrexim is a lipid-soluble antifolate which, like methotrexate, has a potent capacity to inhibit dihydrofolate reductase. We performed a multicentre phase II study with piritrexim in patients with locally advanced or metastatic breast cancer. Twenty-four patients of which sixteen had received prior chemotherapy, were initially treated with 25 mg piritrexim orally administered trice daily for four days, repeated weekly, with provision for dose escalation or reduction according to observed toxicity. Of twenty-one patients evaluable for tumour response, one patient achieved a partial response which lasted for 24 weeks. Three patients had stable disease during 12 weeks of treatment, seventeen had progressive disease. Pirtrexim was generally well tolerated, in eighteen patients the dose could be escalated. Myelotoxicity was the most frequent observed toxicity of this piritrexim regimen. Leucopenia and thrombocytopenia grade 3/4 occurred in 38% of the patients sometime during treatment. Pharmacokinetic analysis of piritrexim in three patients during the first treatment cycle, revealed peak levels 1 to 2 h after an oral dose, with a trend towards a higher peak plasma levels and AUCs on the fourth dosing day compared with the first dosing day. In conclusion, orally administered piritrexim appears to be a regimen with little activity in patients with locally advanced or metastatic breast carcinoma. PMID:8353055

  19. Thermal imaging QC for silicon strip staves of the ATLAS phase II upgrade

    NASA Astrophysics Data System (ADS)

    Vergel Infante, Carlos

    2016-03-01

    A new silicon strip detector is part of the phase II upgrade of the ATLAS inner tracker. Light-material carbon fiber honeycomb sandwich staves serve as mechanical support for the strip sensors and readout modules and to move the dissipated heat out of the detector. A cooling pipe inside the stave is embedded in heat-conducting foam that thermally connects the pipe with the readout modules. The staves are required to pass a set of quality control (QC) tests before they are populated with readout modules. One test uses a non-invasive inspection method of infrared (IR) thermal imaging of the heat path while the stave is cooled to around -40°C at ambient room temperature. Imperfections in the manufacturing, such as the delamination of the stave facing from the foam, will exhibit a different temperature profile compared to a flawless stave. We report on the current status of the thermal imaging QC measurements including a characterization of various contributions to the uncertainties in the temperature reading of the IR camera such as pedestal variations, common-mode noise, vignetting, and statistical fluctuations across the field of view.

  20. Seismicity and crustal structure in the Orozco Fracture Zone: Project Rose Phase II

    NASA Astrophysics Data System (ADS)

    Ouchi, Toru; Ibrahim, Abou-Bakr K.; Latham, Gary V.

    1982-10-01

    A total of 301 earthquakes were recorded in the vicinity of the Orozco fracture zone by seven Texas ocean bottom seismograph stations during the 2-week period of the Rivera Ocean Seismic Experiment (ROSE) (phase II). Using data from the entire ROSE array, hypocenters of 50 earthquakes were determined. These revealed two distinct zones of seismic activity within the fracture zone. In addition to these earthquake families, many very small events were detected by a station located very close to the spreading center of the East Pacific Rise. The magnitudes of these earthquakes, defined by their duration times, were so small that most of them were recorded only at this station (station 14) in continual or swarmlike occurrences. The slope of the frequency-magnitude distribution of these events is significantly larger than those of other earthquake groups detected during the experiment, i.e., they appear to have an unusually high b value. These results suggest that this new population of earthquakes may be associated with volcanic activity or stress release within highly fractured crustal material. Refraction studies in the fracture zone reveal the presence of a rather high-velocity crustal layer (6.9-7.0 km/s) beneath the experiment zone. The Moho velocity and the crustal thickness are estimated at 7.8 km/s and 6.2 km, respectively.

  1. Washington Phase II Fish Diversion Screen Evaluations in the Yakima River Basin, 2002 Annual Report.

    SciTech Connect

    Carter, J.; McMichael, G.; Chamness, M.

    2003-01-01

    In 2002, the Pacific Northwest National Laboratory evaluated 23 Phase II fish screen sites in the Yakima River Basin as part of a multi-year project for the Bonneville Power Administration on the effectiveness of fish screening devices. Pacific Northwest National Laboratory collected data to determine whether velocities in front of the screens and in the bypasses met National Marine Fisheries Service criteria to promote safe and timely fish passage and whether bypass outfall conditions allowed fish to safely return to the river. In addition, Pacific Northwest National Laboratory conducted underwater video surveys to evaluate the environmental and operational conditions of the screen sites with respect to fish passage. Based on evaluations in 2002, PNNL concluded that: (1) In general, water velocity conditions at the screen sites met fish passage criteria set by the National Marine Fisheries Service. (2) Conditions at most facilities would be expected to provide for safe juvenile fish passage. (3) Conditions at some facilities indicate that operation and/or maintenance should be modified to increase safe juvenile fish passage. (4) Automated cleaning brushes generally functioned properly; chains and other moving parts were typically well greased and operative. (5) Removal of sediment buildup and accumulated leafy and woody debris should be improved at some sites.

  2. Washington Phase II Fish Diversion Screen Evaluations in the Yakima River Basin, 2003 Annual Report.

    SciTech Connect

    Vucelick, J.; McMichael, G.; Chamness, M.

    2004-05-01

    In 2003, the Pacific Northwest National Laboratory (PNNL) evaluated 23 Phase II fish screen sites in the Yakima River Basin as part of a multi-year project for the Bonneville Power Administration on the effectiveness of fish screening devices. PNNL collected data to determine whether velocities in front of the screens and in the bypasses met the National Oceanic and Atmospheric Administration Fisheries (NOAA Fisheries, formerly the National Marine Fisheries Service [NMFS]) criteria to promote safe and timely fish passage. In addition, PNNL conducted underwater video surveys to evaluate the environmental and operational conditions of the screen sites with respect to fish passage. Based on evaluations in 2003, PNNL concluded that: (1) In general, water velocity conditions at the screen sites met fish passage criteria set by the NOAA Fisheries. (2) Conditions at most facilities would be expected to provide for safe juvenile fish passage. (3) Conditions at some facilities indicate that operation and/or maintenance should be modified to improve juvenile fish passage conditions. (4) Automated cleaning brushes generally functioned properly; chains and other moving parts were typically well greased and operative. (5) Removal of sediment buildup and accumulated leafy and woody debris could be improved at some sites.

  3. Web-based data management for a phase II clinical trial in ALS.

    PubMed

    Buchsbaum, Richard; Kaufmann, Petra; Barsdorf, Alexandra I; Arbing, Rachel; Montes, Jacqueline; Thompson, John L P

    2009-01-01

    The objective was to report on the creation, features and performance of a web-based data management system for a two-stage phase II randomized clinical trial of Co-Enzyme Q10 in ALS. We created a relatively comprehensive web-based data system that provided electronic data entry; patient management utilities; adverse event reporting, safety monitoring, and invoice generation; and standardized coding for medications and adverse events. In stage 1, clinical sites submitted 7207 forms reporting on 105 patients followed for 10 months. Less than 0.7% of submitted forms contained errors. At the time of the delivery of the analysis data set, only four errors remained unresolved. Data were available quickly, with a median time from event to data posting of two days. The data set was locked and the analysis data set produced nine days after the final patient visit. A survey of trial personnel yielded generally positive feedback, with 75% of respondents wishing to use a similar system in the future. Given sufficient resources, a comprehensive web-based data management system can meet the need for clean, available data in clinical trials in ALS and similar diseases, and can contribute significantly to their efficient execution. PMID:19922127

  4. A Phase I/II study of lomustine and temozolomide in patients with cerebral metastases from malignant melanoma

    PubMed Central

    Larkin, J M G; Hughes, S A; Beirne, D A; Patel, P M; Gibbens, I M; Bate, S C; Thomas, K; Eisen, T G; Gore, M E

    2006-01-01

    Temozolomide is an alkylating agent with activity in the treatment of melanoma metastatic to the brain. Lomustine is a nitrosurea that crosses the blood brain barrier and there is evidence to suggest that temozolomide may reverse resistance to lomustine. A multicentre phase I/II study was conducted to assess the maximum-tolerated dose (MTD), safety and efficacy of the combination of temozolomide and lomustine in melanoma metastatic to the brain. Increasing doses of temozolomide and lomustine were administered in phase I of the study to determine the MTD. Patients were treated at the MTD in phase II of the study to six cycles, disease progression or unacceptable toxicity. Twenty-six patients were enrolled in the study. In phase I of the study, the MTD was defined as temozolomide 150 mg m−2 days 1–5 every 28 days and lomustine 60 mg m–2 on day 5 every 56 days. Dose-limiting neutropaenia and thrombocytopaenia were observed at higher doses. Twenty patients were treated at this dose in phase II of the study. No responses to therapy were observed. Median survival from starting chemotherapy was 2 months. The combination of temozolomide and lomustine in patients with brain metastases from melanoma does not demonstrate activity. The further evaluation of this combination therefore is not warranted. PMID:17146474

  5. A phase I/II study of lomustine and temozolomide in patients with cerebral metastases from malignant melanoma.

    PubMed

    Larkin, J M G; Hughes, S A; Beirne, D A; Patel, P M; Gibbens, I M; Bate, S C; Thomas, K; Eisen, T G; Gore, M E

    2007-01-15

    Temozolomide is an alkylating agent with activity in the treatment of melanoma metastatic to the brain. Lomustine is a nitrosurea that crosses the blood brain barrier and there is evidence to suggest that temozolomide may reverse resistance to lomustine. A multicentre phase I/II study was conducted to assess the maximum-tolerated dose (MTD), safety and efficacy of the combination of temozolomide and lomustine in melanoma metastatic to the brain. Increasing doses of temozolomide and lomustine were administered in phase I of the study to determine the MTD. Patients were treated at the MTD in phase II of the study to six cycles, disease progression or unacceptable toxicity. Twenty-six patients were enrolled in the study. In phase I of the study, the MTD was defined as temozolomide 150 mg m(-2) days 1-5 every 28 days and lomustine 60 mg m(-2) on day 5 every 56 days. Dose-limiting neutropaenia and thrombocytopaenia were observed at higher doses. Twenty patients were treated at this dose in phase II of the study. No responses to therapy were observed. Median survival from starting chemotherapy was 2 months. The combination of temozolomide and lomustine in patients with brain metastases from melanoma does not demonstrate activity. The further evaluation of this combination therefore is not warranted. PMID:17146474

  6. Evaluation of qPCR and phase I and II antibodies for detection of Coxiella burnetii infection in cattle.

    PubMed

    Szymańska-Czerwińska, Monika; Niemczuk, Krzysztof; Jodełko, Agnieszka

    2016-10-01

    Diagnosis of Q fever in cattle is not easy due to the need to test the samples by both serological and molecular methods. Aim of this study was to evaluate qPCR, and phase I and II antibodies for detection of C. burnetii infection in cattle. A total of 187 bovine blood and vaginal swabs, and 97 milk samples, were tested. Limitations of serological tests were that the available indirect enzyme linked immunosorbent assay (iELISA) could lose positive results if antibody titres were low; or phase II antibodies were present. The highest level of correlation between iELISA and complement fixation test (CFT) was noted with the antigen specific phase I antibodies. Neither the mode of shedding nor its intensity correlated with phase I and II antibodies, but positive results in CFT mixed-phase and shedding in vaginal mucous did correlate, and showed the highest correlation. Antigenic diversity, and variability could be crucial in laboratory diagnosis of Q fever. PMID:27663372

  7. Unbiased estimation in seamless phase II/III trials with unequal treatment effect variances and hypothesis-driven selection rules.

    PubMed

    Robertson, David S; Prevost, A Toby; Bowden, Jack

    2016-09-30

    Seamless phase II/III clinical trials offer an efficient way to select an experimental treatment and perform confirmatory analysis within a single trial. However, combining the data from both stages in the final analysis can induce bias into the estimates of treatment effects. Methods for bias adjustment developed thus far have made restrictive assumptions about the design and selection rules followed. In order to address these shortcomings, we apply recent methodological advances to derive the uniformly minimum variance conditionally unbiased estimator for two-stage seamless phase II/III trials. Our framework allows for the precision of the treatment arm estimates to take arbitrary values, can be utilised for all treatments that are taken forward to phase III and is applicable when the decision to select or drop treatment arms is driven by a multiplicity-adjusted hypothesis testing procedure. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. PMID:27103068

  8. Unbiased estimation in seamless phase II/III trials with unequal treatment effect variances and hypothesis-driven selection rules.

    PubMed

    Robertson, David S; Prevost, A Toby; Bowden, Jack

    2016-09-30

    Seamless phase II/III clinical trials offer an efficient way to select an experimental treatment and perform confirmatory analysis within a single trial. However, combining the data from both stages in the final analysis can induce bias into the estimates of treatment effects. Methods for bias adjustment developed thus far have made restrictive assumptions about the design and selection rules followed. In order to address these shortcomings, we apply recent methodological advances to derive the uniformly minimum variance conditionally unbiased estimator for two-stage seamless phase II/III trials. Our framework allows for the precision of the treatment arm estimates to take arbitrary values, can be utilised for all treatments that are taken forward to phase III and is applicable when the decision to select or drop treatment arms is driven by a multiplicity-adjusted hypothesis testing procedure. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

  9. Genome-Wide Transcriptome and Antioxidant Analyses on Gamma-Irradiated Phases of Deinococcus radiodurans R1

    PubMed Central

    Xu, Xun; Feng, Qiang; Jiang, Hui; Dai, Jun; Yuan, Xune; Lu, Yanping; Roberts, Alexandra A.; Luo, Xiao; Chen, Maoshan; Xu, Shengtao; Li, Jun; Hamilton, Chris J.; Fang, Chengxiang; Wang, Jun

    2014-01-01

    Adaptation of D. radiodurans cells to extreme irradiation environments requires dynamic interactions between gene expression and metabolic regulatory networks, but studies typically address only a single layer of regulation during the recovery period after irradiation. Dynamic transcriptome analysis of D. radiodurans cells using strand-specific RNA sequencing (ssRNA-seq), combined with LC-MS based metabolite analysis, allowed an estimate of the immediate expression pattern of genes and antioxidants in response to irradiation. Transcriptome dynamics were examined in cells by ssRNA-seq covering its predicted genes. Of the 144 non-coding RNAs that were annotated, 49 of these were transfer RNAs and 95 were putative novel antisense RNAs. Genes differentially expressed during irradiation and recovery included those involved in DNA repair, degradation of damaged proteins and tricarboxylic acid (TCA) cycle metabolism. The knockout mutant crtB (phytoene synthase gene) was unable to produce carotenoids, and exhibited a decreased survival rate after irradiation, suggesting a role for these pigments in radiation resistance. Network components identified in this study, including repair and metabolic genes and antioxidants, provided new insights into the complex mechanism of radiation resistance in D. radiodurans. PMID:24465634

  10. A Phase I/II Trial of Topotecan and Radiation Therapy for Brain Metastases in Patients With Solid Tumors

    SciTech Connect

    Hedde, Jan-Peter; Neuhaus, Thomas . E-mail: t.neuhaus@jk-bonn.de; Schueller, Heinrich; Metzler, Ute; Schmidt-Wolf, Ingo G.H.; Kleinschmidt, Rolf; Losem, Christoph; Lange, Oliver; Grohe, Christian; Stier, Sebastian; Ko, Yon-Dschun

    2007-07-01

    Purpose: Outcomes in patients with brain metastases undergoing whole-brain radiotherapy (WBRT) are hardly encouraging, and an improvement in results is therefore needed. One possible approach is the addition of chemotherapeutics. However the data presented thus far are also disappointing. A promising substance in this setting could become topotecan, which is known to cross the blood-brain barrier and additionally offers radiosensitizing effects. Therefore we performed a phase I/II trial to evaluate the feasibility of a concurrent radiochemotherapy regimen. Methods and Materials: From January 1999 to July 2001, a total of 75 patients (10 in phase I and 65 in phase II) were included. The WBRT was applied with a fraction size of 2 Gy/day for a total of 40 Gy. Topotecan was administered as a 30-min infusion with 0.2 to 0.5 mg/m{sup 2}/day for 5 days over 4 weeks within 2 h to radiation therapy. Results: Because of the higher toxic rates seen in patients receiving 0.5 mg/m{sup 2}/day, the recommended dosage for phase II was 0.4 mg/m{sup 2}/day. In this group Grade 3/4 hematologic and nonhematologic side effects occurred in 19% and 21% of the patients, respectively. The overall response rate was 72% with an overall survival of 17 weeks and 30 weeks among the responders. Conclusions: Based on the moderate toxicity profile presented here we recommend to perform a phase III trial to confirm the promising phase I/II data.

  11. Application of Colorimetric Solid Phase Extraction (C-SPE) to Monitoring Nickel(II) and Lead(II) in Spacecraft Water Supplies

    NASA Technical Reports Server (NTRS)

    Diaz, Neil C.; Gazda, Daniel B.; Fritz, James S.; Porter, Marc D.; Rutz, Jeff; Mudgett, Paul; Schultz, John

    2004-01-01

    Archived water samples collected on the International Space Station (ISS) and returned to Earth for analysis have, in a few instances, contained trace levels of heavy metals. Building on our previous advances using Colorimetric Solid Phase Extraction (C-SPE) as a biocide monitoring technique, we are devising methods for the low level monitoring of nickel(II), lead(II) and other heavy metals. C-SPE is a sorption-spectrophotometric platform based on the extraction of analytes onto a membrane impregnated with a colorimetric reagent that are then quantified on the surface of the membrane using a diffuse reflectance spectrophotometer. Along these lines, we have determined nickel(II) via complexation with dimethylglyoxime (DMG) and begun to examine the analysis of lead(II) by its reaction with 2,5- dimercapto-1,3,4-thiadiazole (DMTD) and 4-(2- pyridylazo)-resorcinol (PAR). These developments are also extending a new variant of C-SPE in which immobilized reagents are being incorporated into this methodology in order to optimize sample reaction conditions and to introduce the colorimetric reagent. This paper describes the status of our development of these two new methods.

  12. Phase II Hydrologic Data for the Groundwater Flow and Contaminant Transport Model of Corrective Action Unit 98: Frenchman Flat, Nye County, Nevada, Rev. No.: 0

    SciTech Connect

    John McCord

    2004-12-01

    This report documents pertinent hydrologic data and data analyses as part of the Phase II Corrective Action Investigation (CAI) for Frenchman Flat (FF) Corrective Action Unit (CAU): CAU 98. The purpose of this data compilation and related analyses is to provide the primary reference to support the development of the Phase II FF CAU groundwater flow model.

  13. Phase II Contaminant Transport Parameters for the Groundwater Flow and Contaminant Transport Model of Corrective Action Unit 98: Frenchman Flat, Nye County, Nevada, Rev. No.: 0

    SciTech Connect

    DeNovio, Nicole M.; Bryant, Nathan; King, Chrissi B.; Bhark, Eric; Drellack, Sigmund L.; Pickens, John F.; Farnham, Irene; Brooks, Keely M.; Reimus, Paul; Aly, Alaa

    2005-04-01

    This report documents pertinent transport data and data analyses as part of the Phase II Corrective Action Investigation (CAI) for Frenchman Flat (FF) Corrective Action Unit (CAU) 98. The purpose of this data compilation and related analyses is to provide the primary reference to support parameterization of the Phase II FF CAU transport model.

  14. Final Report: Phase II Nevada Water Resources Data, Modeling, and Visualization (DMV) Center

    SciTech Connect

    Jackman, Thomas; Minor, Timothy; Pohll, Gregory

    2013-07-22

    Water is unquestionably a critical resource throughout the United States. In the semi-arid west -- an area stressed by increase in human population and sprawl of the built environment -- water is the most important limiting resource. Crucially, science must understand factors that affect availability and distribution of water. To sustain growing consumptive demand, science needs to translate understanding into reliable and robust predictions of availability under weather conditions that could be average but might be extreme. These predictions are needed to support current and long-term planning. Similar to the role of weather forecast and climate prediction, water prediction over short and long temporal scales can contribute to resource strategy, governmental policy and municipal infrastructure decisions, which are arguably tied to the natural variability and unnatural change to climate. Change in seasonal and annual temperature, precipitation, snowmelt, and runoff affect the distribution of water over large temporal and spatial scales, which impact the risk of flooding and the groundwater recharge. Anthropogenic influences and impacts increase the complexity and urgency of the challenge. The goal of this project has been to develop a decision support framework of data acquisition, digital modeling, and 3D visualization. This integrated framework consists of tools for compiling, discovering and projecting our understanding of processes that control the availability and distribution of water. The framework is intended to support the analysis of the complex interactions between processes that affect water supply, from controlled availability to either scarcity or deluge. The developed framework enables DRI to promote excellence in water resource management, particularly within the Lake Tahoe basin. In principle, this framework could be replicated for other watersheds throughout the United States. Phase II of this project builds upon the research conducted during

  15. Auto-inhibitory regulation of angiotensin II functionality in hamster aorta during the early phases of dyslipidemia.

    PubMed

    Pereira, Priscila Cristina; Pernomian, Larissa; Côco, Hariane; Gomes, Mayara Santos; Franco, João José; Marchi, Kátia Colombo; Hipólito, Ulisses Vilela; Uyemura, Sergio Akira; Tirapelli, Carlos Renato; de Oliveira, Ana Maria

    2016-06-15

    Emerging data point the crosstalk between dyslipidemia and renin-angiotensin system (RAS). Advanced dyslipidemia is described to induce RAS activation in the vasculature. However, the interplay between early dyslipidemia and the RAS remains unexplored. Knowing that hamsters and humans have a similar lipid profile, we investigated the effects of early and advanced dyslipidemia on angiotensin II-induced contraction. Cumulative concentration-response curves for angiotensin II (1.0pmol/l to 1.0µmol/l) were obtained in the hamster thoracic aorta. We also investigated the modulatory action of NAD(P)H oxidase on angiotensin II-induced contraction using ML171 (Nox-1 inhibitor, 0.5µmol/l) and VAS2870 (Nox-4 inhibitor, 5µmol/l). Early dyslipidemia was detected in hamsters treated with a cholesterol-rich diet for 15 days. Early dyslipidemia decreased the contraction induced by angiotensin II and the concentration of Nox-4-derived hydrogen peroxide. Advanced dyslipidemia, observed in hamsters treated with cholesterol-rich diet for 30 days, restored the contractile response induced by angiotensin II by compensatory mechanism that involves Nox-4-mediated oxidative stress. The hyporresponsiveness to angiotensin II may be an auto-inhibitory regulation of the angiotensinergic function during early dyslipidemia in an attempt to reduce the effects of the upregulation of the vascular RAS during the advanced stages of atherogenesis. The recovery of vascular angiotensin II functionality during the advanced phases of dyslipidemia is the result of the upregulation of redox-pro-inflammatory pathway that might be most likely involved in atherogenesis progression rather than in the recovery of vascular function. Taken together, our findings show the early phase of dyslipidemia may be the most favorable moment for effective atheroprotective therapeutic interventions. PMID:27063446

  16. Dual Neuroprotective Pathways of a Pro-Electrophilic Compound via HSF-1-activated Heat Shock Proteins and Nrf2-activated Phase 2 Antioxidant Response Enzymes

    PubMed Central

    Satoh, Takumi; Rezaie, Tayebeh; Seki, Masaaki; Sunico, Carmen R.; Tabuchi, Takahito; Kitagawa, Tomomi; Yanagitai, Mika; Senzaki, Mutsumi; Kosegawa, Chihiro; Taira, Hideharu; McKercher, Scott R.; Hoffman, Jennifer K.; Roth, Gregory P.; Lipton, Stuart A.

    2015-01-01

    Activation of the Keap1/Nrf2 pathway and consequent induction of phase 2 antioxidant enzymes is known to afford neuroprotection. Here, we present a series of novel electrophilic compounds that protect neurons via this pathway. Natural products, such as carnosic acid (CA), are present in high amounts in the herbs rosemary and sage as ortho-dihydroquinones, and have attracted particular attention because they are converted by oxidative stress to their active form (ortho-quinone species) that stimulate the Keap1/Nrf2 transcriptional pathway. Once activated, this pathway leads to the production of a series of antioxidant phase 2 enzymes. Thus, such dihydroquinones function as redox-activated “pro-electrophiles.” Here, we explored the concept that related para-dihydroquinones represent even more effective bioactive pro-electrophiles for the induction of phase 2 enzymes without producing toxic side effects. We synthesized several novel para-hydroquinone-type pro-electrophilic compounds (designated D1 and D2) in order to analyze their protective mechanism. DNA microarray, PCR, and Western blot analyses showed that compound D1 induced expression of heat-shock proteins (HSPs), including HSP70, HSP27 and DnaJ, in addition to phase 2 enzymes such as hemeoxygenase-1 (HO-1), NADP(H) quinine-oxidoreductase1, and the Na+-independent cystine/glutamate exchanger. Treatment with D1 resulted in activation of Nrf2 and HSF-1 transcriptional elements, thus inducing phase 2 enzymes and HSPs, respectively. In this manner, D1 protected neuronal cells from both oxidative and endoplasmic reticulum (ER)-related stress. Additionally, D1 suppressed induction of GRP78, an ER chaperone protein, and inhibited hyperoxidation of peroxiredoxin 2 (PRX2), a molecule that in it reduced state can protect from oxidative stress. These results suggest that D1 is a novel pro-electrophilic compound that activates both the Nrf2 and HSF-1 pathways, and may thus offer protection from oxidative and ER stress

  17. IFAT and ELISA phase I/phase II as tools for the identification of Q fever chronic milk shedders in cattle.

    PubMed

    Lucchese, Laura; Capello, Katia; Barberio, Antonio; Zuliani, Federica; Stegeman, Arjan; Ceglie, Letizia; Guerrini, Eulalia; Marangon, Stefano; Natale, Alda

    2015-08-31

    Q fever is a widespread zoonotic disease caused by Coxiella burnetii. In cattle the bacterial shedding can persist without symptoms for several months and the shedders identification is a critical issue in the control of the infection at herd level. Following the example of the human protocols for the assessment of Q fever infection status, the aim of this study was the evaluation of the antibody response dynamics to phase I and phase II antigens in C. burnetii shedder dairy cows by means of a phase-specific serology, to verify the suitability of the investigated tools in recognising milk shedders. A total of 99 cows were monitored during time and classified on the basis of serological and PCR results in five groups identifying different shedding patterns. The 297 sera collected in three sampling times were tested by means of ELISA IgG for differential phase I and phase II antibodies detection, while a selection of 107 sera were tested by means of phase specific IgM and IgG IFAT. Both ELISA IgG and IFAT IgG highlighted a low reactivity in non-shedder seropositive animals compared to chronic milk shedder animals. ELISA IgG seemed to perform better than IFAT IgG-IgM, showing significant serological differences among groups that allowed recognising specific serological group patterns, in particular for chronic and occasional milk shedders. These results supported the hypothesis that an animal classification based on phase patterns is reasonable, although it needs to be further investigated.

  18. Auto-induction of phase I and phase II metabolism of artemisinin in healthy Chinese subjects after oral administration of a new artemisinin-piperaquine fixed combination

    PubMed Central

    2014-01-01

    Background Artequick is a relatively inexpensive artemisinin (Qing-hao-su; QHS)-based combination therapy (ACT) that contains QHS and piperaquine (PQ), which has not been widely used because of the decreased concentration level of QHS after repeated oral administrations for five to seven days as a monotherapy. This study was designed to evaluate the potential auto-induction metabolism of QHS in healthy Chinese adults after a two-day oral administration of QHS-PQ. The effect of QHS-PQ on the activity of the CYP2B6 and CYP3A4 was also investigated. Methods Fourteen healthy Chinese subjects received two-day oral doses of QHS-PQ (Artequick). A two-drug cocktail consisting of bupropion and midazolam was used to assess the activities of CYP2B6 and CYP3A, respectively. Plasma samples were analysed for QHS and its phase I/II metabolites, probe drugs and their metabolites, using a validated liquid chromatography tandem mass spectrometric (LC-MS) method. Results Four major phase I metabolites of QHS (M1-M3 and deoxy-QHS) and two subsequent phase II metabolites (M4-M5) were detected in human plasma after oral administrations of QHS-PQ. The AUC 0-t of the QHS and its phase I metabolites decreased significantly (P < 0.05) with increased oral clearance (CL/F) after two-day oral doses of QHS-PQ, whereas its phase II metabolites exhibited higher AUC (P < 0.01). The phase I metabolic capability, calculated by the AUC 0-t ratio of all phase I metabolites to QHS, increased 1.5-fold after the repeated dose (P < 0.01), and the phase II metabolic capability increased 1.5-fold for M4 and 3.0-fold for M5. The enzyme activity of CYP2B6 and CYP3A4 increased 2.1-fold and 3.2-fold, respectively, after two-day oral doses of QHS-PQ. Conclusions The auto-induction of both phase I and phase II metabolism of QHS was present in healthy Chinese subjects after a recommended two-day oral dose of QHS-PQ. The auto-induction metabolism also existed for phase I metabolites of QHS. The enzyme activity of

  19. Radiative Forcing of the Direct Aerosol Effect from AeroCom Phase II Simulations

    NASA Technical Reports Server (NTRS)

    Myhre, G.; Samset, B. H.; Schulz, M.; Balkanski, Y.; Bauer, S.; Berntsen, T. K.; Bian, H.; Bellouin, N.; Chin, M.; Diehl, T.; Easter, R. C.; Feichter, J.; Ghan, S. J.; Hauglustaine, D.; Iversen, T.; Kinne, S.; Kirkevag, A.; Lamarque, J.-F.; Lin, G.; Liu, X.; Lund, M. T.; Luo, G.; Ma, X.; vanNoije, T.; Penner, J. E.; Rasch, P. J.; Ruiz, A.; Seland, O.; Skeie, R. B.; Stier, P.; Takemura, T.; Tsigaridis, K.; Wang, P.; Wang, Z.; Xu, L.; Yu, H.; Yu, F.; Yoon, J. -H.; Zhang, K.; Zhang, H.; Zhou, C.

    2013-01-01

    We report on the AeroCom Phase II direct aerosol effect (DAE) experiment where 16 detailed global aerosol models have been used to simulate the changes in the aerosol distribution over the industrial era. All 16 models have estimated the radiative forcing (RF) of the anthropogenic DAE, and have taken into account anthropogenic sulphate, black carbon (BC) and organic aerosols (OA) from fossil fuel, biofuel, and biomass burning emissions. In addition several models have simulated the DAE of anthropogenic nitrate and anthropogenic influenced secondary organic aerosols (SOA). The model simulated all-sky RF of the DAE from total anthropogenic aerosols has a range from -0.58 to -0.02 W m(sup-2), with a mean of -0.27 W m(sup-2 for the 16 models. Several models did not include nitrate or SOA and modifying the estimate by accounting for this with information slightly strengthens the mean. Modifying the model estimates for missing aerosol components and for the time period 1750 to 2010 results in a mean RF for the DAE of -0.35 W m(sup-2). Compared to AeroCom Phase I (Schulz et al., 2006) we find very similar spreads in both total DAE and aerosol component RF. However, the RF of the total DAE is stronger negative and RF from BC from fossil fuel and biofuel emissions are stronger positive in the present study than in the previous AeroCom study.We find a tendency for models having a strong (positive) BC RF to also have strong (negative) sulphate or OA RF. This relationship leads to smaller uncertainty in the total RF of the DAE compared to the RF of the sum of the individual aerosol components. The spread in results for the individual aerosol components is substantial, and can be divided into diversities in burden, mass extinction coefficient (MEC), and normalized RF with respect to AOD. We find that these three factors give similar contributions to the spread in results

  20. Radiative forcing of the direct aerosol effect from AeroCom Phase II simulations

    SciTech Connect

    Myhre, G.; Samset, B. H.; Schulz, M.; Balkanski, Y.; Bauer, S.; Berntsen, T. K.; Bian, H.; Bellouin, N.; Chin, M.; Diehl, T.; Easter, R. C.; Feichter, J.; Ghan, S. J.; Hauglustaine, D.; Iversen, T.; Kinne, S.; Kirkevåg, A.; Lamarque, J. -F.; Lin, G.; Liu, X.; Lund, M. T.; Luo, G.; Ma, X.; van Noije, T.; Penner, J. E.; Rasch, P. J.; Ruiz, A.; Seland, Ø.; Skeie, R. B.; Stier, P.; Takemura, T.; Tsigaridis, K.; Wang, P.; Wang, Z.; Xu, L.; Yu, H.; Yu, F.; Yoon, J. -H.; Zhang, K.; Zhang, H.; Zhou, C.

    2013-01-01

    We report on the AeroCom Phase II direct aerosol effect (DAE) experiment where 16 detailed global aerosol models have been used to simulate the changes in the aerosol distribution over the industrial era. All 16 models have estimated the radiative forcing (RF) of the anthropogenic DAE, and have taken into account anthropogenic sulphate, black carbon (BC) and organic aerosols (OA) from fossil fuel, biofuel, and biomass burning emissions. In addition several models have simulated the DAE of anthropogenic nitrate and anthropogenic influenced secondary organic aerosols (SOA). The model simulated all-sky RF of the DAE from total anthropogenic aerosols has a range from -0.58 to -0.02 Wm-2, with a mean of -0.27 Wm-2 for the 16 models. Several models did not include nitrate or SOA and modifying the estimate by accounting for this with information from the other AeroCom models reduces the range and slightly strengthens the mean. Modifying the model estimates for missing aerosol components and for the time period 1750 to 2010 results in a mean RF for the DAE of -0.35 Wm-2. Compared to AeroCom Phase I (Schulz et al., 2006) we find very similar spreads in both total DAE and aerosol component RF. However, the RF of the total DAE is stronger negative and RF from BC from fossil fuel and biofuel emissions are stronger positive in the present study than in the previous AeroCom study. We find a tendency for models having a strong (positive) BC RF to also have strong (negative) sulphate or OA RF. This relationship leads to smaller uncertainty in the total RF of the DAE compared to the RF of the sum of the individual aerosol components. The spread in results for the individual aerosol components is substantial, and can be divided into diversities in burden, mass extinction coefficient (MEC), and normalized RF with respect to AOD. We find that these three factors give similar contributions to the spread in results.

  1. Cabozantinib in Patients With Advanced Prostate Cancer: Results of a Phase II Randomized Discontinuation Trial

    PubMed Central

    Smith, David C.; Smith, Matthew R.; Sweeney, Christopher; Elfiky, Aymen A.; Logothetis, Christopher; Corn, Paul G.; Vogelzang, Nicholas J.; Small, Eric J.; Harzstark, Andrea L.; Gordon, Michael S.; Vaishampayan, Ulka N.; Haas, Naomi B.; Spira, Alexander I.; Lara, Primo N.; Lin, Chia-Chi; Srinivas, Sandy; Sella, Avishay; Schöffski, Patrick; Scheffold, Christian; Weitzman, Aaron L.; Hussain, Maha

    2013-01-01

    Purpose Cabozantinib (XL184) is an orally bioavailable tyrosine kinase inhibitor with activity against MET and vascular endothelial growth factor receptor 2. We evaluated the activity of cabozantinib in patients with castration-resistant prostate cancer (CRPC) in a phase II randomized discontinuation trial with an expansion cohort. Patients and Methods Patients received 100 mg of cabozantinib daily. Those with stable disease per RECIST at 12 weeks were randomly assigned to cabozantinib or placebo. Primary end points were objective response rate at 12 weeks and progression-free survival (PFS) after random assignment. Results One hundred seventy-one men with CRPC were enrolled. Random assignment was halted early based on the observed activity of cabozantinib. Seventy-two percent of patients had regression in soft tissue lesions, whereas 68% of evaluable patients had improvement on bone scan, including complete resolution in 12%. The objective response rate at 12 weeks was 5%, with stable disease in 75% of patients. Thirty-one patients with stable disease at week 12 were randomly assigned. Median PFS was 23.9 weeks (95% CI, 10.7 to 62.4 weeks) with cabozantinib and 5.9 weeks (95% CI, 5.4 to 6.6 weeks) with placebo (hazard ratio, 0.12; P < .001). Serum total alkaline phosphatase and plasma cross-linked C-terminal telopeptide of type I collagen were reduced by ≥ 50% in 57% of evaluable patients. On retrospective review, bone pain improved in 67% of evaluable patients, with a decrease in narcotic use in 56%. The most common grade 3 adverse events were fatigue (16%), hypertension (12%), and hand-foot syndrome (8%). Conclusion Cabozantinib has clinical activity in men with CRPC, including reduction of soft tissue lesions, improvement in PFS, resolution of bone scans, and reductions in bone turnover markers, pain, and narcotic use. PMID:23169517

  2. A multicentre phase II study of cisplatin and gemcitabine for malignant mesothelioma

    PubMed Central

    Nowak, A K; Byrne, M J; Williamson, R; Ryan, G; Segal, A; Fielding, D; Mitchell, P; Musk, A W; Robinson, B W S

    2002-01-01

    Our previous phase II study of cisplatin and gemcitabine in malignant mesothelioma showed a 47.6% (95% CI 26.2–69.0%) response rate with symptom improvement in responding patients. Here we confirm these findings in a multicentre setting, and assess the effect of this treatment on quality of life and pulmonary function. Fifty-three patients with pleural malignant mesothelioma received cisplatin 100 mg m−2 i.v. day 1 and gemcitabine 1000 mg m−2 i.v. days 1, 8, and 15 of a 28 day cycle for a maximum of six cycles. Quality of life and pulmonary function were assessed at each cycle. The best response achieved in 52 assessable patients was: partial response, 17 (33%, 95% CI 20–46%); stable disease, 31 (60%); and progressive disease, four (8%). The median time to disease progression was 6.4 months, median survival from start of treatment 11.2 months, and median survival from diagnosis 17.3 months. Vital capacity and global quality of life remained stable in all patients and improved significantly in responding patients. Major toxicities were haematological, limiting the mean relative dose intensity of gemcitabine to 75%. This schedule of cisplatin and gemcitabine is active in malignant mesothelioma in a multicentre setting. Investigation of alternative scheduling is needed to decrease haematological toxicity and increase the relative dose intensity of gemcitabine whilst maintaining response rate and quality of life. British Journal of Cancer (2002) 87, 491–496. doi:10.1038/sj.bjc.6600505 www.bjcancer.com © 2002 Cancer Research UK PMID:12189542

  3. Separation of Corn Fiber and Conversion to Fuels and Chemicals Phase II: Pilot-scale Operation

    SciTech Connect

    Abbas, Charles; Beery, Kyle; Orth, Rick; Zacher, Alan

    2007-09-28

    The purpose of the Department of Energy (DOE)-supported corn fiber conversion project, “Separation of Corn Fiber and Conversion to Fuels and Chemicals Phase II: Pilot-scale Operation” is to develop and demonstrate an integrated, economical process for the separation of corn fiber into its principal components to produce higher value-added fuel (ethanol and biodiesel), nutraceuticals (phytosterols), chemicals (polyols), and animal feed (corn fiber molasses). This project has successfully demonstrated the corn fiber conversion process on the pilot scale, and ensured that the process will integrate well into existing ADM corn wet-mills. This process involves hydrolyzing the corn fiber to solubilize 50% of the corn fiber as oligosaccharides and soluble protein. The solubilized fiber is removed and the remaining fiber residue is solvent extracted to remove the corn fiber oil, which contains valuable phytosterols. The extracted oil is refined to separate the phytosterols and the remaining oil is converted to biodiesel. The de-oiled fiber is enzymatically hydrolyzed and remixed with the soluble oligosaccharides in a fermentation vessel where it is fermented by a recombinant yeast, which is capable of fermenting the glucose and xylose to produce ethanol. The fermentation broth is distilled to remove the ethanol. The stillage is centrifuged to separate the yeast cell mass from the soluble components. The yeast cell mass is sold as a high-protein yeast cream and the remaining sugars in the stillage can be purified to produce a feedstock for catalytic conversion of the sugars to polyols (mainly ethylene glycol and propylene glycol) if desirable. The remaining materials from the purification step and any materials remaining after catalytic conversion are concentrated and sold as a corn fiber molasses. Additional high-value products are being investigated for the use of the corn fiber as a dietary fiber sources.

  4. Stereotactic Body Radiotherapy for Localized Prostate Cancer: Interim Results of a Prospective Phase II Clinical Trial

    SciTech Connect

    King, Christopher R. Brooks, James D.; Gill, Harcharan; Pawlicki, Todd; Cotrutz, Cristian; Presti, Joseph C.

    2009-03-15

    Purpose: The radiobiology of prostate cancer favors a hypofractionated dose regimen. We report results of a prospective Phase II clinical trial of stereotactic body radiotherapy (SBRT) for localized prostate cancer. Methods and Materials: Forty-one low-risk prostate cancer patients with 6 months' minimum follow-up received 36.25 Gy in five fractions of 7.25 Gy with image-guided SBRT alone using the CyberKnife. The early (<3 months) and late (>6 months) urinary and rectal toxicities were assessed using validated quality of life questionnaires (International Prostate Symptom Score, Expanded Prostate Cancer Index Composite) and the Radiation Therapy Oncology Group (RTOG) toxicity criteria. Patterns of prostate-specific antigen (PSA) response are analyzed. Results: The median follow-up was 33 months. There were no RTOG Grade 4 acute or late rectal/urinary complications. There were 2 patients with RTOG Grade 3 late urinary toxicity and none with RTOG Grade 3 rectal complications. A reduced rate of severe rectal toxicities was observed with every-other-day vs. 5 consecutive days treatment regimen (0% vs. 38%, p = 0.0035). A benign PSA bounce (median, 0.4 ng/mL) was observed in 12 patients (29%) occurring at 18 months (median) after treatment. At last follow-up, no patient has had a PSA failure regardless of biochemical failure definition. Of 32 patients with 12 months minimum follow-up, 25 patients (78%) achieved a PSA nadir {<=}0.4 ng/mL. A PSA decline to progressively lower nadirs up to 3 years after treatment was observed. Conclusions: The early and late toxicity profile and PSA response for prostate SBRT are highly encouraging. Continued accrual and follow-up will be necessary to confirm durable biochemical control rates and low toxicity profiles.

  5. Samples of exact k-stage group sequential designs for Phase II and Pilot studies.

    PubMed

    Kepner, James L; Chang, Myron N

    2004-06-01

    That the test of H(0): p=p(0) versus H(1): p>p(0) can be based on a binomially distributed random variable is widely known among users of statistical methods. What is not generally known is that under certain very general conditions, it is possible to find an exact k-stage group sequential test whose total sample size is bounded above by the sample size for the single stage binomial test. That is, it is possible to find k-stage tests for detecting H(1) for which the sum of the sample sizes at each of the stages is bounded above by the sample size for the standard binomial test. This result is somewhat remarkable since the total sample size under the group sequential test setting can be strictly less than the sample size for the uniformly most powerful (UMP) one-stage binomial test. In other words, exact group sequential tests cannot only save the average sample size but can also save the maximum sample size when they are compared to the standard binomial test. In this paper, implications of existing theory are explored and a web application written by the authors is presented. No new theory is established. Applications are described and methods are demonstrated that use the web application to rapidly create efficient designs for Phase II and Pilot studies that put a minimum number of patients at risk and that facilitate the rapid progression through a scientific research agenda. While couched here in the context of clinical trials, the results may be used in any field of inquiry where inferences are made based on the size of a binomial random variable.

  6. Washington Phase II Fish Diversion Screen Evaluations in the Yakima River Basin, 1999.

    SciTech Connect

    Blanton, S.L.; Neitzel, Duane A.; McMichael, Geoffrey A.

    2000-04-01

    Pacific Northwest National Laboratory (PNNL) evaluated 20 Phase II screen sites in the Yakima River Basin as part of a multi-year study for the Bonneville Power Administration (BPA) on the effectiveness of fish screening devices. The sites were examined to determine if they were being effectively operated and maintained to provide fish a safe, efficient return to the Yakima River. Data were collected to determine if velocities in front of the screens and in the bypass met current National Marine Fisheries Service (NMFS) criteria to promote safe and timely fish bypass and whether bypass outfall conditions allowed fish to safely return to the river. In general, water velocity conditions at the screen sites met fish passage criteria set forth by the NMFS. Although velocities often fluctuated from one sampling location to the next, average sweep velocities typically exceeded approach velocities and increased toward the bypass. Mean approach velocities were below the NMFS criteria of < 0.4 feet per second (fps) at most sites (Table 1). Based on our observations in 1999, we believe that most facilities were efficiently protecting juvenile fish from entrainment, impingement, or migration delay. Most screens were properly sealed to prevent fish entrainment and injury, although potential problems were identified at several screen sites. Six sites (one fewer than the seven sites identified in 1998) had loose or damaged seals that might have allowed fish to be entrained (Table 1). Other sites still had spaces larger than 3/32 in. where small fish could possibly pass into the irrigation canal.

  7. Phase II evaluation of S-adenosyl-L-methionine (SAMe) for the treatment of hot flashes

    PubMed Central

    Kadakia, Kunal C.; Loprinzi, Charles L.; Atherton, Pamela J.; Fee-Schroeder, Kelliann C.; Sood, Amit; Barton, Debra L.

    2016-01-01

    Purpose Hot flashes are a significant source of symptom burden that negatively impacts quality of life (QOL). For women who have contraindications to, or are unwilling to consider, estrogens or antidepressants for bothersome hot flashes, there are limited effective pharmacologic or complementary and alternative medicines. Methods This single-arm phase II trial studied the efficacy of S-adenosyl-L-methionine (SAMe) for the treatment of hot flashes. Eligible women were required to have reported ≥14 hot flashes per week for ≥1 month. The patients were treated with SAMe at a dose of 400 mg twice daily to evaluate whether a reduction in hot flash score appeared to be better than the historical placebo response of approximately 25 %. The women kept a daily hot flash diary during a baseline week and then daily during weeks 2–7. The primary endpoint was the change from baseline to week 7 in hot flash score and hot flash frequency. Secondary endpoints included toxicity analyses and the effect of SAMe on QOL. Results From October 28, 2010 to January 30, 2012, 43 women were treated with SAMe. The decrease in mean percent of baseline hot flash score and frequency was 35.4 and 32.6 %, respectively. When compared to the historical placebo response of 25 %, the effect of SAMe on hot flash score was not statistically significant (p=0.09). Treatment was well tolerated with expected grade 1/2 gastrointestinal toxicity and no negative effect on QOL. Conclusions The use of SAMe does not appear to significantly reduce hot flashes more than would be expected with a placebo. PMID:26248653

  8. ENGAGE- 501: phase II study of entinostat (SNDX-275) in relapsed and refractory Hodgkin lymphoma

    PubMed Central

    Batlevi, Connie Lee; Kasamon, Yvette; Bociek, R. Gregory; Lee, Peter; Gore, Lia; Copeland, Amanda; Sorensen, Rachel; Ordentlich, Peter; Cruickshank, Scott; Kunkel, Lori; Buglio, Daniela; Hernandez-Ilizaliturri, Francisco; Younes, Anas

    2016-01-01

    Classical Hodgkin lymphoma treatment is evolving rapidly with high response rates from antibody-drug conjugates targeting CD30 and immune checkpoint antibodies. However, most patients do not achieve a complete response, therefore development of novel therapies is warranted to improve patient outcomes. In this phase II study, patients with relapsed or refractory Hodgkin lymphoma were treated with entinostat, an isoform selective histone deacetylase inhibitor. Forty-nine patients were enrolled: 33 patients on Schedule A (10 or 15 mg oral entinostat once every other week); 16 patients on Schedule B (15 mg oral entinostat once weekly in 3 of 4 weeks). Patients received a median of 3 prior treatments (range 1–10), with 80% of the patients receiving a prior stem cell transplant and 8% of patients receiving prior brentuximab vedotin. In the intention-to-treat analysis, the overall response rate was 12% while the disease control rate (complete response, partial response, and stable disease beyond 6 months) was 24%. Seven patients did not complete the first cycle due to progression of disease. Tumor reduction was observed in 24 of 38 (58%) evaluable patients. Median progression-free survival and overall survival was 5.5 and 25.1 months, respectively. The most frequent grade 3 or 4 adverse events were thrombocytopenia (63%), anemia (47%), neutropenia (41%), leukopenia (10%), hypokalemia (8%), and hypophosphatemia (6%). Twenty-five (51%) patients required dose reductions or delays. Pericarditis/pericardial effusion occurred in one patient after 12 cycles of therapy. Future studies are warranted to identify predictive biomarkers for treatment response and to develop mechanism-based combination strategies. (clinicaltrials.gov identifier: 00866333) PMID:27151994

  9. Phase II Study of Aflibercept in Recurrent Malignant Glioma: A North American Brain Tumor Consortium Study

    PubMed Central

    de Groot, John F.; Lamborn, Kathleen R.; Chang, Susan M.; Gilbert, Mark R.; Cloughesy, Timothy F.; Aldape, Kenneth; Yao, Jun; Jackson, Edward F.; Lieberman, Frank; Robins, H. Ian; Mehta, Minesh P.; Lassman, Andrew B.; DeAngelis, Lisa M.; Yung, W.K. Alfred; Chen, Alice; Prados, Michael D.; Wen, Patrick Y.

    2011-01-01

    Purpose Antivascular endothelial growth factor (anti-VEGF) therapy is a promising treatment approach for patients with recurrent glioblastoma. This single-arm phase II study evaluated the efficacy of aflibercept (VEGF Trap), a recombinantly produced fusion protein that scavenges both VEGF and placental growth factor in patients with recurrent malignant glioma. Patients and Methods Forty-two patients with glioblastoma and 16 patients with anaplastic glioma who had received concurrent radiation and temozolomide and adjuvant temozolomide were enrolled at first relapse. Aflibercept 4 mg/kg was administered intravenously on day 1 of every 2-week cycle. Results The 6-month progression-free survival rate was 7.7% for the glioblastoma cohort and 25% for patients with anaplastic glioma. Overall radiographic response rate was 24% (18% for glioblastoma and 44% for anaplastic glioma). The median progression-free survival was 24 weeks for patients with anaplastic glioma (95% CI, 5 to 31 weeks) and 12 weeks for patients with glioblastoma (95% CI, 8 to 16 weeks). A total of 14 patients (25%) were removed from the study for toxicity, on average less than 2 months from treatment initiation. The main treatment-related National Cancer Institute Common Terminology Criteria grades 3 and 4 adverse events (38 total) included fatigue, hypertension, and lymphopenia. Two grade 4 CNS ischemias and one grade 4 systemic hemorrhage were reported. Aflibercept rapidly decreases permeability on dynamic contrast enhanced magnetic resonance imaging, and molecular analysis of baseline tumor tissue identified tumor-associated markers of response and resistance. Conclusion Aflibercept monotherapy has moderate toxicity and minimal evidence of single-agent activity in unselected patients with recurrent malignant glioma. PMID:21606416

  10. Phase II Trials of Erlotinib or Gefitinib in Patients with Recurrent Meningioma

    PubMed Central

    Norden, Andrew D.; Raizer, Jeffrey J.; Abrey, Lauren E.; Lamborn, Kathleen R.; Lassman, Andrew B.; Chang, Susan M.; Yung, W.K. Alfred; Gilbert, Mark R.; Fine, Howard A.; Mehta, Minesh; DeAngelis, Lisa M.; Cloughesy, Timothy F.; Robins, H. Ian; Aldape, Kenneth; Dancey, Janet; Prados, Michael D.; Lieberman, Frank; Wen, Patrick Y.

    2013-01-01

    There are no established treatments for recurrent meningioma when surgical and radiation options are exhausted. The epidermal growth factor receptor (EGFR) is often over-expressed in meningiomas and may promote tumor growth. In open label, single arm phase II studies of the EGFR inhibitors gefitinib (NABTC 00-01) and erlotinib (NABTC 01-03) for recurrent malignant gliomas, we included exploratory subsets of recurrent meningioma patients. We have pooled the data and report the results here. Patients with recurrent histologically confirmed meningiomas with no more than 2 previous chemotherapy regimens were treated with gefitinib 500 mg/day or erlotinib 150 mg/day until tumor progression or unacceptable toxicity. Twenty-five eligible patients were enrolled with median age 57 years (range 29–81) and median Karnofsky performance status (KPS) score 90 (range 60–100). Sixteen patients (64%) received gefitinib and 9 (36%) erlotinib. Eight patients (32%) had benign tumors, 9 (36%) atypical, and 8 (32%) malignant. For benign tumors, the 6-month progression-free survival (PFS6) was 25%, 12-month PFS (PFS12) 13%, 6-month overall survival (OS6) 63%, and 12-month OS (OS12) 50%. For atypical and malignant tumors, PFS6 was 29%, PFS12 18%, OS6 71%, and OS12 65%. The PFS and OS were not significantly different by histology. There were no objective imaging responses, but 8 patients (32%) maintained stable disease. Although treatment was well-tolerated, neither gefitinib nor erlotinib appear to have significant activity against recurrent meningioma. The role of EGFR inhibitors in meningiomas is unclear. Evaluation of multi-targeted inhibitors and EGFR inhibitors in combination with other targeted molecular agents may be warranted. PMID:19562255

  11. Phase II clinical trial of pasireotide long-acting repeatable in patients with metastatic neuroendocrine tumors

    PubMed Central

    Cives, M; Kunz, P L; Morse, B; Coppola, D; Schell, M J; Campos, T; Nguyen, P T; Nandoskar, P; Khandelwal, V; Strosberg, J R

    2015-01-01

    Pasireotide long-acting repeatable (LAR) is a novel somatostatin analog (SSA) with avid binding affinity to somatostatin receptor subtypes 1, 2, 3 (SSTR1,2,3) and 5 (SSTR5). Results from preclinical studies indicate that pasireotide can inhibit neuroendocrine tumor (NET) growth more robustly than octreotide in vitro. This open-label, phase II study assessed the clinical activity of pasireotide in treatment-naïve patients with metastatic grade 1 or 2 NETs. Patients with metastatic pancreatic and extra-pancreatic NETs were treated with pasireotide LAR (60 mg every 4 weeks). Previous systemic therapy, including octreotide and lanreotide, was not permitted. Tumor assessments were performed every 3 months using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), overall radiographic response rate (ORR), and safety. Twenty-nine patients were treated with pasireotide LAR (60 mg every 4 weeks) and 28 were evaluable for response. The median PFS was 11 months. The most favorable effect was observed in patients with low hepatic tumor burden, normal baseline chromogranin A, and high tumoral SSTR5 expression. Median OS has not been reached; the 30-month OS rate was 70%. The best radiographic response was partial response in one patient (4%), stable disease in 17 patients (60%), and progressive disease in ten patients (36%). Although grade 3/4 toxicities were rare, pasireotide LAR treatment was associated with a 79% rate of hyperglycemia including 14% grade 3 hyperglycemia. Although pasireotide appears to be an effective antiproliferative agent in the treatment of advanced NETs, the high incidence of hyperglycemia raises concerns regarding its suitability as a first-line systemic agent in unselected patients. SSTR5 expression is a potentially predictive biomarker for response. PMID:25376618

  12. Erythropoietin Neuroprotection in Neonatal Cardiac Surgery: A Phase I/II Safety and Efficacy Trial

    PubMed Central

    Andropoulos, Dean B.; Brady, Ken; Easley, R. Blaine; Dickerson, Heather A.; Voigt, Robert G.; Shekerdemian, Lara S.; Meador, Marcie R.; Eisenman, Carol A.; Hunter, Jill V.; Turcich, Marie; Rivera, Carlos; McKenzie, E. Dean; Heinle, Jeffrey S.; Fraser, Charles D.

    2012-01-01

    Objectives Neonates undergoing complex congenital heart surgery have a significant incidence of neurological problems. Erythropoietin has anti-apoptotic, anti-excitatory, and anti-inflammatory properties to prevent neuronal cell death in animal models, and improves neurodevelopmental outcomes in full term neonates with hypoxic ischemic encephalopathy. We designed a prospective phase I/II trial of erythropoietin neuroprotection in neonatal cardiac surgery to assess safety, and indicate efficacy. Methods Neonates undergoing surgery for D-transposition of the great vessels, hypoplastic left heart syndrome, or aortic arch reconstruction were randomized to 3 perioperative doses of erythropoietin, or placebo. Neurodevelopmental testing with Bayley Scales of Infant and Toddler Development III was performed at age 12 months. Results 59 patients received study drug. Safety profile, including MRI brain injury, clinical events, and death, was not different between groups. 3 patients in each group died. 42 patients (22 erythropoietin, 20 placebo, 79% of survivors) returned for 12-month follow-up. The mean Cognitive Scores were erythropoietin, 101.1 ± 13.6, placebo, 106.3 ± 10.8 (p=0.19); Language Scores were erythropoietin 88.5 ± 12.8, placebo 92.4 ± 12.4 (p=0.33); and Motor Scores were erythropoietin 89.9 ± 12.3, placebo 92.6 ± 14.1, (p=0.51). Conclusions Safety profile for erythropoietin administration was not different than placebo. Neurodevelopmental outcomes were not different between groups, however this pilot study was not powered to definitively address this outcome. Lessons learned from the current study suggest optimized study design features for a larger prospective trial to definitively address the utility of erythropoietin for neuroprotection in this population. PMID:23102686

  13. Differentiation therapy in poor risk myeloid malignancies: Results of companion phase II studies.

    PubMed

    Norsworthy, Kelly J; Cho, Eunpi; Arora, Jyoti; Kowalski, Jeanne; Tsai, Hua-Ling; Warlick, Erica; Showel, Margaret; Pratz, Keith W; Sutherland, Lesley A; Gore, Steven D; Ferguson, Anna; Sakoian, Sarah; Greer, Jackie; Espinoza-Delgado, Igor; Jones, Richard J; Matsui, William H; Smith, B Douglas

    2016-10-01

    Pre-clinical data in non-M3 AML supports the use of differentiation therapy, but clinical activity has been limited. Myeloid growth factors can enhance anti-leukemic activity of differentiating agents in vitro. We conducted companion phase II trials investigating sargramostim (GM-CSF) 125μg/m(2)/day plus 1) bexarotene (BEX) 300mg/m(2)/day or 2) entinostat (ENT) 4-8mg/m(2)/week in patients with MDS or relapsed/refractory AML. Primary endpoints were response after at least two treatment cycles and toxicity. 26 patients enrolled on the BEX trial had a median of 2 prior treatments and 24 enrolled on the ENT trial had a median of 1. Of 13 response-evaluable patients treated with BEX, the best response noted was hematologic improvement in neutrophils (HI-N) seen in 4 (31%) patients; none achieved complete (CR) or partial remission (PR). Of 10 treated with ENT, there was 1 (10%) partial remission (PR) and 2 (20%) with HI-N. The secondary endpoint responses of HI-N with each combination were accompanied by a numerical increase in ANC (BEX: 524 to 931 cells/mm(3), p=0.096; ENT: 578 to 1 137 cells/mm(3), p=0.15) without increasing marrow blasts. Shared grade 3-4 non-hematologic toxicities included febrile neutropenia, bone pain, fatigue, and dyspnea. GM-CSF plus either BEX or ENT are well tolerated in resistant and refractory MDS and AML and showed modest clinical and biologic activity, most commonly HI-N.

  14. Phase I and pharmacokinetic study of the topoisomerase II catalytic inhibitor fostriecin

    PubMed Central

    Jong, R S de; Mulder, N H; Uges, D R A; Sleijfer, D Th; Höppener, F J P; Groen, H J M; Willemse, P H B; Graaf, W T A van der; Vries, E G E de

    1999-01-01

    We conducted a phase I and pharmacokinetic study of the topoisomerase II catalytic inhibitor fostriecin. Fostriecin was administered intravenously over 60 min on days 1–5 at 4-week intervals. Dose was escalated from 2 mg m−2day−1to 20 mg m−2day−1in 20 patients. Drug pharmacokinetics was analysed with high performance liquid chromatography with UV-detection. Plasma collected during drug administration was tested in vitro for growth inhibition of a teniposide-resistant small-cell lung cancer (SCLC) cell line. The predominant toxicities were elevated liver transaminases (maximum common toxicity criteria (CTC) grade 4) and serum creatinine (maximum CTC grade 2). These showed only a limited increase with increasing doses, often recovered during drug administration and were fully reversible. Duration of elevated alanine–amino transferase (ALT) was dose-limiting in one patient at 20 mg m−2. Other frequent toxicities were grade 1–2 nausea/vomiting, fever and mild fatigue. Mean fostriecin plasma half-life was 0.36 h (initial; 95% CI, 0–0.76 h) and 1.51 h (terminal; 95% CI, 0.41–2.61 h). A metabolite, most probably dephosphorylated fostriecin, was detected in plasma and urine. No tumour responses were observed, but the plasma concentrations reached in the patients were insufficient to induce significant growth inhibition in vitro. The maximum tolerated dose (MTD) has not been reached, because drug supply was stopped at the 20 mg m−2dose level. However, further escalation seems possible and is warranted to achieve potentially effective drug levels. Fostriecin has a short plasma half-life and longer duration of infusion should be considered. © 1999 Cancer Research Campaign PMID:10070885

  15. Intraoperative Radiotherapy in Early-Stage Breast Cancer: Results of the Montpellier Phase II Trial

    SciTech Connect

    Lemanski, Claire; Azria, David; Gourgon-Bourgade, Sophie; Gutowski, Marian; Rouanet, Phillippe; Saint-Aubert, Bernard; Ailleres, Norbert; Fenoglietto, Pascal; Dubois, Jean-Bernard

    2010-03-01

    Purpose: We recently presented the intraoperative radiotherapy (IORT) technique given as a reliable alternative to conventional boost radiation after breast-conserving surgery. The low crude numbers of recurrence in elderly patients led us to investigate the feasibility and the efficacy of this procedure as a sole treatment. Methods and Materials: We included 94 patients older than 65 years in this phase II trial. Among them, 42 patients presented with all the inclusion criteria, i.e., stages pT0 to pT1 and pN0, ductal invasive unifocal carcinoma, and tumor-free margin of >2 mm. IORT was delivered using a dedicated linear accelerator. One 21-Gy fraction was prescribed and specified at the 90% isodose, using electrons. In vivo dosimetry was performed for all patients. The primary endpoint was the quality index. Secondary endpoints were quality of life, local recurrences, cosmetic results, and specific and overall rates of survival. Results: The median follow-up was 30 months (range, 12-49 months), and median age was 72 years (range, 66-80 years). The median tumor diameter was 10 mm. All patients received the total prescribed dose. No acute grade 3 toxicities were observed. Endpoints for all but one patient corresponded to acceptable quality index criteria. Pretreatment quality-of-life scores were maximal, and no significant decrease was observed during follow-up. Cosmesis was good to excellent at 6 months. Two patients experienced recurrence but underwent salvage mastectomy. Conclusion: Our results confirm that exclusive partial-breast IORT is feasible for treating early-stage breast cancer in the elderly. IORT may be considered an alternative treatment for a selected population and offers a safe one-step treatment.

  16. Murine Alveolar Macrophages Are Highly Susceptible to Replication of Coxiella burnetii Phase II In Vitro.

    PubMed

    Fernandes, Talita D; Cunha, Larissa D; Ribeiro, Juliana M; Massis, Liliana M; Lima-Junior, Djalma S; Newton, Hayley J; Zamboni, Dario S

    2016-09-01

    Coxiella burnetii is a Gram-negative bacterium that causes Q fever in humans. Q fever is an atypical pneumonia transmitted through inhalation of contaminated aerosols. In mammalian lungs, C. burnetii infects and replicates in several cell types, including alveolar macrophages (AMs). The innate immunity and signaling pathways operating during infection are still poorly understood, in part because of the lack of relevant host cell models for infection in vitro In the study described here, we investigated and characterized the infection of primary murine AMs by C. burnetii phase II in vitro Our data reveal that AMs show a pronounced M2 polarization and are highly permissive to C. burnetii multiplication in vitro Murine AMs present an increased susceptibility to infection in comparison to primary bone marrow-derived macrophages. AMs support more than 2 logs of bacterial replication during 12 days of infection in culture, similar to highly susceptible host cells, such as Vero and THP-1 cells. As a proof of principle that AMs are useful for investigation of C. burnetii replication, we performed experiments with AMs from Nos2(-/-) or Ifng(-/-) mice. In the absence of gamma interferon and nitric oxide synthase 2 (NOS2), AMs were significantly more permissive than wild-type cells. In contrast, AMs from Il4(-/-) mice were more restrictive to C. burnetii replication, supporting the importance of M2 polarization for the permissiveness of AMs to C. burnetii replication. Collectively, our data account for understanding the high susceptibility of alveolar macrophages to bacterial replication and support the use of AMs as a relevant model of C. burnetii growth in primary macrophages. PMID:27297388

  17. Ethanol production via fungal decomposition and fermentation of biomass. Phase II (FY 1981) annual progress report

    SciTech Connect

    Antonopoulos, A. A.; Wene, E. G.

    1981-10-01

    This program has as its main goal the isolation and development of Fusarium strains that can efficiently and economically decompose plant polysaccharides to pentoses and hexoses and ferment them to ethanol for fuel purposes. During Phase II (FY 1981) of this program, more than 800 new Fusarium isolates were isolated and screened. All showed cellulolytic activity. The Fusarium mutant ANL 3-72181 (derived after uv exposure of ANL 22 isolate) produced 2.45 iu cellulase after 14 days. This cellulase activity was achieved in the presence of 0.7 mg/mL extracellular protein. In separate tests, the use of both proteose peptone and yeast extract with 1% cellulose increased the production of extracellular protein three times over that on cellulose alone. Initial fermentation by Fusarium strains on 1% glucose produced up to 4.2 mg/mL ethanol in 48 hours. All Fusarium isolates and mutants found during this period were screened for xylose fermentation. Ethanol production during early experimentation required from 120 to 144 hours to yield 4.0 to 4.5 mg/mL ethanol from 1% xylose solutions. Through continuous selection of isolates, this time was reduced to 66 hours. By recycling Fusarium cell mass, fermentations of 1% xylose yielded 4.0 to 4.3 mg/mL ethanol in 48 hours. Consecutive fermentations of 2% xylose produced an average of 8.1 mg/mL ethanol in 48 hours. Fermentation of a 4.5% xylose + 2% glucose solution produced 21 mg/mL ethanol and 0.8 mg/mL acetic acid, while fermentation of a 7% xylose + 2% glucose solution yielded 25.5 mg/mL ethanol and 0.85 mg/mL acetic acid; these fermentations were aerated at a rate of 0.03 v/v-min.

  18. A phase II trial of ISIS 3521 in patients with metastatic colorectal cancer.

    PubMed

    Marshall, John L; Eisenberg, Steven G; Johnson, Michael D; Hanfelt, John; Dorr, F Andrew; El-Ashry, Dorraya; Oberst, Michael; Fuxman, Yair; Holmlund, Jon; Malik, Shakun

    2004-11-01

    This phase II study was designed to characterize the clinical activity of ISIS 3521 in patients with metastatic colorectal cancer (CRC). Sixteen patients with pretreated or refractory CRC were treated with ISIS 3521. Eleven patients were given a dose of 2.0 mg/kg per day, and 5 patients received 3.0 mg/kg per day given over 21 days followed by a 7-day rest period. Patients continued with study until evidence of disease progression or unacceptable toxicity was detected. Patients underwent baseline tumor biopsies followed by a second biopsy during the last week of the first 21-day infusion. All 16 patients underwent baseline tumor biopsies, and 12 of the 16 patients underwent on-study tumor biopsies. No evidence of tumor response was observed. One patient had stable disease after 2 cycles and remained on for 1 additional cycle only to demonstrate progression of disease at that time. No dose-limiting or other significant toxicities were observed at both dosages, which could not be explained by progression of disease. Fatigue was common in all patients treated but was not dose limiting, and there was no evidence of coagulopathy. Analysis of the tumor biopsies obtained from the 11 evaluable samples showed marked uptake of ISIS 3521 in the normal liver parenchyma. However, there was minimal uptake within the tumor cells. In addition, no evidence of any alteration in protein kinase C-a within the tumors or any downstream effects leading to apoptosis were observed. ISIS 3521 demonstrated no clinical activity or target modulation in refractory metastatic CRC.

  19. Phase II Trial of Upfront Bevacizumab, Irinotecan, and Temozolomide for Unresectable Glioblastoma

    PubMed Central

    Lou, Emil; Desjardins, Annick; Reardon, David A.; Lipp, Eric S.; Miller, Elizabeth; Herndon, James E.; McSherry, Frances; Friedman, Henry S.; Vredenburgh, James J.

    2015-01-01

    Lessons Learned Trials focusing on unresectable multifocal glioblastoma are needed because of the extremely poor prognosis and challenges in receiving standard therapy, such as concurrent radiation and chemotherapy. Developing a strategy to chemically debulk tumors before radiation and/or surgery is warranted. Background. Extent of resection remains a key prognostic factor in glioblastoma (GBM), with gross total resection providing a better prognosis than biopsy or subtotal resection. We conducted a phase II trial of upfront therapy with bevacizumab (BV), irinotecan (CPT-11), and temozolomide (TMZ) prior to chemoradiation in patients with unresectable, subtotally resected, and/or multifocal GBM. Methods. Patients received up to 4 cycles of TMZ at 200 mg/m2 per day on days 1–5 (standard dosing) and BV at 10 mg/kg every 2 weeks on a 28-day cycle. CPT-11 was given every 2 weeks on a 28-day cycle at 125 mg/m2 or 340 mg/m2 depending on antiepileptic drugs. Magnetic resonance imaging of the brain was done every 4 weeks, and treatment continued as long as there was no tumor progression or unmanageable toxicity. The primary endpoint was tumor response rate, with a goal of 26% or greater. Results. Forty-one patients were enrolled from December 2009 to November 2010. Radiographic responses were as follows: 9 patients (22.0%) had partial respons!e, 25 (61.0%) had stable disease, and 2 (4.9%) had progression; 5 patients were not assessed. Cumulative response rate was 22%. Median overall survival was 12 months (95% confidence interval: 7.2–13.5 months). Conclusion. Upfront treatment with BV, TMZ, and CPT-11 is tolerable and can lead to radiographic response in unresectable and/or subtotally resected GBM. PMID:26025933

  20. Offshore Code Comparison Collaboration, Continuation: Phase II Results of a Floating Semisubmersible Wind System: Preprint

    SciTech Connect

    Robertson, A.; Jonkman, J.; Musial, W.; Vorpahl, F.; Popko, W.

    2013-11-01

    Offshore wind turbines are designed and analyzed using comprehensive simulation tools that account for the coupled dynamics of the wind inflow, aerodynamics, elasticity, and controls of the turbine, along with the incident waves, sea current, hydrodynamics, and foundation dynamics of the support structure. The Offshore Code Comparison Collaboration (OC3), which operated under the International Energy Agency (IEA) Wind Task 23, was established to verify the accuracy of these simulation tools [1]. This work was then extended under the Offshore Code Comparison Collaboration, Continuation (OC4) project under IEA Wind Task 30 [2]. Both of these projects sought to verify the accuracy of offshore wind turbine dynamics simulation tools (or codes) through code-to-code comparison of simulated responses of various offshore structures. This paper describes the latest findings from Phase II of the OC4 project, which involved the analysis of a 5-MW turbine supported by a floating semisubmersible. Twenty-two different organizations from 11 different countries submitted results using 24 different simulation tools. The variety of organizations contributing to the project brought together expertise from both the offshore structure and wind energy communities. Twenty-one different load cases were examined, encompassing varying levels of model complexity and a variety of metocean conditions. Differences in the results demonstrate the importance and accuracy of the various modeling approaches used. Significant findings include the importance of mooring dynamics to the mooring loads, the role nonlinear hydrodynamic terms play in calculating drift forces for the platform motions, and the difference between global (at the platform level) and local (at the member level) modeling of viscous drag. The results from this project will help guide development and improvement efforts for these tools to ensure that they are providing the accurate information needed to support the design and