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Sample records for activities phase ii

  1. Induction by xenobiotics of phase I and phase II enzyme activities in the human keratinocyte cell line NCTC 2544.

    PubMed

    Gelardi, A; Morini, F; Dusatti, F; Penco, S; Ferro, M

    2001-12-01

    This study analyses the expression and induction of several drug-metabolising enzyme activities involved in either phase I or phase II biotransformations in NCTC 2544 human keratinocytes. The phase I activities 7-ethoxycoumarin O-deethylase (ECOD), 7-ethoxyresorufin O-deethylase (EROD) and 7-pentoxyresorufin O-depenthylase (PROD) were easily detectable in basal conditions. During incubations lasting up to 144 h in the presence of the classical cytochrome P450 inducers beta-naphthoflavone (BNF), 3-methylcholanthrene (MC) and phenobarbital (PB), a considerable and significant increase in all the three activities was observed. PROD activity was induced up to 4.5-fold after 96 h in the presence of PB. The MC-induced ECOD and EROD activities were also dose-dependently inhibited by alpha-naphothflavone, which was given to the cells during the incubation with CYP 1A1 inducers. Also the PB-induced PROD activity was decreased by the simultaneous addition of the CYP 2B inhibitor metyrapone. Both cytochrome P450 inhibitors were used at non-cytotoxic concentrations. The phase II enzymes glutathione S-transferase, aldehyde dehydrogenase and quinone reductase were all highly expressed and inducible by MC. The exposure (24 h) of the cells to four hair dyes used in cosmetic formulations resulted in a marked increase in ECOD activity. All data give sustained evidence for the suitability of NCTC 2544 cell line to skin toxicology studies. PMID:11698172

  2. 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. PMID:23201694

  3. Zero-g experiments with a He II active phase separator for space application

    NASA Technical Reports Server (NTRS)

    Denner, H. D.; Klipping, G.; Lueders, K.; Ruppert, U.; Stahnke, F.; Szuecs, Z.; Elleman, D.; Petrac, D.

    1984-01-01

    An active phase separator (APS) for temperature control of He II space cooling systems was tested in a zero-g environment during a series of parabolic flights on a NASA KC 135 aircraft. The APS provides for liquid-gas separation and features an annular gap, a downstream heat exchanger and an upstream ball closure. The apparatus was operated during acceleration and floating and in two different heat load situations. The tests confirmed that adequate mass flow rates could be maintained using a vacuum pump to simulate space vacuum and that residual liquid could be evaporated from the heat exchanger after closing a ball valve to seal off flows.

  4. Modulation of phase-II enzyme activities in benzene treated ovariectomized rats.

    PubMed

    Verma, Yeshvandra; Rana, S V S

    2011-05-01

    The aim of the study was to determine the influence of ovariectomy on phase II enzymes viz. glutathione-S-transferase (GST), glutathione peroxidase (GPX) and catalase (CAT) in liver and kidney of female rats treated with benzene. The results showed the significant decrease of the GST and GPX activity in benzene treated rats after ovariectomy. However progesterone supplementation stimulated the activity of GST and GPX in liver and kidney of benzene treated non ovariectomized and ovariectomized rats. Progesterone supplementation to benzene treated ovariectomized rats helps to gain in CAT activity. Our results on DNA damage using single cell gel electrophoresis also confirmed our findings on antioxidant enzymes. The results showed that lack of protective progesterone against benzene toxicity is reflected in alterations in antioxidant enzyme activities. However progesterone therapy to benzene treated ovariectomized rats results in activating the antioxidant defence system. Since female workers are engaged in industrial sector, these results are important from occupational health point of view. Benzene exposure affects their reproductive health. Nevertheless, it could be modulated by suitable hormonal therapy. PMID:21787707

  5. 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.

  6. 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.

  7. 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.

  8. Turbulent transport of He II in active and passive phase separators using slit devices and porous media

    NASA Technical Reports Server (NTRS)

    Yuan, S. W. K.; Lee, J. M.; Frederking, T. H. K.

    1988-01-01

    The turbulent transport mode of vapor liquid phase separators (VLPS) for He II has been investigated comparing passive porous plug separators with active phase separators (APS) using slits of variable flow paths within a common frame of reference. It is concluded that the basic transport regimes in both devices are identical. An integrated Gorter-Mellink (1949) equation, found previously to predict VLPS results of porous plugs, is employed to analyze APS data published in the literature. It is found that the Gorter-Mellink flow rate parameter for 9-micron and 14-micron APS slit widths are relatively independent of the slit width, having a rate constant of about 9 + or - 10 percent. This agrees with the early heat flow results for He II entropy transport at zero net mass flow in wide capillaries and slits.

  9. 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

  10. 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

  11. 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.

  12. Family and Community Studies (FACS) Fourth Interim Report, Phase I and Activities and Timelines for Phase II.

    ERIC Educational Resources Information Center

    Espinoza, Renato; And Others

    Discussed in this paper is a preliminary analysis of findings from data gathered during the first phase of a research project exploring the processes whereby the nature of the mother's occupation affects her family life, especially (1) her partnership in decisions about housework, child care and education and (2) the negotiation of the allocation…

  13. Evaluation of Vocational Technical Education. Phase II. A Skeletal Model with Suggested Research and Development Activities.

    ERIC Educational Resources Information Center

    New Educational Directions, Crawfordsville, IN.

    Phase 2 of this project presents a skeletal model for evaluating vocational education programs which can be applied to secondary, post-secondary, and adult education programs. The model addresses 13 main components of the vocational education system: descriptive information, demonstration of need, student recruitment and selection, curriculum,…

  14. Development of in vivo biotransformation enzyme assays for ecotoxicity screening: In vivo measurement of phases I and II enzyme activities in freshwater planarians.

    PubMed

    Li, Mei-Hui

    2016-08-01

    The development of a high-throughput tool is required for screening of environmental pollutants and assessing their impacts on aquatic animals. Freshwater planarians can be used in rapid and sensitive toxicity bioassays. Planarians are known for their remarkable regeneration ability but much less known for their metabolic and xenobiotic biotransformation abilities. In this study, the activities of different phase I and II enzymes were determined in vivo by directly measuring fluorescent enzyme substrate disappearance or fluorescent enzyme metabolite production in planarian culture media. For phase I enzyme activity, O-deethylation activities with alkoxyresorufin could not be detected in planarian culture media. By contrast, O-deethylation activities with alkoxycoumarin were detected in planarian culture media. Increases in 7-ethoxycoumarin O-deethylase (ECOD) activities was only observed in planarians exposed to 1μM, but not 10μM, β-naphthoflavone for 24h. ECOD activity was inhibited in planarians exposed to 10 and 100μM rifampicin or carbamazepine for 24h. For phase II enzyme activity, DT-diaphorase, arylsulfatases, uridine 5'-diphospho (UDP)-glucuronosyltransferase or catechol-O-methyltransferase activity was determined in culture media containing planarians. The results of this study indicate that freshwater planarians are a promising model organism to monitor exposure to environmental pollutants or assess their impacts through the in vivo measurement of phase I and II enzyme activities. PMID:27062342

  15. Removal and recovery of mercury(II) from hazardous wastes using 1-(2-thiazolylazo)-2-naphthol functionalized activated carbon as solid phase extractant.

    PubMed

    Starvin, A M; Rao, T Prasada

    2004-09-10

    As a part of removal of toxic heavy metals from hazardous wastes, solid phase extraction (SPE) of mercury(II) at trace and ultra trace levels was studied using 1-(2-thiazolylazo)-2-naphthol (TAN) functionalized activated carbon (AC). The SPE material removes traces of mercury(II) quantitatively in the pH range 6.0 +/- 0.2. Other parameters that influence quantitative recovery of mercury(II), viz. percent concentration of TAN in AC, amount of TAN-AC, preconcentration time and volume of aqueous phase were varied and optimized. The possible means of removal of Hg(II) from other metal ions that are likely to be present in the wastes of the chloroalkali industry is discussed. The potential of TAN-functionalized AC SPE material for decontaminating mercury from the brine sludge and cell house effluent of a chloralkali plant has been evaluated. PMID:15363516

  16. Activity Increase Despite Arthritis (AÏDA): design of a Phase II randomised controlled trial evaluating an active management booklet for hip and knee osteoarthritis [ISRCTN24554946

    PubMed Central

    Williams, Nefyn H; Amoakwa, Elvis; Burton, Kim; Hendry, Maggie; Belcher, John; Lewis, Ruth; Hood, Kerenza; Jones, Jeremy; Bennett, Paul; Edwards, Rhiannon T; Neal, Richard D; Andrew, Glynne; Wilkinson, Clare

    2009-01-01

    Background Hip and knee osteoarthritis is a common cause of pain and disability, which can be improved by exercise interventions. However, regular exercise is uncommon in this group because the low physical activity level in the general population is probably reduced even further by pain related fear of movement. The best method of encouraging increased activity in this patient group is not known. A booklet has been developed for patients with hip or knee osteoarthritis. It focuses on changing disadvantageous beliefs and encouraging increased physical activity. Methods/Design This paper describes the design of a Phase II randomised controlled trial (RCT) to test the effectiveness of this new booklet for patients with hip and knee osteoarthritis in influencing illness and treatment beliefs, and to assess the feasibility of conducting a larger definitive RCT in terms of health status and exercise behaviour. A computerised search of four general medical practice patients' record databases will identify patients older than 50 years of age who have consulted with hip or knee pain in the previous twelve months. A random sample of 120 will be invited to participate in the RCT comparing the new booklet with a control booklet, and we expect 100 to return final questionnaires. This trial will assess the feasibility of recruitment and randomisation, the suitability of the control intervention and outcome measurement tools, and will provide an estimate of effect size. Outcomes will include beliefs about hip and knee pain, beliefs about exercise, fear avoidance, level of physical activity, health status and health service costs. They will be measured at baseline, one month and three months. Discussion We discuss the merits of testing effectiveness in a phase II trial, in terms of intermediate outcome measures, whilst testing the processes for a larger definitive trial. We also discuss the advantages and disadvantages of testing the psychometric properties of the primary outcome

  17. Phase II Study of the Safety and Antitumor Activity of the Hypoxia-Activated Prodrug TH-302 in Combination With Doxorubicin in Patients With Advanced Soft Tissue Sarcoma

    PubMed Central

    Chawla, Sant P.; Cranmer, Lee D.; Van Tine, Brian A.; Reed, Damon R.; Okuno, Scott H.; Butrynski, James E.; Adkins, Douglas R.; Hendifar, Andrew E.; Kroll, Stew; Ganjoo, Kristen N.

    2014-01-01

    Purpose TH-302, a prodrug of the cytotoxic alkylating agent bromo-isophosphoramide mustard, is preferentially activated in hypoxic conditions. This phase II study investigated TH-302 in combination with doxorubicin, followed by single-agent TH-302 maintenance therapy in patients with first-line advanced soft tissue sarcoma (STS) to assess progression-free survival (PFS), response rate, overall survival, safety, and tolerability. Patients and Methods In this open-label phase II study, TH-302 300 mg/m2 was administered intravenously on days 1 and 8 with doxorubicin 75 mg/m2 on day 1 of each 21-day cycle. After six cycles, patients with stable and/or responding disease could receive maintenance monotherapy with TH-302. Results Ninety-one patients initiated TH-302 plus doxorubicin induction treatment. The PFS rate at 6 months (primary efficacy measure) was 58% (95% CI, 46% to 68%). Median PFS was 6.5 months (95% CI, 5.8 to 7.7 months); median overall survival was 21.5 months (95% CI, 16.0 to 26.2 months). Best tumor responses were complete response (n = 2 [2%]) and partial response (n = 30 [34%]). During TH-302 maintenance (n = 48), five patients improved from stable disease to partial response, and one patient improved from partial to complete response. The most common adverse events during induction were fatigue, nausea, and skin and/or mucosal toxicities as well as anemia, thrombocytopenia, and neutropenia. These were less severe and less frequent during maintenance. There was no evidence of TH-302–related hepatic, renal, or cardiac toxicity. Conclusion PFS, overall survival, and tumor response compared favorably with historical outcomes achieved with other first-line chemotherapies for advanced STS. A phase III study of TH-302 is ongoing (NCT01440088). PMID:25185097

  18. BEATRIX-II, phase II: Data summary report

    SciTech Connect

    Slagle, O.D.; Hollenberg, G.W.

    1996-05-01

    The BEATRIX-II experimental program was an International Energy Agency sponsored collaborative effort between Japan, Canada, and the United States to evaluate the performance of ceramic solid breeder materials in a fast-neutron environment at high burnup levels. This report addresses the Phase II activities, which included two in situ tritium-recovery canisters: temperature-change and temperature-gradient. The temperature-change canister contained a Li{sub 2}O ring specimen that had a nearly uniform temperature profile and was capable of temperature changes between 530 and 640{degrees}C. The temperature-gradient canister contained a Li{sub 2}ZrO{sub 3} pebble bed operating under a thermal gradient of 440 to 1100{degrees}C. Postirradiation examination was carried out to characterize the Phase II in situ specimens and a series of nonvented capsules designed to address the compatibility of beryllium with lithium-ceramic solid-breeder materials. The results of the BEATRIX-II, Phase II, irradiation experiment provided an extensive data base on the in situ tritium-release characteristics of Li{sub 2}O and Li{sub 2}ZrO{sub 3} for lithium burnups near 5%. The composition of the sweep gas was found to be a critical parameter in the recovery of tritium from both Li{sub 2}O and Li{sub 2}ZrO{sub 3}. Tritium inventories measured confirmed that Li{sub 2}O and Li{sub 2}ZrO{sub 3} exhibited very low tritium retention during the Phase II irradiation. Tritium inventories in Li{sub 2}ZrO{sub 3} after Phase II tended to be larger than those found for Li{sub 2}ZrO{sub 3} in other in situ experiments, but the larger values may reflect the larger generation rates in BEATRIX-II. A series of 20 capsules was irradiated to determine the compatibility of lithium ceramics and beryllium under conditions similar to a fusion blanket. It is concluded that Li{sub 2}O and Li{sub 2}ZrO{sub 3} should remain leading candidates for use in a solid-breeder fusion-blanket application.

  19. 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

  20. 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.

  1. 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.

  2. Selective Solid-Phase Extraction of Zinc(II) from Environmental Water Samples Using Ion Imprinted Activated Carbon.

    PubMed

    Moniri, Elham; Panahi, Homayon Ahmad; Aghdam, Khaledeh; Sharif, Amir Abdollah Mehrdad

    2015-01-01

    A simple ion imprinted amino-functionalized sorbent was synthesized by coupling activated carbon with iminodiacetic acid, a functional compound for metal chelating, through cyanoric chloride spacer. The resulting sorbent has been characterized using FTIR spectroscopy, elemental analysis, and thermogravimetric analysis and evaluated for the preconcentration and determination of trace Zn(II) in environmental water samples. The optimum pH value for sorption of the metal ion was 6-7.5. The sorption capacity of the functionalized sorbent was 66.6 mg/g. The chelating sorbent can be reused for 10 cycles of sorption-desorption without any significant change in sorption capacity. A recovery of 100% was obtained for the metal ion with 0.5 M nitric acid as the eluent. Compared with nonimprinted polymer particles, the prepared Zn-imprinted sorbent showed high adsorption capacity, significant selectivity, and good site accessibility for Zn(II). Scatchard analysis revealed that the homogeneous binding sites were formed in the polymer. The equilibrium sorption data of Zn(II) by modified resin were analyzed by Langmuir, Freundlich, Temkin, and Redlich-Peterson models. Based on equilibrium adsorption data, the Langmuir, Freundlich, and Temkin constants were determined as 0.139, 12.82, and 2.34, respectively, at 25°C. PMID:25857899

  3. Pretest Predictions for Phase II Ventilation Tests

    SciTech Connect

    Yiming Sun

    2001-09-19

    The objective of this calculation is to predict the temperatures of the ventilating air, waste package surface, and concrete pipe walls that will be developed during the Phase II ventilation tests involving various test conditions. The results will be used as inputs to validating numerical approach for modeling continuous ventilation, and be used to support the repository subsurface design. The scope of the calculation is to identify the physical mechanisms and parameters related to thermal response in the Phase II ventilation tests, and describe numerical methods that are used to calculate the effects of continuous ventilation. The calculation is limited to thermal effect only. This engineering work activity is conducted in accordance with the ''Technical Work Plan for: Subsurface Performance Testing for License Application (LA) for Fiscal Year 2001'' (CRWMS M&O 2000d). This technical work plan (TWP) includes an AP-2.21Q, ''Quality Determinations and Planning for Scientific, Engineering, and Regulatory Compliance Activities'', activity evaluation (CRWMS M&O 2000d, Addendum A) that has determined this activity is subject to the YMP quality assurance (QA) program. The calculation is developed in accordance with the AP-3.12Q procedure, ''Calculations''. Additional background information regarding this activity is contained in the ''Development Plan for Ventilation Pretest Predictive Calculation'' (DP) (CRWMS M&O 2000a).

  4. Upgrades for GERDA Phase II

    NASA Astrophysics Data System (ADS)

    Heisel, Mark

    2014-09-01

    The Germanium Detector Array (GERDA) experiment is searching for the neutrinoless double beta decay (0 νββ) of 76Ge. It is a process that violates lepton number conservation and is predicted to occur in extensions of the standard model of particle physics. GERDA is located underground in the Gran Sasso National Laboratory (LNGS), Italy. An array of bare high-purity germanium detectors enriched in 76Ge is operated in a cryostat with 64 m3 of liquid argon supplemented by a 3 m thick shield of water. The experiment aims at exploring the 0 νββ decay up to a half life of 2 .1026 yr in two phases: Phase I of the experiment has been concluded last year. No signal is observed and the so far best limit is derived for the half life of the 0 νββ decay of 76Ge, T1/20ν <= 2 . 1 .1025 yr (90% C.L.), after an exposure of 21 . 6 kg .yr. The result refutes an earlier claim of discovery with high probability. The background index of 1 .10-2 cts/(keV .kg .yr) is lower by about one order of magnitude compared to previous experiments. At present the experiment is being upgraded to Phase II. The aim is to collect an exposure of 100kg .yr and further reduce the background by another order of magnitude to a level of <=10-3 cts/(keV .kg .yr). The detector mass will be increased by ~20 kg of new Broad Energy Germanium (BEGe) detectors from enriched 76Ge, which exhibit superior pulse shape discrimination and hence background rejection power. Low mass detector holders, cold front-end electronics, contacting and cabling schemes are redesigned for ultra low mass and radiopurity. In addition, a retractable liquid argon veto will be installed to efficiently suppress background events that induce scintillation in the liquid argon. A hybrid solution of photomultiplier tubes and silicon photomultipliers coupled to scintillating fibres was chosen. This talk gives an account of the results and these challenging modifications to meet our design goals. The Germanium Detector Array (GERDA

  5. 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.

  6. The flavonoid, eriodictyol, induces long-term protection in ARPE-19 cells through its effects on Nrf2 activation and phase II gene expression

    PubMed Central

    Johnson, Jennifer; Maher, Pamela

    2009-01-01

    Purpose Eriodictyol, a flavonoid found in citrus fruits, is among the most potent compounds reported to protect human RPE cells from oxidative stress-induced cell death. In the present study, we determined whether eriodictyol-induced phase II protein expression further enhances the resistance of human ARPE-19 cells to oxidative stress. Methods We analyzed the ability of eriodictyol to activate Nrf2 and induce the phase II proteins, heme-oxygenase (HO-1), NAD(P)H: quinone oxidoreductase 1 (NQO-1), and the cellular antioxidant glutathione, (GSH). We performed cytoprotection assays in ARPE-19 cells that were overexpressing HO-1 or NQO-1. We compared cell survival after short-term and long-term eriodictyol treatment and tested the mechanism of protection using a dominant negative Nrf2 and an shRNA specific for HO-1. Results We demonstrate that eriodictyol induces the nuclear translocation of Nrf2, enhances the expression of HO-1 and NQO-1, and increases the levels of intracellular glutathione. We show that ARPE-19 cells that overexpress HO-1 or NQO-1 are more resistant to oxidative stress-induced cell death than control cells. We demonstrate that eriodictyol induces long-term protection that is significantly greater than its short-term protection, and this effect is correlated temporally with both the activation of Nrf2 and the induction of phase II enzymes. We demonstrate that this effect can be blocked with the use of a dominant negative to Nrf2 and an shRNA specific to HO-1. Conclusions These findings indicate the greatest benefit from eriodictyol may be its ability to regulate gene expression and enhance multiple cellular defenses to oxidative injury. PMID:19117929

  7. Liver genomic responses to ciguatoxin: evidence for activation of phase I and phase II detoxification pathways following an acute hypothermic response in mice.

    PubMed

    Morey, Jeanine S; Ryan, James C; Bottein Dechraoui, Marie-Yasmine; Rezvani, Amir H; Levin, Edward D; Gordon, Christopher J; Ramsdell, John S; Van Dolah, Frances M

    2008-06-01

    Ciguatoxins (CTX) are polyether neurotoxins that target voltage-gated sodium channels and are responsible for ciguatera, the most common fish-borne food poisoning in humans. This study characterizes the global transcriptional response of mouse liver to a symptomatic dose (0.26 ng/g) of the highly potent Pacific ciguatoxin-1 (P-CTX-1). At 1 h post-exposure 2.4% of features on a 44K whole genome array were differentially expressed (p < or = 0.0001), increasing to 5.2% at 4 h and decreasing to 1.4% by 24 h post-CTX exposure. Data were filtered (/fold change/ > or = 1.5 and p < or = 0.0001 in at least one time point) and a trend set of 1550 genes were used for further analysis. Early gene expression was likely influenced prominently by an acute 4 degrees C decline in core body temperature by 1 h, which resolved by 8 h following exposure. An initial downregulation of 32 different solute carriers, many involved in sodium transport, was observed. Differential gene expression in pathways involving eicosanoid biosynthesis and cholesterol homeostasis was also noted. Cytochrome P450s (Cyps) were of particular interest due to their role in xenobiotic metabolism. Twenty-seven genes, mostly members of Cyp2 and Cyp4 families, showed significant changes in expression. Many Cyps underwent an initial downregulation at 1 h but were quickly and strongly upregulated at 4 and 24 h post-exposure. In addition to Cyps, increases in several glutathione S-transferases were observed, an indication that both phase I and phase II metabolic reactions are involved in the hepatic response to CTX in mice. PMID:18353800

  8. Water-quality data-collection activities in Colorado and Ohio; Phase II, Evaluation of 1984 field and laboratory quality-assurance practices

    USGS Publications Warehouse

    Childress, C.J.; Chaney, T.M.; Myers, Donna; Norris, J.M.; Hren, Janet

    1987-01-01

    Serious questions have been raised by Congress about the usefulness of water quality data for addressing issues of regional and national scope and, especially, for characterizing the current quality of the Nation 's streams and groundwater. In response, the U.S. Geological Survey conducted a pilot study in Colorado and Ohio to: (1) determine the characteristics of current (1984) water quality data collection activities of Federal, regional, State, and local agencies, and academic institutions; and (2) determine how well the data from these activities, collected for various purposes and using different procedures, can be used to improve the ability to answer major broad scope questions, such as: what are (or were) natural or near-natural water quality conditions; what are existing water quality conditions; and, how water quality has changed and how the changes relate to human activities. Colorado and Ohio were chosen for the pilot study largely because they represent regions with different types of water quality concerns and programs. The study has been divided into three phases, the objectives of which are: Phase I - Inventory water quality data collection programs, including costs, and identify those programs that met a set of broad criteria for producing data that are potentially appropriate for water quality assessments of regional and national scope. Phase II - Evaluate the quality assurance of field and laboratory procedures used in producing the data from programs that met the broad criteria of Phase I. Phase III - Compile the qualifying data and evaluate the adequacy of this data base for addressing selected water quality questions of regional and national scope. (Author 's abstract)

  9. Activation of Single-Component Nickel(II) Polyethylene Catalysts via Phase Transfer of Fluorous Phosphine Ligands.

    PubMed

    Xi, Zhenxing; Bazzi, Hassan S; Gladysz, John A

    2015-09-01

    The nickel salicylaldiminato phosphine complexes [1,2,3-C6H3(9-anthracenyl)O(CH═N(2,6-C6H3(iPr)2)]Ni(Me)[P(4-C6H4R)3] (4; R = a, (CH2)2Rf8; b, (CH2)3Rf8; c, H (Rf8 = (CF2)7CF3)) are prepared from the corresponding phosphines 3a-c and nickel NCMe adduct (46-68%). These are applied as catalysts for ethylene polymerization in toluene and fluorous/toluene liquid/liquid biphasic mixtures. Under the latter conditions, the fluorous phosphines 3a,b that must dissociate to generate the active catalyst migrate to the fluorous phase (partition coefficients 97.5:2.5 and 66.6:33.4 vs <0.5:>99.5 for 4a,b). Catalysts 4a,b show marked accelerations under biphasic conditions, but 4c (which has a lipophilic phosphine ligand) does not. Under all conditions, 4a,b are faster catalysts than the Ni(Ph)(PPh3) analogue, a previously reported benchmark. PMID:26300472

  10. 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

  11. 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.

  12. Jail to Job Phase II. Final Report.

    ERIC Educational Resources Information Center

    Erie City School District, PA.

    Through the Jail to Job Phase II project, the Erie Adult Learning Center provided inmates of the Erie County Prison with employability skills, decision making, problem solving, survival skills, and anger management education. Forty soon-to-be-released inmates participated in 37 hours of class. Prison staff, in concert with the instructor, selected…

  13. 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

  14. Intraocular pressure efficacy of glaucoma medications versus placebo in phase II compared to later phase trials.

    PubMed

    Sharpe, R Allan; Nelson, Lindsay A; Stewart, Jeanette A; Stewart, William C

    2013-02-01

    This review aimed to compare the predictive value between the untreated reduction in intraocular pressure (IOP) from baseline or placebo measured in early phase clinical trials to phase III and IV results for glaucoma medicines. Published, placebo-controlled, randomised, parallel, single-masked or double-masked clinical trials with at least one phase II, III and IV study available were reviewed. This study included 50 articles evaluating 9 medicines from 59 active arms and 18 placebo arms. For all studies the phase II IOP reduction from placebo showed less decrease compared to the decrease from baseline (p<0.04). For all medicines, reductions from morning baseline in phase II did not predict better than the decrease from placebo for phase III (p=0.15) or IV (p=0.08) reductions in IOP. In contrast, diurnal IOP reduction from baseline in phase II predicted decreases better than placebo in phase III (p=0.007) and IV (p=0.02). Generally, for prostaglandins, β blockers and carbonic anhydrase inhibitors for the morning trough and diurnal curve there was no difference in pressure reduction from baseline for phase II compared to phase III or IV (p≥0.23). In contrast, where comparisons were available for the decrease in pressure from placebo there were differences for phase II compared to phase III and phase IV (p≤0.02). This study suggests that in early phase glaucoma trials, using the reduction from untreated baseline in general better approximates the results of later regulatory and post-commercialisation trials than the decrease from placebo. PMID:23060621

  15. A model for gas phase chemistry in interstellar clouds. II - Nonequilibrium effects and effects of temperature and activation energies

    NASA Technical Reports Server (NTRS)

    Prasad, S. S.; Huntress, W. T., Jr.

    1980-01-01

    The chemical evolution of diffuse and dense interstellar clouds is examined via the time-dependent model outlined by Prasad and Huntress (1980). This paper presents specific results for CH, CO, CH4, O2, CH2O, CN, C2, C2H, HC3N, and NH3. Comparison with observations and predictions of other contemporary models show that cloud temperature plays a very important role through the inverse temperature dependence of radiative association reactions and through activation energies in neutral reactions and selected ion-molecule reactions. The observed fractional abundance of CN with respect to H2 and more accurate recent laboratory data on CN + O and CN + O2 reactions suggest that there is an unidentified, yet efficient, mechanism for conversion of O and O2 into polyatomic species. C2H and HC3N are synthesized early in the history of dense clouds. The value of the fractional abundance of C2H remains high, because as the cloud cools down the activation energy in the C2H + O reaction closes down this most important loss channel. A rapidly decreasing fractional abundance of O with time can also accomplish the same result. The value of the fractional abundance of HC3N remains high because it is an unreactive molecule and probably does not condense readily onto grains.

  16. {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.

  17. Laparoscopic Radiofrequency Fibroid Ablation: Phase II and Phase III Results

    PubMed Central

    Pemueller, Rodolfo Robles; Garza Leal, José Gerardo; Abbott, Karen R.; Falls, Janice L.; Macer, James

    2014-01-01

    Background and Objectives: To review phase II and phase III treatments of symptomatic uterine fibroids (myomas) using laparoscopic radiofrequency volumetric thermal ablation (RFVTA). Methods: We performed a retrospective, multicenter clinical analysis of 206 consecutive cases of ultrasound-guided laparoscopic RFVTA of symptomatic myomas conducted on an outpatient basis under two phase II studies at 2 sites (n = 69) and one phase III study at 11 sites (n = 137). Descriptive and exploratory, general trend, and matched-pair analyses were applied. Results: From baseline to 12 months in the phase II study, the mean transformed symptom severity scores improved from 53.9 to 8.8 (P < .001) (n = 57), health-related quality-of-life scores improved from 48.5 to 92.0 (P < .001) (n = 57), and mean uterine volume decreased from 204.4 cm3 to 151.4 cm3 (P = .008) (n = 58). Patients missed a median of 4 days of work (range, 2–10 days). The rate of possible device-related adverse events was 1.4% (1 of 69). In the phase III study, approximately 98% of patients were assessed at 12 months, and their transformed symptom severity scores, health-related quality-of-life scores, mean decrease in uterine volume, and mean menstrual bleeding reduction were also significant. Patients in phase III missed a median of 5 days of work (range, 1–29 days). The rate of periprocedural device-related adverse events was 3.5% (5 of 137). Despite the enrollment requirement for patients in both phases to have completed childbearing, 4 pregnancies occurred within the first year after treatment. Conclusions: RFVTA does not require any uterine incisions and provides a uterine-sparing procedure with rapid recovery, significant reduction in uterine size, significant reduction or elimination of myoma symptoms, and significant improvement in quality of life. PMID:24960480

  18. Phase II-I-II Study of Two Different Doses and Schedules of Pralatrexate, a High-Affinity Substrate for the Reduced Folate Carrier, in Patients With Relapsed or Refractory Lymphoma Reveals Marked Activity in T-Cell Malignancies

    PubMed Central

    O'Connor, Owen A.; Horwitz, Steven; Hamlin, Paul; Portlock, Carol; Moskowitz, Craig H.; Sarasohn, Debra; Neylon, Ellen; Mastrella, Jill; Hamelers, Rachel; MacGregor-Cortelli, Barbara; Patterson, Molly; Seshan, Venkatraman E.; Sirotnak, Frank; Fleisher, Martin; Mould, Diane R.; Saunders, Mike; Zelenetz, Andrew D.

    2009-01-01

    Purpose To determine the maximum-tolerated dose (MTD) and efficacy of pralatrexate in patients with lymphoma. Patients and Methods Pralatrexate, initially given at a dose of 135 mg/m2 on an every-other-week basis, was associated with stomatitis. A redesigned, weekly phase I/II study established an MTD of 30 mg/m2 weekly for six weeks every 7 weeks. Patients were required to have relapsed/refractory disease, an absolute neutrophil greater than 1,000/μL, and a platelet count greater than 50,000/μL for the first dose of any cycle. Results The every-other-week, phase II experience was associated with an increased risk of stomatitis and hematologic toxicity. On a weekly schedule, the MTD was 30 mg/m2 weekly for 6 weeks every 7 weeks. This schedule modification resulted in a 50% reduction in the major hematologic toxicities and abrogation of the grades 3 to 4 stomatitis. Stomatitis was associated with elevated homocysteine and methylmalonic acid, which were reduced by folate and vitamin B12 supplementation. Of 48 assessable patients, the overall response rate was 31% (26% by intention to treat), including 17% who experienced complete remission (CR). When analyzed by lineage, the overall response rates were 10% and 54% in patients with B- and T-cell lymphomas, respectively. All eight patients who experienced CR had T-cell lymphoma, and four of the six patients with a partial remission were positron emission tomography negative. The duration of responses ranged from 3 to 26 months. Conclusion Pralatrexate has significant single-agent activity in patients with relapsed/refractory T-cell lymphoma. PMID:19652067

  19. 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.

  20. [Experiences with ambulatory cardiologic phase II rehabilitation].

    PubMed

    Schönstedt, S; Beckmann, S; Disselhoff, W; Rüssmann, B

    1999-04-01

    The phase II cardiac rehabilitation in Germany differs markedly from other European countries and the USA. Most of the patients enter a 3-week full residential program. In contrast we developed an outpatient phase II cardiac rehabilitation program. Since 1979 we treated more than 8,500 patients with different indications (i.e. after myocardial infarction, coronary bypass surgery, valve replacement and reconstruction). Patients with a daily commuting time over 60 minutes are not suitable for outpatient rehabilitation. Our model corresponds to the German intrahospital rehabilitation. The rehabilitation is carried out in 3 weeks offering approximately 66 hours of therapy. Groups of 8 patients with a similar level of physical capacity stay together during the rehabilitation. A comprehensive program with exercise training, physical therapy, psychological support, education in life style changes and risk factor modification has been developed. The compliance of the patients as well as the acceptance by the family are excellent. Long-lasting reduction in LDL cholesterol levels and increments in work-load capacities have been demonstrated. A high percentage of patients returned to work. Cost analysis demonstrates a reduction up to 40% in comparison to the full residential program. Therefore the outpatient phase II cardiac rehabilitation is a good alternative especially in urban areas. PMID:10372303

  1. Improving Alzheimer's disease phase II clinical trials.

    PubMed

    Greenberg, Barry D; Carrillo, Maria C; Ryan, J Michael; Gold, Michael; Gallagher, Kim; Grundman, Michael; Berman, Robert M; Ashwood, Timothy; Siemers, Eric R

    2013-01-01

    Over the past 30 years, many drugs have been studied as possible treatments for Alzheimer's disease, but only four have demonstrated sufficient efficacy to be approved as treatments, of which three are in the same class. This lack of success has raised questions both in the pharmaceutical industry and academia about the future of Alzheimer's disease therapy. The high cost and low success rate of drug development across many disease areas can be attributed, in large part, to late-stage clinical failures (Schachter and Ramoni, Nat Rev Drug Discov 2007;6:107-8). Thus, identifying in phase II, or preferably phase I, drugs that are likely to fail would have a dramatic impact on the costs associated with developing new drugs. With this in mind, the Alzheimer's Association convened a Research Roundtable on June 23 and 24, 2011, in Washington, DC, bringing together scientists from academia, industry, and government regulatory agencies to discuss strategies for improving the probability of phase II trial results predicting success when considering the go/no-go decision-making process leading to the initiation of phase III. PMID:23164548

  2. Imaging the Lipid-Phase-Dependent Pore Formation of Equinatoxin II in Droplet Interface Bilayers

    PubMed Central

    Rojko, N.; Cronin, B.; Danial, J.S.H.; Baker, M.A.B.; Anderluh, G.; Wallace, M.I.

    2014-01-01

    Using phase-separated droplet interface bilayers, we observe membrane binding and pore formation of a eukaryotic cytolysin, Equinatoxin II (EqtII). EqtII activity is known to depend on the presence of sphingomyelin in the target membrane and is enhanced by lipid phase separation. By imaging the ionic flux through individual pores in vitro, we observe that EqtII pores form predominantly within the liquid-disordered phase. We observe preferential binding of labeled EqtII at liquid-ordered/liquid-disordered domain boundaries before it accumulates in the liquid-disordered phase. PMID:24739162

  3. Athena: Assessment Phase Activities

    NASA Astrophysics Data System (ADS)

    Lumb, David; Ayre, Mark

    2015-09-01

    The Athena mission concept has been proposed by the community in response to science themes of the Hot and Energetic Universe. Unlike other, competitive, mission selection exercises this "Large" class observatory mission has essentially been pre-selected. Nevertheless it has to be demonstrated that Athena meets the programmatic constraints of 1Bn euro cost cap, and a readiness level appropriate for formal mission adoption by the end 2019. This should be confirmed through a Phase A study conducted with two parallel industry activities. We describe the technical and programmatic content of these and latest progress in space and ground segment definition.

  4. Status of the GERDA Phase II upgrade

    NASA Astrophysics Data System (ADS)

    Wagner, Victoria

    2016-06-01

    The GERDA experiment is designed to search for neutrinoless double beta (0νββ) decay of 76Ge. In Phase I of the experiment a background index of 10-2 cts/(keV.kg.yr) was reached. A lower limit on the half-life of the 0νββ decay of 76Ge was set to 2.1.1025 yr (at 90% C.L.). The aim of Phase II is to reach a sensitivity of the half-life of about 1026 yr. To increase the exposure thirty new Broad Energy Germanium (BEGe) detectors have been produced. These detectors are distinct for their improved energy resolution and enhanced pulse shape discrimination of signal from background events. Further background reduction will be reached by a light instrumentation to read out argon scintillation light. In April 2015 the light instrumentation together with eight BEGe detectors has been successfully deployed in the GERDA cryostat. In a commissioning run it was shown that two of the major background components, external γ-rays from 214Bi and 208Tl decays, were suppressed up to two orders of magnitude. We are confident to reach a background index of 10-3 cts/(keV.kg.yr) which is the design goal for GERDA Phase II.

  5. 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.

  6. CATALYST ACTIVITY MAINTENANCE FOR THE LIQUID PHASE SYNTHESIS GAS-TO-DIMETHYL ETHER PROCESS PART II: DEVELOPMENT OF ALUMINUM PHOSPHATE AS THE DEHYDRATION CATALYST FOR THE SINGLE-STEP LIQUID PHASE SYNGAS-TO-DME PROCESS

    SciTech Connect

    Xiang-Dong Peng

    2002-05-01

    At the heart of the single-step liquid phase syngas-to-DME process (LPDME{trademark}) is a catalyst system that can be active as well as stable. In the Alternative Fuels I program, a dual-catalyst system containing a Cu-based commercial methanol synthesis catalyst (BASF S3-86) and a commercial dehydration material ({gamma}-alumina) was demonstrated. It provided the productivity and selectivity expected from the LPDME process. However, the catalyst system deactivated too rapidly to warrant a viable commercial process [1]. The mechanistic investigation in the early part of the DOE's Alternative Fuels II program revealed that the accelerated catalyst deactivation under LPDME conditions is due to detrimental interaction between the methanol synthesis catalyst and methanol dehydration catalyst [2,3]. The interaction was attributed to migration of Cu- and/or Zn-containing species from the synthesis catalyst to the dehydration catalyst. Identification of a dehydration catalyst that did not lead to this detrimental interaction while retaining adequate dehydration activity was elusive. Twenty-nine different dehydration materials were tested, but none showed the desired performance [2]. The search came to a turning point when aluminum phosphate was tested. This amorphous material is prepared by precipitating a solution containing Al(NO{sub 3}){sub 3} and H{sub 3}PO{sub 4} with NH{sub 4}OH, followed by washing, drying and calcination. The aluminum phosphate catalyst has adequate dehydration activity and good stability. It can co-exist with the Cu-based methanol synthesis catalyst without negatively affecting the latter catalyst's stability. This report documents the details of the development of this catalyst. These include initial leads, efforts in improving activity and stability, investigation and development of the best preparation parameters and procedures, mechanistic understanding and resulting preparation guidelines, and the accomplishments of this work.

  7. 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.

  8. The TGV II Experiment (Phase I Results)

    NASA Astrophysics Data System (ADS)

    Beneš, P.; Briançon, Ch.; Brudanin, V. B.; Čermák, P.; Egorov, V. G.; Gusev, K. N.; Klimenko, A. A.; Kovalenko, V. E.; Kovalik, A.; Rukhadze, N. I.; Salamatin, A. V.; Šimkovic, F.; Štekl, I.; Timkin, V. V.; Vylov, Ts.

    2007-10-01

    The TGV II (Telescope Germanium Vertical) facility is a low background spectrometer operated in Modane Underground Laboratory. It aims at the study of double electron capture of 106Cd. The spectrometer is composed of 32 HPGe planar detectors interleaved with thin-foil samples made of Cd-106 enriched to 75% (total mass about 10 g). In 2006, the main run of phase I (1 year duration) was terminated yielding a new limit on half-life for two-neutrino double electron capture (g.s.→g.s.) in 106Cd as 2.0×1020 years. This limit is significantly higher (by almost three orders of magnitude) than those already published.

  9. The TGV II Experiment (Phase I Results)

    SciTech Connect

    Benes, P.; Cermak, P.; Stekl, I.; Brudanin, V. B.; Egorov, V. G.; Gusev, K. N.; Klimenko, A. A.; Kovalenko, V. E.; Rukhadze, N. I.; Salamatin, A. V.; Timkin, V. V.; Vylov, Ts.; Kovalik, A.; Simkovic, F.

    2007-10-12

    The TGV II (Telescope Germanium Vertical) facility is a low background spectrometer operated in Modane Underground Laboratory. It aims at the study of double electron capture of {sup 106}Cd. The spectrometer is composed of 32 HPGe planar detectors interleaved with thin-foil samples made of Cd-106 enriched to 75% (total mass about 10 g). In 2006, the main run of phase I (1 year duration) was terminated yielding a new limit on half-life for two-neutrino double electron capture (g.s.{yields}g.s.) in {sup 106}Cd as 2.0x10{sup 20} years. This limit is significantly higher (by almost three orders of magnitude) than those already published.

  10. 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.

  11. 40 CFR 73.10 - Initial allocations for phase I and phase II.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 17 2012-07-01 2012-07-01 false Initial allocations for phase I and phase II. 73.10 Section 73.10 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) SULFUR DIOXIDE ALLOWANCE SYSTEM Allowance Allocations § 73.10 Initial allocations for phase I and phase II. (a) Phase...

  12. The PICASSO Dark Matter Experiment - Getting Ready for Phase II

    NASA Astrophysics Data System (ADS)

    Krauss, Carsten B.; Picasso Collaboration

    2011-12-01

    PICASSO is a dark matter search experiment that uses the superheated droplet technique to find spin-dependently interacting WIMPs. A set of 1 l detectors with a total active mass of 19.4 g was used to prove the validity of the technique. The data from this run disfavors WIMP-proton cross sections larger than 1.3 pb for a WIMP mass of 29 GeV. Currently phase II of PICASSO is getting started. It will consist of 32 4.5 l detectors with a projected active mass of 2.5 kg and improved detectors.

  13. 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.

  14. Cytomegalovirus vaccine: phase II clinical trial results.

    PubMed

    Rieder, F; Steininger, C

    2014-05-01

    Cytomegalovirus (CMV) is one of the most significant viral pathogens during pregnancy and in immunocompromised patients. Antiviral prophylactic strategies are limited by toxicities, drug-drug interactions and development of antiviral resistance. A safe and protective vaccine against CMV is highly desirable in view of the potential positive impact on CMV-associated morbidity and mortality as well as healthcare costs. Unfortunately, this demand could not be met in the past four decades although development of a CMV vaccine has been ranked at the highest priority by the US Institute of Medicine. Multiple different vaccine candidates have been developed and evaluated in phase I clinical trials and few succeeded to phase II trials. Nevertheless, two different vaccines showed recently promising results in trials that studied healthy adults and immunocompromised solid-organ and bone-marrow transplant recipients, respectively. The gB/MF59 vaccine exhibited a vaccine efficacy of 50% in healthy, postpartum females. In transplant patients, gB/MF59 and the DNA vaccine TransVax both limited the periods of viraemia and consequently the need for antiviral treatment. The success of these trials is encouraging and will probably give new impetus to the development of an effective CMV vaccine. Sterilizing immunity may not be attainable in the near future and may not be necessary for a CMV vaccine to have a significant impact on health care as discussed in the present review. PMID:24283990

  15. The SIMPLE Phase II dark matter search

    NASA Astrophysics Data System (ADS)

    Felizardo, M.; Girard, T. A.; Morlat, T.; Fernandes, A. C.; Ramos, A. R.; Marques, J. G.; Kling, A.; Puibasset, J.; Auguste, M.; Boyer, D.; Cavaillou, A.; Poupeney, J.; Sudre, C.; Carvalho, F. P.; Prudêncio, M. I.; Marques, R.; Simple Collaboration

    2014-04-01

    Phase II of SIMPLE (Superheated Instrument for Massive ParticLe Experiments) searched for astroparticle dark matter using superheated liquid C2ClF5 droplet detectors. Each droplet generally requires an energy deposition with linear energy transfer (LET) ≳150 keV/μm for a liquid-to-gas phase transition, providing an intrinsic rejection against minimum ionizing particles of order 10-10, and reducing the backgrounds to primarily α and neutron-induced recoil events. The droplet phase transition generates a millimetric-sized gas bubble that is recorded by acoustic means. We describe the SIMPLE detectors, their acoustic instrumentation, and the characterizations, signal analysis and data selection, which yield a particle-induced, "true nucleation" event detection efficiency of better than 97% at a 95% C.L. The recoil-α event discrimination, determined using detectors first irradiated with neutrons and then doped with alpha emitters, provides a recoil identification of better than 99%; it differs from those of COUPP and PICASSO primarily as a result of their different liquids with lower critical LETs. The science measurements, comprising two shielded arrays of fifteen detectors each and a total exposure of 27.77 kgd, are detailed. Removal of the 1.94 kgd Stage 1 installation period data, which had previously been mistakenly included in the data, reduces the science exposure from 20.18 to 18.24 kgd and provides new contour minima of σp=4.3×10-3 pb at 35 GeV /c2 in the spin-dependent sector of astroparticle dark matter-proton interactions and σN=3.6×10-6 pb at 35 GeV /c2 in the spin-independent sector. These results are examined with respect to the fluorine spin and halo parameters used in the previous data analysis.

  16. 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.

  17. Configuration management: Phase II implementation guidance

    SciTech Connect

    Not Available

    1994-03-01

    Configuration management (CM) is essential to maintaining an acceptable level of risk to the public, workers, environment, or mission success. It is a set of activities and techniques used to maintain consistency among physical and functional configuration, applicable requirements, and key documents. This document provides guidance for continuing the implementation of CM in a phased and graded manner. It describes a cost-effective approach to documented consistency with requirements, with early emphasis on items most important to safety and environmental protection. It is intended to help responsible line managers and configuration management staff personnel in meeting the Energy Systems configuration management policy standard.

  18. 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.

  19. 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.

  20. 40 CFR 72.44 - Phase II repowering extensions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Phase II repowering extensions. 72.44 Section 72.44 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) PERMITS REGULATION Acid Rain Compliance Plan and Compliance Options § 72.44 Phase II repowering extensions. (a) Applicability. (1)...

  1. 40 CFR 72.44 - Phase II repowering extensions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... (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...

  2. 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...

  3. 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...

  4. 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...

  5. 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

  6. Condensin II initiates sister chromatid resolution during S phase

    PubMed Central

    Ono, Takao; Yamashita, Daisuke

    2013-01-01

    Condensins I and II are multisubunit complexes that play essential yet distinct functions in chromosome condensation and segregation in mitosis. Unlike condensin I, condensin II localizes to the nucleus during interphase, but it remains poorly understood what functions condensin II might have before mitotic entry. Here, we report that condensin II changes its chromatin-binding property during S phase. Remarkably, advanced premature chromosome condensation (PCC) assays enabled us to visualize condensin II forming “sister axes” in replicated regions of chromosomes in S phase cells. Depletion of condensin II compromised PCC-driven sister chromatid resolution during S phase. Moreover, fluorescence in situ hybridization assays revealed that condensin II, but not condensin I, promotes disjoining duplicated chromosomal loci during S phase. Application of mild replicative stress partially impaired this process and further exacerbated phenotypes arising from condensin II depletion. Our results suggest that condensin II initiates structural reorganization of duplicated chromosomes during S phase to prepare for their proper condensation and segregation in mitosis. PMID:23401001

  7. First Results of the Phase II SIMPLE Dark Matter Search

    NASA Astrophysics Data System (ADS)

    Felizardo, M.; Morlat, T.; Fernandes, A. C.; Girard, T. A.; Marques, J. G.; Ramos, A. R.; Auguste, M.; Boyer, D.; Cavaillou, A.; Sudre, C.; Poupeney, J.; Payne, R. F.; Miley, H. S.; Puibasset, J.

    2010-11-01

    We report results of a 14.1kgd measurement with 15 superheated droplet detectors of total active mass 0.208 kg, comprising the first stage of a 30kgd Phase II experiment. In combination with the results of the neutron-spin sensitive XENON10 experiment, these results yield a limit of |ap|<0.32 for MW=50GeV/c2 on the spin-dependent sector of weakly interacting massive particle-nucleus interactions with a 50% reduction in the previously allowed region of the phase space, formerly defined by XENON, KIMS, and PICASSO. In the spin-independent sector, a limit of 2.3×10-5pb at MW=45GeV/c2 is obtained.

  8. First Results of the Phase II SIMPLE Dark Matter Search

    SciTech Connect

    Felizardo, M.; Morlat, T.; Girard, T. A.; Fernandes, A. C.; Marques, J. G.; Ramos, A. R.; Auguste, M.; Boyer, D.; Cavaillou, A.; Sudre, C.; Poupeney, J.; Payne, R. F.; Miley, H. S.; Puibasset, J.

    2010-11-19

    We report results of a 14.1 kg d measurement with 15 superheated droplet detectors of total active mass 0.208 kg, comprising the first stage of a 30 kg d Phase II experiment. In combination with the results of the neutron-spin sensitive XENON10 experiment, these results yield a limit of |a{sub p}|<0.32 for M{sub W}=50 GeV/c{sup 2} on the spin-dependent sector of weakly interacting massive particle-nucleus interactions with a 50% reduction in the previously allowed region of the phase space, formerly defined by XENON, KIMS, and PICASSO. In the spin-independent sector, a limit of 2.3x10{sup -5} pb at M{sub W}=45 GeV/c{sup 2} is obtained.

  9. 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

  10. [Phase I-II study of recombinant interferon gamma].

    PubMed

    Adachi, K; Ogawa, M; Usui, N; Inagaki, J; Horikoshi, N; Inoue, K; Nakada, H; Tada, A; Yamazaki, H; Mukaiyama, T

    1985-06-01

    A phase I-II study of human recombinant interferon gamma (rIFN-gamma) was conducted in patients with various advanced cancer refractory to standard chemotherapies. In the phase I study, seven patients received 14 courses of escalating doses ranging from 2 X 10(6)U/m2 to 64 X 10(6)U/m2 by 1-hour intravenous infusion for 5 consecutive days. The toxicities were high fever with chills, anorexia, occasional nausea and vomiting, elevation of serum GOT, and dose-related leukopenia and neurotoxic symptoms such as heavy fatigue with somnolence or lethargy, both of which were reversible. The pharmacokinetics showed that the peak levels of serum rIFN-gamma activity were dose-related but decreased rapidly to below measurable levels within 6 hours after infusion in patients receiving less than 12 X 10(6)U/m2. Considering these data, the dosage of rIFN-gamma 6 X 10(6) U/m2 by daily intramuscular injection for more than 4 weeks was selected for the early phase II study. There was no partial response out of 11 evaluable patients but a stable condition was observed in 2 cases of renal cell carcinoma and one case each of breast cancer and ovarian cancer. All toxicities seen were similar to those observed in the phase I study, but no tachyphylaxis developed with continued dosage. The antitumor effect of rIFN-gamma remains to be evaluated in a further study employing higher doses. PMID:2988459

  11. Active membrane phased array radar

    NASA Technical Reports Server (NTRS)

    Moussessian, Alina; Del Castillo, Linda; Huang, John; Sadowy, Greg; Hoffman, James; Smith, Phil; Hatake, Toshiro; Derksen, Chuck; Lopez, Bernardo; Caro, Ed

    2005-01-01

    We have developed the first membrane-based active phased array in L-band (1.26GHz). The array uses membrane compatible Transmit/Receive (T/R) modules (membrane T/R) for each antenna element. We use phase shifters within each T/R module for electronic beam steering. We will discuss the T/R module design and integration with the membrane, We will also present transmit and receive beam-steering results for the array.

  12. 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…

  13. Cell cycle-dependent regulation of RNA polymerase II basal transcription activity.

    PubMed Central

    Yonaha, M; Chibazakura, T; Kitajima, S; Yasukochi, Y

    1995-01-01

    Regulation of transcription by RNA polymerase II (pol II) in eukaryotic cells requires both basal and regulatory transcription factors. In this report we have investigated in vitro pol II basal transcription activity during the cell cycle by using nuclear extracts from synchronized HeLa cells. It is shown that pol II basal transcription activity is low in the S and G2 phases and high in early G1 phase and TFIID is the rate limiting component of pol II basal transcription activity during the cell cycle. Further analyses reveal that TFIID exists as a less active form in the S and G2 phases and nuclear extracts from S and G2 phase cells contain a heat-sensitive repressor(s) of TATA box binding protein (TBP). These results suggest that pol II basal transcription activity is regulated by a qualitative change in the TFIID complex, which could involve repression of TBP, during the cell cycle. Images PMID:7479063

  14. Prospective Evaluation of First-Line Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Carrying an Activating EGFR Mutation: A Multicenter Academic Phase II Study in Caucasian Patients (FIELT)

    PubMed Central

    De Grève, Jacques; Van Meerbeeck, Jan; Vansteenkiste, Johan F.; Decoster, Lore; Meert, Anne-Pascale; Vuylsteke, Peter; Focan, Christian; Canon, Jean-Luc; Humblet, Yves; Berchem, Guy; Colinet, Benoit; Galdermans, Danny; Bosquée, Lionel; Vermeij, Joanna; Dewaele, Alex; Geers, Caroline; Schallier, Denis; Teugels, Erik

    2016-01-01

    Introduction Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibition is the preferred first-line treatment of advanced adenocarcinoma of the lung that harbors EGFR activating tyrosine kinase domain mutations. Most data available pertain to Asian populations in which such mutations are more prevalent. We report on the long-term results of first-line treatment with erlotinib in Caucasian patients with advanced adenocarcinoma of the lung that have a somatic EGFR mutation in their tumor. Methods Multicenter academic prospective phase II study with erlotinib in patients with an activating EGFR tyrosine kinase (TK) domain somatic mutation (any exon encoding the kinase domain) in the tumor and no prior treatment for their advanced disease. Results Phenotypic preselecting of 229 patients led to a high EGFR mutation detection rate of 24% of which 46 patients were included in the phase II study. With a progression free survival (PFS) of 81% at three months the study met its primary endpoint for presumed superiority over chemotherapy. With an overall median PFS of 11 months and a median overall survival (OS) of 23 months, the results compare favorably with results obtained in randomized studies using TKI in first line in EGFR mutation positive adenocarcinoma of the lung. Conclusion The present study reinforces the use of EGFR tyrosine kinase inhibition (TKI) as a first line treatment of choice for advanced adenocarcinoma of the lung carrying an activating EGFR mutation. The mutation rate in preselected Caucasian patients is higher than previously reported. Issues relevant for clinical practice are discussed. Trial Registration ClinicalTrials.gov NCT00339586 PMID:27032107

  15. 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

  16. Inhibition of dihydroceramide desaturase activity by the sphingosine kinase inhibitor SKI II[S

    PubMed Central

    Cingolani, Francesca; Casasampere, Mireia; Sanllehí, Pol; Casas, Josefina; Bujons, Jordi; Fabrias, Gemma

    2014-01-01

    Sphingosine kinase inhibitor (SKI) II has been reported as a dual inhibitor of sphingosine kinases (SKs) 1 and 2 and has been extensively used to prove the involvement of SKs and sphingosine-1-phosphate (S1P) in cellular processes. Dihydroceramide desaturase (Des1), the last enzyme in the de novo synthesis of ceramide (Cer), regulates the balance between dihydroceramides (dhCers) and Cers. Both SKs and Des1 have interest as therapeutic targets. Here we show that SKI II is a noncompetitive inhibitor (Ki = 0.3 μM) of Des1 activity with effect also in intact cells without modifying Des1 protein levels. Molecular modeling studies support that the SKI II-induced decrease in Des1 activity could result from inhibition of NADH-cytochrome b5 reductase. SKI II, but not the SK1-specific inhibitor PF-543, provoked a remarkable accumulation of dhCers and their metabolites, while both SKI II and PF-543 reduced S1P to almost undetectable levels. SKI II, but not PF543, reduced cell proliferation with accumulation of cells in the G0/G1 phase. SKI II, but not PF543, induced autophagy. These overall findings should be taken into account when using SKI II as a pharmacological tool, as some of the effects attributed to decreased S1P may actually be caused by augmented dhCers and/or their metabolites. PMID:24875537

  17. 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.

  18. 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.

  19. 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…

  20. Phoenix Violence Prevention Initiative, Phase II Report.

    ERIC Educational Resources Information Center

    Waits, Mary Jo; Johnson, Ryan; Kornreich, Toby; Klym, Mark; Leland, Karen

    In 1996, drawing from religious, educational, social services, media, neighborhoods, nonprofits, and health-providing sectors of the community, the Phoenix Violence Prevention Initiative (PVPI) was conceived. During Phase One of the initiative, the following seven points regarding prevention and prevention design strategies were assembled: (1)…

  1. Vinflunine – an active chemotherapy for treatment of advanced non-small-cell lung cancer previously treated with a platinum-based regimen: results of a phase II study

    PubMed Central

    Bennouna, J; Breton, J-L; Tourani, J-M; Ottensmeier, C; O'Brien, M; Kosmidis, P; Huat, T E; Pinel, M-C; Colin, C; Douillard, J-Y

    2006-01-01

    A multicentre, single-arm, phase II trial designed to determine the efficacy of single-agent vinflunine in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with a platinum-based regimen. The objectives were to assess efficacy in terms of tumour response rate (primary end point), duration of response, progression-free survival (PFS) and overall survival (OS), and to evaluate the toxicity associated with this treatment. Patients with advanced NSCLC with progressive disease having failed prior platinum-based first-line treatment for advanced disease. Five responses out of the 63 treated patients were documented by WHO criteria and validated by an independent panel review (IRP), yielding a response rate of 7.9% (95% CI: 2.6–17.6) in the intent-to-treat analysis and 8.3% (95% CI: 2.8–18.4) in the evaluable population. Disease control was achieved in 35 out of 60 evaluable patients (58.3%). The median duration of response (complete response+partial response), according to modified WHO criteria was 7.8 months (95% CI: 4.6–NR). Median PFS was 2.6 months (95% CI: 1.4–3.8), and the median survival was 7.0 months (95% CI: 5.8–9.2). Grades 3–4 neutropenia was reported in 50% of patients; febrile neutropenia was observed in two patients (3.2%); grades 3–4 myalgia and grade 3 constipation were experienced by 10 (15.9%) and six (9.5%) of patients, respectively. Constipation was manageable, noncumulative and could be prevented with laxative prophylaxis. The encouraging results from this phase II study with vinflunine warrant further investigations in phase III trials as second- or first-line treatment of advanced non-small-cell lung carcinoma, as a single agent or in combination with other active drugs. PMID:16641911

  2. 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

  3. ADMX Phase II : Relocation and Millikelvin Cooling

    SciTech Connect

    Heilman, Jesse; Tracy, Kyle

    2010-08-30

    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 10{sup 14} cm{sup -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. 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

  5. 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.

  6. CYANIDE HEAP BILOGICAL DETOXIFICATION - PHASE II

    EPA Science Inventory

    Many active mine sites, mines in closure stage and some abandoned mines are and have utilized cyanidation to remove and recover precious metals. Discharges from these sites normally contain significant amounts of metal cyanide complexes and concentrations of thiocyanate, soluble...

  7. Phase II Trial of Gemcitabine and Tanespimycin (17AAG) in Metastatic Pancreatic Cancer: A Mayo Clinic Phase II Consortium Study

    PubMed Central

    Pedersen, Katrina S.; Kim, George P.; Foster, Nathan R.; Wang-Gillam, Andrea; Erlichman, Charles; McWilliams, Robert R.

    2016-01-01

    Objectives Heat Shock Protein 90 (HSP90) is a molecular chaperone that stabilizes many oncogenic proteins. HSP90 inhibitors may sensitize tumors to cytotoxic agents by causing client protein degradation. Gemcitabine, which has modest activity in pancreas cancer, activates Chk1, a client protein of HSP90. This phase II trial was designed to determine whether 17AAG could enhance the clinical activity of gemcitabine through degradation of Chk1 in patients with stage IV pancreatic cancer. Methods A multicenter, prospective study combining gemcitabine and 17AAG enrolled patients with stage IV pancreatic adenocarcinoma, adequate liver and kidney function, ECOG performance status 0-2, and no prior chemotherapy for metastatic disease. The primary goal was to achieve a 60% overall survival at six months. Sixty-six patients were planned for accrual, with an interim analysis after 25 patients enrolled. Results: After a futility analysis to achieve the endpoint, accrual was halted with 21 patients enrolled. No complete or partial responses were seen. 40% of patients were alive at 6 months. Median overall survival was 5.4 months. Tolerability was moderate, with 65% of patients having ≥ grade 3 adverse events (AE), and 15% having grade 4 events. Conclusions The lack of clinical activity suggests that targeting Chk1 by inhibiting HSP90 is not important in pancreatic cancer sensitivity to gemcitabine alone. Further studies of HSP90 targeted agents with gemcitabine alone are not warranted. PMID:25952464

  8. Health Activities Project (HAP), Trial Edition II.

    ERIC Educational Resources Information Center

    Buller, Dave; And Others

    Contained within this Health Activities Project (HAP) trial edition (set II) are a teacher information folio and numerous student activity folios which center around the idea that students in grades 5-8 can control their own health and safety. Each student folio is organized into a Synopsis, Health Background, Materials, Setting Up, and Activities…

  9. CYANIDE HEAP BIOLOGICAL DETOXIFICATION - PHASE II

    EPA Science Inventory

    Many active mine sites, mines in the closure stage and some abandoned mines are and have utilized cyanidation to remove and recover precious metals. Discharges from these sites normally contain significant amounts of metal cyanide complexes and concentrations of thiocyanate, solu...

  10. 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. PMID:27178907

  11. 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.

  12. Phase II trial of carboplatin, S-1, and gefitinib as first-line triplet chemotherapy for advanced non-small cell lung cancer patients with activating epidermal growth factor receptor mutations.

    PubMed

    Tamiya, Akihiro; Tamiya, Motohiro; Shiroyama, Takayuki; Saijo, Nobuhiko; Nakatani, Takeshi; Minomo, Shojiro; Tsuji, Taisuke; Takeuchi, Naoko; Omachi, Naoki; Kurata, Kanako; Suzuki, Hidekazu; Okamoto, Norio; Okishio, Kyoichi; Hirashima, Tomonori; Atagi, Shinji

    2015-03-01

    Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is an effective treatment for advanced non-small cell lung cancer (NSCLC) in patients with activating EGFR mutations. However, there have been little evidence-based studies of gefitinib in combination with platinum-doublet therapy in these patients. We performed a phase II trial to determine the efficacy and safety of triplet chemotherapy with gefitinib, carboplatin, and S-1 as a first-line treatment. This was a multicentre, single-arm, phase II trial of carboplatin, S-1, and gefitinib in advanced NSCLC patients with activating EGFR mutations. Patients received four courses of these drugs in 3-4 week cycles. In each cycle, carboplatin (area under curve = 5) was administered on day 1, S-1 (80 mg/m(2)) on days 1-14, and gefitinib (250 mg) every day. Subsequently, the same regimen without carboplatin was administered until disease progression or unacceptable toxicity occurred. The 1-year progression-free survival (PFS) was the primary endpoint, while response rate (RR), PFS, overall survival (OS), and safety were secondary endpoints. Thirty-five patients were enrolled into this study. The 1-year PFS was 74.3% and the overall RR was 85.7%. The median PFS for all patients was 17.6 months (95% confidence interval 15.5-∞), but the median OS was not reached, because 28 patients were still alive after a median follow-up time of 21.4 months. Haematological adverse events (grade 3 or higher) included neutropaenia (17.1%), thrombocytopenia (14.3%), and anaemia (5.7%), while non-haematological adverse events (grade 3 or higher) included elevated aminotransferase (20.0%), diarrhoea (14.3%), and febrile neutropaenia (2.9%). No interstitial lung disease or treatment-related deaths occurred. Combination chemotherapy with carboplatin, S-1, and gefitinib is efficacious and well tolerated as a first-line treatment in advanced NSCLC patients with activating EGFR mutations. PMID:25616723

  13. Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death.

    PubMed

    Zou, X; Gao, J; Zheng, Y; Wang, X; Chen, C; Cao, K; Xu, J; Li, Y; Lu, W; Liu, J; Feng, Z

    2014-01-01

    Zeaxanthin (Zea) is a major carotenoid pigment contained in human retina, and its daily supplementation associated with lower risk of age-related macular degeneration. Despite known property of Zea as an antioxidant, its underlying molecular mechanisms of action remain poorly understood. In this study, we aim to study the regulation mechanism of Zea on phase II detoxification enzymes. In normal human retinal pigment epithelium cells, Zea promoted the nuclear translocation of NF-E2-related factor 2 (Nrf2) and induced mRNA and protein expression of phase II enzymes, the induction was suppressed by specific knockdown of Nrf2. Zea also effectively protected against tert-butyl hydroperoxide-induced mitochondrial dysfunction and apoptosis. Glutathione (GSH) as the most important antioxidant was also induced by Zea through Nrf2 activation in a time- and dose-dependent manner, whereas the protective effects of Zea were decimated by inhibition of GSH synthesis. Finally, Zea activated the PI3K/Akt and MAPK/ERK pathway, whereas only PI3K/Akt activation correlated with phase II enzymes induction and Zea protection. In further in vivo analyses, Zea showed effects of inducing phase II enzymes and increased GSH content, which contributed to the reduced lipid and protein peroxidation in the retina as well as the liver, heart, and serum of the Sprague-Dawley rats. For the first time, Zea is presented as a phase II enzymes inducer instead of being an antioxidant. By activating Nrf2-mediated phase II enzymes, Zea could enhance anti-oxidative capacity and prevent cell death both in vivo and in vitro. PMID:24810054

  14. Frio II Brine Pilot: Report on GEOSEQ Activities

    SciTech Connect

    Daley, T.M.; Freifeld, B.M.; Ajo-Franklin, J.B.; Doughty, C.; Benson, S.M.

    2007-11-17

    LBNL's GEOSEQ project is a key participant in the Frio IIbrine pilot studying geologic sequestration of CO2. During During theinjection phase of the Frio-II brine pilot, LBNL collected multiple datasets including seismic monitoring, hydrologic monitoring and geochemicalsampling. These data sets are summarized in this report including allCASSM (continuous active source seismic monitoring) travel time data,injection pressure and flow rate data and gaseous sampling and tracerdata. Additional results from aqueous chemistry analysis performed by theU. S. Geological Survey (USGS) are summarized. Post injectionmodification of the flow model for Frio II is shown. Thesemodificationsare intended to facilitate integration with the monitoring data andincorporation of model heterogeneity. Current activities of LBNL's GEOSEQproject related to the Frio II test are shown, including development of anew petrophysical model for improved interpretation of seismic monitoringdata and integration of this data with flow modeling.

  15. ACTG 260: a Randomized, Phase I-II, Dose-Ranging Trial of the Anti-Human Immunodeficiency Virus Activity of Delavirdine Monotherapy

    PubMed Central

    Para, Michael F.; Meehan, Patricia; Holden-Wiltse, Jeanne; Fischl, Margaret; Morse, Gene; Shafer, Robert; Demeter, Lisa M.; Wood, Kenneth; Nevin, Tom; Virani-Ketter, Nzeera; Freimuth, William W.

    1999-01-01

    ACTG 260 was an open-label, four-arm trial designed to study the safety and anti-human immunodeficiency virus (anti-HIV) activity of delavirdine monotherapy at three ranges of concentrations in plasma compared to those of control therapy with zidovudine or didanosine. Delavirdine doses were adjusted weekly until subjects were within their target trough concentration range (3 to 10, 11 to 30, or 31 to 50 μM). A total of 113 subjects were analyzed. At week 2, the mean HIV type 1 (HIV-1) RNA level declines among the subjects in the three delavirdine arms were similar (0.87, 1.08, and 1.02 log10 for the low, middle, and high target arms, respectively), but by week 8, the subjects in the pooled delavirdine arms showed only a 0.10 log10 reduction. In the subjects in the nucleoside arm, mean HIV-1 RNA level reductions at weeks 2 and 8 were 0.67 and 0.55 log10, respectively. Because viral suppression by delavirdine was not maintained, the trial was stopped early. Rash, which was usually self-limited, developed in 36% of subjects who received delavirdine. Delavirdine monotherapy has potent anti-HIV activity at 2 weeks, but its activity is time limited due to the rapid emergence of drug resistance. PMID:10348755

  16. 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 (CONTINUED) PROCEDURES GOVERNING TESTING CONSENT AGREEMENTS AND TEST RULES Implementation, Enforcement, and Modification of Test Rules §...

  17. Peer Review in the National Science Foundation: Phase II.

    ERIC Educational Resources Information Center

    Cole, Jonathan R.; Cole, Stephen

    A two part study was conducted to determine if the peer review system of proposals to the National Science Foundation (NSF) operates fairly and if changes are warranted. Part I (reported in ED 167376) extensively described the peer review process and indicated that it is indeed equitable. Phase II, summarized, investigated the issue further by…

  18. 40 CFR 790.52 - Phase II test rule.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 32 2011-07-01 2011-07-01 false Phase II test rule. 790.52 Section 790.52 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) PROCEDURES GOVERNING TESTING CONSENT AGREEMENTS AND TEST RULES Implementation, Enforcement, and Modification of Test Rules §...

  19. 40 CFR 790.52 - Phase II test rule.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... protocol section of the study plan, as defined by § 790.50(c)(1)(v) of this chapter, as the test standard... Modification of Test Rules § 790.52 Phase II test rule. (a) If EPA determines that the proposed study plan... Federal Register requesting comments on the ability of the proposed study plan to ensure that data...

  20. 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

  1. Safety and efficacy of hCDR1 (Edratide) in patients with active systemic lupus erythematosus: results of phase II study

    PubMed Central

    Urowitz, Murray B; Isenberg, David A; Wallace, Daniel J

    2015-01-01

    Objective To evaluate the safety and efficacy of hCDR1 (Edratide) in patients with systemic lupus erythematosus (SLE). Methods Patients (n=340) with SLE ≥4 ACR criteria (4–11, mean 7) with active disease (SLEDAI-2K of 6–12). Patients were on average 7.1 years post-diagnosis and their organ involvement was mainly musculoskeletal, mucocutaneous and haematologic. Placebo or Edratide was administered subcutaneously weekly at doses of 0.5, 1.0 or 2.5 mg. The co-primary endpoints were SLEDAI-2K SLE Disease Activity and Adjusted Mean SLEDAI (AMS) reduction in patients compared with controls using a landmark analysis. Secondary outcomes were improvement in British Isles Lupus Assessment Group (BILAG) Responder Index and medicinal flare analysis. Results Edratide was safe and well tolerated. The primary endpoints based solely on SLEDAI-2K and AMS were not met. The secondary predefined endpoint, BILAG, was met for the 0.5 mg Edratide arm in the intention to treat (ITT) cohort (N=316) (OR=2.09, p=0.03) with trends in the 1.0 and 2.5 mg doses. There was also a positive trend in the Composite SLE Responder Index of the ITT cohort. Post hoc analysis showed that the BILAG secondary endpoint was also met for the 0.5 mg Edratide for a number of subgroup dose levels, including low or no steroids, seropositivity and patients with 2 grade BILAG improvement. Conclusions The favourable safety profile and encouraging clinically significant effects noted in some of the endpoints support the need for additional longer term Edratide studies that incorporate recent advances in the understanding and treatment of SLE, including steroid treatment algorithms, and using a composite primary endpoint which is likely to include BILAG. Trial registration number NCT00203151. PMID:26301100

  2. 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

  3. Evidence that venoconstriction reverses the phase II sympathoinhibitory and bradycardic response to haemorrhage.

    PubMed

    Potas, J R; Dampney, R A L

    2004-03-31

    Severe hypotensive haemorrhage results in a biphasic response, characterized by an initial increase in heart rate and sympathetic vasomotor activity (phase I) followed by a life-threatening hypotension, accompanied by profound sympathoinhibition and bradycardia (phase II). The phase II response is believed to be dependent on inputs from cardiopulmonary receptors, and may be triggered by the reduction in venous return and cardiac filling associated with severe haemorrhage. In this study, we tested the hypothesis that the phase II response could be reversed by venoconstriction, which is known to enhance venous return and cardiac filling, by comparing the effects of phenylephrine (which constricts veins as well as arterioles) with that of vasopressin (which constricts arterioles but not veins). In sodium pentobarbitone-anaesthetised rats, haemorrhage evoked an initial increase in heart rate (HR) and renal sympathetic activity (RSNA) followed by a large decrease in both variables to levels below the pre-haemorrhage baseline levels (phase II response). During the phase II response, an intravenous injection of phenylephrine, sufficient to restore mean arterial pressure to the pre-haemorrhage level, resulted in a gradually developing increase (over 3-4 min) in HR and RSNA back to the baseline levels. In contrast, intravenous injection of an equipressor dose of vasopressin did not result in any increase in RSNA and only a transient increase in HR. Injection of phenylephrine, but not vasopressin, also increased the pulsatile component of central venous pressure, indicative of reduced venous capacitance. The findings indicate that venoconstriction reverses the phase II sympathoinhibition and bradycardia. PMID:15109933

  4. 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...

  5. 77 FR 63410 - SBIR/STTR Phase I to Phase II Transition Benchmarks

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-16

    ... 4(a)(3)(iii) of the SBIR Policy Directive, which was published on August 6, 2012, at 77 FR 46806 and the STTR Policy Directive, which was published the same day at 77 FR 46855, requires each agency to... ADMINISTRATION SBIR/STTR Phase I to Phase II Transition Benchmarks AGENCY: U.S. Small Business...

  6. Division II: Commission 10: Solar Activity

    NASA Astrophysics Data System (ADS)

    van Driel-Gesztelyi, Lidia; Scrijver, Karel J.; Klimchuk, James A.; Charbonneau, Paul; Fletcher, Lyndsay; Hasan, S. Sirajul; Hudson, Hugh S.; Kusano, Kanya; Mandrini, Cristina H.; Peter, Hardi; Vršnak, Bojan; Yan, Yihua

    2015-08-01

    The Business Meeting of Commission 10 was held as part of the Business Meeting of Division II (Sun and Heliosphere), chaired by Valentin Martínez-Pillet, the President of the Division. The President of Commission 10 (C10; Solar activity), Lidia van Driel-Gesztelyi, took the chair for the business meeting of C10. She summarised the activities of C10 over the triennium and the election of the incoming OC.

  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. Steam generator tube integrity program: Phase II, Final report

    SciTech Connect

    Kurtz, R.J.; Bickford, R.L.; Clark, R.A.; Morris, C.J.; Simonen, F.A.; Wheeler, K.R.

    1988-08-01

    The Steam Generator Tube Integrity Program (SGTIP) was a three phase program conducted for the US Nuclear Regulatory Commission (NRC) by Pacific Northwest Laboratory (PNL). The first phase involved burst and collapse testing of typical steam generator tubing with machined defects. The second phase of the SGTIP continued the integrity testing work of Phase I, but tube specimens were degraded by chemical means rather than machining methods. The third phase of the program used a removed-from-service steam generator as a test bed for investigating the reliability and effectiveness of in-service nondestructive eddy-current inspection methods and as a source of service degraded tubes for validating the Phase I and Phase II data on tube integrity. This report describes the results of Phase II of the SGTIP. The object of this effort included burst and collapse testing of chemically defected pressurized water reactor (PWR) steam generator tubing to validate empirical equations of remaining tube integrity developed during Phase I. Three types of defect geometries were investigated: stress corrosion cracking (SCC), uniform thinning and elliptical wastage. In addition, a review of the publicly available leak rate data for steam generator tubes with axial and circumferential SCC and a comparison with an analytical leak rate model is presented. Lastly, nondestructive eddy-current (EC) measurements to determine accuracy of defect depth sizing using conventional and alternate standards is described. To supplement the laboratory EC data and obtain an estimate of EC capability to detect and size SCC, a mini-round robin test utilizing several firms that routinely perform in-service inspections was conducted.

  9. INSERTION DEVICE ACTIVITIES FOR NSLS-II.

    SciTech Connect

    TANABE,T.; HARDER, D.A.; HULBERT, S.; RAKOWSKI, G.; SKARITKA, J.

    2007-06-25

    National Synchrotron Light Source-II (NSLS-II) will be a medium energy storage ring of 3GeV electron beam energy with sub-nm.rad horizontal emittance and top-off capability at 500mA. Damping wigglers will be used not only to reduce the beam emittance but also used as broadband sources for users. Cryo-Permanent Magnet Undulators (CPMUs) are considered for hard X-ray linear device, and permanent magnet based elliptically polarized undulators (EPUs) for variable polarization devices for soft X-ray. 6T superconducting wiggler with minimal fan angle will be installed in the second phase as well as quasi-periodic EPU for VUV and possibly high-temperature superconducting undulator. R&D plans have been established to pursue the performance enhancement of the baseline devices and to design new types of insertion devices. A new insertion device development laboratory will also be established.

  10. A phase I/II trial of the safety and clinical activity of a HER2-protein based immunotherapeutic for treating women with HER2-positive metastatic breast cancer.

    PubMed

    Curigliano, Giuseppe; Romieu, Gilles; Campone, Mario; Dorval, Thierry; Duck, Lionel; Canon, Jean-Luc; Roemer-Becuwe, Celia; Roselli, Mario; Neciosup, Silvia; Burny, Wivine; Callegaro, Andrea; de Sousa Alves, Pedro Miguel; Louahed, Jamila; Brichard, Vincent; Lehmann, Frédéric F

    2016-04-01

    The objectives of this phase I/II study (NCT00140738) were to evaluate the safety and clinical activity of a cancer immunotherapeutic agent (recombinant HER2 protein (dHER2) and the immunostimulant AS15) in patients with HER2-overexpressing metastatic breast cancer (MBC). Forty HER2-positive MBC patients received up to 18 doses (12q2w, 6q3w) of dHER2 immunotherapeutic, as first- or second-line therapy following response to trastuzumab-based treatment as maintenance. Toxicity was graded by the Common Terminology Criteria for Adverse Events (CTCAE) and clinical activity was evaluated by target lesion assessment according to the Response Evaluation Criteria in Solid Tumors (RECIST). Immunogenicity was assessed. The dHER2 immunotherapeutic was well tolerated: grade 1/2 adverse events (AEs) were most common. No cardiac events were observed and one patient experienced an asymptomatic decrease of left ventricular ejection fraction below the normal range (47 %). Both humoral and cellular immunogenicity to the dHER2 antigen was observed. No patient discontinued the immunizations because of AEs but 35/40 withdrew prematurely, 34 because of disease progression (24/34 before or at the tumor assessment after dose 6). One patient achieved a complete response lasting 11 months and one patient had a partial response lasting 3.5 months. Ten patients experienced stable disease ≥26 weeks with 4/10 still in stable disease at the last tumor assessment after 47 weeks. Immunization of MBC patients with the dHER2 immunotherapeutic was associated with minimal toxicity and no cardiac events. Clinical activity was observed with two objective responses and prolonged stable disease for 10/40 patients. PMID:26975189

  11. Cleome rutidosperma and Euphorbia thymifolia Suppress Inflammatory Response via Upregulation of Phase II Enzymes and Modulation of NF-κB and JNK Activation in LPS-Stimulated BV2 Microglia.

    PubMed

    Ding, Hsiou-Yu; Wu, Pei-Shan; Wu, Ming-Jiuan

    2016-01-01

    Cleome rutidosperma DC. and Euphorbia thymifolia L. are herbal medicines used in traditional Indian and Chinese medicine to treat various illnesses. Reports document that they have antioxidant and anti-inflammatory activities; nonetheless, the molecular mechanisms involved in their anti-inflammatory actions have not yet been elucidated. The anti-neuroinflammatory activities and underlying mechanisms of ethanol extracts of Cleome rutidosperma (CR) and Euphorbia thymifolia (ET) were studied using lipopolysaccharide (LPS)-stimulated microglial cell line BV2. The morphology changes and production of pro-inflammatory mediators were assayed. Gene expression of inflammatory genes such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, interleukin (IL)-1β, and CC chemokine ligand (CCL)-2, as well as phase II enzymes such as heme oxygenase (HO)-1, the modifier subunit of glutamate cysteine ligase (GCLM) and NAD(P)H quinone dehydrogenase 1 (NQO1), were further investigated using reverse transcription quantitative-PCR (RT-Q-PCR) and Western blotting. The effects of CR and ET on mitogen activated protein kinases (MAPKs) and nuclear factor (NF)-κB signaling pathways were examined using Western blotting and specific inhibitors. CR and ET suppressed BV2 activation, down-regulated iNOS and COX-2 expression and inhibited nitric oxide (NO) overproduction without affecting cell viability. They reduced LPS-mediated tumor necrosis factor (TNF) and IL-6 production, attenuated IL-1β and CCL2 expression, but upregulated HO-1, GCLM and NQO1 expression. They also inhibited p65 NF-κB phosphorylation and modulated Jun-N terminal kinase (JNK) activation in BV2 cells. SP600125, the JNK inhibitor, significantly augmented the anti-IL-6 activity of ET. NF-κB inhibitor, Bay 11-7082, enhanced the anti-IL-6 effects of both CR and ET. Znpp, a competitive inhibitor of HO-1, attenuated the anti-NO effects of CR and ET. Our results show that CR and ET exhibit anti

  12. Experiment TGV II—results of Phases I and II

    NASA Astrophysics Data System (ADS)

    Briançon, Ch.; Brudanin, V. B.; Čermák, P.; Egorov, V. G.; Klimenko, A. A.; Kovalík, A.; Mamedov, F.; Rukhadze, N. I.; Sandukovski, V. G.; Shitov, Yu. A.; Šimkovic, F.; Stekl, I.; Timkin, V. V.; Vylov, Ts.; Zinatulina, D. R.

    2009-11-01

    Currently, the TGV collaboration is investigating the two-neutrino double electron capture (2vEC/EC) of 106Cd at the Modane underground laboratory. The study is performed with low-background multi-HPGe detector TGV II, which has been constructed for measurements of the rare processes. The half-life limits of T1/2>2.6×1020 years (for Phase I, 8687 hours) and T1/2>3.6×1020 years (for Phase II, 9003 hours) were obtained for the ground state to ground state 2vEC/EC of 106Cd. The results already allow to rule out some of the previous nuclear structure calculations.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. Heat Shock Protein 70 (Hsp70) Peptide Activated Natural Killer (NK) Cells for the Treatment of Patients with Non-Small Cell Lung Cancer (NSCLC) after Radiochemotherapy (RCTx) – From Preclinical Studies to a Clinical Phase II Trial

    PubMed Central

    Specht, Hanno M.; Ahrens, Norbert; Blankenstein, Christiane; Duell, Thomas; Fietkau, Rainer; Gaipl, Udo S.; Günther, Christine; Gunther, Sophie; Habl, Gregor; Hautmann, Hubert; Hautmann, Matthias; Huber, Rudolf Maria; Molls, Michael; Offner, Robert; Rödel, Claus; Rödel, Franz; Schütz, Martin; Combs, Stephanie E.; Multhoff, Gabriele

    2015-01-01

    Heat shock protein 70 (Hsp70) is frequently overexpressed in tumor cells. An unusual cell surface localization could be demonstrated on a large variety of solid tumors including lung, colorectal, breast, squamous cell carcinomas of the head and neck, prostate and pancreatic carcinomas, glioblastomas, sarcomas and hematological malignancies, but not on corresponding normal tissues. A membrane (m)Hsp70-positive phenotype can be determined either directly on single cell suspensions of tumor biopsies by flow cytometry using cmHsp70.1 monoclonal antibody or indirectly in the serum of patients using a novel lipHsp70 ELISA. A mHsp70-positive tumor phenotype has been associated with highly aggressive tumors, causing invasion and metastases and resistance to cell death. However, natural killer (NK), but not T cells were found to kill mHsp70-positive tumor cells after activation with a naturally occurring Hsp70 peptide (TKD) plus low dose IL-2 (TKD/IL-2). Safety and tolerability of ex vivo TKD/IL-2 stimulated, autologous NK cells has been demonstrated in patients with metastasized colorectal and non-small cell lung cancer (NSCLC) in a phase I clinical trial. Based on promising clinical results of the previous study, a phase II randomized clinical study was initiated in 2014. The primary objective of this multicenter proof-of-concept trial is to examine whether an adjuvant treatment of NSCLC patients after platinum-based radiochemotherapy (RCTx) with TKD/IL-2 activated, autologous NK cells is clinically effective. As a mHsp70-positive tumor phenotype is associated with poor clinical outcome only mHsp70-positive tumor patients will be recruited into the trial. The primary endpoint of this study will be the comparison of the progression-free survival of patients treated with ex vivo activated NK cells compared to patients who were treated with RCTx alone. As secondary endpoints overall survival, toxicity, quality-of-life, and biological responses will be determined in both

  19. Water ice phases II, III, and V - Plastic deformation and phase relationships

    NASA Technical Reports Server (NTRS)

    Durham, W. B.; Boro, C. O.; Kirby, S. H.; Stern, L. A.; Heard, H. C.

    1988-01-01

    The ordinary water phase I was transformed to the ice phases that are known to exist in the interiors of large ice moons, such as Ganymede and Callisto for the purpose of investigating plastic deformation behavior of these ices. Ices II, III, and V were prepared using an apparatus and techniques similar to those described by Durham et al. (1983) and subsequently deformed in a gas deformation apparatus, and their deformation data were obtained. It was found that ice II was the strongest of the high-pressure phases, with a strength that was comparable to that of ice I; ice III was very weak, with the flow rate 100 to 1000 times higher than that of ice II at the same levels of stress. It was also found that ices III and V can exist metastably within the ice II field and that they may be deformed plastically within much of the metastable region without reverting to ice II. It is suggested that the weakness of the ice III phase may have profoundly influenced the evolution and the present-day behavior of the icy moons.

  20. Shock and Recovery of Polytetrafluoroethylene Above and Below the Phase II to Phase III Transition

    NASA Astrophysics Data System (ADS)

    Brown, Eric N.; Rae, Philip J.; Trujillo, Carl P.; Dattelbaum, Dana M.; Gray, George T.; Bourne, Neil K.

    2006-07-01

    Polytetrafluoroethylene (PTFE) is a semi-crystalline polymer exhibiting complicated pressure and temperature dependent phases. High strain rate applications in aerospace, defense, and automotive industries have lead to interest in the shock response of PTFE and resulting changes in the polymer structure. Experimental studies on pressure-induced phase transitions using shock-loading techniques and the resulting changes in crystalline structure are presented. Gas launcher experiments were performed on pedigreed PTFE 7C momentum trapped assemblies with impact pressures from 0.4 to 0.85 GPa to investigate the material response above and below the phase II to phase III crystalline transition. [LAUR-05-5945

  1. 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.

  2. Myosin II Activity Softens Cells in Suspension

    PubMed Central

    Chan, Chii J.; Ekpenyong, Andrew E.; Golfier, Stefan; Li, Wenhong; Chalut, Kevin J.; Otto, Oliver; Elgeti, Jens; Guck, Jochen; Lautenschläger, Franziska

    2015-01-01

    The cellular cytoskeleton is crucial for many cellular functions such as cell motility and wound healing, as well as other processes that require shape change or force generation. Actin is one cytoskeleton component that regulates cell mechanics. Important properties driving this regulation include the amount of actin, its level of cross-linking, and its coordination with the activity of specific molecular motors like myosin. While studies investigating the contribution of myosin activity to cell mechanics have been performed on cells attached to a substrate, we investigated mechanical properties of cells in suspension. To do this, we used multiple probes for cell mechanics including a microfluidic optical stretcher, a microfluidic microcirculation mimetic, and real-time deformability cytometry. We found that nonadherent blood cells, cells arrested in mitosis, and naturally adherent cells brought into suspension, stiffen and become more solidlike upon myosin inhibition across multiple timescales (milliseconds to minutes). Our results hold across several pharmacological and genetic perturbations targeting myosin. Our findings suggest that myosin II activity contributes to increased whole-cell compliance and fluidity. This finding is contrary to what has been reported for cells attached to a substrate, which stiffen via active myosin driven prestress. Our results establish the importance of myosin II as an active component in modulating suspended cell mechanics, with a functional role distinctly different from that for substrate-adhered cells. PMID:25902426

  3. Myosin II Activity Softens Cells in Suspension.

    PubMed

    Chan, Chii J; Ekpenyong, Andrew E; Golfier, Stefan; Li, Wenhong; Chalut, Kevin J; Otto, Oliver; Elgeti, Jens; Guck, Jochen; Lautenschläger, Franziska

    2015-04-21

    The cellular cytoskeleton is crucial for many cellular functions such as cell motility and wound healing, as well as other processes that require shape change or force generation. Actin is one cytoskeleton component that regulates cell mechanics. Important properties driving this regulation include the amount of actin, its level of cross-linking, and its coordination with the activity of specific molecular motors like myosin. While studies investigating the contribution of myosin activity to cell mechanics have been performed on cells attached to a substrate, we investigated mechanical properties of cells in suspension. To do this, we used multiple probes for cell mechanics including a microfluidic optical stretcher, a microfluidic microcirculation mimetic, and real-time deformability cytometry. We found that nonadherent blood cells, cells arrested in mitosis, and naturally adherent cells brought into suspension, stiffen and become more solidlike upon myosin inhibition across multiple timescales (milliseconds to minutes). Our results hold across several pharmacological and genetic perturbations targeting myosin. Our findings suggest that myosin II activity contributes to increased whole-cell compliance and fluidity. This finding is contrary to what has been reported for cells attached to a substrate, which stiffen via active myosin driven prestress. Our results establish the importance of myosin II as an active component in modulating suspended cell mechanics, with a functional role distinctly different from that for substrate-adhered cells. PMID:25902426

  4. Active phase locking of thirty fiber channels using multilevel phase dithering method.

    PubMed

    Huang, Zhimeng; Tang, Xuan; Luo, Yongquan; Liu, Cangli; Li, Jianfeng; Zhang, Dayong; Wang, Xiaojun; Chen, Tunan; Han, Mei

    2016-03-01

    An active phase locking of a large-scale fiber array with thirty channels has been demonstrated experimentally. In the experiment, the first group of thirty phase controllers is used to compensate the phase noises between the elements and the second group of thirty phase modulators is used to impose additional phase disturbances to mimic the phase noises in the high power fiber amplifiers. A multi-level phase dithering algorithm using dual-level rectangular-wave phase modulation and time division multiplexing can achieve the same phase control as single/multi-frequency dithering technique, but without coherent demodulation circuit. The phase locking efficiency of 30 fiber channels is achieved about 98.68%, 97.82%, and 96.50% with no additional phase distortion, modulated phase distortion I (±1 rad), and phase distortion II (±2 rad), corresponding to the phase error of λ/54, λ/43, and λ/34 rms. The contrast of the coherent combined beam profile is about 89%. Experimental results reveal that the multi-level phase dithering technique has great potential in scaling to a large number of laser beams. PMID:27036760

  5. Active phase locking of thirty fiber channels using multilevel phase dithering method

    NASA Astrophysics Data System (ADS)

    Huang, Zhimeng; Tang, Xuan; Luo, Yongquan; Liu, Cangli; Li, Jianfeng; Zhang, Dayong; Wang, Xiaojun; Chen, Tunan; Han, Mei

    2016-03-01

    An active phase locking of a large-scale fiber array with thirty channels has been demonstrated experimentally. In the experiment, the first group of thirty phase controllers is used to compensate the phase noises between the elements and the second group of thirty phase modulators is used to impose additional phase disturbances to mimic the phase noises in the high power fiber amplifiers. A multi-level phase dithering algorithm using dual-level rectangular-wave phase modulation and time division multiplexing can achieve the same phase control as single/multi-frequency dithering technique, but without coherent demodulation circuit. The phase locking efficiency of 30 fiber channels is achieved about 98.68%, 97.82%, and 96.50% with no additional phase distortion, modulated phase distortion I (±1 rad), and phase distortion II (±2 rad), corresponding to the phase error of λ/54, λ/43, and λ/34 rms. The contrast of the coherent combined beam profile is about 89%. Experimental results reveal that the multi-level phase dithering technique has great potential in scaling to a large number of laser beams.

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

    PubMed Central

    Bertrand, J; Chenel, M; Comets, E

    2016-01-01

    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

  7. 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

  8. Phosphorylation-independent stimulation of DNA topoisomerase II alpha activity.

    PubMed

    Kimura, K; Saijo, M; Tanaka, M; Enomoto, T

    1996-05-01

    It has been suggested that casein kinase II phosphorylates DNA topoisomerase II alpha (topo II alpha) in mouse FM3A cells, by comparison of phosphopeptide maps of topo II alpha labeled in intact cells and of topo II alpha phosphorylated by various kinases in vitro. The phosphorylation of purified topo II alpha by casein kinase II, which attached a maximum of two phosphate groups per topo II alpha molecule, had no effect on the activity of topo II alpha. Dephosphorylation of purified topo II alpha by potato acid phosphatase, which almost completely dephosphorylated the topo II alpha, did not reduce the activity of topo II alpha. The incubation itself, regardless of phosphorylation or dephosphorylation status, stimulated the enzyme activity in both reactions. Topo II alpha activity was stimulated by incubation in a medium containing low concentrations of glycerol but not in that containing high concentrations of glycerol, such as the 50% in which purified topo II alpha is stored. The stimulation of topo II alpha activity by incubation was dependent on the concentration of topo II alpha, requiring a relatively high concentration of topo II alpha. PMID:8631919

  9. 40 CFR 72.74 - Federal issuance of Phase II permits.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Federal issuance of Phase II permits. 72.74 Section 72.74 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.74 Federal issuance of Phase II permits. (a)(1) The Administrator will...

  10. 40 CFR 72.73 - State issuance of Phase II permits.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false State issuance of Phase II permits. 72.73 Section 72.73 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.73 State issuance of Phase II permits. (a) State Permit Issuance. (1) A...

  11. 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...

  12. 48 CFR 1852.219-81 - Limitation on subcontracting-SBIR Phase II program.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 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...

  13. 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...

  14. 48 CFR 1852.219-81 - Limitation on subcontracting-SBIR Phase II program.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 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...

  15. 48 CFR 1852.219-81 - Limitation on subcontracting-SBIR Phase II program.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 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...

  16. Active heterodimers are formed from human DNA topoisomerase II alpha and II beta isoforms.

    PubMed Central

    Biersack, H; Jensen, S; Gromova, I; Nielsen, I S; Westergaard, O; Andersen, A H

    1996-01-01

    DNA topoisomerase II is a nuclear enzyme essential for chromosome dynamics and DNA metabolism. In mammalian cells, two genetically and biochemically distinct topoisomerase II forms exist, which are designated topoisomerase II alpha and topoisomerase II beta. In our studies of human topoisomerase II, we have found that a substantial fraction of the enzyme exists as alpha/beta heterodimers in HeLa cells. The ability to form heterodimers was verified when human topoisomerases II alpha and II beta were coexpressed in yeast and investigated in a dimerization assay. Analysis of purified heterodimers shows that these enzymes maintain topoisomerase II specific catalytic activities. The natural existence of an active heterodimeric subclass of topoisomerase II merits attention whenever topoisomerases II alpha and II beta function, localization, and cell cycle regulation are investigated. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8710863

  17. Leaching of Phase II Mercury Control Technology By-Products

    SciTech Connect

    Hesbach, P.A.; Kachur, E.K.

    2007-07-01

    The U.S. EPA has issued a final regulation for control of mercury from coal-fired power plants. 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. These adulterated by-products, both ashes and FGD material, represent the greatest challenge to the DOE goal of increased utilization of by-products. The degree of stability of capture by-products and their potential for release of mercury can have a large economic impact on material sales or the approach to disposal. One of the considerations for mercury control technology is the potential trade-off between effective but temporary mercury capture and less effective but more permanent sequestration. As part of a greater characterization effort of Phase II facility baseline and control technology sample pairs, NETL in-house laboratories have performed aqueous leaching procedures on a select subset of the available sample pairs. This report describes batch leaching results for mercury, arsenic, and selenium.

  18. Active site specificity of plasmepsin II.

    PubMed Central

    Westling, J.; Cipullo, P.; Hung, S. H.; Saft, H.; Dame, J. B.; Dunn, B. M.

    1999-01-01

    Members of the aspartic proteinase family of enzymes have very similar three-dimensional structures and catalytic mechanisms. Each, however, has unique substrate specificity. These distinctions arise from variations in amino acid residues that line the active site subsites and interact with the side chains of the amino acids of the peptides that bind to the active site. To understand the unique binding preferences of plasmepsin II, an enzyme of the aspartic proteinase class from the malaria parasite, Plasmodium falciparum, chromogenic octapeptides having systematic substitutions at various positions in the sequence were analyzed. This enabled the design of new, improved substrates for this enzyme (Lys-Pro-Ile-Leu-Phe*Nph-Ala/Glu-Leu-Lys, where * indicates the cleavage point). Additionally, the crystal structure of plasmepsin II was analyzed to explain the binding characteristics. Specific amino acids (Met13, Ser77, and Ile287) that were suspected of contributing to active site binding and specificity were chosen for site-directed mutagenesis experiments. The Met13Glu and Ile287Glu single mutants and the Met13Glu/Ile287Glu double mutant gain the ability to cleave substrates containing Lys residues. PMID:10548045

  19. Regulation of Hepatic Phase II Metabolism in Pregnant Mice

    PubMed Central

    Wen, Xia; Donepudi, Ajay C.; Thomas, Paul E.; Slitt, Angela L.; King, Roberta S.

    2013-01-01

    Phase II enzymes, including Ugts, Sults, and Gsts, are critical for the disposition and detoxification of endo- and xenobiotics. In this study, the mRNA and protein expression of major phase II enzymes, as well as key regulatory transcription factors, were quantified in livers of time-matched pregnant and virgin control C57BL/6 mice on gestation days (GD) 7, 11, 14, 17, and postnatal days (PND) 1, 15, and 30. Compared with virgin controls, the mRNA expression of Ugt1a1, 1a6, 1a9, 2a3, 2b1, 2b34, and 2b35 decreased 40 to 80% in pregnant dams. Protein expression of Ugt1a6 also decreased and corresponded with reduced in vitro glucuronidation of bisphenol A in S9 fractions from livers of pregnant mice. Similar to Ugts levels, Gsta1 and a4 mRNAs were reduced in pregnant dams in mid to late gestation; however no change in protein expression was observed. Conversely, Sult1a1, 2a1/2, and 3a1 mRNAs increased 100 to 500% at various time points in pregnant and lactating mice and corresponded with enhanced in vitro sulfation of acetaminophen in liver S9 fractions. Coinciding with maximal decreases in Ugts as well as increases in Sults, the expression of transcription factors CAR, PPARα, and PXR and their target genes were downregulated, whereas ERα mRNA was upregulated. Collectively, these data demonstrate altered regulation of hepatic phase II metabolism in mice during pregnancy and suggest that CAR, PPARα, PXR, and ERα signaling pathways may be candidate signaling pathways responsible for these changes. PMID:23055538

  20. 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.

  1. Sirukumab, a human anti-interleukin-6 monoclonal antibody: a randomised, 2-part (proof-of-concept and dose-finding), phase II study in patients with active rheumatoid arthritis despite methotrexate therapy

    PubMed Central

    Smolen, Josef S; Weinblatt, Michael E; Sheng, Shihong; Zhuang, Yanli; Hsu, Benjamin

    2014-01-01

    Objectives The safety and efficacy of sirukumab, an anti-interleukin-6 (IL-6) monoclonal antibody, were evaluated in a 2-part, placebo-controlled phase II study of patients with active rheumatoid arthritis (RA) despite methotrexate therapy. Methods In Part A (proof-of-concept), 36 patients were randomised to placebo or sirukumab 100 mg every 2 weeks (q2w) through week 10, with crossover treatment during weeks 12–22. In Part B (dose finding), 151 patients were randomised to sirukumab (100 mg q2w, 100 mg q4w, 50 mg q4w, or 25 mg q4w) through week 24, or placebo through week 10 with crossover to sirukumab 100 mg q2w (weeks 12–24). The proportion of patients with an American College of Rheumatology 50 (ACR50) response and the change from baseline in the 28-joint count disease activity score using C-reactive protein (DAS28-CRP) were determined. Safety was evaluated through week 38 in both parts. Results The primary endpoint (ACR50 at week 12 in Part B) was achieved only with sirukumab 100 mg q2w versus placebo (26.7% vs 3.3%; p=0.026). Greater improvements in mean DAS28-CRP at week 12 were observed with sirukumab 100 mg q2w versus placebo in Parts A (2.1 vs 0.6, p<0.001) and B (2.2 vs 1.1; p<0.001). The incidence of adverse events (AEs) was similar for sirukumab-treated and placebo-treated patients through week 12 in Part A (70.6% and 63.2%, respectively) and B (67.8% and 66.7%, respectively). Infections were the most common type of AE; one death occurred (Part B, sirukumab 100 mg q2w, brain aneurysm). Conclusions Sirukumab-treated patients experienced improvements in the signs/symptoms of RA. Safety results through 38 weeks were consistent with other IL-6 inhibitors. Trial registration number NCT00718718. PMID:24699939

  2. 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.

  3. High consistency forming process for papermaking. Phase II. Final report

    SciTech Connect

    Kranz, W.T.; Judd, M.; Rotherham, J.

    1980-09-01

    The demonstration program for saving energy that can be obtained by forming paper and paperboard products at initial high fiber concentration is discussed. Under Phase II, a limited number of design modifications were made to the low speed high consistency headbox. These resulted in improved sheet formation for samples used in subsequent press studies. Comparisons of sheet physical and drainage properties were made between low and high consistency sheets. Equipment for these tests was designed and fabricated during Phase II, including a laboratory scale dynamic roll nip press with single felt. The high consistency sheet had significantly higher permeability and compressive modulus than the low consistency sheet. In simulated three nip press studies the high consistency sheet demonstrated a 1.5 to 2.5% higher solids content than the low consistency sheet under the same operating parameters. The effect of variables such as machine speed, sheet basis weight, nip loading and entering sheet consistency were investigated. Rules for scaling between laboratory and full size press nips have been established. The energy saving potential for the paper industry through the use of high consistency forming was estimated as 6 to 7% of current total consumption.

  4. Purification, crystallization, X-ray diffraction analysis and phasing of an engineered single-chain PvuII restriction endonuclease

    SciTech Connect

    Meramveliotaki, Chrysi; Kotsifaki, Dina; Androulaki, Maria; Hountas, Athanasios; Eliopoulos, Elias; Kokkinidis, Michael

    2007-10-01

    PvuII is the first type II restriction endonuclease to be converted from its wild-type homodimeric form into an enzymatically active single-chain variant. The enzyme was crystallized and phasing was successfully performed by molecular replacement. The restriction endonuclease PvuII from Proteus vulgaris has been converted from its wild-type homodimeric form into the enzymatically active single-chain variant scPvuII by tandemly joining the two subunits through the peptide linker Gly-Ser-Gly-Gly. scPvuII, which is suitable for the development of programmed restriction endonucleases for highly specific DNA cleavage, was purified and crystallized. The crystals diffract to a resolution of 2.35 Å and belong to space group P4{sub 2}, with unit-cell parameters a = b = 101.92, c = 100.28 Å and two molecules per asymmetric unit. Phasing was successfully performed by molecular replacement.

  5. ISAC SC-LINAC PHASE-II HELIUM REFRIGERATOR COMMISSIONING AND FIRST OPERATIONAL EXPERIENCE AT TRIUMF

    SciTech Connect

    Sekachev, I.; Kishi, D.; Laxdal, R. E.

    2010-04-09

    ISAC Phase-II is an upgrade of the radioactive isotope superconducting linear accelerator, SC-linac, at TRIUMF. The Phase-I section of the accelerator, medium-beta, is operational and is cooled with a 600 W helium refrigerator, commissioned in March 2005. An identical refrigerator is being used with the Phase-II segment of the accelerator; which is now under construction. The second refrigerator has been commissioned and tested with the Phase-I section of the linac and is used for Phase-II linac development, including new SC-cavity performance tests. The commissioning of the Phase-II refrigeration system and recent operational experience is presented.

  6. Isac Sc-Linac Phase-II Helium Refrigerator Commissioning and First Operational Experience at Triumf

    NASA Astrophysics Data System (ADS)

    Sekachev, I.; Kishi, D.; Laxdal, R. E.

    2010-04-01

    ISAC Phase-II is an upgrade of the radioactive isotope superconducting linear accelerator, SC-linac, at TRIUMF. The Phase-I section of the accelerator, medium-beta, is operational and is cooled with a 600 W helium refrigerator, commissioned in March 2005. An identical refrigerator is being used with the Phase-II segment of the accelerator; which is now under construction. The second refrigerator has been commissioned and tested with the Phase-I section of the linac and is used for Phase-II linac development, including new SC-cavity performance tests. The commissioning of the Phase-II refrigeration system and recent operational experience is presented.

  7. Yakima Fish Passage : Phase II : Fish Screen Construction.

    SciTech Connect

    United States. Bureau of Reclamation. Pacific Northwest Region.

    2003-03-01

    Accomplishments in 2001--2002 were spotty and limited due primarily to right-of-way problems at several sites and unanticipated changes in scope at some sites. Changes in BPA funding procedures have also impacted our ability to accomplish previously scheduled work. The following is a brief summary of work accomplished and scheduled at the remaining Phase II sites. (1) Selah-Moxee Fish Screen--Construction at this site was started in October 2001 and was completed in March 2002. We have settled the contractor claims and have closed out the construction contract. The O&M Agreement with the irrigation district was also completed in 2002. Work remains to complete the Designer's Operating Criteria. (2) Scott Fish Screen--Considerable effort was spent in 2001 and 2002 to try to resolve right-of-way issues at this site. However, these problems proved to be insurmountable, and this site has been dropped from the Phase n Program. The only thing remaining on Scott (as far as the Phase n program is concerned) is to prepare a brief wrap-up report to send to all interested parties to summarize what has been done and to explain the status of the diversion from a fish passage standpoint. (3) Packwood Fish Screen--Designs and specifications for the civil works were completed for this screen in 2002. The screen, screen cleaner, and other metal work have already been fabricated by WDFW Screen Shop. Award of a construction contract was scheduled for September 2002. The BP A lands staff has experienced significant delays in obtaining an easement from the state of Washington for a piece of the John Wayne Trail right-of-way currently occupied by the existing screen. As a result, the construction contract has been rescheduled for award in the fall of 2003. We are ready to proceed with construction if BP A can obtain the necessary easements by May 2003. (4) Fogarty Fish Screen--We opened bids on this site in August, 2002. There was only one responsive bidder and the bid was nearly double

  8. Lipolytic and metabolic response to glucagon in fasting king penguins: phase II vs. phase III.

    PubMed

    Bernard, Servane F; Thil, Marie-Anne; Groscolas, Rene

    2003-02-01

    This study aims to determine how glucagon intervenes in the regulation of fuel metabolism, especially lipolysis, at two stages of a spontaneous long-term fast characterized by marked differences in lipid and protein availability and/or utilization (phases II and III). Changes in the plasma concentration of various metabolites and hormones, and in lipolytic fluxes as determined by continuous infusion of [2-3H]glycerol and [1-14C]palmitate, were examined in vivo in a subantarctic bird (king penguin) before, during, and after a 2-h glucagon infusion. In the two fasting phases, glucagon infusion at a rate of 0.025 microg. kg(-1). min(-1) induced a three- to fourfold increase in the plasma concentration and in the rate of appearance (Ra) of glycerol and nonesterified fatty acids, the percentage of primary reesterification remaining unchanged. Infusion of glucagon also resulted in a progressive elevation of the plasma concentration of glucose and beta-hydroxybutyrate and in a twofold higher insulinemia. These changes were not significantly different between the two phases. The plasma concentrations of triacylglycerols and uric acid were unaffected by glucagon infusion, except for a 40% increase in plasma uric acid in phase II birds. Altogether, these results indicate that glucagon in a long-term fasting bird is highly lipolytic, hyperglycemic, ketogenic, and insulinogenic, these effects, however, being similar in phases II and III. The maintenance of the sensitivity of adipose tissue lipolysis to glucagon could suggest that the major role of the increase in basal glucagonemia observed in phase III is to stimulate gluconeogenesis rather than fatty acid delivery. PMID:12388477

  9. Shock and Recovery of Polytetrafluoroethylene Above and Below the Phase II To Phase III Transition

    NASA Astrophysics Data System (ADS)

    Brown, Eric N.; Bourne, Neil K.

    2005-07-01

    Polytetrafluoroethylene (PTFE) is semi-crystalline in nature with its linear chains forming complicated temperature and pressure dependent phases. Due to its desirable mechanical properties applications of PTFE include structures designed for dynamic largescale plasticity excursions. Experimental studies on pressure-induced phase transitions using shock-loading techniques and the resulting changes in crystalline structure are presented. Disks of pedigreed PTFE 7C have been shock loaded in momentum trapped assemblies using a 80 mm gas launcher. Challenges in momentum trapping and soft recovery arising from the low yield stress of PTFE (9 MPa at room temperature) are discussed. Experiments were performed with impact pressures from 0.4 to 0.85 GPa to investigate the material response above and below the phase II to phase III crystalline transition. Changes in crystalline structure of the recovered materials were quantified using dynamic scanning calorimetry (DSC) and density.

  10. 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.

  11. 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.

  12. Quantitative spectroscopy of photospheric-phase type II supernovae

    NASA Astrophysics Data System (ADS)

    Dessart, L.; Hillier, D. J.

    2005-07-01

    We present first results on the quantitative spectroscopic analysis of the photospheric-phase of type II supernovae (SN). The analyses are based on the model atmosphere code, CMFGEN, of Hillier & Miller (1998) which solves the radiative transfer and statistical equilibrium equations in expanding outflows under the constraint of radiative equilibrium. A key asset of CMFGEN is its thorough treatment of line-blanketing due to metal species. From its applicability to hot star environments, the main modifications to the source code were to allow a linear velocity law, a power-law density distribution, an adaptive grid to handle the steep H recombination/ionization front occurring in some SN models, and a routine to compute the gray temperature structure in the presence of large velocities. In this first paper we demonstrate the ability of CMFGEN to reproduce, with a high level of accuracy, the UV and optical observations of a sample of well observed type II SN, i.e. SN1987A and SN1999em, at representative stages of their photospheric evolution. Two principal stages of SN are modeled that where hydrogen is fully ionized, and that in which H is only partially ionized. For models with an effective temperature below ~8000 K, hydrogen recombines and gives rise to a steep ionization front. The effect of varying the location of the outer grid radius on the spectral energy distribution (SED) is investigated. We find that going to 5-6 times the optically-thick base radius is optimal, since above that, the model becomes prohibitively large, while below this, significant differences appear because of the reduced line-blanketing (which persists even far above the photosphere) and the truncation of line-formation regions. To constrain the metallicity and the reddening of SN, the UV spectral region of early-time spectra is essential. We find that the density of the photosphere and effect of line blanketing decline as the spatial scale of the SN increases. The density distribution is

  13. Evaluation of Phase II glass formulations for vitrification of Hanford Site low-level waste

    SciTech Connect

    Feng, X.; Hrma, P.R.; Schweiger, M.J.

    1996-03-01

    A vendor glass formulation study was carried out at Pacific Northwest Laboratory (PNL), supporting the Phase I and Phase II melter vendor testing activities for Westinghouse Hanford Company. This study is built upon the LLW glass optimization effort that will be described in a separate report. For Phase I vendor melter testing, six glass formulations were developed at PNL and additional were developed by Phase I vendors. All the doses were characterized in terms of viscosity and chemical durability by the 7-day Product Consistency Test. Twelve Phase II glass formulations (see Tables 3.5 and 3.6) were developed to accommodate 2.5 wt% P{sub 2}O{sub 5} and 1.0 wt% S0{sub 3} without significant processing problems. These levels of P{sub 2}O{sub 5} and SO{sub 3} are expected to be the highest possible concentrations from Hanford Site LLW streams at 25 wt% waste loading in glass. The Phase H compositions formulated were 6 to 23 times more durable than the environmental assessment (EA) glass. They melt within the temperature range of 1160{degrees} to 1410{degrees}C to suit different melting technologies. The composition types include boron-free for volatilization sensitive melters; boron-containing glasses for coId-cap melters; Zr-containing, glasses for enhanced Iong-term durability; and Fe-containing glasses for reducing melting temperature and melt volatility while maintaining chemical durability.

  14. Nonlinear optical properties of the active medium in intracavity phase conjugation of the radiation of a pulsed electron-beam-controlled discharge CO{sub 2} laser. II. Theoretical analysis

    SciTech Connect

    Galushkin, M G; Mitin, Konstantin V; Ionin, Andrei A; Kotkov, A A

    1998-10-31

    Numerical simulation is used as the basis of an analysis of nonlinear optical properties of the active medium in intracavity four-wave mixing of the radiation of a pulsed electron-beam-controlled discharge CO{sub 2} laser on saturated-gain and refractive-index diffraction gratings. The reflection coefficient of the phase-conjugated signal is determined for various cavity Q-factors, specific input energies, and pressures of the laser-active mixture. A comparison is made of the theoretical and experimental results. It is found that the rate of formation of amplitude gratings is governed primarily by the initial population inversion and by the intensities of the interacting waves. It is shown that transient phase gratings make the dominant contribution to the phase-conjugate reflection coefficient at high pressures of the mixture. (nonlinear optical phenomena)

  15. 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…

  16. 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.

  17. Tritium proof-of-principle pellet injector - phase II

    SciTech Connect

    Fisher, P.W.; Gouge, M.J.

    1995-06-01

    As part of the International Thermonuclear Engineering Reactor (ITER) plasma fueling development program, Oak Ridge National Laboratory (ORNL) has fabricated a pellet injection system to test the mechanical and thermal properties of extruded tritium. This repeating, single-stage, pneumatic injector, called the Tritium-Proof-of-Principle Phase II (TPOP-II) Pellet Injector, has a piston-driven mechanical extruder and is designed to extrude hydrogenic pellets sized for the ITER device. The TPOP-II program has the following development goals: evaluate the feasibility of extruding tritium and DT mixtures for use in future pellet injection systems; determine the mechanical and thermal properties of tritium and DT extrusions; integrate, test and evaluate the extruder in a repeating, single-stage light gas gun sized for the ITER application (pellet diameter {approximately} 7-8 mm); evaluate options for recycling propellant and extruder exhaust gas; evaluate operability and reliability of ITER prototypical fueling systems in an environment of significant tritium inventory requiring secondary and room containment systems. In initial tests with deuterium feed at ORNL, up to thirteen pellets have been extruded at rates up to 1 Hz and accelerated to speeds of order 1.0-1.1 km/s using hydrogen propellant gas at a supply pressure of 65 bar. The pellets are typically 7.4 mm in diameter and up to 11 mm in length and are the largest cryogenic pellets produced by the fusion program to date. These pellets represent about a 11% density perturbation to ITER. Hydrogenic pellets will be used in ITER to sustain the fusion power in the plasma core and may be crucial in reducing first wall tritium inventories by a process called isotopic fueling where tritium-rich pellets fuel the burning plasma core and deuterium gas fuels the edge.

  18. Phase Diagrams and Electronic Structure of II-VI Alloys

    NASA Astrophysics Data System (ADS)

    de Gironcoli, Stefano

    1998-03-01

    Among II-VI wide-gap semiconductor solid solutions, Zn_xMg_1-xS_ySe_1-y alloy is the most studied for its potential applications in the blue-green light-emitter technology. In spite of this enormous technological interest little is known about its fundamental thermodynamical and structural properties. In this work the structural and thermodynamical properties of the Zn_xMg_1-xS_ySe_1-y solid solutions are determined by a combination of the computational alchemy (S. de Gironcoli, P. Giannozzi, and S. Baroni, Phys. Rev. Lett. 66), 2116 (1991); N. Marzari, S. de Gironcoli, and S. Baroni, Phys. Rev. Lett. 72, 4001 (1994). and the cluster expansion (S.-H. Wei, L. G. Ferreira, and A. Zunger, Phys. Rev. B 41), 8240 (1990). methods with Monte Carlo simulations. We determine the phase diagram of the alloy and show that the system is completely mixible at the tipical growth temperatures and phase separates at lower temperatures into two or three phases. The homogeneous phase is characterized by a large amount of short-range order occurring among first-nearest neighbors. Electronic-structure calculations, performed extending the special quasi-random structures approach (A. Zunger, S.-H. Wei, L. G. Ferreira, and J. E. Bernard, Phys. Rev. Lett. 65), 353 (1990). to the quaternary alloy case, indicate that the energy gap of the alloy is rather sensitive to this short-range order.

  19. 7 CFR 3403.8 - Proposal format for phase II applications.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...) Commercialization Plan. A succinct commercialization plan must be included in each SBIR Phase II proposal moving... of a product or service for which an SBIR award is made; (ii) Revenue from the sale of new...

  20. 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…

  1. Screened selection design for randomised phase II oncology trials: an example in chronic lymphocytic leukaemia

    PubMed Central

    2013-01-01

    Background As there are limited patients for chronic lymphocytic leukaemia trials, it is important that statistical methodologies in Phase II efficiently select regimens for subsequent evaluation in larger-scale Phase III trials. Methods We propose the screened selection design (SSD), which is a practical multi-stage, randomised Phase II design for two experimental arms. Activity is first evaluated by applying Simon’s two-stage design (1989) on each arm. If both are active, the play-the-winner selection strategy proposed by Simon, Wittes and Ellenberg (SWE) (1985) is applied to select the superior arm. A variant of the design, Modified SSD, also allows the arm with the higher response rates to be recommended only if its activity rate is greater by a clinically-relevant value. The operating characteristics are explored via a simulation study and compared to a Bayesian Selection approach. Results Simulations showed that with the proposed SSD, it is possible to retain the sample size as required in SWE and obtain similar probabilities of selecting the correct superior arm of at least 90%; with the additional attractive benefit of reducing the probability of selecting ineffective arms. This approach is comparable to a Bayesian Selection Strategy. The Modified SSD performs substantially better than the other designs in selecting neither arm if the underlying rates for both arms are desirable but equivalent, allowing for other factors to be considered in the decision making process. Though its probability of correctly selecting a superior arm might be reduced, it still performs reasonably well. It also reduces the probability of selecting an inferior arm. Conclusions SSD provides an easy to implement randomised Phase II design that selects the most promising treatment that has shown sufficient evidence of activity, with available R codes to evaluate its operating characteristics. PMID:23819695

  2. 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).

  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. 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.

  5. 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).

  6. 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.

  7. 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.

  8. Phase Transitions in Model Active Systems

    NASA Astrophysics Data System (ADS)

    Redner, Gabriel S.

    The amazing collective behaviors of active systems such as bird flocks, schools of fish, and colonies of microorganisms have long amazed scientists and laypeople alike. Understanding the physics of such systems is challenging due to their far-from-equilibrium dynamics, as well as the extreme diversity in their ingredients, relevant time- and length-scales, and emergent phenomenology. To make progress, one can categorize active systems by the symmetries of their constituent particles, as well as how activity is expressed. In this work, we examine two categories of active systems, and explore their phase behavior in detail. First, we study systems of self-propelled spherical particles moving in two dimensions. Despite the absence of an aligning interaction, this system displays complex emergent dynamics, including phase separation into a dense active solid and dilute gas. Using simulations and analytic modeling, we quantify the phase diagram and separation kinetics. We show that this nonequilibrium phase transition is analogous to an equilibrium vapor-liquid system, with binodal and spinodal curves and a critical point. We also characterize the dense active solid phase, a unique material which exhibits the structural signatures of a crystalline solid near the crystal-hexatic transition point, as well as anomalous dynamics including superdiffusive motion on intermediate timescales. We also explore the role of interparticle attraction in this system. We demonstrate that attraction drastically changes the phase diagram, which contains two distinct phase-separated regions and is reentrant as a function of propulsion speed. We interpret this complex situation with a simple kinetic model, which builds from the observed microdynamics of individual particles to a full description of the macroscopic phase behavior. We also study active nematics, liquid crystals driven out of equilibrium by energy-dissipating active stresses. The equilibrium nematic state is unstable in these

  9. 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

  10. Emerging Roles of Nrf2 and Phase II Antioxidant Enzymes in Neuroprotection

    PubMed Central

    Zhang, Meijuan; An, Chengrui; Gao, Yanqin; Leak, Rehana K.; Chen, Jun; Zhang, Feng

    2013-01-01

    Phase II metabolic enzymes are a battery of critical proteins that detoxify xenobiotics by increasing their hydrophilicity and enhancing their disposal. These enzymes have long been studied for their preventative and protective effects against mutagens and carcinogens and for their regulation via the Keap1 (Kelch-like ECH associated protein 1) / Nrf2 (Nuclear factor erythroid 2 related factor 2) / ARE (antioxidant response elements) pathway. Recently, a series of studies have reported the altered expression of phase II genes in postmortem tissue of patients with various neurological diseases. These observations hint at a role for phase II enzymes in the evolution of such conditions. Furthermore, promising findings reveal that overexpression of phase II genes, either by genetic or chemical approaches, confers neuroprotection in vitro and in vivo. Therefore, there is a need to summarize the current literature on phase II genes in the central nervous system (CNS). This should help guide future studies on phase II genes as therapeutic targets in neurological diseases. In this review, we first briefly introduce the concept of phase I, II and III enzymes, with a special focus on phase II enzymes. We then discuss their expression regulation, their inducers and executors. Following this background, we expand our discussion to the neuroprotective effects of phase II enzymes and the potential application of Nrf2 inducers to the treatment of neurological diseases. PMID:23025925

  11. Phase I and Phase II Objective Response Rates are Correlated in Pediatric Cancer Trials: An Argument for Better Clinical Trial Efficiency.

    PubMed

    Yeh, Jonathan C; Huang, Peng; Cohen, Kenneth J

    2016-07-01

    Although many phase I trials report tumor response, formal analysis of efficacy is deferred to phase II. We reviewed paired phase I and II pediatric oncology trials to ascertain the relationship between phase I and II objective response rate (OR%). Single-agent phase I trials were paired with corresponding phase II trials (comparable study drug, dosing schedule, and population). Phase I trials without efficacy data or a matching phase II trial were excluded. OR% was tabulated for all trials, and phase II authors' subjective conclusions regarding efficacy were documented; 35 pairs of trials were analyzed. The correlation between phase I and II OR% was 0.93. Between phase II studies with a "positive" conclusion versus a "negative" one, there was a statistically significant difference in mean phase I OR% (32.0% vs. 4.5%, P<0.001). Thirteen phase II studies were undertaken despite phase I OR% of 0%; only 1 had a "positive" conclusion, and none exceeded OR% of 15%. OR% are highly correlated between phase I and II pediatric oncology trials. Although not a formal measure of drug efficacy, phase I OR% may provide an estimate of phase II response, inform phase II study design, and should be given greater consideration. PMID:27164535

  12. The effect of quercetin phase II metabolism on its MRP1 and MRP2 inhibiting potential.

    PubMed

    van Zanden, Jelmer J; van der Woude, Hester; Vaessen, Judith; Usta, Mustafa; Wortelboer, Heleen M; Cnubben, Nicole H P; Rietjens, Ivonne M C M

    2007-07-15

    The present study characterises the effect of phase II metabolism, especially methylation and glucuronidation, of the model flavonoid quercetin on its capacity to inhibit human MRP1 and MRP2 activity in Sf9 inside-out vesicles. The results obtained reveal that 3'-O-methylation does not affect the MRP inhibitory potential of quercetin. However, 4'-O-methylation appeared to reduce the potential to inhibit both MRP1 and MRP2. In contrast, glucuronidation in general, and especially glucuronidation at the 7-hydroxylmoiety, resulting in 7-O-glucuronosyl quercetin, significantly increased the potential of quercetin to inhibit MRP1 and MRP2 mediated calcein transport with inhibition of MRP1 being generally more effective than that of MRP2. Overall, the results of this study reveal that the major phase II metabolites of quercetin are equally potent or even better inhibitors of human MRP1 and MRP2 than quercetin itself. This finding indicates that phase II metabolism of quercetin could enhance the potential use of quercetin- or flavonoids in general-as an inhibitor to overcome MRP-mediated multidrug resistance. PMID:17509533

  13. 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.

  14. 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.

  15. 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.

  16. Phase I/II trial of 2-weekly docetaxel combined with cisplatin plus fluorouracil in metastatic esophageal cancer (JCOG0807).

    PubMed

    Hironaka, Shuichi; Tsubosa, Yasuhiro; Mizusawa, Junki; Kii, Takayuki; Kato, Ken; Tsushima, Takahiro; Chin, Keisho; Tomori, Akihisa; Okuno, Tatsuya; Taniki, Toshikatsu; Ura, Takashi; Matsushita, Hisayuki; Kojima, Takashi; Doki, Yuichiro; Kusaba, Hitoshi; Fujitani, Kazumasa; Taira, Koichi; Seki, Shiko; Nakamura, Tsutomu; Kitagawa, Yuko

    2014-09-01

    We carried out a phase I/II trial of adding 2-weekly docetaxel to cisplatin plus fluorouracil (CF) therapy (2-weekly DCF regimen) in esophageal cancer patients to investigate its safety and antimetastatic activity. Patients received 2-weekly docetaxel (30 mg/m(2) [dose level (DL)1] or 40 mg/m(2) [DL2] with a 3 + 3 design in phase I, on days 1 and 15) in combination with fixed-dose CF (80 mg/m(2) cisplatin, day 1; 800 mg/m(2) fluorouracil, days 1-5) repeated every 4 weeks. The primary endpoint was dose-limiting toxicity (DLT) in phase I and central peer review-based response rate in phase II. At least 22 responders among 50 patients were required to satisfy the primary endpoint with a threshold of 35%. Sixty-two patients were enrolled in phase I and II. In phase I, 10 patients were enrolled with DLT of 0/3 at DL1 and 2/7 in DL2. Considering DLT and treatment compliance, the recommended phase II dose was determined as DL1. In phase II, the response rate was 62% (P < 0.0001; 95% confidence interval, 48-75%); median overall survival and progression-free survival were 11.1 and 5.8 months, respectively. Common grade 3/4 adverse events were neutropenia (25%), anemia (36%), hyponatremia (29%), anorexia (24%), and nausea (11%). No febrile neutropenia was observed. Pneumonitis caused treatment-related death in one patient. The 2-weekly DCF regimen showed promising antimetastatic activity and tolerability. A phase III study comparing this regimen with CF therapy is planned by the Japan Clinical Oncology Group. This study was registered at the UMIN Clinical Trials Registry as UMIN 000001737. PMID:25041052

  17. Active interlock for the NSLS-II damping wiggler

    NASA Astrophysics Data System (ADS)

    Choi, J.; Willeke, F.

    2012-07-01

    The NSLS-II is a 3rd generation light source with ultra-low beam emittance that is currently under construction at the Brookhaven National Laboratory. Because the power of the synchrotron radiation from the damping wiggler (DW) is about 64 kW, a slight mis-steer can result in severe damage to the vacuum chamber. To avoid such problems, an active interlock system is being considered. The system dumps the beam when it departs from the predefined safe window in the phase space. In this paper, we present simple geometric arguments from which we define the safe window on the basis of betatron amplitudes. This window can be applied to any DW around the ring. For the entrance of the wiggler, we obtained window of Δx=±8.4 mm, Δx'=±429 μrad and Δy=±2.1 mm, Δy'=±449 μrad.

  18. 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.

  19. Background rejection of n+ surface events in GERDA Phase II

    NASA Astrophysics Data System (ADS)

    Lehnert, Björn

    2016-05-01

    The GERDA experiment searches for neutrinoless double beta (0vββ) decay in 76Ge using an array of high purity germanium (HPGe) detectors immersed in liquid argon (LAr). Phase II of the experiment uses 30 new broad energy germanium (BEGe) detectors with superior pulse shape discrimination capabilities compared to the previously used semi-coaxial detector design. By far the largest background component for BEGe detectors in GERDA are n+-surface events from 42K β decays which are intrinsic in LAr. The β particles with up to 3.5 MeV can traverse the 0.5 to 0.9 mm thick electrode and deposit energy within the region of interest for the 0vββ decay. However, those events have particular pulse shape features allowing for a strong discrimination. The understanding and simulation of this background, showing a reduction by up to a factor 145 with pulse shape discrimination alone, is presented in this work.

  20. Combined Forward Calorimetry Option for Phase II CMS Endcap Upgrade

    NASA Astrophysics Data System (ADS)

    Akchurin, Nural

    2015-02-01

    Traditionally, EM and HAD compartments are thought to be separate and are often optimized individually. However, it is possible to optimize a robust and economical combined calorimeter system for myriad physics objectives. By employing event-by-event compensation afforded by the dual-readout technique, we have shown that excellent jet performance can be attained with a longitudinally un-segmented calorimeter that is calibrated only with electrons. In addition, the linear hadronic energy scale renders complex off-line correction schemes unnecessary. The proposed replacement of the CMS EE and HE calorimeters with a single Combined Forward Calorimeter (CFC) shows excellent jet performance complemented by good EM object detection. In this paper, we give brief snapshots on basic design criteria, timing characteristics of Cherenkov and scintillation pulses, trigger generation criteria and performance under high radiation fields. Although CMS has recently chosen different technologies for its endcap calorimetry in Phase II, the concepts developed here are likely to remain valuable for some time to come.

  1. 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.

  2. [Phase II trial of peplomycin in non-Hodgkin's lymphoma].

    PubMed

    Sampi, K; Kumai, R; Hattori, M; Kaneko, Y; Sakurai, M

    1985-05-01

    Seventeen patients with malignant lymphoma were entered into a phase II study of peplomycin (PEP) to determine the efficacy of the drug. There were 8 males and 9 females with a median age of 64 yrs (range 3-74 yrs) and a median PS 3 (range 2-4). Three of these were children. At first PEP was given intermittently and intramuscularly (8 cases) at a dose of 10 mg every one (3 cases) or two (5 cases) weeks, and then intravenously by 22-hr continuous infusion (9 cases) at a dose of 5 mg per day for 5 days. Mean cumulative dose was 78 mg. Objective responses were obtained in 6 patient (35%). CR lasting 4 weeks was obtained in one patient with diffuse mixed-type lymphoma. Five patients, one with diffuse medium-sized cell type and 3 with diffuse large cell type, had PR, lasting 6, 7, 7, 9, and 50+ weeks, respectively. Pulmonary fibrosis was found in two patients on autopsy and interstitial pneumonia in two patients clinically. Temporary high fever occurred in 7 patients, stomatitis in 3 patients and anorexia in 3 patients. PMID:2581513

  3. 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

  4. Basic mechanisms of RNA polymerase II activity and alteration of gene expression in Saccharomyces cerevisiae.

    PubMed

    Kaplan, Craig D

    2013-01-01

    Transcription by RNA polymerase II (Pol II), and all RNA polymerases for that matter, may be understood as comprising two cycles. The first cycle relates to the basic mechanism of the transcription process wherein Pol II must select the appropriate nucleoside triphosphate (NTP) substrate complementary to the DNA template, catalyze phosphodiester bond formation, and translocate to the next position on the DNA template. Performing this cycle in an iterative fashion allows the synthesis of RNA chains that can be over one million nucleotides in length in some larger eukaryotes. Overlaid upon this enzymatic cycle, transcription may be divided into another cycle of three phases: initiation, elongation, and termination. Each of these phases has a large number of associated transcription factors that function to promote or regulate the gene expression process. Complicating matters, each phase of the latter transcription cycle are coincident with cotranscriptional RNA processing events. Additionally, transcription takes place within a highly dynamic and regulated chromatin environment. This chromatin environment is radically impacted by active transcription and associated chromatin modifications and remodeling, while also functioning as a major platform for Pol II regulation. This review will focus on our basic knowledge of the Pol II transcription mechanism, and how altered Pol II activity impacts gene expression in vivo in the model eukaryote Saccharomyces cerevisiae. This article is part of a Special Issue entitled: RNA Polymerase II Transcript Elongation. PMID:23022618

  5. 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...

  6. 40 CFR 76.8 - Early election 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 Early election for Group 1, Phase II boilers. 76.8 Section 76.8 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1, Phase II boilers. (a) General...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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

  15. 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.

  16. 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 America Phase II support may be made available for census blocks or other areas identified as eligible...

  17. MECHANISM AND KINETICS OF THE FORMATION OF NOX AND OTHER COMBUSTION POLLUTANTS. PHASE II. MODIFIED COMBUSTION

    EPA Science Inventory

    The report gives Phase II results of a combined experimental/theoretical study to define the mechanisms and kinetics of the formation of NOx and other combustion pollutants. Two experimental devices were used in Phase II. A special flat-flame burner with a controlled-temperature ...

  18. 47 CFR 54.309 - Connect America Fund Phase II Public Interest Obligations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 3 2014-10-01 2014-10-01 false Connect America Fund Phase II Public Interest Obligations. 54.309 Section 54.309 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) UNIVERSAL SERVICE Universal Service Support for High Cost Areas § 54.309 Connect America Fund Phase II...

  19. 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…

  20. 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.

  1. Safety and Clinical Activity of a Combination Therapy Comprising Two Antibody-Based Targeting Agents for the Treatment of Non-Hodgkin Lymphoma: Results of a Phase I/II Study Evaluating the Immunoconjugate Inotuzumab Ozogamicin With Rituximab

    PubMed Central

    Fayad, Luis; Offner, Fritz; Smith, Mitchell R.; Verhoef, Gregor; Johnson, Peter; Kaufman, Jonathan L.; Rohatiner, Ama; Advani, Anjali; Foran, James; Hess, Georg; Coiffier, Bertrand; Czuczman, Myron; Giné, Eva; Durrant, Simon; Kneissl, Michelle; Luu, Kenneth T.; Hua, Steven Y.; Boni, Joseph; Vandendries, Erik; Dang, Nam H.

    2013-01-01

    Purpose Inotuzumab ozogamicin (INO) is an antibody-targeted chemotherapy agent composed of a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic agent. We performed a phase I/II study to determine the maximum-tolerated dose (MTD), safety, efficacy, and pharmacokinetics of INO plus rituximab (R-INO) for treatment of relapsed/refractory CD20+/CD22+ B-cell non-Hodgkin lymphoma (NHL). Patients and Methods A dose-escalation phase to determine the MTD of R-INO was followed by an expanded cohort to further evaluate the efficacy and safety at the MTD. Patients with relapsed follicular lymphoma (FL), relapsed diffuse large B-cell lymphoma (DLBCL), or refractory aggressive NHL received R-INO every 4 weeks for up to eight cycles. Results In all, 118 patients received one or more cycles of R-INO (median, four cycles). Most common grade 3 to 4 adverse events were thrombocytopenia (31%) and neutropenia (22%). Common low-grade toxicities included hyperbilirubinemia (25%) and increased AST (36%). The MTD of INO in combination with rituximab (375 mg/m2) was confirmed to be the same as that for single-agent INO (1.8 mg/m2). Treatment at the MTD yielded objective response rates of 87%, 74%, and 20% for relapsed FL (n = 39), relapsed DLBCL (n = 42), and refractory aggressive NHL (n = 30), respectively. The 2-year progression-free survival (PFS) rate was 68% (median, not reached) for FL and 42% (median, 17.1 months) for relapsed DLBCL. Conclusion R-INO demonstrated high response rates and long PFS in patients with relapsed FL or DLBCL. This and the manageable toxicity profile suggest that R-INO may be a promising option for CD20+/CD22+ B-cell NHL. PMID:23295790

  2. Mutual interactions between flavonoids and enzymatic and transporter elements responsible for flavonoid disposition via phase II metabolic pathways

    PubMed Central

    Jiang, Wen; Hu, Ming

    2014-01-01

    Flavonoids, existing mainly as glycosides in nature, have multiple “claimed” beneficial effects in humans. Flavonoids are extensively metabolized in enterocytes and hepatocytes by phase II enzymes such as UGTs and SULTs to form glucuronides and sulfates, respectively. These glucuronides and sulfates are subsequently excreted via ABC transporters (e.g., MRP2 or BCRP). Therefore, it is the interplay between phase II enzymes and efflux transporters that affects the disposition of flavonoids and leads to the low bioavailability of flavonoid aglycones. Flavonoids can also serve as chemical regulators that affect the activity or expression levels of phase II enzymes including UGTs, SULTs and GSTs, and transporters including P-gp, MRP2, BCRP, OATP and OAT. In general, flavonoids may exert the inhibitory or inductive effects on the phase II enzymes and transporters via multiple mechanisms that may involve different nuclear receptors. Since flavonoids may affect the metabolic pathways shared by many important clinical drugs, drug-flavonoid interaction is becoming an increasingly important concern. This review article focused on the disposition of flavonoids and effects of flavonoids on relevant enzymes (e.g. UGTs and SULTs) and transporters (e.g. MRP2 and BCRP) involved in the interplay between phase II enzymes and efflux transporters. The effects of flavonoids on other metabolic enzymes (e.g. GSTs) or transporters (e.g. P-gp, OATP and OAT) are also addressed but that is not the emphasis of this review. PMID:25400909

  3. Mechanical and Thermal Prototype Testing for a Rotatable Collimator for the LHC Phase II Collimation Upgrade

    SciTech Connect

    Smith, Jeffrey Claiborne; Doyle, Eric; Keller, Lewis; Lundgren, Steven; Markiewicz, Thomas Walter; /SLAC

    2010-08-26

    The Phase II upgrade to the LHC collimation system calls for complementing the robust Phase I graphite collimators with high Z, low impedance Phase II collimators. The design for the collimation upgrade has not been finalized. One option is to use metallic rotatable collimators and testing of this design will be discussed here. The Phase II collimators must be robust in various operating conditions and accident scenarios. A prototype collimator jaw has been tested for both mechanical and thermal compliance with the design goals. Thermal expansion bench-top tests are compared to ANSYS simulation results.

  4. 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.

  5. Ultrafiltration of Kraft Black Liquor: Phase II, Final report

    SciTech Connect

    Hill, M.K.

    1987-09-01

    The major justification for examining ultrafiltration was to lower the viscosity of the Kraft Black Liquor by recovering it as an ultrafiltration permeate from which the highest MW lignin had been removed. The liquor could then be concentrated to a higher percentage solids before firing into the recovery boiler. Consequent energy savings for the 1000 ton/day pulp mill would be 2.05 x 10 Btu/y for each percentage increase in TDS (total dissolved solids) to the recovery boiler. This Phase II report gives data on viscosity with percentage solids of KBL permeates. Another favorable effect of ultrafiltration on the permeate properties is disproportionate removal of multivalent ions including the major scaling ion CaS . If this high-viscosity high-Ca retentate could be treated to lower its viscosity and to release the Ca in a non-scaling form, this would enhance the possibility that ultrafiltration might be useful in a mill situation. Included in this report are data on the results of treating the retentate fraction. Other justifications for this program included further information in KBL properties: lignin MW in the KBL at high pH; elemental and sugar analyses; and differential properties of lignins in the retentate and the permeate fractions. A preliminary economic analysis of ultrafiltration is contained in this report. These analyses indicate that with flux rates now attainable, ultrafiltration would not be economically justified at this time if the only justification is to lower KBL viscosity. For certain situations where high Ca liquors present a scaling problem, especially in an evaporator-limited mill, the economics are more favorable. There are also unsolved problems relating to the use of the high viscosity retentate.

  6. 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

  7. [Phase II study of CIS-diamminedichloroplatinum (II) by collaborative study].

    PubMed

    Kato, T

    1982-04-01

    Since the discovery of platinum compounds by Rosenberg, et al. in 1965 on the mitosis inhibitory action against Escherichia coli, the anticancer action of cis-diamminedichloroplatinum (II) (cisplatin) one of the platinum compounds, has called attention, and recently clinical trials of this compounds have been actively performed in the treatment of testicular and ovarian malignancies not only in the U.S.A. but also in Japan. We carried out a joint controlled trial of cisplatin (NK-801, Nippon Kayaku Co.) in the treatment of ovarian malignancies. The eligibility of the patients and evaluation of response were assessed according to the general response criteria proposed by Drs. Koyama and Saito. Fifty-seven patients were evaluable for the tumor response. Complete response were 11%, partial response 47%, and overall response rates 58% in ovarian malignancies, respectively. Toxicities were noted in the gastro-intestinal tract. Myelosupression and renal dysfunction were other prominent adverse effects. PMID:6892198

  8. Basic Mechanisms of RNA Polymerase II Activity and Alteration of Gene Expression in Saccharomyces cerevisiae

    PubMed Central

    Kaplan, Craig D.

    2014-01-01

    Transcription by RNA Polymerase II (Pol II), and all RNA polymerases for that matter, may be understood as comprising two cycles. The first cycle relates to the basic mechanism of the transcription process wherein Pol II must select the appropriate nucleoside triphosphate (NTP) substrate complementary to the DNA template, catalyze phosphodiester bond formation, and translocate to the next position on the DNA template. Performing this cycle in an iterative fashion allows the synthesis of RNA chains that can be over one million nucleotides in length in some larger eukaryotes. Overlaid upon this enzymatic cycle, transcription may be divided into another cycle of three phases: initiation, elongation, and termination. Each of these phases has a large number of associated transcription factors that function to promote or regulate the gene expression process. Complicating matters, each phase of the latter transcription cycle are coincident with cotranscriptional RNA processing events. Additionally, transcription takes place within a highly dynamic and regulated chromatin environment. This chromatin environment is radically impacted by active transcription and associated chromatin modifications and remodeling, while also functioning as a major platform for Pol II regulation. This review will focus on our basic knowledge of the Pol II transcription mechanism, and how altered Pol II activity impacts gene expression in vivo in the model eukaryote Saccharomyces cerevisiae. PMID:23022618

  9. 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.

  10. 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

  11. Efficacy and Safety of FospropofolFD Compared to Propofol When Given During the Induction of General Anaesthesia: A Phase II, Multi-centre, Randomized, Parallel-Group, Active-Controlled, Double-Blind, Double-Dummy Study.

    PubMed

    Liu, Rong; Luo, Chaozhi; Liu, Jin; Zhang, Wensheng; Li, Yan; Xu, Jing

    2016-07-01

    The present phase II study aimed to compare the efficacy and safety of fospropofol disodium for injection (FospropofolFD ) and propofol when given during the induction of general anaesthesia in patients scheduled for elective surgery. FospropofolFD is a water-soluble prodrug of propofol. Approved by the Ethical Committee, 240 participants aged 18-65 years were equally randomly allocated to receive an intravenous bolus of FospropofolFD 20 mg/kg or propofol 2 mg/kg without any anaesthetic pre-treatment. The primary efficacy end-point was the sedation success rate within 5 min. after administering investigational drugs (the sedation success is defined as obtaining Modified Observer's Assessment of Alertness/Sedation scale score of 1). All the participants completed the induction and intubation within 25 min. after administration. The sedation success rates within 5 min. after administration of FospropofolFD 20 mg/kg and propofol 2 mg/kg were 94.50% versus 100% in the intention-to-treat population and 95.10% versus 100% in the per-protocol population, respectively. The non-inferiority test obtained a p-value less than 0.025, and the lower limits of the one-sided 97.5% confidence interval were more than -0.09. This meant that FospropofolFD 20 mg/kg was considered non-inferior to propofol 2 mg/kg for the primary efficacy end-point. Compared with propofol 2 mg/kg, FospropofolFD 20 mg/kg had a slower sedation efficacy. No serious adverse events were observed in the two groups. The sedation success rate within 5 min. after administration of FospropofolFD 20 mg/kg was non-inferior to propofol 2 mg/kg, and FospropofolFD 20 mg/kg can be used for the induction of general anaesthesia safely. PMID:26781338

  12. Competing dynamic phases of active polymer networks

    NASA Astrophysics Data System (ADS)

    Freedman, Simon; Banerjee, Shiladitya; Dinner, Aaron R.

    Recent experiments on in-vitro reconstituted assemblies of F-actin, myosin-II motors, and cross-linking proteins show that tuning local network properties can changes the fundamental biomechanical behavior of the system. For example, by varying cross-linker density and actin bundle rigidity, one can switch between contractile networks useful for reshaping cells, polarity sorted networks ideal for directed molecular transport, and frustrated networks with robust structural properties. To efficiently investigate the dynamic phases of actomyosin networks, we developed a coarse grained non-equilibrium molecular dynamics simulation of model semiflexible filaments, molecular motors, and cross-linkers with phenomenologically defined interactions. The simulation's accuracy was verified by benchmarking the mechanical properties of its individual components and collective behavior against experimental results at the molecular and network scales. By adjusting the model's parameters, we can reproduce the qualitative phases observed in experiment and predict the protein characteristics where phase crossovers could occur in collective network dynamics. Our model provides a framework for understanding cells' multiple uses of actomyosin networks and their applicability in materials research. Supported by the Department of Defense (DoD) through the National Defense Science & Engineering Graduate Fellowship (NDSEG) Program.

  13. The active RS Canum Venaticorum binary II Pegasi. II. Surface images for 1992-1996

    NASA Astrophysics Data System (ADS)

    Berdyugina, S. V.; Berdyugin, A. V.; Ilyin, I.; Tuominen, I.

    1998-12-01

    Using new high-resolution and high signal-to-noise ratio spectroscopic observations carried out in 1992-1996, nine surface images of II Peg are obtained. The inversion technique applied is the recently developed Occamian approach, which does not put any artificial constraints on the solution and provides an error analysis of the solution. The surface imaging is applied to Ca{ i, Fe{ i, and Ni{ i lines simultaneously, a number of blending atomic and molecular lines being included into the line list. Two high-latitude active regions are found to dominate in all seasons, which determine the spectroscopic and photometric variability. No cool polar cap is seen. The positions of the spots are constantly migrating to earlier orbital phases with approximately the same rate. This motion of the spot configuration means a shorter rotational period, which is just about the mean photometric period. The mean longitude separation between the active regions is about 180°. This is considered as two active longitudes. The largest of the two spots seems to be close to the central meridian, i.e. tends to be faced toward the secondary. In 1994 it changed its position from one active longitude to another, showing the effect of switching the activity between the longitudes. based on observations collected at the Nordic Optical Telescope (NOT), La Palma, Spain; the McMath telescope of the National Solar Observatory, USA; the 2.6 m and 1.25 m telescopes of the Crimean Astrophysical Observatory, Ukraine; the 2m telescope of the National Astronomical Observatory, Rozhen, Bulgaria; the 2m telescope of the Pic du Midi Observatory, France

  14. 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

  15. 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.

  16. 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

  17. Ulex europaeus agglutinin II (UEA-II) is a novel, potent inhibitor of complement activation.

    PubMed

    Lekowski, R; Collard, C D; Reenstra, W R; Stahl, G L

    2001-02-01

    Complement is an important mediator of vascular injury following oxidative stress. We recently demonstrated that complement activation following endothelial oxidative stress is mediated by mannose-binding lectin (MBL) and activation of the lectin complement pathway. Here, we investigated whether nine plant lectins which have a binding profile similar to that of MBL competitively inhibit MBL deposition and subsequent complement activation following human umbilical vein endothelial cell (HUVEC) oxidative stress. HUVEC oxidative stress (1% O(2), 24 hr) significantly increased Ulex europaeus agglutinin II (UEA-II) binding by 72 +/- 9% compared to normoxic cells. UEA-II inhibited MBL binding to HUVEC in a concentration-dependent manner following oxidative stress. Further, MBL inhibited UEA-II binding to HUVEC in a concentration-dependent manner following oxidative stress, suggesting a common ligand. UEA-II (< or = 100 micromol/L) did not attenuate the hemolytic activity, nor did it inhibit C3a des Arg formation from alternative or classical complement pathway-specific hemolytic assays. C3 deposition (measured by ELISA) following HUVEC oxidative stress was inhibited by UEA-II in a concentration-dependent manner (IC(50) = 10 pmol/L). UEA-II inhibited C3 and MBL co-localization (confocal microscopy) in a concentration-dependent manner on HUVEC following oxidative stress (IC(50) approximately 1 pmol/L). Finally, UEA-II significantly inhibited complement-dependent neutrophil chemotaxis, but failed to inhibit fMLP-mediated chemotaxis, following endothelial oxidative stress. These data demonstrate that UEA-II is a novel, potent inhibitor of human MBL deposition and complement activation following human endothelial oxidative stress. PMID:11266613

  18. Decreased organ failure in patients with severe SIRS and septic shock treated with the platelet-activating factor antagonist TCV-309: a prospective, multicenter, double-blind, randomized phase II trial. TCV-309 Septic Shock Study Group.

    PubMed

    Poeze, M; Froon, A H; Ramsay, G; Buurman, W A; Greve, J W

    2000-10-01

    Sepsis and organ failure remain the main cause of death on the ICU. Sepsis is characterized by a severe inflammatory response, in which platelet-activating factor (PAF) is considered to play an important role. This study investigated whether treatment with the PAF-antagonist TCV-309 reduces morbidity and mortality in patients with septic shock. The study was conducted as a double-blind, randomized, placebo controlled multicenter study. The included patients had to fulfill the SIRS criteria with a clinical suspicion of infection, an admission APACHE II score greater than 15, and shock, defined as a mean arterial pressure <70 mmHg and/or a decrease > or =40 mmHg despite adequate fluid resuscitation. Patients received 1.0 mg/kg TCV-309 or placebo, twice daily, intravenously during 14 days. The prospectively set goals were MOF score, recovery from shock, mortality, and assessment of the safety of the medication. A total of 98 patients were included of which 97 were analyzed on an intention-to-treat basis. The overall survival at day 56 of TCV-309 treated patients was similar compared to placebo treated patients (51.0% vs. 41.7%, P = 0.47). In contrast, the mean percentage of failed organs per patient present after 14 days in the TCV-309 treated patients was significantly lower compared to the placebo treated patients (11.9% vs. 25.1%, P = 0.04), leading to a reduced need for vasopressors, dialysis, and ventilatory support. Furthermore, the mean APACHE-II score during treatment with TCV-309 was significantly lower and the number of patients recovered from shock after day 14 was significantly higher in the TCV-309 treated patient group (2/32 vs. 9/29, P = 0.01). The number of adverse events was not significantly different between the TCV-309 and placebo treated patients. TCV-309 did not change overall mortality of septic shock, however a substantial reduction in organ dysfunction and morbidity, frequently associated with septic shock was achieved, without significant

  19. Introductory Industrial Technology II. Laboratory Activities.

    ERIC Educational Resources Information Center

    Towler, Alan L.

    This guide contains 29 learning modules intended for use by technology teachers and students in grade 8. Each module includes a student laboratory activity and instructor's resource sheet. Each student activity includes the following: activity topic and overview, challenge statement, objectives, vocabulary/concepts reinforced, equipment/supplies,…

  20. Phased activity in Heterorhabditis megidis infective juveniles.

    PubMed

    Dempsey, C M; Griffin, C T

    2002-06-01

    The infectivity of Heterorhabditis megidis infective juveniles (IJs) increases during storage in water. We investigated whether this change can be related to other features of the IJs' behaviour. IJs were stored in water for 4 weeks at 20 degrees C, and the following parameters were assessed at intervals: infectivity for Galleria mellonella, dispersal in sand, host-finding on agar, and the percentage of IJs active in water. In addition, the behaviour of the IJs in water was described using 7 categories. Immediately after emerging from the host cadaver, IJs were highly active (99% of IJs in water were active and 65% displayed 'waving', the normal method of forward movement). Maximum responsiveness to host volatiles in an agar plate assay was recorded on day 2 (69% of IJs moved from the point of application and 44% of all IJs in the agar arena moved towards a host) and maximum dispersal in sand (5.8 cm) on day 0. These tendencies declined gradually with age, while infectivity underwent a significant increase from 11 nematodes per insect on day 0 to 38 nematodes per insect on day 9. Three phases could be distinguished in the behaviour of H. megidis IJs: an initial dispersal phase, during which infectivity was low; an infective phase, during which dispersal tendency was declining, and a third phase during which all behaviours (dispersal, infectivity and activity) were declining. Over the 4-week storage period, infectivity of H. megidis IJs was correlated (R2 = 0.83) with the percentage time IJs engaged in 'head thrusting' (a behaviour that resembles penetration). There is no evidence that the observed increase in infectivity of H. megidis strain UK211 could be accounted for by a generally greater level of motor activity, nor by an increase in responsiveness to volatile host cues, and it is suggested that it is due to an increased tendency to attempt penetration. PMID:12118716

  1. The Phase II Campaign for the Pegasus Toroidal Experiment

    NASA Astrophysics Data System (ADS)

    Squires, B.

    2005-10-01

    The Pegasus upgrade has been completed with the installation of a new 130 MV-A IGCT switched OH power system to provide a programmable Vloop(t) with sub-ms response time. New diagnostics include a multichannel bolometer array, an imaging visible bremsstrahlung array, an X-ray pulse height analyzer, and an improved 1mm interferometer. Initial operation has demonstrated active control of all coil currents and hence more control over plasma formation. The present campaign is using these new capabilities to develop scenarios to access the high Ip/ITF, high IN, high βt regime of interest. The Phase I performance of Ip˜ 0.15 MA has been recovered with < 1/2 the V-s used previously. Vloop(t) programming has demonstrated increasing control of the plasma formation and mitigation of tearing modes which had constrained the operational space. An array of plasma gun current injectors is planned as a DC-helicity source to extend the effective use of V-s from the OH solenoid and test a new plasma formation scheme.

  2. Action of Halowax 1051 on Enzymes of Phase I (CYP1A1) and Phase II (SULT1A and COMT) Metabolism in the Pig Ovary

    PubMed Central

    Barć, Justyna; Karpeta, Anna; Gregoraszczuk, Ewa Łucja

    2013-01-01

    Polychlorinated naphthalenes (PCNs) are a group of organochlorinated compounds exhibiting dioxin-like properties. Previously published data showed the direct action of PCN-rich Halowax 1051 on ovarian follicular steroidogenesis. Taking into consideration that the observed biological effects of PCNs may be frequently side effects of metabolites generated by their detoxification, the aim of this study was to determine the activity and expression of enzymes involved in phase I (cytochrome P450, family 1 (CYP1A1)) and phase II (sulfotransferase (SULT1A) and catechol-O-methyltransferase (COMT)) detoxification metabolism. Cocultures of granulosa and theca interna cells collected from sexually mature pigs were exposed to 1 pg/mL to 10 ng/mL of Halowax 1051 for 1 to 48 hours, after which levels and activities of CYP1A1, SULT1A, and COMT were measured. Dose-dependent increases of CYP1A1 activity and expression were observed. High doses of Halowax 1051 were inhibitory to COMT and SULT1A activity and reduced their protein levels. In conclusion, fast activation of phase I enzymes with simultaneous inhibition of phase II enzymes indicates that the previously observed effect of Halowax 1051 on follicular steroidogenesis may partially result from metabolite action occurring locally in ovarian follicles. PMID:23653643

  3. Science Activities in Energy: Solar Energy II.

    ERIC Educational Resources Information Center

    Oak Ridge Associated Universities, TN.

    Included in this science activities energy package are 14 activities related to solar energy for secondary students. Each activity is outlined on a single card and is introduced by a question such as: (1) how much solar heat comes from the sun? or (2) how many times do you have to run water through a flat-plate collector to get a 10 degree rise in…

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 76 FR 55947 - Industrial Relations Promotion Project, Phase II in Vietnam

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-09

    ... of the Secretary Industrial Relations Promotion Project, Phase II in Vietnam AGENCY: Bureau of... funded.. DAI, through its Industrial Relations Promotion Project (IRRP), is the only organization that... disputes and sound industrial relations by developing approaches in cooperation with trade...

  10. Active sites residues of beef liver carnitine octanoyltransferase (COT) and carnitine palmitoyltransferase (CPT-II).

    PubMed Central

    Nic a'Bháird, N; Yankovskaya, V; Ramsay, R R

    1998-01-01

    The carnitine acyltransferases which catalyse the reversible transfer of fatty acyl groups between carnitine and coenzyme A have been proposed to contain a catalytic histidine. Here, the chemical reactivity of active site groups has been used to demonstrate differences between the active sites of beef liver carnitine octanoyltransferase (COT) and carnitine palmitoyltransferase-II (CPT-II). Treatment of CPT-II with the histidine-selective reagent, diethyl pyrocarbonate (DEPC), resulted in simple linear pseudo-first-order kinetics. The reversal of the inhibition by hydroxylamine and the pKa (7.1) of the modified residue indicated that the residue was a histidine. The order of the inactivation kinetics showed that 1mol of histidine was modified per mol of CPT-II.When COT was treated with DEPC the kinetics of inhibition were biphasic with an initial rapid loss of activity followed by a slower loss of activity. The residue reacting in the faster phase of inhibition was not a histidine but possibly a serine. The modification of this residue did not lead to complete loss of activity suggesting that a direct role in catalysis is unlikely. It was deduced that the residue modified by DEPC in the slower phase was a lysine and indeed fluorodinitrobenzene (FDNB) inactivated COT with linear pseudo-first-order kinetics. The COT peptide containing the FDNB-labelled lysine was isolated and sequenced. Alignment of this sequence placed it 10 amino acids downstream of the putative active-site histidine. PMID:9480926

  11. Efficacy of a Community-Based Physical Activity Program KM2H2 for Stroke and Heart Attack Prevention among Senior Hypertensive Patients: A Cluster Randomized Controlled Phase-II Trial

    PubMed Central

    Gong, Jie; Chen, Xinguang; Li, Sijian

    2015-01-01

    Objective To evaluate the efficacy of the program Keep Moving toward Healthy Heart and Healthy Brain (KM2H2) in encouraging physical activities for the prevention of heart attack and stroke among hypertensive patients enrolled in the Community-Based Hypertension Control Program (CBHCP). Design Cluster randomized controlled trial with three waves of longitudinal assessments at baseline, 3 and 6 months post intervention. Setting Community-based and patient-centered self-care for behavioral intervention in urban settings of China. Participants A total of 450 participants diagnosed with hypertension from 12 community health centers in Wuhan, China were recruited, and were randomly assigned by center to receive either KM2H2 plus standard CBHCP care (6 centers and 232 patients) or the standard care only (6 centers and 218 patients). Intervention KM2H2 is a behavioral intervention guided by the Transtheoretical Model, the Model of Personalized Medicine and Social Capital Theory. It consists of six intervention sessions and two booster sessions engineered in a progressive manner. The purpose is to motivate and maintain physical activities for the prevention of heart attack and stroke. Outcome Measures Heart attack and stroke (clinically diagnosed, primary outcome), blood pressure (measured, secondary outcome), and physical activity (self-report, tertiary outcome) were assessed at the individual level during the baseline, 3- and 6-month post-intervention. Results Relative to the standard care, receiving KM2H2 was associated with significant reductions in the incidence of heart attack (3.60% vs. 7.03%, p < .05) and stroke (5.11% vs. 9.90%, p<0.05), and moderate reduction in blood pressure (-3.72mmHg in DBP and -2.92 mmHg in DBP) at 6-month post-intervention; and significant increases in physical activity at 3- (d = 0.53, 95% CI: 0.21, 0.85) and 6-month (d = 0.45, 95% CI: 0.04, 0.85) post-intervention, respectively. Conclusion The program KM2H2 is efficacious to reduce the

  12. Angiotensin II and angiotensin II receptor blocker modulate the arrhythmogenic activity of pulmonary veins

    PubMed Central

    Chen, Yi-Jen; Chen, Yao-Chang; Tai, Ching-Tai; Yeh, Hung-I; Lin, Cheng-I; Chen, Shih-Ann

    2005-01-01

    Angiotensin II receptor blockers (AIIRBs) have been shown to prevent atrial fibrillation. The pulmonary veins (PVs) are the most important focus for the generation of atrial fibrillation. The aim of this study was to evaluate whether angiotensin II or AIIRB may change the arrhythmogenic activity of the PVs. Conventional microelectrodes and whole-cell patch clamps were used to investigate the action potentials (APs) and ionic currents in isolated rabbit PV tissue and single cardiomyocytes before and after administering angiotensin II or losartan (AIIRB). In the tissue preparations, angiotensin II induced delayed after-depolarizations (1, 10, and 100 nM) and accelerated the automatic rhythm (10 and 100 nM). Angiotensin II (100 nM) prolonged the AP duration and increased the contractile force (10 and 100 nM). Losartan (1 and 10 μM) inhibited the automatic rhythm. Losartan (10 μM) prolonged the AP duration and reduced the contractile force (1 and 10 μM). Angiotensin II reduced the transient outward potassium current (Ito) but increased the L-type calcium, delayed rectifier potassium (IK), transient inward (Iti), pacemaker, and Na+–Ca2+ exchanger (NCX) currents in the PV cardiomyocytes. Losartan decreased the Ito, IK, Iti, and NCX currents. In conclusion, angiotensin II and AIIRB modulate the PV electrical activity, which may play a role in the pathophysiology of atrial fibrillation. PMID:16273119

  13. 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

  14. NATIONAL SURFACE WATER SURVEY: EASTERN LAKE SURVEY PHASE II NORTHEASTERN LAKES, DATABASE DICTIONARY

    EPA Science Inventory

    The purpose of this data dictionary is to provide information pertaining to the contents and structure of the Eastern Lakes Survey-Phase II (ELS-II) chemistry database. he data dictionary does not describe the design, protocols, or findings of the study, which are described in He...

  15. 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

  16. HLW Salt Disposition Alternatives Preconceptual Phase II Summary Report

    SciTech Connect

    Piccolo, S.F.

    1999-07-09

    The purpose of the report is to summarize the process used to identify the Short List alternatives that will be evaluated during Phase III and to document the results of the selection process. The Phase III evaluation will result in the determination of the preferred alternative(s) to be used for final disposition of the HLW salt to a permitted waste form.

  17. Public Library Information and Referral Project, Phase II. Final Report.

    ERIC Educational Resources Information Center

    Childers, Thomas; Krauser, Cheri

    This study is the second of a two-phase survey of public library information and referral (I&R) service. In this phase, seven public libraries offering I&R services were studied in depth to provide descriptions of their operations, organizational factors, and the reactions of their users. Organizational factors and operations were studied through…

  18. 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.

  19. Angiotensin II activates different calcium signaling pathways in adipocytes.

    PubMed

    Dolgacheva, Lyudmila P; Turovskaya, Maria V; Dynnik, Vladimir V; Zinchenko, Valery P; Goncharov, Nikolay V; Davletov, Bazbek; Turovsky, Egor A

    2016-03-01

    Angiotensin II (Ang II) is an important mammalian neurohormone involved in reninangiotensin system. Ang II is produced both constitutively and locally by RAS systems, including white fat adipocytes. The influence of Ang II on adipocytes is complex, affecting different systems of signal transduction from early Са(2+) responses to cell proliferation and differentiation, triglyceride accumulation, expression of adipokine-encoding genes and adipokine secretion. It is known that white fat adipocytes express all RAS components and Ang II receptors (АТ1 and АТ2). The current work was carried out with the primary white adipocytes culture, and Са(2+) signaling pathways activated by Ang II were investigated using fluorescent microscopy. Са(2+)-oscillations and transient responses of differentiated adipocytes to Ang II were registered in cells with both small and multiple lipid inclusions. Using inhibitory analysis and selective antagonists, we now show that Ang II initiates periodic Са(2+)-oscillations and transient responses by activating АТ1 and АТ2 receptors and involving branched signaling cascades: 1) Ang II → Gq → PLC → IP3 → IP3Rs → Ca(2+) 2) Gβγ → PI3Kγ → PKB 3) PKB → eNOS → NO → PKG 4) CD38 → cADPR → RyRs → Ca(2+) In these cascades, AT1 receptors play the leading role. The results of the present work open a perspective of using Ang II for correction of signal resistance of adipocytes often observed during obesity and type 2 diabetes. PMID:26850364

  20. 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.

  1. The optical flares of active star II Pegasi in 2005

    NASA Astrophysics Data System (ADS)

    Gu, Shenghong; Kim, Kang Min; Lee, Byeong-Cheol

    2015-08-01

    We observed the active star II Peg using high-resolution spectrographs of 2.16m telescope at Xinglong station of NAOC and 1.8m telescope at BOAO of KASI from November to December, 2005. By means of spectral subtraction technique, the chromospheric activities of II Peg are analyzed at several activity indicators, including CaII IRT, Hα, NaI D1D2 and HeI D3 lines. The results demonstrate that the magnetic activity of II Peg is very strong, and its chromospheric activities show rotational modulations which imply there are active regions in its chromosphere. Two flare events were hunted during the observations, which were identified by HeI D3 line emission above the continuum. The first flare was happened in November 2005, the second one in December 2005, and they were located in different hemisphere of the star. This may indicate the evolution of active regions. Considering the photospheric spot activities, the possible origin of the detected flares is discussed.

  2. 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

  3. Evaluation of the Emergency School Assistance Program. Volume III: Design and Findings of Phase II Case Studies. Parts A, B, and C. Final Report.

    ERIC Educational Resources Information Center

    RMC Research Corp., Arlington, VA.

    Phase II of the Emergency School Assistance Program (ESAP), a federal program designed to aid local education agencies in bringing about racial desegregation of their public school systems is discussed. This phase is an intensive study of 20 selected ESAP districts, which identifies and documents ESAP activities that have successfully aided the…

  4. Iterative phase retrieval algorithms. Part II: Attacking optical encryption systems.

    PubMed

    Guo, Changliang; Liu, Shi; Sheridan, John T

    2015-05-20

    The modified iterative phase retrieval algorithms developed in Part I [Guo et al., Appl. Opt.54, 4698 (2015)] are applied to perform known plaintext and ciphertext attacks on amplitude encoding and phase encoding Fourier-transform-based double random phase encryption (DRPE) systems. It is shown that the new algorithms can retrieve the two random phase keys (RPKs) perfectly. The performances of the algorithms are tested by using the retrieved RPKs to decrypt a set of different ciphertexts encrypted using the same RPKs. Significantly, it is also shown that the DRPE system is, under certain conditions, vulnerable to ciphertext-only attack, i.e., in some cases an attacker can decrypt DRPE data successfully when only the ciphertext is intercepted. PMID:26192505

  5. Workjobs II: Number Activities for Early Childhood.

    ERIC Educational Resources Information Center

    Baratta-Lorton, Mary

    This curriculum guide presents a program of 20 open-ended math activities to be used to supplement the math programs in kindergarten, first, or second grade classrooms. The program consists of child-oriented counters and gameboards used to explore the concept of number from counting to making up and solving addition and subtraction equations. Each…

  6. Activities in Developmental Physical Education; Volume II.

    ERIC Educational Resources Information Center

    Guarnieri, Barbara; Sandeen, Cecile

    Presented in the curriculum guide are activities for a sequenced physical education program to be used with trainable mentally retarded students (TMR). Defined are teaching approaches such as station teaching. Reviewed are a brief history of adaptive physical education (APE), APE literature on TMR children, and local APE program development.…

  7. Ligand field spectroscopy of Cu(II) and Ag(II) complexes in the gas phase: theory and experiment.

    PubMed

    Puskar, Ljiljana; Cox, Hazel; Goren, Alan; Aitken, Georgina D C; Stace, Anthony J

    2003-01-01

    Ligand field spectra have been recorded in the gas phase for the two series of complexes containing either Cu(II) or Ag(II) in association with pyridine. Where comparisons are possible, the gas phase spectra match those recorded in the condensed phase; however, for Ag(II) systems the results differ in interpretation. The Ag(II) data are attributed to a ligand-to-metal charge transfer process, and the Cu(II) data (spectral region and extinction coefficient) match the characteristics of a d-d transition. A detailed theoretical analysis of two complexes. [Cu(py)4]2+ and [Ag(py)4]2+ provides evidence of a minimum energy, D4h structure and two less stable D2h and D2d structures within approximately 60 kJ mol(-1). From these structures it is possible to identify a range of optically and vibronically allowed transitions that could contribute to spectra observed in the gas phase. In the case of calculations on [Ag(py)4]2+ there is strong evidence of an electronic transition that would account for the observation of charge transfer in the experiments. Less detailed calculations on [Cu(py)6]2+ and [Ag(py)6]2+ show structural evidence of extensive Jahn Teller distortion. Taken together with incremental binding energies calculated for complexes containing between two and six pyridine molecules, these results show that the level of theory adopted is capable of providing a semi-quantitative understanding of the experimental data. PMID:14527220

  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. Measurement of gas-phase ionic mercury(II) species in ambient air

    SciTech Connect

    Stratton, W.J.; Lindberg, S.E.

    1995-12-31

    One of the important questions in the biogeochemical cycling of mercury is the speciation of mercury in the atmosphere. Although a large fraction of Hg in ambient air is Hg(O), a small fraction is believed to be gas-phase Hg(II). This fraction is highly water-soluble and thus is important to explaining the high concentration of Hg in precipitation. We have developed a novel technique for measuring gas-phase Hg(II), using a high-flow refluxing mist chamber to trap the water-soluble Hg(II) in an aerosol mist. Measured concentrations of gas-phase Hg(II) in ambient air are generally in the range 0.05-0.1 ng/m{sup 3}, or 2-4% of the total gaseous Hg. In this talk, representative data under different atmospheric and geographic conditions will be presented, along with a summary of some of the experimental difficulties and unanswered questions.

  10. 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.

  11. 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. his phase consisted primarily of the construction and testing of a Gas Pretreatment Unit (GPU) whose function is to remove those impur...

  12. 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...

  13. 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...

  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. 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…

  17. 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... States (including but not limited to fish, shellfish, wildlife, other natural resources, and the public... substantial threat to the public health or welfare of the United States (including, but not limited to...

  18. 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... States (including but not limited to fish, shellfish, wildlife, other natural resources, and the public... substantial threat to the public health or welfare of the United States (including, but not limited to...

  19. 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... States (including but not limited to fish, shellfish, wildlife, other natural resources, and the public... substantial threat to the public health or welfare of the United States (including, but not limited to...

  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... States (including but not limited to fish, shellfish, wildlife, other natural resources, and the public... substantial threat to the public health or welfare of the United States (including, but not limited to...

  1. Extension and Public Service in the University of Illinois. Phase II Report.

    ERIC Educational Resources Information Center

    Illinois Univ., Urbana.

    Phase II of the report on the problem outlined in Phase I deals with specific recommendations for expanding and improving the extension and public service functions of the University of Illinois. To be effective, the university needs a master plan in which the four essential ingredients must be (1) broad, strong and explicit policy commitments by…

  2. 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...

  3. Career Ladders and Core Curriculum in Human Services. Phase II Final Report.

    ERIC Educational Resources Information Center

    Soong, Robert K.

    This portion of Phase II of the Social Service Aide Project, a program of exemplary education for the career development of paraprofessionals in social and/or human services, represented an attempt to broaden the career ladders developed during Phase I and to extend the core curriculum above and below the Associate in Arts degree. The scheme of…

  4. 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 ...

  5. Investigation of stripping of volatile organic contaminants in municipal wastewater treatment systems, Phase II

    SciTech Connect

    Thompson, D.

    1990-01-01

    Volatile organic contaminants (VOCs) are the largest group of compounds on the effluent monitoring priority pollutant list and are among the most frequently detected in raw wastewater. Their removal by treatment facilities is a major concern in Ontario's Municipal Industrial Strategy for Abatement (MISA) program. In 1987 an investigation of VOC stripping at water pollution control plants was begun. Phase I concluded that many VOCs are stripped from wastewater treatment plants. Phase II was conducted from January 1988 to April 1989 and consisted of a validation of the accuracy of sampling and analytical protocols used in Phase I; a determination of the relative importance of stripping, biological removal and sorption on to secondary sludge from activated sludge aeration basins; and an examination of the impact of the diffuser type (fine or coarse bubble diffusers), airflow rate and solids retention time on VOC stripping. An experimental design was developed using tap water dosed with 10 candidate VOCs as the aeration basin influent; Burlington Skyway wastewater; and Toronto Highland Creek wastewater.

  6. 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.

  7. Toward Active X-ray Telescopes II

    NASA Technical Reports Server (NTRS)

    O'Dell, Stephen L.; Aldroft, Thomas L.; Atkins, Carolyn; Button, Timothy W.; Cotroneo, Vincenzo; Davis, William N.; Doel, Peter; Feldman, Charlotte H.; Freeman, Mark D.; Gubarev, Mikhail V.; Johnson-Wilke, Raegan L.; Kolodziejczak, Jeffery J.; Lillie, Charles F.; Michette, Alan G.; Ramsey, Brian D.; Reid, Paul B.; Sanmartin, Daniel Rodriguez; Saha, Timo T.; Schwartz, Daniel A.; Trolier-McKinstry, Susan E.; Ulmer, Melville P.; Wilke, Rudeger H. T.; Willingale, Richard; Zhang, William W.

    2012-01-01

    In the half century since the initial discovery of an astronomical (non-solar) x-ray source, the sensitivity for detection of cosmic x-ray sources has improved by ten orders of magnitude. Largely responsible for this dramatic progress has been the refinement of the (grazing-incidence) focusing x-ray telescope. The future of x-ray astronomy relies upon the development of x-ray telescopes with larger aperture areas (greater than 1 m2) and finer angular resolution (less than 1.). Combined with the special requirements of grazing-incidence optics, the mass and envelope constraints of space-borne telescopes render such advances technologically challenging.requiring precision fabrication, alignment, and assembly of large areas (greater than 100 m2) of lightweight (approximately 1 kg m2 areal density) mirrors. Achieving precise and stable alignment and figure control may entail active (in-space adjustable) x-ray optics. This paper discusses relevant programmatic and technological issues and summarizes progress toward active x-ray telescopes.

  8. 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. PMID:26970663

  9. Heat transfer in the plastic phases I and II of cyclopentane

    NASA Astrophysics Data System (ADS)

    Konstantinov, V. A.; Sagan, V. V.; Revyakin, V. P.; Karachevtseva, A. V.; Pursky, O. I.

    2014-09-01

    Thermal conductivity of solid cyclopentane C5H10 has been measured at isochoric conditions in the plastic phases I and II for samples of different densities. Isochoric thermal conductivity is nearly constant in phase II and increases with temperature in phase I. Such behaviour is attributed to weakening of the translational orientational coupling which, in turn, leads to a decrease of phonon scattering on rotational excitations. The experimental data are described in terms of a modified Debye model of thermal conductivity with allowance for heat transfer by both low-frequency phonons and diffusive modes.

  10. 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…

  11. LOW COST IMAGER FOR POLLUTANT GAS LEAK DETECTION - PHASE II

    EPA Science Inventory

    An inexpensive imaging Instrument to quickly locate leaks of methane and other greenhouse and VOC gases would reduce the cost and effort expended by industry to comply with EPA regulations. In Phase I, of this WBIR program, a new gas leak visualization camera was demonstrated...

  12. VOLATILIZATION RATES FROM WATER TO INDOOR AIR PHASE II

    EPA Science Inventory

    Contaminated water can lead to volatilization of chemicals to residential indoor air. Previous research has focused on only one source (shower stalls) and has been limited to chemicals in which gas-phase resistance to mass transfer is of marginal significance. As a result, attemp...

  13. Evaluation in Adult Literacy Research. Project ALERT. Phase II.

    ERIC Educational Resources Information Center

    Ntiri, Daphne Williams, Ed.

    This document contains an evaluation handbook for adult literacy programs and feedback from/regarding the evaluation instruments developed during the project titled Adult Literacy and Evaluation Research Team (also known as Project ALERT), a two-phase project initiated by the Detroit Literacy Coalition (DLC) for the purpose of developing and…

  14. DEVELOPMENT OF OIL-IN-WATER MONITOR. PHASE II

    EPA Science Inventory

    A novel approach to quantitatively monitoring suspended hydrocarbons in water. This new oil-in-water monitor technique brings together for the first time two previously unrelated technologies: (1) reversed-phase liquid chromatography and (2) fiber optics. A special organophilic o...

  15. ENVIRONMENTALLY SAFE, NO VOC AUTOMOTIVE COATING - PHASE II

    EPA Science Inventory

    The EPA recognizes that volatile organic compounds (VOCs) must be eliminated from automotive coating formulations to improve worker safety and reduce environmental pollution. The phase I project resulted in the production of a polymer-based coating material that was clear, ...

  16. Phase II trial of hu14.18-IL2 for patients with metastatic melanoma.

    PubMed

    Albertini, Mark R; Hank, Jacquelyn A; Gadbaw, Brian; Kostlevy, Jordan; Haldeman, Jennifer; Schalch, Heidi; Gan, Jacek; Kim, KyungMann; Eickhoff, Jens; Gillies, Stephen D; Sondel, Paul M

    2012-12-01

    Phase I testing of the hu14.18-IL2 immunocytokine in melanoma patients showed immune activation, reversible toxicities, and a maximal tolerated dose of 7.5 mg/m(2)/day. In this phase II study, 14 patients with measurable metastatic melanoma were scheduled to receive hu14.18-IL2 at 6 mg/m(2)/day as 4-h intravenous infusions on Days 1, 2, and 3 of each 28 day cycle. Patients with stable disease (SD) or regression following cycle 2 could receive two additional treatment cycles. The primary objective was to evaluate antitumor activity and response duration. Secondary objectives evaluated adverse events and immunologic activation. All patients received two cycles of treatment. One patient had a partial response (PR) [1 PR of 14 patients = response rate of 7.1 %; confidence interval, 0.2-33.9 %], and 4 patients had SD and received cycles 3 and 4. The PR and SD responses lasted 3-4 months. All toxicities were reversible and those resulting in dose reduction included grade 3 hypotension (2 patients) and grade 2 renal insufficiency with oliguria (1 patient). Patients had a peripheral blood lymphocytosis on Day 8 and increased C-reactive protein. While one PR in 14 patients met protocol criteria to proceed to stage 2 and enter 16 additional patients, we suspended stage 2 due to limited availability of hu14.18-IL2 at that time and the brief duration of PR and SD. We conclude that subsequent testing of hu14.18-IL2 should involve melanoma patients with minimal residual disease based on compelling preclinical data and the confirmed immune activation with some antitumor activity in this study. PMID:22678096

  17. Biomarkers in phase I–II chemoprevention trials: lessons from the NCI experience

    PubMed Central

    Szabo, Eva

    2015-01-01

    Early phase clinical trials are an essential component of chemopreventive drug development to identify signals of drug efficacy that can subsequently be explored definitively in phase III trials. Whereas phase I trials focus on safety and identification of optimal dose and schedule for cancer prevention, phase II trials focus on intermediate endpoints that are variably related to cancer development. The United States National Cancer Institute supports a programme devoted to early phase cancer prevention clinical trials. The experience, along with the benefits and limitations of the range of biomarker endpoints used in these studies, are reviewed here. PMID:26635903

  18. Program Activity/Training Plans. STIP II (Skill Training Improvement Programs Round II).

    ERIC Educational Resources Information Center

    Los Angeles Community Coll. District, CA.

    Detailed operational guidelines, training objectives, and learning activities are provided for the Los Angeles Community College District's Skill Training Improvement Programs (STIP II), which are designed to train students for immediate employment. The first of four reports covers Los Angeles Southwest College's computer programming trainee…

  19. 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.

  20. 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.

  1. Platelet activation during angiotensin II infusion in healthy volunteers.

    PubMed

    Larsson, P T; Schwieler, J H; Wallén, N H

    2000-01-01

    The present study was undertaken to evaluate the effects of an intravenous infusion of angiotensin II (10 ng/kg per min) on platelet function and coagulation in vivo in 18 healthy males. The infusion increased mean arterial pressure by 23+/-2 mm Hg. Plasma beta-thromboglobulin levels, reflecting platelet secretion, increased by 66+/-24% during the infusion, as did also platelet surface expression of P-selectin as measured by flow cytometry. Platelet fibrinogen binding increased, whereas platelet aggregability, assessed by ex vivo filtragometry, was unaltered. Angiotensin II caused mild activation of the coagulation cascade with increases in plasma levels of thrombin-antithrombin complex and prothrombin fragment F1 + 2. In conclusion, angiotensin II has mild platelet-activating effects in vivo and also enhances coagulation. Markers of platelet secretion are significantly increased, whereas markers of platelet aggregability are less affected. The clinical relevance of these findings remains to be clarified. PMID:10691100

  2. World War II Commemoration Committee: Fact Sheet and Suggested Activities.

    ERIC Educational Resources Information Center

    Department of Defense, Washington, DC.

    This packet suggests activities and events that school districts, schools, classes, and educational organizations can conduct to commemorate World War II. Suggestions are made to include local veterans, including those in veteran's and nursing homes and hospitals, and youth at every possible opportunity. Recognition can take the form of military…

  3. Stationary phase deletions in Escherichia coli. II. Mutations which stimulate stationary phase deletions in plasmid pMC874.

    PubMed

    Balbinder, E

    2001-08-01

    Deletions in the plasmid pMC874 take place in resting cells incubating on McConkey's or minimal lactose agar and are time rather than generation dependent. These deletions join the km(r) promoter to a promoterless lac operon giving rise to Lac(+) papillae on McConkey's lactose agar, and can occur in the absence of sequence homologies such as direct or inverted repeats. Using this as a selective screen we isolated 31 mutants designated dli (for deletion increase), which enhanced to different extents the frequency of this unusual class of deletions. Six of these were characterized by phenotypic tests and their ability to stimulate other deletion events such as the excision of Tn10 from various chromosomal sites and the loss of cloned fragments between two EcoR1 sites in the gene for chloramphenicol resistance (cat) of plasmid pBR325. Two of them showed contrasting phenotypes and were studied further: one (dli1) stimulated Lac(+) deletions in pMC874 in resting cells but not Tn10 excision from chromosomal locations in log phase cells, and the other one (dli2) did exactly the reverse, i.e. it enhanced Tn10 excision but not Lac(+) deletion incidence. Mapping and complementation tests showed that dli1 is a null mutation in recC and was renamed recC2251. This is strong evidence that resting phase deletions in pMC874 are stimulated by the absence of a functional RecBCD enzyme. The dli2 mutation was identified by mapping and phenotypic tests as a mutation in uvrD, the gene for helicase II, and it was tentatively designated uvrD(-)dli2. These results show that (1) pMC874 is an excellent system to select mutants for genetic functions involved in the generation of resting phase deletions, and (2) there are at least two major deletion pathways in E. coli, one active in resting and the other in actively dividing cells. PMID:11470479

  4. 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

  5. Effect of Pulse Duration on Polytetrafluoroethylene Shocked above the Crystalline Phase II-Iii Transition

    NASA Astrophysics Data System (ADS)

    Brown, E. N.; Gray, G. T.; Rae, P. J.; Trujillo, C. P.; Bourne, N. K.

    2007-12-01

    We present an experimental study of crystalline structure evolution of polytetrafluoroethylene (PTFE) due to pressure-induced phase transitions in a semi-crystalline polymer using soft-recovery, shock-loading techniques coupled with mechanical and chemical post-shock analysis. Gas-launched, plate impact experiments have been performed on pedigreed PTFE 7C, mounted in momentum-trapped, shock assemblies, with impact pressures above and below the phase II to phase III crystalline transition. Below the phase transition only subtle changes were observed in the crystallinity, microstructure, and mechanical response of PTFE. Shock loading of PTFE 7C above the phase II-III transition was seen to cause both an increase in crystallinity from 38% to ˜53% and a finer crystalline microstructure, and changed the yield and flow stress behavior. We particularly focus on the effect of pulse duration on the microstructure evolution.

  6. Shock Pulse Effects in PTFE Shocked Through the Crystalline Phase II--III Transition

    NASA Astrophysics Data System (ADS)

    Brown, Eric N.; Gray, George T., III; Rae, Philip J.; Bourne, Neil K.

    2008-03-01

    We present an experimental study of crystalline structure evolution of polytetrafluoroethylene (PTFE) due to pressure-induced phase transitions in a semi-crystalline polymer using soft-recovery, shock-loading techniques coupled with mechanical and chemical post-shock analysis. Gas-launched, plate impact experiments have been performed on pedigreed PTFE 7C, mounted in momentum-trapped, shock assemblies, with impact pressures above and below the phase II to phase III crystalline transition. Below the phase transition only subtle changes were observed in the crystallinity, microstructure, and mechanical response of PTFE. Shock loading of PTFE 7C above the phase II--III transition was seen to cause both an increase in crystallinity from 38% to ˜53% (by Differential Scanning Calorimetry, DSC) and a finer crystalline microstructure, and changed the yield and flow stress behavior. We particularly focus on the effect of pulse duration on the microstructure evolution.

  7. Effect of Pulse Duration on Polytetrafluoroethylene Shocked Above the Crystalline Phase II--III Transition

    NASA Astrophysics Data System (ADS)

    Brown, Eric N.; Gray, George T., III; Rae, Philip J.; Trujillo, Carl P.; Bourne, Neil K.

    2007-06-01

    We present an experimental study of crystalline structure evolution of polytetrafluoroethylene (PTFE) due to pressure-induced phase transitions in a semi-crystalline polymer using soft-recovery, shock-loading techniques coupled with mechanical and chemical post-shock analysis. Gas-launched, plate impact experiments have been performed on pedigreed PTFE 7C, mounted in momentum-trapped, shock assemblies, with impact pressures above and below the phase II to phase III crystalline transition. Below the phase transition only subtle changes were observed in the crystallinity, microstructure, and mechanical response of PTFE. Shock loading of PTFE 7C above the phase II--III transition was seen to cause both an increase in crystallinity from 38% to ˜53% (by Differential Scanning Calorimetry, DSC) and a finer crystalline microstructure, and changed the yield and flow stress behavior. We particularly focus on the effect of pulse duration on the microstructure evolution.

  8. 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

  9. Randomized phase II trial of sulindac, atorvastatin, and prebiotic dietary fiber for colorectal cancer chemoprevention.

    PubMed

    Limburg, Paul J; Mahoney, Michelle R; Ziegler, Katie L Allen; Sontag, Stephen J; Schoen, Robert E; Benya, Richard; Lawson, Michael J; Weinberg, David S; Stoffel, Elena; Chiorean, Michael; Heigh, Russell; Levine, Joel; Della'Zanna, Gary; Rodriguez, Luz; Richmond, Ellen; Gostout, Christopher; Mandrekar, Sumithra J; Smyrk, Thomas C

    2011-02-01

    Sulindac, atorvastatin, or prebiotic dietary fiber may reduce colorectal cancer (CRC) risk. However, clinical trial data are currently limited. We conducted a randomized, phase II chemoprevention trial involving subjects 40 years or older, with previously resected colon cancer or multiple/advanced colorectal adenomas. Magnification chromoendoscopy (MCE) was performed to identify and characterize rectal aberrant crypt foci (ACF); eligibility criteria required five or more rectal ACFs at baseline. Intervention assignments were as follows: (a) atorvastatin 20 mg qd; (b) sulindac 150 mg bid; (c) oligofructose-enriched inulin (as ORAFTI®Synergy1) 6 gm bid; or (d) control (maltodextrin) 6 gm bid, for 6 months. Percent change in rectal ACF number (%ΔACF) within arm was the primary endpoint. Secondary endpoints included changes in proliferation (Ki67) and apoptosis (caspase-3), as measured from normal mucosa biopsy samples. Among 85 eligible randomized subjects, 76 (86%) completed the trial per protocol. The median (range) of rectal ACF was 9 (5-34) and 8 (0-37) at baseline and postintervention, respectively. The median (SD) for %ΔACF was 5.6 (-69% to 143%), -18.6 (-83% to 160%), -3.6 (-88% to 83%), and -10.0 (-100% to 117%) in the atorvastatin, sulindac, ORAFTI®Synergy1 and control arms, respectively. Neither within-arm (P = 0.12-0.59) nor between-arm (P = 0.30-0.92) comparisons of %ΔACF were statistically significant. The active and control interventions also seemed to have similar effects on mucosal proliferation and apoptosis (P > 0.05 for each comparison). Data from this multicenter, phase II trial do not provide convincing evidence of CRC risk reduction from 6-month interventions with atorvastatin, sulindac, or ORAFTI®Synergy1, although statistical power was limited by the relatively small sample size. PMID:21209397

  10. 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.

  11. 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. PMID:27306016

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

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

    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.

  13. Modeling of fluidized-bed combustion of coal: Phase II, final reports. Volume IV. FBC-Model-II manual

    SciTech Connect

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

    1980-10-01

    This document is the fourth of the seven volume series of our Phase II Final Report. The purpose of this manual is to describe how to access and use M.I.T.'s Fluidized Bed Combustor (FBC) System Program. Presently, the FBC program is stored in a Honeywell Computer System and can be accessed using the Multics interactive system. The intention in writing this manual is to answer the questions that may arise regarding the mechanics of operating the system program, as well as warn the user of possible pitfalls and mistakes that could be made. No attempt is made here to describe the internals of the systems program. The manual describes the procedures an individual would follow to become an active user of the system program. It then explains the various options available for reaching the Multics interactive system on Honeywell 6180 computer on which the program runs. For users outside the Metropolitan Boston area, a public network for data communications is described which is relatively inexpensive. As the system program is approached through Multics using a special command facility TPSA, a separate introduction is provided for Multics TPSA. This facility allows commands appropriate for testing the program and carrying out parametric studies to be executed in a convenient way. Multics TPSA was formulated to meet the needs of the FBC project in particular. Finally, some sample sessions are presented which illustrate the login and logout procedures, the command language, and the data manipulation features of the FBC program. The use of commands helpful in debugging the program is also illustrated.

  14. 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...

  15. Final Phase II report : QuickSite(R) investigation, Everest, Kansas.

    SciTech Connect

    LaFreniere, L. M.

    2003-11-01

    field work at Everest. The main session of field work for the Phase II QuickSite{reg_sign} investigation of the Everest site began on March 6, 2001. Work was suspended at the site on April 6, 2001, (1) because of access limitations to key properties, located north and west of the former CCC/USDA facility, imposed by the private owners at the onset of the spring planting season and (2) to permit further documentation by Argonne, at the request of the CCC/USDA, of the land use and ownership history of the Nigh property as a precursor to completion of the field work. This period is termed the second session of Phase II field work at Everest. Investigation of the Nigh property history was prompted by groundwater contamination evidence obtained during the second session of Phase II field activities (discussed in Section 3.7).

  16. 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

  17. 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. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26526165

  18. GERDA phase II detectors: Behind the production and characterisation at low background conditions

    NASA Astrophysics Data System (ADS)

    Maneschg, Werner; Gerda Collaboration

    2013-08-01

    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 76Ge. 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.

  19. 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.

  20. 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.

  1. 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.

  2. Developmental Effects of the ToxCast™ Phase I and Phase II Chemicals in Caenorhabditis elegans and Corresponding Responses in Zebrafish, Rats, and Rabbits

    PubMed Central

    Boyd, Windy A.; Smith, Marjolein V.; Co, Caroll A.; Pirone, Jason R.; Rice, Julie R.; Shockley, Keith R.; Freedman, Jonathan H.

    2015-01-01

    Background: Modern toxicology is shifting from an observational to a mechanistic science. As part of this shift, high-throughput toxicity assays are being developed using alternative, nonmammalian species to prioritize chemicals and develop prediction models of human toxicity. Methods: The nematode Caenorhabditis elegans (C. elegans) was used to screen the U.S. Environmental Protection Agency’s (EPA’s) ToxCast™ Phase I and Phase II libraries, which contain 292 and 676 chemicals, respectively, for chemicals leading to decreased larval development and growth. Chemical toxicity was evaluated using three parameters: a biologically defined effect size threshold, half-maximal activity concentration (AC50), and lowest effective concentration (LEC). Results: Across both the Phase I and Phase II libraries, 62% of the chemicals were classified as active ≤ 200 μM in the C. elegans assay. Chemical activities and potencies in C. elegans were compared with those from two zebrafish embryonic development toxicity studies and developmental toxicity data for rats and rabbits. Concordance of chemical activity was higher between C. elegans and one zebrafish assay across Phase I chemicals (79%) than with a second zebrafish assay (59%). Using C. elegans or zebrafish to predict rat or rabbit developmental toxicity resulted in balanced accuracies (the average value of the sensitivity and specificity for an assay) ranging from 45% to 53%, slightly lower than the concordance between rat and rabbit (58%). Conclusions: Here, we present an assay that quantitatively and reliably describes the effects of chemical toxicants on C. elegans growth and development. We found significant overlap in the activity of chemicals in the ToxCast™ libraries between C. elegans and zebrafish developmental screens. Incorporating C. elegans toxicological assays as part of a battery of in vitro and in vivo assays provides additional information for the development of models to predict a chemical

  3. POLLUTION-ENHANCED ALLERGIC INFLAMMATION AND PHASE II ENZYMES

    EPA Science Inventory

    During Year 2, we intend to recruit adults and children for Aim #1, commence recruitment for Aim #2, and repeat our mouse/sulforaphane experiment in Nrf-2 knock-out mice to confirm that the action of sulforaphane is indeed through activation of Nrf-2.

  4. MIDDLE TO UPPER ATLANTIC REGIONAL ASSESSMENT (PHASE II)

    EPA Science Inventory

    The objective of this assessment activity is to enhance the ability of decision-makers and other stakeholders in the Middle to Upper Atlantic Region who are vulnerable to land use change and climate change to access and use the best scientific information when making decisions th...

  5. Active metasurface terahertz deflector with phase discontinuities.

    PubMed

    Su, Xiaoqiang; Ouyang, Chunmei; Xu, Ningning; Cao, Wei; Wei, Xin; Song, Guofeng; Gu, Jianqiang; Tian, Zhen; O'Hara, John F; Han, Jiaguang; Zhang, Weili

    2015-10-19

    Metasurfaces provide great flexibility in tailoring light beams and reveal unprecedented prospects on novel functional components. However, techniques to dynamically control and manipulate the properties of metasurfaces are lagging behind. Here, for the first time to our knowledge, we present an active wave deflector made from a metasurface with phase discontinuities. The active metasurface is capable of delivering efficient real-time control and amplitude manipulation of broadband anomalous diffraction in the terahertz regime. The device consists of complementary C-shape split-ring resonator elements fabricated on a doped semiconductor substrate. Due to the Schottky diode effect formed by the hybrid metal-semiconductor, the real-time conductivity of the doped semiconductor substrate is modified by applying an external voltage bias, thereby effectively manipulating the intensity of the anomalous deflected terahertz wave. A modulation depth of up to 46% was achieved, while the characteristics of broadband frequency responses and constant deflected angles were well maintained during the modulation process. The modulation speed of diffraction amplitude reaches several kilohertz, limited by the capacitance and resistance of the depletion region. The scheme proposed here opens up a novel approach to develop tunable metasurfaces. PMID:26480376

  6. Strategies for the modulation of phase II metabolism in a series of PKCε inhibitors.

    PubMed

    Clemens, Jeremy J; Coon, Timothy; Busch, Brett B; Asgian, Juliana L; Hudson, Sarah; Termin, Andreas; Flores, Tina B; Tran, Dao; Chiang, Peggy; Sperry, Sam; Gross, Ray; Abt, Jeffrey; Heim, Roger; Lechner, Sandra; Twin, Heather; Studley, John; Brenchley, Guy; Collier, Philip N; Pierard, Francoise; Miller, Andrew; Mak, Chau; Dvornikovs, Vadims; Jimenez, Juan-Miguel; Stamos, Dean

    2014-08-01

    Extensive phase II metabolism of an advanced PKCε inhibitor resulted in sub-optimal pharmacokinetics in rat marked by elevated clearance. Synthesis of the O-glucuronide metabolite as a standard was followed by three distinct strategies to specifically temper phase II metabolic degradation of the parent molecule. In this study, it was determined that the introduction of proximal polarity to the primary alcohol generally curbed O-glucuronidation and improved PK and physical chemical properties while maintaining potency against the target. Utilization of a Jacobsen hydrolytic kinetic resolution to obtain optically enriched final compounds is also discussed. PMID:24939756

  7. 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.

  8. Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial

    PubMed Central

    Motzer, Robert J.; Rini, Brian I.; McDermott, David F.; Redman, Bruce G.; Kuzel, Timothy M.; Harrison, Michael R.; Vaishampayan, Ulka N.; Drabkin, Harry A.; George, Saby; Logan, Theodore F.; Margolin, Kim A.; Plimack, Elizabeth R.; Lambert, Alexandre M.; Waxman, Ian M.; Hammers, Hans J.

    2015-01-01

    Purpose Nivolumab is a fully human immunoglobulin G4 programmed death–1 immune checkpoint inhibitor antibody that restores T-cell immune activity. This phase II trial assessed the antitumor activity, dose-response relationship, and safety of nivolumab in patients with metastatic renal cell carcinoma (mRCC). Patients and Methods Patients with clear-cell mRCC previously treated with agents targeting the vascular endothelial growth factor pathway were randomly assigned (blinded ratio of 1:1:1) to nivolumab 0.3, 2, or 10 mg/kg intravenously once every 3 weeks. The primary objective was to evaluate the dose-response relationship as measured by progression-free survival (PFS); secondary end points included objective response rate (ORR), overall survival (OS), and safety. Results A total of 168 patients were randomly assigned to the nivolumab 0.3- (n = 60), 2- (n = 54), and 10-mg/kg (n = 54) cohorts. One hundred eighteen patients (70%) had received more than one prior systemic regimen. Median PFS was 2.7, 4.0, and 4.2 months, respectively (P = .9). Respective ORRs were 20%, 22%, and 20%. Median OS was 18.2 months (80% CI, 16.2 to 24.0 months), 25.5 months (80% CI, 19.8 to 28.8 months), and 24.7 months (80% CI, 15.3 to 26.0 months), respectively. The most common treatment-related adverse event (AE) was fatigue (24%, 22%, and 35%, respectively). Nineteen patients (11%) experienced grade 3 to 4 treatment-related AEs. Conclusion Nivolumab demonstrated antitumor activity with a manageable safety profile across the three doses studied in mRCC. No dose-response relationship was detected as measured by PFS. These efficacy and safety results in mRCC support study in the phase III setting. PMID:25452452

  9. Microstructure and density changes in Li 2O during irradiation in BEATRIX-II, Phase I and II

    NASA Astrophysics Data System (ADS)

    Takahashi, Tadashi; Noda, Kenji; Slagle, O. D.; Hobbs, F. D.

    1996-10-01

    BEATRIX-II Phase I and II were in-situ tritium recovery experiments to characterize the behavior of ceramic breeders irradiated to high burn-up using the fast flux test facility (FFTF). A thin-walled, Li 2O-sintered ring specimen and single crystals specimen were irradiated to total lithium burn-ups of about 5 at%. Scanning electron microscopy of the ring specimen in Phase II revealed a substantial increase of open porosity and platelet-shaped grains and a decrease in grain size for most parts of the specimens. At the top end of the specimen hexagonal-shaped bubbles were observed in addition to the increase of porosity and the decrease of grain size. The increase of open porosity and the decrease of grain size were considered to arise from a significant link-up of the bubbles. Such increase of open porosity led to volumetric swelling in the order of 20%. Fracture surfaces of the single crystals exhibited morphological changes resembling blisters.

  10. A two-stage patient enrichment adaptive design in phase II oncology trials.

    PubMed

    Song, James X

    2014-01-01

    Illustrated is the use of a patient enrichment adaptive design in a randomized phase II trial which allows the evaluation of treatment benefits by the biomarker expression level and makes interim adjustment according to the pre-specified rules. The design was applied to an actual phase II metastatic hepatocellular carcinoma (HCC) trial in which progression-free survival (PFS) in two biomarker-defined populations is evaluated at both interim and final analyses. As an extension, a short-term biomarker is used to predict the long-term PFS in a Bayesian model in order to improve the precision of hazard ratio (HR) estimate at the interim analysis. The characteristics of the extended design are examined in a number of scenarios via simulations. The recommended adaptive design is shown to be useful in a phase II setting. When a short-term maker which correlates with the long-term PFS is available, the design can be applied in smaller early phase trials in which PFS requires longer follow-up. In summary, the adaptive design offers flexibility in randomized phase II patient enrichment trials and should be considered in an overall personalized healthcare (PHC) strategy. PMID:24342820

  11. 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

  12. 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.

  13. Shear banding in a lyotropic lamellar phase. II. Temporal fluctuations

    NASA Astrophysics Data System (ADS)

    Salmon, Jean-Baptiste; Manneville, Sébastien; Colin, Annie

    2003-11-01

    We analyze the temporal fluctuations of the flow field associated with a shear-induced transition in a lyotropic lamellar phase: the layering transition of the onion texture. In the first part of this work [Salmon et al., Phys. Rev. E 68, 051503 (2003)], we have evidenced banded flows at the onset of this shear-induced transition which are well accounted for by the classical picture of shear banding. In the present paper, we focus on the temporal fluctuations of the flow field recorded in the coexistence domain. These striking dynamics are very slow (100 1000 s) and cannot be due to external mechanical noise. Using velocimetry coupled to structural measurements, we show that these fluctuations are due to a motion of the interface separating the two differently sheared bands. Such a motion seems to be governed by the fluctuations of σ*, the local stress at the interface between the two bands. Our results thus provide more evidence for the relevance of the classical mechanical approach of shear banding even if the mechanism leading to the fluctuations of σ* remains unclear.

  14. Modular activation of Rho1 by GPCR signalling imparts polarized myosin II activation during morphogenesis.

    PubMed

    Kerridge, Stephen; Munjal, Akankshi; Philippe, Jean-Marc; Jha, Ankita; de las Bayonas, Alain Garcia; Saurin, Andrew J; Lecuit, Thomas

    2016-03-01

    Polarized cell shape changes during tissue morphogenesis arise by controlling the subcellular distribution of myosin II. For instance, during Drosophila melanogaster gastrulation, apical constriction and cell intercalation are mediated by medial-apical myosin II pulses that power deformations, and polarized accumulation of myosin II that stabilizes these deformations. It remains unclear how tissue-specific factors control different patterns of myosin II activation and the ratchet-like myosin II dynamics. Here we report the function of a common pathway comprising the heterotrimeric G proteins Gα12/13, Gβ13F and Gγ1 in activating and polarizing myosin II during Drosophila gastrulation. Gα12/13 and the Gβ13F/γ1 complex constitute distinct signalling modules, which regulate myosin II dynamics medial-apically and/or junctionally in a tissue-dependent manner. We identify a ubiquitously expressed GPCR called Smog required for cell intercalation and apical constriction. Smog functions with other GPCRs to quantitatively control G proteins, resulting in stepwise activation of myosin II and irreversible cell shape changes. We propose that GPCR and G proteins constitute a general pathway for controlling actomyosin contractility in epithelia and that the activity of this pathway is polarized by tissue-specific regulators. PMID:26780298

  15. 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

  16. Contribution of myosin II activity to cell spreading dynamics.

    PubMed

    Nisenholz, Noam; Paknikar, Aishwarya; Köster, Sarah; Zemel, Assaf

    2016-01-14

    Myosin II activity and actin polymerization at the leading edge of the cell are known to be essential sources of cellular stress. However, a quantitative account of their separate contributions is still lacking; so is the influence of the coupling between the two phenomena on cell spreading dynamics. We present a simple analytic elastic theory of cell spreading dynamics that quantitatively demonstrates how actin polymerization and myosin activity cooperate in the generation of cellular stress during spreading. Consistent with experiments, myosin activity is assumed to polarize in response to the stresses generated during spreading. The characteristic response time and the overall spreading time are predicted to determine different evolution profiles of cell spreading dynamics. These include, a (regular) monotonic increase of cell projected area with time, a non-monotonic (overshooting) profile with a maximum, and damped oscillatory modes. In addition, two populations of myosin II motors are distinguished based on their location in the lamella; those located above the major adhesion zone at the cell periphery are shown to facilitate spreading whereas those in deeper regions of the lamella are shown to oppose spreading. We demonstrate that the attenuation of myosin activity in the two regions may result in reciprocal effects on spreading. These findings provide important new insight into the function of myosin II motors in the course of spreading. PMID:26481613

  17. Anticancer activity assessment of two novel binuclear platinum (II) complexes.

    PubMed

    Shahsavani, Mohammad Bagher; Ahmadi, Shamseddin; Aseman, Marzieh Dadkhah; Nabavizadeh, S Masoud; Rashidi, Mehdi; Asadi, Zahra; Erfani, Nasrollah; Ghasemi, Atiyeh; Saboury, Ali Akbar; Niazi, Ali; Bahaoddini, Aminollah; Yousefi, Reza

    2016-08-01

    In the current study, two binuclear Pt (II) complexes, containing cis, cis-[Me2Pt (μ-NN) (μ-dppm) PtMe2] (1), and cis,cis-[Me2Pt(μ-NN)(μ dppm) Pt((CH2)4)] (2) in which NN=phthalazine and dppm=bis (diphenylphosphino) methane were evaluated for their anticancer activities and DNA/purine nucleotide binding properties. These Pt (II) complexes, with the non-classical structures, demonstrated a significant anticancer activity against Jurkat and MCF-7 cancer cell lines. The results of ethidium bromide/acridine orange staining and Caspase-III activity suggest that these complexes were capable to stimulate an apoptotic mechanism of cell death in the cancer cells. Using different biophysical techniques and docking simulation analysis, we indicated that these complexes were also capable to interact efficiently with DNA via a non-intercalative mechanism. According to our results, substitution of cyclopentane (in complex 2) with two methyl groups (in complex 1) results in significant improvement of the complex ability to interact with DNA and subsequently to induce the anticancer activity. Overall, these binuclear Pt (II) complexes are promising group of the non-classical potential anticancer agents which can be considered as molecular templates in designing of highly efficient platinum anticancer drugs. PMID:27289447

  18. 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.

  19. 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.

  20. Phase I/II study of 131I-MIBG with vincristine and 5 days of irinotecan for advanced neuroblastoma

    PubMed Central

    DuBois, S G; Allen, S; Bent, M; Hilton, J F; Hollinger, F; Hawkins, R; Courtier, J; Mosse, Y P; Matthay, K K

    2015-01-01

    Background: 131I-metaiodobenzylguanidine (MIBG) is an active radiopharmaceutical in neuroblastoma. A previous study demonstrated that MIBG could be combined with vincristine and prolonged irinotecan, although 25% of first courses had grade 3 diarrhoea. The current phase I/II study evaluated MIBG with vincristine and 5 days of higher-dose irinotecan. Methods: Patients 1–30 years old with advanced neuroblastoma were eligible. Patients received cefixime on days −1 to +6, irinotecan (50 mg m−2 per dose IV) on days 0–4, vincristine (2 mg m−2) on day 0, MIBG (555 or 666 MBq kg−1) on day 1, and peripheral blood stem cells on day 13. UGT1A1 genotyping was performed in consenting patients. Results: Thirty-two patients (12 phase I ; 20 phase II) received 42 courses. No dose-limiting toxicities were seen during dose escalation and the recommended administered activity was 666 MBq kg−1. Myelosuppression and diarrhoea were the most common toxicities, with grade 3 diarrhoea in 6% of first courses. Patients homozygous for UGT1A1*28 had more grade 4 thrombocytopenia (80% vs 37% P=0.14). Responses (five complete and four partial) occurred in 9 out of 32 (28%) patients. Conclusions: MIBG (666 MBq kg−1) with vincristine and this irinotecan schedule is tolerable and active, with less severe diarrhoea compared with a regimen using more protracted irinotecan. PMID:25602966

  1. Advanced Direct Liquefaction Concepts for PETC Generic Units - Phase II

    SciTech Connect

    1997-12-01

    The results of Laboratory and Bench-Scale experiments and supporting technical and economic assessments conducted under DOE Contract No. DE-AC22-91PC91040 are reported for the period July 1, 1997 to September 30, 1997. This contract is with the University of Kentucky Research Foundation which supports work with the University of Kentucky Center for Applied Energy Research, CONSOL, Inc., LDP Associates, and Hydrocarbon Technologies, Inc. This work involves the introduction into the basic two stage liquefaction process several novel concepts which include dispersed lower-cost catalysts, coal cleaning by oil agglomeration, and distillate hydrotreating and dewaxing. Results are reported from experiments in which various methods were tested to activate dispersed Mo precursors. Several oxothiomolybdates precursors having S/Mo ratios from two to six were prepared. Another having a S/Mo ratio of eleven was also prepared that contained an excess of sulfur. In the catalyst screening test, none of these precursors exhibited an activity enhancement that might suggest that adding sulfur into the structure of the Mo precursors would be beneficial to the process. In another series of experiments, AHM impregnated coal slurried in the reaction mixture was pretreated withH S/H under pressure and successively heated for 30 min at 120, 250 2 2 and 360 C. THF conversions in the catalyst screening test were not affected while resid conversions o increased such that pretreated coals impregnated with 100 ppm Mo gave conversions equivalent to untreated coals impregnated with 300 ppm fresh Mo. Cobalt, nickel and potassium phosphomolybdates were prepared and tested as bimetallic precursors. The thermal stability of these compounds was evaluated in TG/MS to determine whether the presence of the added metal would stabilize the Keggin structure at reaction temperature. Coals impregnated with these salts showed the Ni and Co salts gave the same THF conversion as PMA while the Ni salt gave higher

  2. 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

  3. 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

  4. Catalytically active lead(ii)-imidazolium coordination assemblies with diversified lead(ii) coordination geometries.

    PubMed

    Naga Babu, Chatla; Suresh, Paladugu; Srinivas, Katam; Sathyanarayana, Arruri; Sampath, Natarajan; Prabusankar, Ganesan

    2016-05-10

    Five Pb(ii)-imidazolium carboxylate coordination assemblies with novel structural motifs were derived from the reaction between the corresponding flexible, semi flexible or rigid imidazolium carboxylic acid ligands and lead nitrate. The imidazolium linker present in these molecules likely plays a triple role such as the counter ion to balance the metal charge, the ligand being an integral part of the final product and the catalyst facilitating carbon-carbon bond formation reaction. These lead-imidazolium coordination assemblies exhibit, variable chemical and thermal stabilities, as well as catalytic activity. These newly prepared catalysts are highly active towards benzoin condensation reactions with good functional group tolerance. PMID:27093629

  5. 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…

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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 NOX emission limitations for Group 1,...

  14. 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...

  15. 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...

  16. 77 FR 73586 - Further Inquiry Into Issues Related to Mobility Fund Phase II

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-11

    ...The Wireless Telecommunications Bureau and Wireline Competition Bureau (collectively, the Bureaus) seek further comment on specific issues relating to the implementation of Phase II of the Mobility Fund. The Bureaus also seek to develop a more comprehensive record on certain issues relating to the award of ongoing support for advanced mobile...

  17. 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...

  18. 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.

  19. DEVELOPMENT OF AN ENVIRONMENTALLY FRIENDLY AND ECONOMICAL PROCESS FOR PLUGGING ABANDONED WELLS (PHASE II)

    EPA Science Inventory

    The phase II of this project was successfully completed with field tests being presently underway. It was found from the laboratory study that the fly ash slurry had sufficient thickening time and could be pumped successfully through coiled and straight tubing. Pumping through...

  20. VTAE Equity Staff Development Workshops and Services--Phase II. Final Report.

    ERIC Educational Resources Information Center

    Baldus, Lorayne; Nelson, Orville

    The Phase II Equity Staff Development project was revised in response to a need to develop an equity strategic planning model with a vision statement, goals, and objectives. The Equity Strategic Planning Model was presented to administrators of Wisconsin Vocational, Technical, and Adult Education (VTAE) colleges for their use in district strategic…

  1. 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,…

  2. 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

    ... DEEPWATER HORIZON Oil Spill; Final Phase II Early Restoration Plan and Environmental Review AGENCY: Interior... Addressing Injuries Resulting from the DEEPWATER HORIZON Oil Spill (Framework Agreement), notice is hereby... services injured or lost as a result of the DEEPWATER HORIZON oil spill, which occurred on or about...

  3. Phase II Update and Guidelines forCycle 17 Users of COS

    NASA Astrophysics Data System (ADS)

    Soderblom, David R.

    2008-06-01

    This ISR presents a summary of recommended practice and suggestions for observers preparingtheir Phase II COS program submissions for Cycle 17. Several important modificationsto the COS Instrument Handbook and the COS Exposure Time Calculator are noted.Procedures for Bright Object Protection checking are described.

  4. CONTROL OF UTILITY BOILER AND GAS TURBINE POLLUTANT EMISSIONS BY COMBUSTION MODIFICATION--PHASE II

    EPA Science Inventory

    The report gives results of Phase II of a field study to assess the applicability of combustion modification (CM) techniques to control NOx and other pollutant emissions from utility boilers and gas turbines without causing deleterious side effects. Comprehensive, statistically d...

  5. Phase II Feasibility Study to Gather Information for Implementing Telecommunications into Office Technology Curriculum. Final Report.

    ERIC Educational Resources Information Center

    Henson, Linda; Sanders, Myrna

    Phase II of a feasibility study to gather information for implementing telecommunications into the office systems and technologies curriculum at Jefferson College began in January 1984. The objectives were to provide the instructional staff with the technical information needed to teach telecommunications and to explore the possibility of…

  6. 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.

  7. European Xfel-Linac Two-Phase he II Flow Simulations

    NASA Astrophysics Data System (ADS)

    Gubarev, V.; Petersen, B.; Sellmann, D.; Xiang, Y.

    2008-03-01

    The superconducting 1.3-GHz niobium cavities of the XFEL linear accelerator will be cooled in a bath of saturated liquid He II at a temperature of 2 K. The liquid He II supply of the 1.7-km long linac is subdivided in sections of about 150 m length. In these sections a two-phase flow of He II liquid and corresponding vapor occurs. A stable stratified smooth helium flow has to be maintained for the RF operation of the cavities, to avoid any vibrations or microphonic effects. A computer code has been developed to simulate the two-phase flow patterns in the XFEL-linac, based on an existing model. The flow characteristics at different cryogenic loads and helium temperatures have been calculated. The results are shown and the consequences for the design of the XFEL-linac cryogenic system are discussed.

  8. Modulation of Rubisco Activity during the Diurnal Phases of the Crassulacean Acid Metabolism Plant Kalanchoë daigremontiana.

    PubMed

    Maxwell; Borland; Haslam; Helliker; Roberts; Griffiths

    1999-11-01

    The regulation of Rubisco activity was investigated under high, constant photosynthetic photon flux density during the diurnal phases of Crassulacean acid metabolism in Kalanchoë daigremontiana Hamet et Perr. During phase I, a significant period of nocturnal, C(4)-mediated CO(2) fixation was observed, with the generated malic acid being decarboxylated the following day (phase III). Two periods of daytime atmospheric CO(2) fixation occurred at the beginning (phase II, C(4)-C(3) carboxylation) and end (phase IV, C(3)-C(4) carboxylation) of the day. During the 1st h of the photoperiod, when phosphoenolpyruvate carboxylase was still active, the highest rates of atmospheric CO(2) uptake were observed, coincident with the lowest rates of electron transport and minimal Rubisco activity. Over the next 1 to 2 h of phase II, carbamylation increased rapidly during an initial period of decarboxylation. Maximal carbamylation (70%-80%) was reached 2 h into phase III and was maintained under conditions of elevated CO(2) resulting from malic acid decarboxylation. Initial and total Rubisco activity increased throughout phase III, with maximal activity achieved 9 h into the photoperiod at the beginning of phase IV, as atmospheric CO(2) uptake recommenced. We suggest that the increased enzyme activity supports assimilation under CO(2)-limited conditions at the start of phase IV. The data indicate that Rubisco activity is modulated in-line with intracellular CO(2) supply during the daytime phases of Crassulacean acid metabolism. PMID:10557233

  9. 20 CFR 404.1311 - Ninety-day active service requirement for World War II veterans.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... World War II veterans. 404.1311 Section 404.1311 Employees' Benefits SOCIAL SECURITY ADMINISTRATION... Uniformed Services World War II Veterans § 404.1311 Ninety-day active service requirement for World War II veterans. (a) The 90 days of active service required for World War II veterans do not have to...

  10. 20 CFR 404.1311 - Ninety-day active service requirement for World War II veterans.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... World War II veterans. 404.1311 Section 404.1311 Employees' Benefits SOCIAL SECURITY ADMINISTRATION... Uniformed Services World War II Veterans § 404.1311 Ninety-day active service requirement for World War II veterans. (a) The 90 days of active service required for World War II veterans do not have to...

  11. 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.

  12. Irradiation of lithium zirconate pebble-bed in BEATRIX-II Phase II

    NASA Astrophysics Data System (ADS)

    Verrall, R. A.; Slagle, O. D.; Hollenberg, G. W.; Kurasawa, T.; Sullivan, J. D.

    1994-09-01

    BEATRIX-II was an in-situ tritium recovery experiment that was designed to characterize the behavior of lithium ceramics irradiated to a high burnup, and to assess their suitability for use in a fusion reactor blanket. This paper describes the results from the vented canister containing 29.47 g of lithium zirconate spheres packed in a bed 13.2 mm OD, 2.3 mm ID and 103 mm long. The enriched lithium spheres (85% 6Li) were irradiated to a burnup of 5.2% (total lithium) in a steep temperature profile -400°C edge, 1100°C center. The sweep gas was He-O.1% H 2, with systematic tests using alternate compositions: He-0.01% H 2 and pure He (maximum duration 8 days). Tritium recovery decreased slightly at lower H 2 concentrations; for example, the buildup of inventory during a 4-day test in pure He was 0.8 Ci, approximately 6.5% of the tritium generated in the lithium zirconate during that period. The steadiness of the bed central temperature and the tritium release rate, together with low moisture release indicate good performance of the zirconate bed.

  13. Oral administration of non-absorbable delayed release 6-mercaptopurine is locally active in the gut, exerts a systemic immune effect and alleviates Crohn's disease with low rate of side effects: results of double blind Phase II clinical trial.

    PubMed

    Israeli, E; Goldin, E; Fishman, S; Konikoff, F; Lavy, A; Chowers, Y; Melzer, E; Lahat, A; Mahamid, M; Shirin, H; Nussinson, E; Segol, O; Ya'acov, A Ben; Shabbat, Y; Ilan, Y

    2015-08-01

    Therapy for Crohn's disease (CD) with thiopurines is limited by systemic side effects. A novel formulation of fixed-dose, delayed-release 6-mercaptopurine (DR-6MP) was developed, with local effect on the gut immune system and minimal absorption. The aim of this study was to evaluate the safety and efficacy of DR-6MP in patients with moderately severe CD compared to systemically delivered 6-mercaptopurine (Purinethol). Seventy CD patients were enrolled into a 12-week, double-blind controlled trial. The primary end-point was the percentage of subjects with clinical remission [Crohn's Disease Activity Index (CDAI) < 150] or clinical response (100-point CDAI reduction). Twenty-six (56·5%) and 13 (54·2%) subjects from the DR-6MP and Purinethol cohorts, respectively, completed the study. DR-6MP had similar efficacy to Purinethol following 12 weeks of treatment. However, the time to maximal clinical response was 8 weeks for DR-6MP versus 12 weeks for Purinethol. A higher proportion of patients on DR-6MP showed clinical remission at week 8. A greater improvement in Inflammatory Bowel Disease Questionnaire (IBDQ) score was noted in the DR-6MP group. DR-6MP led to a decrease of CD62(+) expression on T cells, implying a reduction of lymphocyte adhesion to site of inflammation. DR-6MP was safer than Purinethol, with significantly fewer adverse events (AEs). There was no evidence of drug-induced leucopenia in the DR-6MP group; the proportion of subjects who developed hepatotoxicity was lower for the DR-6MP. Non-absorbable DR-6MP is safe and biologically active in the gut. It is clinically effective, exerting a systemic immune response with low systemic bioavailability and a low incidence of side effects. PMID:25846055

  14. Activation of shallow dopants in II-VI compounds

    SciTech Connect

    Walukiewicz, W.

    1995-08-01

    The amphoteric native defect model is applied to the understanding of the variations in the dopant activation efficiency in II-VI compounds. It is shown that the location of the common energy reference, the Fermi level stabilization energy, relative to the band edges can be used to determine the doping induced reduction of the formation energy and the enhancement of the concentration of compensating native defects. The model is applied to the most extensively studied compound semiconductors as well as to ternary and quaternary alloys. The effects of the compound ionicity on the dopant activation are briefly discussed.

  15. Hemolytic anemia and induction of phase II detoxification enzymes by diprop-1-enyl sulfide in rats: dose-response study.

    PubMed

    Munday, Rex; Munday, Christine M; Munday, John S

    2005-12-14

    Epidemiological evidence indicates that a high dietary intake of plants of the Allium family, such as garlic and onions, is associated with a decreased risk of cancer in humans. It has been suggested that this chemopreventative effect involves the ability of the aliphatic sulfides derived from these vegetables to increase tissue activities of phase II detoxification enzymes. Several highly effective inducers from garlic have been identified, but most of the previously studied compounds from onion have proved to be only weakly active. In the present study, the inductive activity of another onion-derived sulfide, diprop-1-enyl sulfide, has been investigated. This substance was a potent inducer of phase II enzymes in rats, showing significant effects in the lungs and in the lower part of the gastrointestinal tract, suggesting that diprop-1-enyl sulfide could be a useful chemopreventative agent at these sites. At high dose levels, diprop-1-enyl sulfide caused hemolytic anemia, which may be due to in vivo conversion of the sulfide to active metabolites. PMID:16332117

  16. 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.

  17. 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.

  18. Deficiency of endogenous acute phase serum amyloid A protects apoE−/− mice from angiotensin II-induced abdominal aortic aneurysm formation

    PubMed Central

    Webb, NR; De Beer, MC; Wroblewski, JM; Ji, A; Bailey, W; Shridas, P; Charnigo, RJ; Noffsinger, VP; Witta, J; Howatt, DA; Balakrishnan, A; Rateri, DL; Daugherty, A; De Beer, FC

    2016-01-01

    Objective Rupture of abdominal aortic aneurysm (AAA), a major cause of death in the aged population, is characterized by vascular inflammation and matrix degradation. Serum amyloid A (SAA), an acute phase reactant linked to inflammation and matrix metalloproteinase induction, correlates with aortic dimensions before aneurysm formation in humans. We investigated whether SAA deficiency in mice impacts AAA formation during angiotensin II (AngII) infusion. Approach and Results Plasma SAA increased ~60-fold in apoE−/− mice 24 hours after i.p. AngII injection (100 μg/kg; n = 4) and ~15-fold after chronic 28-day AngII infusion (1,000 ng/kg/min; n = 9). AAA incidence and severity after 28-day AngII infusion was significantly reduced in apoE−/− mice lacking both acute phase SAA isoforms (SAAKO; n = 20) compared to apoE−/− mice (SAAWT; n = 20) as assessed by in vivo ultrasound and ex vivo morphometric analyses, despite a significant increase in systolic blood pressure in SAAKO mice compared to SAAWT mice after AngII infusion. Atherosclerotic lesion area of the aortic arch was similar in SAAKO and SAAWT mice after 28-day AngII infusion. Immunostaining detected SAA in AAA tissues of AngII-infused SAAWT mice that co-localized with macrophages, elastin breaks, and enhanced matrix metalloproteinase (MMP) activity. MMP-2 activity was significantly lower in aortas of SAAKO mice compared to SAAWT mice after 10-day AngII infusion. Conclusion Lack of endogenous acute phase SAA protects against experimental AAA through a mechanism that may involve reduced MMP-2 activity. PMID:25745063

  19. DNA Binding and Antitumor Activity of α-Diimineplatinum(II) and Palladium(II) Dithiocarbamate Complexes

    PubMed Central

    Mansouri-Torshizi, Hassan; Saeidifar, Maryam; Khosravi, Fatemeh; Divsalar, Adeleh; Saboury, Ali Akbar; Hassani, Fatemeh

    2011-01-01

    The two water-soluble designed platinum(II) complex, [Pt(Oct-dtc)(bpy)]NO3 (Oct-dtc = Octyldithiocarbamate and bpy = 2,2′ -bipyridine) and palladium(II) complex, [Pd(Oct-dtc)(bpy)]NO3, have been synthesized and characterized by elemental analyses, molar conductivity measurements, IR, 1H NMR, and electronic spectra studies. Studies of antitumor activity of these complexes against human cell tumor lines (K562) have been carried out. They show Ic50 values lower than that of cisplatin. The complexes have been investigated for their interaction with calf thymus DNA (CT-DNA) by utilizing the electronic absorption spectroscopy, fluorescence spectra, and ethidium bromide displacement and gel filtration techniques. Both of these water-soluble complexes bound cooperatively and intercalatively to the CT-DNA at very low concentrations. Several binding and thermodynamic parameters are also described. PMID:22110410

  20. Phase II Upgrade of the GERDA Experiment for the Search of Neutrinoless Double Beta Decay

    NASA Astrophysics Data System (ADS)

    Majorovits, B.

    Observation of neutrinoless double beta decay could answer the question regarding the Majorana or Dirac nature of neutrinos. The GERDA experiment utilizes HPGe detectors enriched with the isotope 76Ge to search for this process. Recently the GERDA collaboration has unblinded data of Phase I of the experiment. In order to further improve the sensitivity of the experiment, additionally to the coaxial detectors used, 30 BEGe detectors made from germanium enriched in 76Ge will be deployed in GERDA Phase II. BEGe detectors have superior PSD capability, thus the background can be further reduced. The liquid argon surrounding the detector array will be instrumented in order to reject background by detecting scintillation light induced in the liquid argon by radiation. After a short introduction the hardware preparations for GERDA Phase II as well as the processing and characterization of the 30 BEGe detectors are discussed.

  1. 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.

  2. 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.).

  3. Effects of triclosan on the detoxification system in the yellow catfish (Pelteobagrus fulvidraco): expressions of CYP and GST genes and corresponding enzyme activity in phase I, II and antioxidant system.

    PubMed

    Ku, Peijia; Wu, Xiaoyan; Nie, Xiangping; Ou, Ruikang; Wang, Lan; Su, Tian; Li, Yigang

    2014-11-01

    Triclosan (TCS), a broad-spectrum antibacterial agent widely used in pharmaceuticals and personal case products (PPCPs), has been universally detected in aquatic ecosystem in recent years. Unfortunately, there is limited information about its potential impacts on responses of genes and enzymes related to fish detoxification. In the present work, we cloned CYP3A and alpha-GST of yellow catfish (Pelteobagrus fulvidraco) and tested the transcriptional expression of CYP1A, CYP3A and GST as well as the alterations of their corresponding enzymes, including ethoxyresorufin-O-deethylase (EROD), aminopyrine N-demethylase (APND), erythromycin N-demethylase (ERND), glutathione S-transferase (GST) and catalase (CAT), and also the oxidative product malondialdehyde (MDA) content in the liver of P. fulvidraco exposed to TCS. Amino acids of CYP3A and GST were deduced and phylogenetic tree was constructed respectively. High identity percent was exhibited between P. fulvidraco and other species, such as other fish, birds and mammals. Results indicated that TCS significantly elevated CYP1A and GST but decreased CYP3A expression, EROD activity and MDA content at lower concentrations of TCS at 24h. Moreover, CYP3A and GST were significantly inhibited at 72 h but induced at 168 h at lower concentrations. However, CYP3A was always induced at the highest concentration during the exposure period. Furthermore, CYP3A, GST, GST enzyme and MDA content exhibited a dose-effect relationship to some extent, but no significant responses were observed in ERND, APND and CAT except for individual treatments. Taken together, EROD was the most sensitive to TCS exposure as compared to other enzymes. Meanwhile, mRNA responses were more sensitive in yellow catfish. PMID:25064140

  4. Active impedance metasurface with full 360° reflection phase tuning

    PubMed Central

    Zhu, Bo O.; Zhao, Junming; Feng, Yijun

    2013-01-01

    Impedance metasurface is composed of electrical small scatters in two dimensional plane, of which the surface impedance can be designed to produce desired reflection phase. Tunable reflection phase can be achieved by incorporating active element into the scatters, but the tuning range of the reflection phase is limited. In this paper, an active impedance metasurface with full 360° reflection phase control is presented to remove the phase tuning deficiency in conventional approach. The unit cell of the metasurface is a multiple resonance structure with two resonance poles and one resonance zero, capable of providing 360° reflection phase variation and active tuning within a finite frequency band. Linear reflection phase tuning can also be obtained. Theoretical analysis and simulation are presented and validated by experiment at microwave frequency. The proposed approach can be applied to many cases where fine and full phase tuning is needed, such as beam steering in reflectarray antennas. PMID:24162366

  5. Active impedance metasurface with full 360° reflection phase tuning.

    PubMed

    Zhu, Bo O; Zhao, Junming; Feng, Yijun

    2013-01-01

    Impedance metasurface is composed of electrical small scatters in two dimensional plane, of which the surface impedance can be designed to produce desired reflection phase. Tunable reflection phase can be achieved by incorporating active element into the scatters, but the tuning range of the reflection phase is limited. In this paper, an active impedance metasurface with full 360° reflection phase control is presented to remove the phase tuning deficiency in conventional approach. The unit cell of the metasurface is a multiple resonance structure with two resonance poles and one resonance zero, capable of providing 360° reflection phase variation and active tuning within a finite frequency band. Linear reflection phase tuning can also be obtained. Theoretical analysis and simulation are presented and validated by experiment at microwave frequency. The proposed approach can be applied to many cases where fine and full phase tuning is needed, such as beam steering in reflectarray antennas. PMID:24162366

  6. Hexagonal and nematic phases of chains. I - Correlation functions. II - Phase transitions

    NASA Technical Reports Server (NTRS)

    Selinger, Jonathan V.; Bruinsma, Robijn F.

    1991-01-01

    The statistical mechanics of a system of semiflexible chains, which can represent polymer liquid crystals, long-chain biomolecules, stiff wormlike micelles, or columns of discotic liquid crystals, are examined. A continuum theory is used to calculate static correlation functions in the hexagonal and nematic phases. Two correlation functions are considered: (1) the structure factor which describes fluctuations in the density; and (2) the director fluctuation spectrum, which describes fluctuations in the local optical axis. In addition, a model is developed for the phase transitions of a system of infinitely long, semiflexible chains which interact through a steric, excluded-volume repulsion. The model yields generic phase diagrams in terms of pressure or density vs. persistence length or temperature.

  7. Evaluating the performance of copula models in phase I-II clinical trials under model misspecification

    PubMed Central

    2014-01-01

    Background Traditionally, phase I oncology trials are designed to determine the maximum tolerated dose (MTD), defined as the highest dose with an acceptable probability of dose limiting toxicities(DLT), of a new treatment via a dose escalation study. An alternate approach is to jointly model toxicity and efficacy and allow dose escalation to depend on a pre-specified efficacy/toxicity tradeoff in a phase I-II design. Several phase I-II trial designs have been discussed in the literature; while these model-based designs are attractive in their performance, they are potentially vulnerable to model misspecification. Methods Phase I-II designs often rely on copula models to specify the joint distribution of toxicity and efficacy, which include an additional correlation parameter that can be difficult to estimate. We compare and contrast three models for the joint probability of toxicity and efficacy, including two copula models that have been proposed for use in phase I-II clinical trials and a simple model that assumes the two outcomes are independent. We evaluate the performance of the various models through simulation both when the models are correct and under model misspecification. Results Both models exhibited similar performance, as measured by the probability of correctly identifying the optimal dose and the number of subjects treated at the optimal dose, regardless of whether the data were generated from the correct or incorrect copula, even when there is substantial correlation between the two outcomes. Similar results were observed for a simple model that assumes independence, even in the presence of strong correlation. Further simulation results indicate that estimating the correlation parameter in copula models is difficult with the sample sizes used in Phase I-II clinical trials. Conclusions Our simulation results indicate that the operating characteristics of phase I-II clinical trials are robust to misspecification of the copula model but that a simple

  8. 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.

  9. The chemopreventive effects of Saussurea salicifolia through induction of apoptosis and phase II detoxification enzyme.

    PubMed

    Kang, Kyungsu; Lee, Hee Ju; Kim, Chul Young; Lee, Saet Byoul; Tunsag, Jigjidsuren; Batsuren, Dulamjav; Nho, Chu Won

    2007-12-01

    The ethanol extract of the aerial part of the Mongolian medicinal plant Saussurea salicifolia induced a dose-dependent cell growth inhibition in both human gastric adenocarcinoma AGS cells and mouse hepatoma Hepa 1c1c7 cells (IC(50)=30.22 and 116.96 mug/ml), respectively. The extract induced an apoptosis in AGS cells inference from the externalization of the phosphatidylserine, the increase of the sub G0/G1 content (%) and the apoptotic morphological changes including membrane blebbing, the formation of apoptotic bodies and chromatin condensation. In order to identify active substances causing the apoptosis, we further isolated major compounds present in Saussurea salicifolia and 7 compounds were isolated including a sesquiterpene lactone, cynaropicrin, 3 lignans (trachelogenin, matairesinol and arctigenin) and 3 lignan glycosides (tracheloside, matairesinoside and arctiin). In general the lignan aglycones were more cytotoxic than their lignan glycosides in both AGS cells and Hepa 1c1c7 cells. Cynaropicrin not only showed the most potent cytotoxicity among the 7 major compounds but also it induced an apoptosis and a weak G2/M arrest in AGS cells. Arctigenin had the second-best cytotoxicity among 7 major compounds, and induced an apoptosis. In order to evaluate the induction of the phase II detoxification enzyme, we measured the induction of quinone reductase activity of the extract, fractions and compounds in Hepa 1c1c7 cells. The ethyl acetate fraction and arctigenin showed the strongest cancer chemopreventive activity (chemoprevention index=9.88 and 7.57, respectively). These data suggest that the extract as well as the lignan compounds (especially arctigenin) originated from Saussurea salicifolia may be served as potential cancer chemopreventive agents for prevention or treatment of human cancers. PMID:18057725

  10. Phase II Study of Temozolomide (TMZ) and Everolimus (RAD001) Therapy for Metastatic Melanoma

    PubMed Central

    Dronca, Roxana S.; Allred, Jacob B.; Perez, Domingo G.; Nevala, Wendy K.; Lieser, Elizabeth A.T.; Thompson, Michael; Maples, William J.; Creagan, Edward T.; Pockaj, Barbara A.; Kaur, Judith S.; Moore, Timothy D.; Marchello, Benjamin T.; Markovic, Svetomir N.

    2014-01-01

    Objective Mammalian target of rapamycin (mTOR) pathway is activated in malignant melanoma and in situ lesions as opposed to benign nevi. Inhibition of PI3K-Akt-mTOR signaling is implicated in sensitization of melanoma cells to alkylating agents [temozolomide (TMZ)] and inhibition of tumor angiogenesis. Methods We conducted a single-arm phase II multi-institution cooperative group study to assess the antitumor activity and safety profile of the combination of TMZ and the rapamycin derivative everolimus in patients with metastatic unresectable malignant melanoma. Patients received 10 mg/d of RAD001 for 5 of 7 days (ie, 50 mg/ wk) and 200 mg/m2/d of TMZ for 5 days each cycle. Results Of the first 39 eligible patients, 17 were PFS-9 successes, for a predetermined threshold of 18/39 patients for a positive trial. Overall, 21 of 48 patients were progression free at 9 weeks, for an event-free survival rate of 44% (95% confidence interval, 29%–59%). The median progression-free survival was 2.4 months and the median overall survival was 8.6 months. Four patients achieved a partial response; the median duration of response was 15.1 months. No complete remissions were observed. Treatment was in general well tolerated with only 1 patient discontinuing therapy due to toxicity (hyperlipidemia). Conclusions The combination of TMZ and RAD001 was well tolerated but failed to meet/exceed our study threshold for promising clinical activity in patients with metastatic melanoma. PMID:23357973

  11. Phase II Trial of Imatinib in AIDS-Associated Kaposi's Sarcoma: AIDS Malignancy Consortium Protocol 042

    PubMed Central

    Koon, Henry B.; Krown, Susan E.; Lee, Jeannette Y.; Honda, Kord; Rapisuwon, Suthee; Wang, Zhenghe; Aboulafia, David; Reid, Erin G.; Rudek, Michelle A.; Dezube, Bruce J.; Noy, Ariela

    2014-01-01

    Purpose Kaposi's sarcoma (KS) is a disease of multifocal vascular proliferation that requires infection with KS herpes virus (KSHV/HHV-8). Activation of the c-kit and platelet-derived growth factor (PDGF) receptors by autocrine/paracrine mechanisms follows endothelial cell KSHV infection. In a pilot study, imatinib, a c-kit/PDGF-receptor inhibitor, induced partial regression of AIDS-associated KS (AIDS-KS) in five of 10 patients. Patients and Methods This multicenter phase II study was designed to estimate the response rate to imatinib in AIDS-KS. Secondary objectives included investigation of predictors of response and imatinib pharmacokinetics in patients on antiretrovirals. Patients received imatinib 400 mg/day by mouth for up to 12 months with dose escalation up to 600 mg/day at 3 months if their disease was stable. Results Thirty patients were treated at 12 AIDS Malignancy Consortium sites. Ten patients (33.3%) achieved partial response, six (20%) had stable disease, and seven (23.3%) exhibited KS progression. Nine patients completed 52 weeks of imatinib therapy. The median treatment duration was 22.5 weeks. Only five patients (16.7%) discontinued therapy owing to adverse events. Antiretroviral regimens did not significantly alter imatinib metabolism. Activating mutations in PDGF-R and c-kit were not found at baseline or at disease progression. We found no correlation with response with changes in any of the candidate cytokines. Conclusion Imatinib has activity in AIDS-KS. Pharmacokinetic interactions with antiretroviral drugs did not correlate with toxicity. Thirty percent of patients showed long-term clinical benefit and remained on imatinib for the entire year. These results suggest imatinib is well tolerated and may be an alternative therapy for some patients with AIDS-KS. PMID:24378417

  12. 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…

  13. 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....

  14. Counselor Competencies for Regional Delivery Systems. Final Report--Phase II. July 1, 1986 to June 30, 1987.

    ERIC Educational Resources Information Center

    Hofstrand, Richard K.

    The narrative portion of this report summarizes the highlights of Phase II of a project to identify competencies needed by regional delivery system personnel in delivering career guidance. It identifies the six informational modules that were prepared during Phases I and II. Appendixes contain the six modules for guidance counselors/coordinators…

  15. Phase II trial of carboplatin plus oral etoposide for elderly patients with small-cell lung cancer.

    PubMed Central

    Matsui, K.; Masuda, N.; Fukuoka, M.; Yana, T.; Hirashima, T.; Komiya, T.; Kobayashi, M.; Kawahara, M.; Atagi, S.; Ogawara, M.; Negoro, S.; Kudoh, S.; Furuse, K.

    1998-01-01

    A phase II trial was conducted to evaluate the efficacy and toxicity of the Egorin's carboplatin dosing formula with 14-day oral etoposide in 38 elderly patients with small-cell lung cancer (SCLC). The overall response rate was 81%. Median survival times were 15.1 months for 16 limited-disease (LD) and 8.6 months for 22 extensive-disease (ED) patients. Myelosuppression was the principal side-effect. This regimen is an active regimen in the treatment of elderly SCLC patients. PMID:9667675

  16. 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

  17. Phase II trial of cyclophosphamide, leucovorin, 5-fluorouracil 24-hour infusion and tamoxifen in pancreatic cancer.

    PubMed

    Eckel, F; Lersch, C; Lippl, F; Assmann, G; Schulte-Frohlinde, E

    2000-09-01

    Leucovorin modulates the cytotoxic effects of 5-fluorouracil (5-FU) in the treatment of cancer. 24-hour infusion of 5-FU has been shown to enhance antitumor activity in colorectal cancer compared to bolus infusion. According to experimental data cyclophosphamide and tamoxifen may enhance the effectiveness of leucovorin and 5-FU. A phase II trial was initiated to evaluate the effect of a combination of low-dose cyclophosphamide (C), leucovorin (L), 5-FU (F) and tamoxifen (T) (CLFT) in advanced pancreatic cancer. Fifty patients were treated monthly with 300 mg/m2 cyclophosphamide and weekly with 500 mg/m2 leucovorin followed by a 24-hour infusion of 2000 mg/m2 5-FU and tamoxifen 20 mg bid. Three patients had a partial response (6%), two a minor response (4%) and 32 (64%) no change of disease. The median survival time was 8.5 months for all patients, the median time to progression of disease was 4.6 months and the 1-year survival rate was 28%. CLFT was fairly well tolerated. These data suggest that biochemical modulation of 24-hour infusional 5-FU with leucovorin together with cyclophosphamide and tamoxifen has some positive effects in the treatment of pancreatic cancer. PMID:11144522

  18. Phase II studies of recombinant human interferon gamma in metastatic renal cell carcinoma.

    PubMed

    Quesada, J R; Kurzrock, R; Sherwin, S A; Gutterman, J U

    1987-02-01

    Thirty-three patients with metastatic renal cell carcinoma were treated with recombinant human interferon gamma (rIFN gamma) in two sequential, nonrandomized phase II studies. Fifteen patients received rIFN gamma by daily i.m. injection in doses ranging from 0.25 to 1.0 mg/m2, and 18 patients received it by daily continuous i.v. infusion in doses ranging from 0.01 to 0.05 mg/m2. Partial remissions were achieved by one of 14 (7%) evaluable patients in the i.m. study and in one of 16 in the i.v. study (6%). The incidence of clinical toxicity was similar for both studies. Toxicity was severe in patients receiving rIFN gamma by the i.m. route at 1.0 mg/m2 and by the i.v. route at 0.05 mg/m2. Toxicity includes constitutional symptoms (fatigue, anorexia, weight loss), leukopenia, abnormalities in liver function tests, and hypertriglyceridemia. At the doses and schedules used, rIFN gamma had minimal therapeutic activity as a single agent in metastatic renal cell carcinoma. PMID:3104544

  19. Recombinant leukocyte A interferon in advanced breast cancer. Results of a phase II efficacy trial.

    PubMed

    Sherwin, S A; Mayer, D; Ochs, J J; Abrams, P G; Knost, J A; Foon, K A; Fein, S; Oldham, R K

    1983-05-01

    Nineteen patients with advanced refractory metastatic breast cancer no longer responsive to chemotherapy were treated in the first phase II efficacy trial of recombinant leukocyte A interferon (IFL-rA), a highly purified single molecular species of alpha interferon prepared by recombinant DNA methods. Patients received a previously determined maximum tolerated dose for this agent (50 X 10(6) U/m2 body surface area) by intramuscular injection three times weekly for up to 3 months. The symptoms of toxicity observed in this trial resemble those previously reported for alpha interferons and include fever, chills, fatigue, anorexia, and leukopenia. All patients required dose reductions, most often for reasons of severe fatigue. Of the 17 patients evaluable for tumor response, one patient had stable disease and 16 had evidence of tumor progression. We conclude that IFL-rA is not an active agent in the treatment of advanced, refractory breast cancer when used at a maximum tolerated dose on this treatment schedule. PMID:6342490

  20. 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

  1. Dinitrogen activation upon reduction of a triiron(II) complex.

    PubMed

    Lee, Yousoon; Sloane, Forrest T; Blondin, Geneviève; Abboud, Khalil A; García-Serres, Ricardo; Murray, Leslie J

    2015-01-26

    Reaction of a trinuclear iron(II) complex, Fe3 Br3 L (1), with KC8 under N2 leads to dinitrogen activation products (2) from which Fe3 (NH)3 L (2-1; L is a cyclophane bridged by three β-diketiminate arms) was characterized by X-ray crystallography. (1) H NMR spectra of the protonolysis product of 2 synthesized under (14) N2 and (15) N2 confirm atmospheric N2 reduction, and ammonia is detected by the indophenol assay (yield ∼30 %). IR and Mössbauer spectroscopy, and elemental analysis on 2 and 2-1 as well as the tri(amido)triiron(II) 3 and tri(methoxo)triiron 4 congeners support our assignment of the reduction product as containing protonated N-atom bridges. PMID:25504859

  2. 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

  3. 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

  4. Phase II dose-finding study of balugrastim in breast cancer patients receiving myelosuppressive chemotherapy.

    PubMed

    Gladkov, Oleg; Moiseyenko, Vladimir; Bondarenko, Igor N; Shparyk, Yaroslav; Barash, Steven; Adar, Liat; Bias, Peter; Avisar, Noa

    2015-06-01

    Balugrastim is a once-per-cycle, fixed-dose recombinant protein comprising human serum albumin and granulocyte colony-stimulating factor under development for prevention of severe neutropenia in cancer patients receiving myelosuppressive chemotherapy. This phase II, multicenter, active-controlled, dose-finding pilot study evaluated balugrastim safety and efficacy versus pegfilgrastim in breast cancer patients scheduled to receive myelosuppressive chemotherapy and investigated two doses with similar efficacy to pegfilgrastim for a subsequent phase III study. Patients received four cycles of doxorubicin/docetaxel chemotherapy and with each successive cycle were randomized sequentially to escalating doses of balugrastim [30 (n = 11), 40 (n = 21), or 50 mg (n = 20)] or a fixed dose of pegfilgrastim [6 mg (n = 26)] post-chemotherapy. Balugrastim doses were escalated as planned. The incidence of adverse events was similar among the balugrastim groups and between all balugrastim doses and pegfilgrastim. The most frequently reported adverse events were neutropenia, alopecia, and nausea. During cycle 1, severe neutropenia (absolute neutrophil count of <0.5 × 10(9)/L) occurred in 40, 67, and 50 % and febrile neutropenia occurred in 20.0, 9.5, and 10.0 % of patients receiving balugrastim 30, 40, and 50 mg, respectively; in patients receiving pegfilgrastim, 48 % experienced severe neutropenia and 8 % experienced febrile neutropenia. Duration of severe neutropenia (DSN) for each treatment group was 0.9, 1.6, 1.1, and 0.9 days, respectively. In the remaining three chemotherapy cycles, DSN was ≤1 day across all treatment groups. Balugrastim 50 mg was comparable to pegfilgrastim in terms of safety and overall efficacy in breast cancer patients receiving myelosuppressive chemotherapy. PMID:25966791

  5. The active RS Canum Venaticorum binary II Pegasi. IV. The SPOT activity cycle

    NASA Astrophysics Data System (ADS)

    Berdyugina, S. V.; Berdyugin, A. V.; Ilyin, I.; Tuominen, I.

    1999-10-01

    A total of 6 new surface images of II Peg obtained for the years 1997 and 1998 confirms the recently revealed permanent active longitude structure. The lower limit of the active longitudes' lifetime is now extended up to 25 years. A new ``flip-flop'' phenomenon, redefined as a switch of the activity between the active longitudes, has started in summer of 1998. It coincides reasonably well with the moment predicted from the activity cycle of the star. This confirms definitely the cyclic behaviour of the activity of II Peg we recently discovered. Therefore, we assign numbers to the cycles of 4.65 yr since the earliest photoelectric observations of II Peg and define the active longitudes as ``odd'' and ``even'' corresponding to odd and even numbers of cycles. With such a definition, in late 1998 the 7th cycle began and the ``odd'' active longitude became more active. From the analysis of the spot area evolution within the active longitudes we conclude that the activity cycle is developed as a rearrangement of the nearly constant amount of the spot area between the active longitudes. We discuss the ``flip-flop'' phenomenon as a tracer of stellar activity and the role of the unseen secondary in establishing the cycle. Based on observations collected at the Nordic Optical Telescope (NOT), La Palma, Spain; the 1.25m telescope of the Crimean Astrophysical Observatory, Ukraine; the Phoenix 10 robotic telescope, APT Observatory, Arizona, USA.}

  6. Frequency translating phase conjugation circuit for active retrodirective antenna array

    NASA Astrophysics Data System (ADS)

    Chernoff, R.

    1980-11-01

    An active retrodirective antenna array which has central phasing from a reference antenna element through a "tree" structured network of transmission lines utilizes a number of phase conjugate circuits (PCCs) at each node and a phase reference regeneration circuit (PRR) at each node except the initial node. Each node virtually coincides with an element of the array. A PCC generates the exact conjugate phase of an incident signal using a phase locked loop which combines the phases in an up converter, divides the sum by 2 and mixes the result with the phase in a down converter for phase detection. The PRR extracts the phase from the conjugate phase. Both the PCC and the PRR are not only exact but also free from mixer degeneracy.

  7. Co(II), Mn(II), and Cr(III) iminodiacetate complexes heterogenized on silica gel in the liquid-phase oxidation of cyclohexene

    SciTech Connect

    Berentsveig, V.V.; Barinova, T.V.; Lisichkin, G.V.; Nga, C.B.

    1985-06-01

    A study was carried out on the catalytic properties of Co(II), Mn(II), and Cr(III) iminodiacetate complexes heterogenized on silica gel. The liquid-phase oxidation of cyclohexene in the presence of these catalysts proceeds mainly by a heterogeneous-homogeneous radical chain methanism. Variation in the selectivity of this liquid-phase reaction is possible by changing the nature of the transition metal ion.

  8. Altered Erythrocyte Glycolytic Enzyme Activities in Type-II Diabetes.

    PubMed

    Mali, Aniket V; Bhise, Sunita S; Hegde, Mahabaleshwar V; Katyare, Surendra S

    2016-07-01

    The activity of enzymes of glycolysis has been studied in erythrocytes from type-II diabetic patients in comparison with control. RBC lysate was the source of enzymes. In the diabetics the hexokinase (HK) activity increased 50 % while activities of phosphoglucoisomerase (PGI), phosphofructokinase (PFK) and aldolase (ALD) decreased by 37, 75 and 64 % respectively but were still several folds higher than that of HK. Hence, it is possible that in the diabetic erythrocytes the process of glycolysis could proceed in an unimpaired or in fact may be augmented due to increased levels of G6P. The lactate dehydrogenase (LDH) activity was comparatively high in both the groups; the diabetic group showed 85 % increase. In control group the HK, PFK and ALD activities showed strong positive correlation with blood sugar level while PGI activity did not show any correlation. In the diabetic group only PFK activity showed positive correlation. The LDH activity only in the control group showed positive correlation with marginal increase with increasing concentrations of glucose. PMID:27382204

  9. A varying-stage adaptive phase II/III clinical trial design.

    PubMed

    Dong, Gaohong

    2014-04-15

    Currently, adaptive phase II/III clinical trials are typically carried out with a strict two-stage design. The first stage is a learning stage called phase II, and the second stage is a confirmatory stage called phase III. Following phase II analysis, inefficacious or harmful dose arms are dropped, then one or two promising dose arms are selected for the second stage. However, there are often situations in which researchers are in dilemma to make 'go or no-go' decision and/or to select 'best' dose arm(s), as data from the first stage may not provide sufficient information for their decision making. In this case, it is challenging to follow a strict two-stage plan. Therefore, we propose a varying-stage adaptive phase II/III clinical trial design, in which we consider whether there is a need to have an intermediate stage to obtain more data, so that a more informative decision could be made. Hence, the number of further investigational stages in our design is determined on the basis of data accumulated to the interim analysis. With respect to adaptations, we consider dropping dose arm(s), switching another plausible endpoint as the primary study endpoint, re-estimating sample size, and early stopping for futility. We use an adaptive combination test to perform final analyses. By applying closed testing procedure, we control family-wise type I error rate at the nominal level of α in the strong sense. We delineate other essential design considerations including the threshold parameters and the proportion of alpha allocated in the two-stage versus three-stage setting. PMID:24273128

  10. Novel therapies for resistant focal segmental glomerulosclerosis (FONT) phase II clinical trial: study design

    PubMed Central

    2011-01-01

    Background The lack of adequate randomized clinical trials (RCT) has hindered identification of new therapies that are safe and effective for patients with primary focal segmental glomerulosclerosis (FSGS), especially in patients who fail to respond to corticosteroids and immunosuppressive therapies. Recent basic science advances have led to development of alternative treatments that specifically target aberrant pathways of fibrosis which are relevant to disease progression in FSGS. There is a need for a flexible Phase II study design which will test such novel antifibrotic strategies in order to identify agents suitable for phase III testing. Methods/Design The Novel Therapies for Resistant Focal Segmental Glomerulosclerosis (FONT) project is a multicenter Phase I/II RCT designed to investigate the potential efficacy of novel therapies for resistant FSGS. Adalimumab and galactose will be evaluated against conservative therapy consisting of the combination of lisinopril, losartan and atorvastatin. The sample size is defined to assure that if one of the treatments has a superior response rate compared to that of the other treatments, it will be selected with high probability for further evaluation. Comparison of primary and secondary endpoints in each study arm will enable a choice to be made of which treatments are worthy of further study in future Phase III RCT. Discussion This report highlights the key features of the FONT II RCT including the two-step outcome analysis that will expedite achievement of the study objectives. The proposed phase II study design will help to identify promising agents for further testing while excluding ineffective agents. This staged approach can help to prevent large expenditures on unworthy therapeutic agents in the management of serious but rare kidney diseases Trial Registration ClinicalTrials.gov, NCT00814255 PMID:21310077

  11. 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.

  12. Ulysses observations of wave activity at interplanetary shocks and implications for type II radio bursts

    SciTech Connect

    Lengyel-Frey, D. |; Thejappa, G.; MacDowall, R.J.; Stone, R.G.; Phillips, J.L. |

    1997-02-01

    We present the first quantitative investigation of interplanetary type II radio emission in which in situ waves measured at interplanetary shocks are used to compute radio wave intensities for comparison with type II observations. This study is based on in situ measurements of 42 in-ecliptic forward shocks as well as 10 intervals of type II emission observed by the Ulysses spacecraft between 1 AU and 5 AU. The analysis involves comparisons of statistical properties of type II bursts and in situ waves. Most of the 42 shocks are associated with the occurrence of electrostatic waves near the time of shock passage at Ulysses. These waves, which are identified as electron plasma waves and ion acoustic-like waves, are typically most intense several minutes before shock passage. This suggests that wave-wave interactions might be of importance in electromagnetic wave generation and that type II source regions are located immediately upstream of the shocks. We use the in situ wave measurements to compute type II brightness temperatures, assuming that emission at the fundamental of the electron plasma frequency is generated by the merging of electron plasma waves and ion acoustic waves or the decay of electron plasma waves into ion acoustic and transverse waves. Second harmonic emission is assumed to be produced by the merging of electron plasma waves. The latter mechanism requires that a portion of the electron plasma wave distribution is backscattered, presumably by density inhomogeneities in regions of observed ion acoustic wave activity. The computed type II brightness temperatures are found to be consistent with observed values for both fundamental and second harmonic emission, assuming that strong ({approx_equal}10{sup {minus}4}V/m) electron plasma waves and ion acoustic waves are coincident and that the electron plasma waves have phase velocities less than about 10 times the electron thermal velocity. (Abstract Truncated)

  13. RNA-Sequencing Quantification of Hepatic Ontogeny and Tissue Distribution of mRNAs of Phase II Enzymes in Mice

    PubMed Central

    Gunewardena, Sumedha; Cui, Julia Y.; Yoo, Byunggil; Zhong, Xiao-bo; Klaassen, Curtis D.

    2013-01-01

    Phase II conjugating enzymes play key roles in the metabolism of xenobiotics. In the present study, RNA sequencing was used to elucidate hepatic ontogeny and tissue distribution of mRNA expression of all major known Phase II enzymes, including enzymes involved in glucuronidation, sulfation, glutathione conjugation, acetylation, methylation, and amino acid conjugation, as well as enzymes for the synthesis of Phase II cosubstrates, in male C57BL/6J mice. Livers from male C57BL/6J mice were collected at 12 ages from prenatal to adulthood. Many of these Phase II enzymes were expressed at much higher levels in adult livers than in perinatal livers, such as Ugt1a6b, -2a3, -2b1, -2b5, -2b36, -3a1, and -3a2; Gsta1, -m1, -p1, -p2, and -z1; mGst1; Nat8; Comt; Nnmt; Baat; Ugdh; and Gclc. In contrast, hepatic mRNA expression of a few Phase II enzymes decreased during postnatal liver development, such as mGst2, mGst3, Gclm, and Mat2a. Hepatic expression of certain Phase II enzymes peaked during the adolescent stage, such as Ugt1a1, Sult1a1, Sult1c2, Sult1d1, Sult2as, Sult5a1, Tpmt, Glyat, Ugp2, and Mat1a. In adult mice, the total transcripts for Phase II enzymes were comparable in liver, kidney, and small intestine; however, individual Phase II enzymes displayed marked tissue specificity among the three organs. In conclusion, this study unveils for the first time developmental changes in mRNA abundance of all major known Phase II enzymes in mouse liver, as well as their tissue-specific expression in key drug-metabolizing organs. The age- and tissue-specific expression of Phase II enzymes indicate that the detoxification of xenobiotics is highly regulated by age and cell type. PMID:23382457

  14. Evaluation of medicinal value of Epimedium elatum on the basis of pharmacologically active constituents, Icariin and Icariside-II.

    PubMed

    Arief, Zargar Mohmad; Munshi, Abid Hussain; Shawl, Abdul Sami

    2015-09-01

    Epimedium L. is well known medicinal genus of Chinese pharmacopoeia. Various species are ethno-botanically used against diseases of eye and kidney, impotence, asthma, arthritis and hypertension; besides being used as analeptic, expectorant, antibacterial, hypoglycemic, vasodilator and refrigerant. Recent studies have attributed most of these medicinal properties to its flavonoid glycosides, especially Icariin which is the major pharmacologically active constituent. Icariin has been found to possess effective aphrodisiac, antioxidant, immunomodulatory, hepatoprotective, cardioprotective, vasodilatory, antidepressant and anti-osteoporosis activities. Icariside-II, another active constituent, has cytotoxic and cytostatic effects on 6 cancer cell-lines, and immunosuppressive effects on allograft rejection. In this present study, Epimedium elatum Morr. and Decne., the only species of this genus growing in Indian subcontinent, has been investigated for its medicinal value by determining the content of pharmacologically active constituents, Icariin and Icariside-II, by HPLC method. HPLC analysis of alcohol extract of its shade dried parts was performed with reverse phase C-18 column. The mobile phase for Icariin was acetonitrile-water in gradient mode; while for Icariside-II, it was methanol-water. The effluent was monitored at 270 nm. The results have revealed an appreciable content of Icariin and Icariside-II in its aerial and underground parts; the content being higher in populations growing at higher altitudes. The substantial presence of pharmacologically active constituents, Icariin and Icariside-II, in this species of Epimedium, signifies its value as a medicinal plant. PMID:26408886

  15. Casein kinase II stimulates rat liver mitochondrial glycerophosphate acyltransferase activity.

    PubMed

    Onorato, Thomas M; Haldar, Dipak

    2002-09-01

    Rat liver mitochondrial glycerophosphate acyltransferase (mtGAT) possesses 14 consensus sites for casein kinase II (CKII) phosphorylation. To study the functional relevance of phosphorylation to the activity of mtGAT, we treated isolated rat liver mitochondria with CKII and found that CKII stimulated mtGAT activity approximately 2-fold. Protein phosphatase-lambda treatment reversed the stimulation of mtGAT by CKII. Labeling of both solubilized and non-solubilized mitochondria with CKII and [gamma-32P]ATP resulted in a 32P-labeled protein of 85kDa, the molecular weight of mtGAT. Our findings suggest that CKII stimulates mtGAT activity by phosphorylation of the acyltransferase. The significance of this observation with respect to hormonal control of the enzyme is discussed. PMID:12207885

  16. A phase II trial of RCHOP followed by radioimmunotherapy for early stage (stages I/II) diffuse large B-cell non-Hodgkin lymphoma: ECOG3402.

    PubMed

    Witzig, Thomas E; Hong, Fangxin; Micallef, Ivana N; Gascoyne, Randy D; Dogan, Ahmet; Wagner, Henry; Kahl, Brad S; Advani, Ranjana H; Horning, Sandra J

    2015-09-01

    Patients with early stage diffuse large B-cell lymphoma (DLBCL) receive RCHOP (rituximab cyclophosphamide, doxorubicin, vincristine, prednisone) alone or with involved field radiotherapy (IFRT). Anti-CD20 radioimmunotherapy (RIT) delivers radiation to microscopic sites outside of known disease. This phase II study aimed to achieve a functional complete response (CR) rate of ≥75% to RCHOP and (90) Yttrium-ibritumomab tiuxetan RIT. Patients with stages I/II DLBCL received 4-6 cycles of RCHOP followed by RIT [14·8 MBq/kg (0·4 mCi/kg)]; patients with positron emission tomographypositive sites of disease after RCHOP/RIT received 30 Gy IFRT. Of the 62 patients enrolled; 53 were eligible. 42% (22/53) had stage I/IE; 58% (31/53) stage II/IIE. After RCHOP, 79% (42/53) were in CR/unconfirmed CR. Forty-eight patients proceeded to RIT. One partial responder after RIT received IFRT and achieved a CR. The best response after RCHOP + RIT in all 53 patients was a functional CR rate of 89% (47/53; 95% confidence interval: 77-96%). With a median follow-up of 5·9 years, 7 (13%) patients have progressed and 4 (8%) have died (2 with DLBCL). At 5 years, 78% of patients remain in remission and 94% are alive. Chemoimmunotherapy and RIT is an active regimen for early stage DLBCL patients. Eighty-nine percent of patients achieved functional CR without the requirement of IFRT. This regimen is worthy of further study for early stage DLBCL in a phase III trial. PMID:25974212

  17. The photospheric filling factor of the active binary II Pegasi

    NASA Astrophysics Data System (ADS)

    Marino, G.; Rodonó, M.; Leto, G.; Cutispoto, G.

    1999-12-01

    UBV and JHK photometry of the active single-lined binary II Peg, we performed in 1995, is presented. A method to determine the fraction of the photosphere covered by spots (filling factor) and to check the accuracy of generally assumed values of photospheric parameters has been developed. The procedure is based on the comparison between multiband fluxes and low resolution synthetic spectra weighted on the base of the spot filling factor and scaled with the ratio between the star radius and distance (R/d), so that we can also estimate the R/d ratio. A chi 2 fit has been performed for II Peg observations close to the light maximum and minimum by assuming reliable values of the photospheric parameters. Although a unique solution cannot be reached, we found clear indication for a spot filling factor at light maximum >= 40%. We find that the same set of parameters that gives us the best fit solutions at light maximum also provides the best fit at light minimum. The resulting solutions are consistent with the observed amplitude of the photometric wave, and with the commonly accepted value of R, unspotted V magnitude and spectral classification for II Pegasi.

  18. Synthesis and evaluation of phase detectors for active bit synchronizers

    NASA Technical Reports Server (NTRS)

    Mcbride, A. L.

    1974-01-01

    Self-synchronizing digital data communication systems usually use active or phase-locked loop (PLL) bit synchronizers. The three main elements of PLL synchronizers are the phase detector, loop filter, and the voltage controlled oscillator. Of these three elements, phase detector synthesis is the main source of difficulty, particularly when the received signals are demodulated square-wave signals. A phase detector synthesis technique is reviewed that provides a physically realizable design for bit synchronizer phase detectors. The development is based upon nonlinear recursive estimation methods. The phase detector portion of the algorithm is isolated and analyzed.

  19. 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.

  20. Phase II trial of irinotecan and metronomic temozolomide in patients with recurrent glioblastoma.

    PubMed

    Reynés, Gaspar; Martínez-Sales, Vicenta; Vila, Virtudes; Balañá, Carmen; Pérez-Segura, Pedro; Vaz, María A; Benavides, Manuel; Gallego, Oscar; Palomero, Isabel; Gil-Gil, Miguel; Fleitas, Tania; Reche, Encarnación

    2016-02-01

    This phase II study was conducted to determine the efficacy and safety of metronomic temozolomide (TMZ) in combination with irinotecan in glioblastoma (GB) at first relapse. Patients with GB at first relapse received TMZ 50 mg/m/2day divided into three doses, except for a single 100 mg/m2 dose, administered between 3 and 6 h before every irinotecan infusion. Irinotecan was given intravenously at the previously established dose of 100 mg/m2 on days 8 and 22 of 28-day cycles. Treatment was given for a maximum of nine cycles or until progression or unacceptable toxicity occurred. Vascular endothelial growth factor and its soluble receptor 1, thrombospondin-1, microparticles, and microparticle-dependent procoagulant activity were measured in blood before treatment. The primary objective was 6-month progression-free survival (PFS). Twenty-seven evaluable patients were enrolled. Six-month PFS was 20.8%. Median PFS was 11.6 weeks (95% confidence interval: 7.5-15.7). Stable disease was the best response for nine (37.5%) patients, with a median duration of 11.2 weeks (4.2-35.85 weeks). No differences in PFS or response were observed among patients who relapsed during or after completion of adjuvant TMZ. Grade 3/4 adverse events included lymphopenia (15%), fatigue, diarrhea and febrile neutropenia (3.7% each), lymphopenia, neutropenia, and nausea/vomiting (11.1% each). One patient died from pneumonia and one patient died from pulmonary thromboembolism. Pretreatment levels of angiogenesis biomarkers, microparticles, and microparticle-related procoagulant activity were elevated in patients compared with healthy volunteers. This regimen is feasible, but failed to improve the results obtained with other second-line therapies in recurrent GB. PMID:26574999

  1. Revised Phase II Plan for the National Education Practice File Development Project Including: Creation; Pilot Testing; and Evaluation of a Test Practice File. Product 1.7/1.8 (Product 1.6 Appended).

    ERIC Educational Resources Information Center

    Benson, Gregory, Jr.; And Others

    A detailed work plan is presented for the conduct of Phase II activities, which are concerned with creating a pilot test file, conducting a test of it, evaluating the process and input of the file, and preparing the file management plan. Due to the outcomes of activities in Phase I, this plan was revised from an earlier outline. Included in the…

  2. 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)

  3. 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

  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. 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.

  6. 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

  7. 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., Jr.

    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.

  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. Functionalized mesoporous silica supported copper(II) and nickel(II) catalysts for liquid phase oxidation of olefins.

    PubMed

    Nandi, Mahasweta; Roy, Partha; Uyama, Hiroshi; Bhaumik, Asim

    2011-12-14

    Highly ordered 2D-hexagonal mesoporous silica has been functionalized with 3-aminopropyltriethoxysilane (3-APTES). This is followed by its condensation with a dialdehyde, 4-methyl-2,6-diformylphenol to produce an immobilized Schiff-base ligand (I). This material is separately treated with methanolic solution of copper(II) chloride and nickel(II) chloride to obtain copper and nickel anchored mesoporous materials, designated as Cu-AMM and Ni-AMM, respectively. The materials have been characterized by Fourier transform infrared (FT-IR) and UV-vis diffuse reflectance (DRS) spectroscopy, powder X-ray diffraction (XRD), transmission electron microscopy (TEM), N(2) adsorption-desorption studies and (13)C CP MAS NMR spectroscopy. The metal-grafted mesoporous materials have been used as catalysts for the efficient and selective epoxidation of alkenes, viz. cyclohexene, trans-stilbene, styrene, α-methyl styrene, cyclooctene and norbornene to their corresponding epoxides in the presence of tert-butyl hydroperoxide (TBHP) as the oxidant under mild liquid phase conditions. PMID:21989952

  10. A liquid/gas phase separator for He-I and He-II

    NASA Technical Reports Server (NTRS)

    Shirron, P. J.; Zahniser, J. L.; Dipirro, M. J.

    1991-01-01

    A liquid/gas phase separator has been developed which separates both liquid He-I and He-II from their vapor. The phase separator was designed for the Superfluid Helium On Orbit Transfer (SHOOT) Flight Demonstration both to cool the liquid He after launch (at temperatures between 2.8 and 4.3 K) to the operating temperature of 1.4 K and as a low rate vent on orbit to maintain operating temperature. The phase separator is made of high-purity copper disks held apart by 6 micron Kevlar fibers. It works on the principle of conducting heat from within the dewar to vaporize liquid as it is throttled in the slits to efficiently cool the remaining liquid. Laboratory tests have demonstrated perfect phase separation for both He at its saturated vapor pressure from 1.2 to 4.3 K and for He-II at 2.13 K at pressures from 4.6 to 112 kPa. The performance of this phase separator during lab testing as well as expected performance in space is discussed.

  11. Soft recovery of polytetrafluoroethylene shocked through the crystalline phase II-III transition

    NASA Astrophysics Data System (ADS)

    Brown, E. N.; Trujillo, C. P.; Gray, G. T.; Rae, P. J.; Bourne, N. K.

    2007-01-01

    Polymers are increasingly being utilized as monolithic materials and composite matrices for structural applications historically reserved for metals. High strain-rate applications in aerospace, defense, and the automotive industries have lead to interest in the shock response of polytetrafluoroethylene (PTFE) and the ensuing changes in polymer structure due to shock prestraining. We present an experimental study of crystalline structure evolution due to pressure-induced phase transitions in a semicrystalline polymer using soft-recovery, shock loading techniques coupled with mechanical and chemical postshock analyses. Gas-launched, plate impact experiments have been performed on pedigreed PTFE 7C, mounted in momentum trapped, shock assemblies, with impact pressures above and below the phase II to phase III crystalline transition. Below the phase transition only subtle changes were observed in the crystallinity, microstructure, and mechanical response of PTFE. Shock loading of PTFE 7C above the phase II-III transition was seen to cause both an increase in crystallinity from 38% to ˜53% (by differential scanning calorimetry) and a finer crystalline microstructure, and changed the yield and flow stress behavior.

  12. Final Report: Phase II Geothermal Exploration and Geothermal Power Plant Update for Ascension Island, South Atlantic Ocean

    SciTech Connect

    Nielson, D.L.; Sibbett, B.S.; Shane, M.K.; Whitbeck, J.F.

    1984-07-01

    The Phase I study of the geothermal potential of Ascension Island concluded that the possibility of a geothermal resource existing under the island was excellent. This conclusion was based on the presence of young volcanic rocks (a heat source close to the surface), an ample supply of water from the sea, and high permeability of many of the rocks which make up the island. The assumption was made that the resource would be similar to geothermal systems in the Azores or Japan, and a conceptual design of a power plant to utilize the resource was prepared upon which cost estimates and an economic analysis were subsequently performed. The results of the economic analysis were very favorable, and the Air Force decided to proceed into Phase II of the project. Under Phase II, an exploration program was designed and carried out. The purpose of the program was to ascertain whether or not a geothermal resource existed beneath Ascension island and, to the extent possible, to evaluate the quality of that resource. The exploration involved a detailed aeromagnetic survey of the island, reconnaissance and detailed electrical resistivity surveys, and drilling of holes for the measurement of temperatures. These methods have confirmed the existence of geothermal activity beneath Ascension. Measured temperature gradients and bottom hole temperatures as well as chemical geothermometers indicate temperatures sufficient for the generation of electricity within reasonable drilling depths. This report documents those conclusions and the supporting data. This report also documents the results of the power plant update with new data supplied from the Phase II exploration activities on the island. The power plant scenario has been changed to reflect the fact that the resource temperature may not be as high as that originally assumed in the Phase I study, the location of the production wells will in all likelihood be farther from the existing Air Force facilities--either north of Grazing

  13. Sintered plug flow modulation of a vapor-liquid phase separator for a helium II vessel

    NASA Technical Reports Server (NTRS)

    Frederking, T. H. K.; Chuang, C.; Kamioka, Y.; Lee, J. M.; Yuan, S. W. K.

    1984-01-01

    Presented is a system for modulation of a superfluid (helium II) flow in a vapor-liquid phase separator, for use in cryogenic storage tanks in future space missions. The system consists of a semicircular mechanically operated shutter, downstream of the separator plug, rotated at 0.1 rpm to control the operational surface area of the separator. The mass flow rate was varied from 10 to 22 mg/s. Pressure gradients across the plug are also discussed.

  14. Phase II NOx controls for the Marama and Nescaum regions. Final report

    SciTech Connect

    1995-11-01

    This technical report discusses Phase II NOx controls for utility boilers in the Mid-Atlantic Regional Air Management Association (MARAMA) and the Northeast States for Coordinated Air Use Management (NESCAUM) regions. The subject areas include: Utility boiler population profile in the MARAMA and NESCAUM regions; Discussion of RACT controls; Available NOx controls and their levels of performance; and Costs and cost effectiveness of NOx controls.

  15. 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.

  16. In Vivo Profiling and Distribution of Known and Novel Phase I and Phase II Metabolites of Efavirenz in Plasma, Urine, and Cerebrospinal Fluid.

    PubMed

    Aouri, Manel; Barcelo, Catalina; Ternon, Béatrice; Cavassini, Matthias; Anagnostopoulos, Alexia; Yerly, Sabine; Hugues, Henry; Vernazza, Pietro; Günthard, Huldrych F; Buclin, Thierry; Telenti, Amalio; Rotger, Margalida; Decosterd, Laurent A

    2016-01-01

    Efavirenz (EFV) is principally metabolized by CYP2B6 to 8-hydroxy-efavirenz (8OH-EFV) and to a lesser extent by CYP2A6 to 7-hydroxy-efavirenz (7OH-EFV). So far, most metabolite profile analyses have been restricted to 8OH-EFV, 7OH-EFV, and EFV-N-glucuronide, even though these metabolites represent a minor percentage of EFV metabolites present in vivo. We have performed a quantitative phase I and II metabolite profile analysis by tandem mass spectrometry of plasma, cerebrospinal fluid (CSF), and urine samples in 71 human immunodeficiency virus patients taking efavirenz, prior to and after enzymatic (glucuronidase and sulfatase) hydrolysis. We have shown that phase II metabolites constitute the major part of the known circulating efavirenz species in humans. The 8OH-EFV-glucuronide (gln) and 8OH-EFV-sulfate (identified for the first time) in humans were found to be 64- and 7-fold higher than the parent 8OH-EFV, respectively. In individuals (n = 67) genotyped for CYP2B6, 2A6, and CYP3A metabolic pathways, 8OH-EFV/EFV ratios in plasma were an index of CYP2B6 phenotypic activity (P < 0.0001), which was also reflected by phase II metabolites 8OH-EFV-glucuronide/EFV and 8OH-EFV-sulfate/EFV ratios. Neither EFV nor 8OH-EFV, nor any other considered metabolites in plasma were associated with an increased risk of central nervous system (CNS) toxicity. In CSF, 8OH-EFV levels were not influenced by CYP2B6 genotypes and did not predict CNS toxicity. The phase II metabolites 8OH-EFV-gln, 8OH-EFV-sulfate, and 7OH-EFV-gln were present in CSF at 2- to 9-fold higher concentrations than 8OH-EFV. The potential contribution of known and previously unreported EFV metabolites in CSF to the neuropsychological effects of efavirenz needs to be further examined in larger cohort studies. PMID:26553012

  17. Normal protein content but abnormally inhibited enzyme activity in muscle carnitine palmitoyltransferase II deficiency.

    PubMed

    Lehmann, Diana; Zierz, Stephan

    2014-04-15

    The biochemical consequences of the disease causing mutations of muscle carnitine palmitoyltransferase II (CPT II) deficiency are still enigmatic. Therefore, CPT II was characterized in muscle biopsies of nine patients with genetically proven muscle CPT II deficiency. Total CPT activity (CPT I+CPT II) of patients was not significantly different from that of controls. Remaining activities upon inhibition by malonyl-CoA and Triton X-100 were significantly reduced in patients. Immunohistochemically CPT II protein was predominantly expressed in type-I-fibers with the same intensity in patients as in controls. Western blot showed the same CPT II staining intensity ratio in patients and controls. CPT I and CPT II protein concentrations estimated by ELISA were not significantly different in patients and in controls. Citrate synthase activity in patients was significantly increased. Total CPT activity significantly correlated with both CPT I and CPT II protein concentrations in patients and controls. This implies (i) that normal total CPT activity in patients with muscle CPT II deficiency is not due to compensatory increase of CPT I activity and that (ii) the mutant CPT II is enzymatically active. The data further support the notion that in muscle CPT II deficiency enzyme activity and protein content are not reduced, but rather abnormally inhibited when fatty acid metabolism is stressed. PMID:24602495

  18. The antimicrobial and antibiofilm activities of copper(II) complexes.

    PubMed

    Beeton, Michael L; Aldrich-Wright, Janice R; Bolhuis, Albert

    2014-11-01

    Biofilm-related bacterial infections pose a significant problem, as they are generally more tolerant to antibiotics and the immune system. Development of novel compounds with antibiofilm activity is therefore paramount. In this study we have analysed metal complexes of the general structure [M(IL)(AL)](2+) (where IL represents functionalised 1,10-phenanthrolines and AL represents 1S,2S- or 1R,2R-diaminocyclohexane) and [Cu(IL)3](2+). Antimicrobial activity was tested on a number of bacterial strains, showing that copper(II) compounds were active against both Gram-positive and Gram-negative bacteria, albeit that activity was generally higher for the former. The antibiofilm activity was then determined against a clinical isolate of meticillin-resistant Staphylococcus aureus (MRSA). Strikingly, the copper complexes tested showed significant activity against biofilms, and were better in the removal of biofilms than vancomycin, an antibiotic that is currently used in the treatment of MRSA infections. PMID:25124857

  19. Historical controls for phase II surgically based trials requiring gross total resection of glioblastoma multiforme.

    PubMed

    Butowski, Nicholas; Lamborn, Kathleen R; Berger, Mitchel S; Prados, Michael D; Chang, Susan M

    2007-10-01

    New treatments for patients with glioblastoma multiforme (GBM) are frequently tested in phase II surgically based clinical trials that require gross total resection (GTR). In order to determine efficacy in such single-arm phase II clinical trials, the results are often compared to those from a historical control group that is not limited to patients with GTR. Recursive partitioning analysis (RPA) can define risk groups within historical control groups; however, RPA analyses to date included patients irrespective of whether a patient had a GTR or not. To provide a more appropriate historical control group for surgically based trials requiring a GTR, we sought to determine survival for a group of patients with newly diagnosed GBM, all of who underwent GTR and were treated on prospective clinical trials. GTR was defined as removal of >90% of the enhancing mass, determined by postoperative magnetic resonance imaging. Of 893 patients with GBM treated during these trials, 153 underwent GTR. The median survival for the GTR group was 71 weeks (95% CI 65-76) which was better than those who did not have a GTR. Within the GTR group, the median age was 54 years (range 25-77 years), and median Karnofsky Performance Score was 90 (range 60-100). Considering only patients with GTR, age at diagnosis continued to be a statistically significant prognostic factor. Patients treated during surgically based phase II studies should be matched with a historical control group restricted to patients with similar pretreatment variables, including GTR. PMID:17457513

  20. 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. PMID:25274584

  1. Optimal adaptive two-stage designs for phase II cancer clinical trials.

    PubMed

    Englert, Stefan; Kieser, Meinhard

    2013-11-01

    In oncology, single-arm two-stage designs with binary endpoint are widely applied in phase II for the development of cytotoxic cancer therapies. Simon's optimal design with prefixed sample sizes in both stages minimizes the expected sample size under the null hypothesis and is one of the most popular designs. The search algorithms that are currently used to identify phase II designs showing prespecified characteristics are computationally intensive. For this reason, most authors impose restrictions on their search procedure. However, it remains unclear to what extent this approach influences the optimality of the resulting designs. This article describes an extension to fixed sample size phase II designs by allowing the sample size of stage two to depend on the number of responses observed in the first stage. Furthermore, we present a more efficient numerical algorithm that allows for an exhaustive search of designs. Comparisons between designs presented in the literature and the proposed optimal adaptive designs show that while the improvements are generally moderate, notable reductions in the average sample size can be achieved for specific parameter constellations when applying the new method and search strategy. PMID:23868324

  2. Spectroscopic observations of the surface-active binary II Pegasi /HD 224085/

    NASA Astrophysics Data System (ADS)

    Bopp, B. W.; Noah, P. V.

    1980-06-01

    Spectroscopy of the surface-active binary II Peg (HD 224085) shows the H-alpha emission feature to be variable in equivalent width (EW) by a factor of ten on time scales of several days. Most of the EW variability is in phase with the stellar rotation period, suggesting strong localization of H-alpha emitting regions. However, sudden, flare-like enhancements of H-alpha are seen which exhibit decay times of days. Echelle spectrograms of the H-alpha profile show a noticeable red asymmetry, reminiscent of the emission profile exhibited by the RS CVn binary V711 Tau (HR 1099). An interpretation of the behavior of II Peg in the context of BY Dra or pre-main-sequence variability does not appear to be necessary.

  3. Phase II Trial of Dolastatin-10, a Novel Anti-Tubulin Agent, in Metastatic Soft Tissue Sarcomas

    PubMed Central

    Balcerzak, S. P.; Kraft, A. S.; Edmonson, J. H.; Okuno, S. H.; Davey, M.; Mclaughlin, S.; Beard, M. T.; Rogatko, A.

    2004-01-01

    Patients:Soft tissue sarcomas are uncommon malignancies with few therapeutic options for recurrent or metastatic disease. Dolastatin-10 (Dol-10) is a pentapeptide anti-microtubule agent that binds to tubulin sites distinct from vinca alkaloids. Based on the novel mechanism of action, limited activity of other anti-microtubular agents, and anti-neoplastic activity in pre-clinical screening of Dol-10, this multi-institutional phase II study was conducted to determine the objective response rate of Dol-10 in recurrent or metastatic soft tissue sarcomas that had not been treated with chemotherapy outside of the adjuvant setting. Methods: Dol-10 was given intravenously at a dose of 400 μg/m2 and repeated every 21 days. Toxicities were assessed using the Common Toxicity Criteria (version 2.0). Radiographic studies and tumor measurements were repeated every two cycles to assess response [Miller AB, et al. Cancer 1981; 47(1): 207]. Results: Dol-10 was associated with hematological toxicity and with some vascular toxicities. There was no significant gastrointestinal, hepatic or renal toxicity. There was one death on study due to respiratory failure. There were no objective responses in 12 patients treated with Dol-10. Discussion: Based on this phase II trial, further study of Dol-10 on this schedule is not recommended in advanced or metastatic soft tissue sarcomas. PMID:18521404

  4. Final phase I report and phase II work plan : QuickSite{reg_sign} investigation, Centralia, Kansas.

    SciTech Connect

    LaFreniere, L. M.

    2003-03-01

    flow direction at the former CCC/USDA facility is not toward the Morris well, and thus the former facility is not responsible for the carbon tetrachloride measured in that well. The town of Centralia and all residents near the former CCC/USDA facility currently obtain their water from Rural Water District No.3 (RWD 3). Therefore, these local residents are not drinking and using contaminated groundwater. The investigation at Centralia 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 environmental site characterization methodology. QuickSite is Argonne's proprietary implementation system for the expedited site characterization (ESC) process. Argonne's Environmental Research Division developed the ESC process to optimize preremedial site characterization work at hazardous waste sites by obtaining and then applying a thorough understanding of a site's geology, hydrogeology, and hydrogeochemistry (e.g., Burton 1994). This approach is fundamental to successful site characterization because the geology and hydrogeology of a site largely govern the mobility and fate of contaminants there. Argonne's ESC process has been used 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. This report documents the findings of the Phase I activities at Centralia. Section 1 provides a brief history of the area and the QuickSite process, a summary of the geologic

  5. Enhanced dewaterability of waste activated sludge by Fe(II)-activated peroxymonosulfate oxidation.

    PubMed

    Liu, Jun; Yang, Qi; Wang, Dongbo; Li, Xiaoming; Zhong, Yu; Li, Xin; Deng, Yongchao; Wang, Liqun; Yi, Kaixin; Zeng, Guangming

    2016-04-01

    The effect of Fe(II)-activated peroxymonosulfate (Fe(II)-PMS) oxidation on the waste activated sludge (WAS) dewatering and its mechanisms were investigated in this study. The capillary suction time (CST), specific resistance to filterability (SRF) of sludge and water content (WC) of dewatered sludge cake were chosen as the main parameters to evaluate the sludge dewaterability. Experimental results showed that Fe(II)-PMS effectively disintegrated sludge and improved sludge dewaterability. High CST and SRF reduction (90% and 97%) was achieved at the optimal conditions of PMS (HSO5(-)) 0.9mmol/gVSS, Fe(II) 0.81mmol/gVSS, and pH 6.8. Extracellular polymeric substances (EPS) and three-dimensional excitation-emission matrix (3D-EEM) fluorescence spectroscopy before and after Fe(II)-PMS oxidation were determined to explain the enhanced dewatering mechanism. The release of EPS-bound water induced by the destruction of EPS was the primary reason for the improvement of sludge dewaterability during Fe(II)-PMS oxidation. PMID:26851897

  6. Phase I/II Trial of Imatinib and Bevacizumab in Patients With Advanced Melanoma and Other Advanced Cancers

    PubMed Central

    Hamilton, Betty K.; Rosen, Mark A.; Amaravadi, Ravi K.; Schuchter, Lynn M.; Gallagher, Maryann; Chen, Helen; Sehgal, Chandra; O’Dwyer, Peter J.

    2015-01-01

    Background. Vascular endothelial growth factor and platelet-derived growth factor signaling in the tumor microenvironment appear to cooperate in promoting tumor angiogenesis. Patients and Methods. We conducted a phase I trial combining bevacizumab (i.v. every 2 weeks) and imatinib (oral daily). Once a recommended phase II dose combination was established, a phase II trial was initiated in patients with metastatic melanoma. A Simon 2-stage design was used with 23 patients required in the first stage and 41 patients in total should the criteria to proceed be met. We required that 50% of the patients be progression-free at 16 weeks. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and power Doppler ultrasonography were performed in patients with metastatic tumors amenable to imaging with these methods at baseline and after 4 weeks. Results. A total of 17 patients were accrued to 4 dose and combination levels. Bevacizumab 10 mg/kg every 2 weeks could be safely combined with imatinib 800 mg daily. Common toxicities included fatigue, nausea, vomiting, edema, proteinuria, and anemia, but were not commonly severe. A total of 23 patients with metastatic melanoma (48% with American Joint Commission on Cancer stage M1c; median age, 63 years) were enrolled in the first stage of phase II. The 16-week progression-free survival rate was 35%, leading to termination of phase II after the first stage. In the small subset of patients who remained on study with lesions evaluable by DCE-MRI, significant decreases in tumor vascular permeability were noted, despite early disease progression using the Response Evaluation Criteria In Solid Tumors. Conclusion. Bevacizumab and imatinib can be safely combined at the maximum doses used for each agent. We did not observe significant clinical activity with this regimen in melanoma patients. Implications for Practice: Vascular endothelial growth factor (VEGF)-targeted antiangiogenic therapy has proven clinical efficacy as a

  7. 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.

  8. Antiviral activity of platinum (II) and palladium (II) complexes of pyridine-2-carbaldehyde thiosemicarbazone.

    PubMed

    Varadinova, T; Kovala-Demertzi, D; Rupelieva, M; Demertzis, M; Genova, P

    2001-04-01

    A heterocyclic compound, pyridine-2-carbaldehyde thiosemicarbazone (HFoTsc), and its six metal coordinated bound complexes, three with platinum (II) and three with palladium (II), were studied for their activity against herpes simplex virus 1 (HSV-1) infection in cultured cells. According to their cytotoxicity the compounds were divided into two groups. Group I (cytotoxic compounds) included all three palladium complexes and [Pt(HFoTsc)2] Cl2, with maximum non-toxic concentration (MNC) of 1-10 micromol/l and a 50% cytotoxic concentration (CC50) of 20-100 micromol/l. Group 2 (low cytotoxic compounds) with MNC of 100 micromol/l and CC50 of 548-5820 micromol/l included compounds in the following order: [Pt(HFoTsc)2] Cl2activity. IC50 and SI values of HFoTsc increased in parallel with the duration of action in HSV-1-infected cells. All three platinum complexes as well as [Pd(HFoTsc)2]Cl2 and [Pd(FoTsc)2] inhibited HSV- I infection following a structure-activity relationship but only [Pt(HFoTsc)2]Cl2 expressed a significant selectivity comparable to that of HFoTsc. However, [PdCl(FoTsc)] acting 48 hrs gave a higher infectious HSV-1 titer (170%) compared to control (100%, no compound). PMID:11719987

  9. Synthesis, Characterization and Antiproliferative Activity of the Co(II), Ni(II), Cu(II), Pd(II) and Pt(II) Complexes of 2-(4-Thiazolyl)Benzimidazole (Thiabendazole)

    PubMed Central

    Glowiak, Tadeusz; Opolski, Adam; Wietrzyk, Joanna

    2001-01-01

    Complexes of 2-(4-thiazolyi)benzimidazole (thiabendazole, THBD) with Co(II), Ni(II), Cu(ll) of general formula ML2(NO3)2 H2O and complexes of Pd(II) and Pt(II) of general formula ML2Cl2 H2O have been obtained and characterized by elemental analyses, IR and far IR spectroscopy and magnetic measurements. The X-ray crystal structure of the copper(II) complex has been determined. The in vitro cell proliferation inhibitory activity of these compounds was examined against human cancer cell lines A 549 (lung carcinoma), HCV-29 T (urinary bladder carcinoma), MCF-7 (breast cancer), T47D (breast cancer), MES-SA (uterine carcinoma) and HL-60 (promyelocytic leukemia). Pt-THBD has been found to exhibit an antileukemic activity of the HL-60 line cells matching that of an arbitrary criterion. PMID:18475995

  10. Binuclear Rhodium(II) Complexes With Selective Antibacterial Activity.

    PubMed

    Bień, M; Lachowicz, T M; Rybka, A; Pruchnik, F P; Trynda, L

    1997-01-01

    Binuclear rhodium(II) complexes [Rh(2)Cl(2)(mu-OOCR)(2)(N-N)(2)] {R = H, Me; N-N = 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen)} and [Rh(2)(mu-OOCR)(2)(N-N)(2)(H(2)O)(2)](RCOO)(2) (R = Me, Et;) have been synthesized and their structure and properties have been studied by electronic, IR and (1)H NMR spectroscopy. Antibacterial activity of these complexes against Escherichia coli and Staphylococcus aureus has been investigated. The most active antibacterial agents against E. coli were [Rh(2)Cl(2)(mu-OOCR)(2)(N-N)(2)] and [Rh(2)(mu-OOCR)(2)(N-N)(2)(H(2)O)(2)](RCOO)(2) {R = H and Me} which were considerably more active than the appropriate nitrogen ligands. The complexes show low activity against S. aureus. The activity of the complexes [Rh(2)(OOCR)(2)(N-N)(2)(H(2)O)(2)](OOCR)(2) against E. coli decreases in the series: R=H congruent withCH(3)>C(2)H(5)>C(3)H(7) congruent withC(4)H(9). The reverse order was found in the case of S. aureus. PMID:18475773

  11. Phase I/II Study of Erlotinib Combined With Cisplatin and Radiotherapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck

    SciTech Connect

    Herchenhorn, Daniel; Dias, Fernando L.; Viegas, Celia M.P.; Federico, Miriam H.; Araujo, Carlos Manoel M.; Small, Isabelle; Bezerra, Marcos; Fontao, Karina M.D.; Knust, Renata E.; Ferreira, Carlos G.; Martins, Renato G.

    2010-11-01

    Purpose: Erlotinib, an oral tyrosine kinase inhibitor, is active against head-and-neck squamous cell carcinoma (HNSCC) and possibly has a synergistic interaction with chemotherapy and radiotherapy. We investigated the safety and efficacy of erlotinib added to cisplatin and radiotherapy in locally advanced HNSCC. Methods and Materials: In this Phase I/II trial 100 mg/m{sup 2} of cisplatin was administered on Days 8, 29, and 50, and radiotherapy at 70 Gy was started on Day 8. During Phase I, the erlotinib dose was escalated (50 mg, 100 mg, and 150 mg) in consecutive cohorts of 3 patients, starting on Day 1 and continuing during radiotherapy. Dose-limiting toxicity was defined as any Grade 4 event requiring radiotherapy interruptions. Phase II was initiated 8 weeks after the last Phase I enrollment. Results: The study accrued 9 patients in Phase I and 28 in Phase II; all were evaluable for efficacy and safety. No dose-limiting toxicity occurred in Phase I, and the recommended Phase II dose was 150 mg. The most frequent nonhematologic toxicities were nausea/vomiting, dysphagia, stomatitis, xerostomia and in-field dermatitis, acneiform rash, and diarrhea. Of the 31 patients receiving a 150-mg daily dose of erlotinib, 23 (74%; 95% confidence interval, 56.8%-86.3%) had a complete response, 3 were disease free after salvage surgery, 4 had inoperable residual disease, and 1 died of sepsis during treatment. With a median 37 months' follow-up, the 3-year progression-free and overall survival rates were 61% and 72%, respectively. Conclusions: This combination appears safe, has encouraging activity, and deserves further studies in locally advanced HNSCC.

  12. 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…

  13. Junctionally restricted RhoA activity is necessary for apical constriction during phase 2 inner ear placode invagination.

    PubMed

    Sai, Xiaorei; Yonemura, Shigenobu; Ladher, Raj K

    2014-10-15

    After induction, the inner ear is transformed from a superficially located otic placode into an epithelial vesicle embedded in the mesenchyme of the head. Invagination of this epithelium is biphasic: phase 1 involves the expansion of the basal aspect of the otic cells, and phase 2, the constriction of their apices. Apical constriction is important not only for otic invagination, but also the invagination of many other epithelia; however, its molecular basis is still poorly understood. Here we show that phase 2 otic morphogenesis, like phase 1 morphogenesis, results from the activation of myosin-II. However unlike the actin depolymerising activity observed basally, active myosin-II results in actomyosin contractility. Myosin-II activation is triggered by the accumulation of the planar cell polarity (PCP) core protein, Celsr1 in apical junctions (AJ). Apically polarized Celsr1 orients and recruits the Rho Guanine exchange factor (GEF) ArhGEF11 to apical junctions, thus restricting RhoA activity to the junctional membrane where it activates the Rho kinase ROCK. We suggest that myosin-II and RhoA activation results in actomyosin dependent constriction in an apically polarised manner driving otic epithelium invagination. PMID:25173873

  14. Lipoamide Acts as an Indirect Antioxidant by Simultaneously Stimulating Mitochondrial Biogenesis and Phase II Antioxidant Enzyme Systems in ARPE-19 Cells.

    PubMed

    Zhao, Lin; Liu, Zhongbo; Jia, Haiqun; Feng, Zhihui; Liu, Jiankang; Li, Xuesen

    2015-01-01

    In our previous study, we found that pretreatment with lipoamide (LM) more effectively than alpha-lipoic acid (LA) protected retinal pigment epithelial (RPE) cells from the acrolein-induced damage. However, the reasons and mechanisms for the greater effect of LM than LA are unclear. We hypothesize that LM, rather than the more direct antioxidant LA, may act more as an indirect antioxidant. In the present study, we treated ARPE-19 cells with LA and LM and compared their effects on activation of mitochondrial biogenesis and induction of phase II enzyme systems. It is found that LM is more effective than LA on increasing mitochondrial biogenesis and inducing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its translocation to the nucleus, leading to an increase in expression or activity of phase II antioxidant enzymes (NQO-1, GST, GCL, catalase and Cu/Zn SOD). Further study demonstrated that mitochondrial biogenesis and phase II enzyme induction are closely coupled via energy requirements. These results suggest that LM, compared with the direct antioxidant LA, plays its protective effect on oxidative damage more as an indirect antioxidant to simultaneously stimulate mitochondrial biogenesis and induction of phase II antioxidant enzymes. PMID:26030919

  15. Lipoamide Acts as an Indirect Antioxidant by Simultaneously Stimulating Mitochondrial Biogenesis and Phase II Antioxidant Enzyme Systems in ARPE-19 Cells

    PubMed Central

    Zhao, Lin; Liu, Zhongbo; Jia, Haiqun; Feng, Zhihui; Liu, Jiankang; Li, Xuesen

    2015-01-01

    In our previous study, we found that pretreatment with lipoamide (LM) more effectively than alpha-lipoic acid (LA) protected retinal pigment epithelial (RPE) cells from the acrolein-induced damage. However, the reasons and mechanisms for the greater effect of LM than LA are unclear. We hypothesize that LM, rather than the more direct antioxidant LA, may act more as an indirect antioxidant. In the present study, we treated ARPE-19 cells with LA and LM and compared their effects on activation of mitochondrial biogenesis and induction of phase II enzyme systems. It is found that LM is more effective than LA on increasing mitochondrial biogenesis and inducing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its translocation to the nucleus, leading to an increase in expression or activity of phase II antioxidant enzymes (NQO-1, GST, GCL, catalase and Cu/Zn SOD). Further study demonstrated that mitochondrial biogenesis and phase II enzyme induction are closely coupled via energy requirements. These results suggest that LM, compared with the direct antioxidant LA, plays its protective effect on oxidative damage more as an indirect antioxidant to simultaneously stimulate mitochondrial biogenesis and induction of phase II antioxidant enzymes. PMID:26030919

  16. Transcription activation at class II CRP-dependent promoters: the role of different activating regions.

    PubMed Central

    Rhodius, V A; West, D M; Webster, C L; Busby, S J; Savery, N J

    1997-01-01

    Transcription activation by the Escherichia coli cyclic AMP receptor protein (CRP) at Class II promoters is dependent on direct interactions between two surface-exposed activating regions (AR1 and AR2) and two contact sites in RNA polymerase. The effects on transcription activation of disrupting either AR1 or AR2 have been measured at different Class II promoters. AR2 but not AR1 is essential for activation at all the Class II promoters that were tested. The effects of single positive control substitutions in AR1 and AR2 vary from one promoter to another: the effects of the different substitutions are contingent on the -35 hexamer sequence. Abortive initiation assays have been used to quantify the effects of positive control substitutions in each activating region on the kinetics of transcription initiation at the Class II CRP- dependent promoter pmelRcon. At this promoter, the HL159 substitution in AR1 results in a defect in the initial binding of RNA polymerase whilst the KE101 substitution in AR2 reduces the rate of isomerization from the closed to the open complex. PMID:9016561

  17. 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

  18. Phase II trials of erlotinib or gefitinib in patients with recurrent meningioma.

    PubMed

    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

    2010-01-01

    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

  19. 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

  20. Metronomic Capecitabine in Advanced Hepatocellular Carcinoma Patients: A Phase II Study

    PubMed Central

    de Rosa, Francesco; Agostini, Valentina; di Girolamo, Stefania; Andreone, Pietro; Bolondi, Luigi; Serra, Carla; Sama, Claudia; Golfieri, Rita; Gramenzi, Annagiulia; Cucchetti, Alessandro; Pinna, Antonio Daniele; Trevisani, Franco; Biasco, Guido

    2013-01-01

    Background. Anti-angiogenic treatment with targeted agents is effective in advanced hepatocellular carcinoma (HCC). This trial evaluated the safety and efficacy of metronomic capecitabine in patients with HCC. Methods. This single-institution phase II trial included 59 previously untreated patients with advanced HCC and 31 patients resistant to or intolerant of sorafenib. The treatment schedule was capecitabine 500 mg twice daily until progression of disease, unacceptable toxicity level, or withdrawal of informed consent. Progression-free survival (PFS) was chosen as the primary endpoint. Results. A total of 59 previously untreated and 31 previously treated patients with HCC were enrolled. The first cohort achieved a median PFS of 6.03 months and an overall survival (OS) of 14.47 months. Two patients achieved a complete response, 1 patient achieved partial response, and in 30 patients, stable disease was the best outcome. The second cohort achieved a median PFS of 3.27 months and a median OS of 9.77 months. No complete or partial responses were observed, but 10 patients had stable disease. An unscheduled comparison of the first cohort of patients with 3,027 untreated patients with HCC from the Italian Liver Cancer (ITA.LI.CA) database was performed. One-to-one matching according to demographic/etiologic/oncologic features was possible for 50 patients. The median OS for these 50 capecitabine-treated patients was 15.6 months, compared with a median OS of 8.0 months for the matched untreated patients (p = .043). Conclusion. Metronomic capecitabine is well tolerated by patients with advanced HCC and appears to have activity both in treatment-naive patients and in those previously treated with sorafenib. PMID:24232581

  1. 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

  2. Phase II study of low-dose recombinant leukocyte A interferon in disseminated malignant melanoma.

    PubMed

    Creagan, E T; Ahmann, D L; Green, S J; Long, H J; Frytak, S; O'Fallon, J R; Itri, L M

    1984-09-01

    Thirty patients with disseminated malignant melanoma received intramuscular recombinant leukocyte A interferon (rIFN-alpha A), 12 X 10(6) U/m2, three times weekly for a planned treatment duration of three months. This dose was selected in view of our prior phase II data indicating that 50 X 10(6) U/m2 three times weekly produced excessive toxicity. In this current trial we observed three objective partial regressions (20%) among the 15 better-risk patients (performance score 0, 1, and no prior chemotherapy) with times to disease progression of 1.9, 9.6, and 12.9+ months. There were also three regressions (one complete and two partial) among the 15 poor-risk patients (performance score 2, 3, or prior chemotherapy) with progression times of 3, 3.2, and 9.6+ months. For all patients, the median survival time was 4.2 months. One half of the patients were observed to have progressive disease within one month of commencing treatment. Responding metastatic lesions were limited to soft tissue, although one patient also had a partial response of a lung nodule. The most substantial toxicities were moderate-to-severe myalgias (27%), nausea (33%), anorexia (47%), and fatigue (50%). Among the 22 patients with weight loss, the median was 2.3 kg (range, 0.6 to 8.4 kg). Hematologic and hepatic toxicity was transient and of little clinical significance. Our study indicates that rIFN-alpha A in the dose and schedule that we used is clinically tolerable and has antitumor activity in malignant melanoma. The response rate was similar to results observed in our previous study of a higher dose regimen. PMID:6470751

  3. 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

  4. Phase II Study of Nilotinib in Melanoma Harboring KIT Alterations Following Progression to Prior KIT Inhibition

    PubMed Central

    Carvajal, Richard D.; Lawrence, Donald P.; Weber, Jeffrey S.; Gajewski, Thomas F.; Gonzalez, Rene; Lutzky, Jose; O’Day, Steven J.; Hamid, Omid; Wolchok, Jedd D.; Chapman, Paul B.; Sullivan, Ryan J.; Teitcher, Jerrold B.; Ramaiya, Nikhil; Giobbie-Hurder, Anita; Antonescu, Cristina R.; Heinrich, Michael C.; Bastian, Boris C.; Corless, Christopher L.; Fletcher, Jonathan A.; Hodi, F. Stephen

    2016-01-01

    Purpose Although durable responses can be achieved with tyrosine kinase inhibitors such as imatinib in melanomas harboring KIT mutations, the efficacy of alternative inhibitors after progression to imatinib and the activity of these agents on brain metastases is unknown. Experimental Design We conducted a phase II study of nilotinib 400 mg BID in two cohorts of patients with melanomas harboring KIT mutations or amplification: A) those refractory or intolerant to a prior KIT inhibitor; and B) those with brain metastases. The primary endpoint was 4-month disease control rate. Secondary endpoints included response rate, time-to-progression and overall survival. A Simon two-stage and a single-stage design was planned to assess for the primary endpoint in Cohorts A and B, respectively. Results Twenty patients were enrolled and 19 treated (11-Cohort A; 8-Cohort B). Three patients on Cohort A (27%; 95% CI, 8% – 56%) and 1 on Cohort B (12.5%; 90% CI, 0.6% – 47%) achieved the primary endpoint. Two partial responses were observed in Cohort A (18.2%, 90% CI, 3% – 47%); none were observed in Cohort B. The median time-to-progression and overall survival was 3·3 (90% CI, 2.1 – 3.9 months) and 9.1 months (90% CI, 4.3 – 14.2 months), respectively, in all treated patients. Conclusion Nilotinib may achieve disease control in patients with melanoma harboring KIT alterations and whose disease progressed after imatinib therapy. The efficacy of this agent in KIT altered melanoma with brain metastasis is limited. PMID:25695690

  5. 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

  6. Liver protein kinase A activity is decreased during the late hypoglycemic phase of sepsis.

    PubMed

    Hsu, C; Hsu, H K; Yang, S L; Jao, H C; Liu, M S

    1999-10-01

    Changes in protein kinase A (PKA, or cAMP-dependent protein kinase) activity in the rat liver during different metabolic phases of sepsis were investigated. Sepsis was induced by cecal ligation and puncture (CLP). Experiments were divided into 3 groups: control, early sepsis, and late sepsis. Early and late sepsis refer to those animals killed at 9 and 18 h, respectively, after CLP. Hepatic PKA was extracted and partially purified by acid precipitation, ammonium sulfate fractionation, and diethylaminoethyl (DEAE)-cellulose chromatography. PKA was eluted from DEAE-cellulose column with a linear NaCl gradient. Two peaks of PKA, type I (eluted at low ionic strength) and type II (eluted at high ionic strength), were collected and their activities were determined on the basis of the rate of incorporation of [gamma-32-P]ATP into histone. The results show that during early sepsis, both type I and type II PKA activities remained unchanged. During late sepsis, type I PKA activity was decreased by 40.7-53.6%, whereas type II PKA activity was unaffected. Kinetic analysis of the data on type I PKA during the late phase of sepsis reveals that the Vmax (maximal velocity) values for ATP, cAMP, and histone were decreased by 40.7, 53.6, and 47.3%, respectively whereas the Km (substrate concentration required for half-maximal enzymatic activity) values for ATP, cAMP, and histone were unaltered. These data indicate that type I PKA was inactivated during the late hypoglycemic phase of sepsis in the rat liver. Because PKA-mediated phosphorylation plays an important role in the regulation of hepatic glucose metabolism, an inactivation of PKA may contribute to the development of hypoglycemia during the late phase of sepsis. PMID:10509629

  7. In vitro studies of the loss of antibacterial activity of oxytetracycline in presence of Ca(II) or Mg(II) ions.

    PubMed

    Naz, S; Khan, K A; Zubairi, S A

    1996-07-01

    The results of a comparative study, which evaluated the in vitro effect on the antibacterial activity of oxytetracycline (OTC, CAS 79-57-2) in presence of Ca(II)/Mg(II) ions suggest that susceptibility of Staphylococcus aureus, Bacillus pumilis and Bacillus subtilis to OTC is reduced in presence of Ca(II)/Mg(II) ions. As the ratio of concentration of Ca(II)/Mg(II) to OTC was increased, antibacterial activity of OTC declined. In addition to the difference observed between the antibacterial effect of pure OTC and its Ca(II)/Mg(II) complexes, it was found that decline in antibacterial activity is greater for Mg(II)-OTC complex than Ca(II)-OTC complex for the same concentration of Ca(II)/Mg(II) ions. PMID:8842342

  8. 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. PMID:26461851

  9. Synthesis, spectroscopic characterization and biological activities of N4O2 Schiff base ligand and its metal complexes of Co(II), Ni(II), Cu(II) and Zn(II)

    NASA Astrophysics Data System (ADS)

    Al-Resayes, Saud I.; Shakir, Mohammad; Abbasi, Ambreen; Amin, Kr. Mohammad Yusuf; Lateef, Abdul

    The Schiff base ligand, bis(indoline-2-one)triethylenetetramine (L) obtained from condensation of triethylenetetramine and isatin was used to synthesize the complexes of type, [ML]Cl2 [M = Co(II), Ni(II), Cu(II) and Zn(II)]. L was characterized on the basis of the results of elemental analysis, FT-IR, 1H and 13C NMR, mass spectroscopic studies. The stoichiometry, bonding and stereochemistries of complexes were ascertained on the basis of results of elemental analysis, magnetic susceptibility values, molar conductance and various spectroscopic studies. EPR, UV-vis and magnetic moments revealed an octahedral geometry for complexes. L and its Cu(II) and Zn(II) complexes were screened for their antibacterial activity. Analgesic activity of Cu(II) and Zn(II) complexes was also tested in rats by tail flick method. Both complexes were found to possess good antibacterial and moderate analgesic activity.

  10. Copper(II) and nickel(II) complexes of benzyloxybenzaldehyde-4-phenyl-3-thiosemicarbazone: Synthesis, characterization and biological activity

    NASA Astrophysics Data System (ADS)

    Prathima, B.; Subba Rao, Y.; Adinarayana Reddy, S.; Reddy, Y. P.; Varada Reddy, A.

    2010-09-01

    Benzyloxybenzaldehyde-4-phenyl-3-thiosemicarbazone ligand (L) has been synthesized from benzyloxybenzaldehyde and 4-phenyl-3-thiosemicarbazide. Complexes of this ligand with chlorides of Cu(II) and Ni(II) have been prepared. The structure of the ligand (L) is proposed based on elemental analysis, IR and 1H NMR spectra. Its complexes with Cu(II) and Ni(II) ions are characterized from the studies of electronic as well as EPR spectra. On the basis of electronic and EPR studies, rhombically distorted octahedral structure has been proposed for Cu(II) complex while the Ni(II) complex has been found to acquire an octahedral structure. The ligand and their metal complexes have been tested in vitro for their biological effects. Their antibacterial activities against Gram-negative bacteria ( Escherichia coli and Klebsiella pneumoniae) and Gram-positive bacteria ( Staphylococcus aureus and Bacillus subtilis) have been investigated. The prepared metal complexes exhibit higher antibacterial activities than the parent ligand. The in vitro antioxidant activity of free ligand and its metal(II) complexes have also been investigated and the results however reveal that the ligand exhibits greater antioxidant activity than its complexes.

  11. Residential construction demonstration project, Cycle II: Active ventilation

    SciTech Connect

    Not Available

    1991-01-01

    This report documents the analysis of the performance of natural and mechanical ventilation in Pacific Northwest homes. The analysis was part of Cycle II of the Residential Construction Demonstration Project, sponsored by Bonneville Power Administration (BPA). Since 1986, the Residential Construction Demonstration Project (RCDP) has sponsored the collection of data on energy efficient homes in the Pacific Northwest that comply with these new standards and requirements. Cycle II of RCDP was conducted between September 1987 and April 1990. It concentrated on energy innovations in homes built to the Super Good Cents specification. All of the test homes have electric heat and mechanical ventilation systems. Seven different types of active ventilation systems are represented in the homes. Three of these system types are equipped with heat recovery devices, and are represented in approximately a quarter of the test homes. The potential for both natural and mechanical ventilation was measured. Potential structural leakage was measured by blower door testing. Flow rate and operating time of mechanical ventilation systems were measured with flow hoods and hour meters. Actual ventilation was measured by using a passive tracer gas technique for several weeks during the heating season and at times of normal occupancy.

  12. Residential construction demonstration project, Cycle II: Active ventilation

    SciTech Connect

    Not Available

    1991-12-31

    This report documents the analysis of the performance of natural and mechanical ventilation in Pacific Northwest homes. The analysis was part of Cycle II of the Residential Construction Demonstration Project, sponsored by Bonneville Power Administration (BPA). Since 1986, the Residential Construction Demonstration Project (RCDP) has sponsored the collection of data on energy efficient homes in the Pacific Northwest that comply with these new standards and requirements. Cycle II of RCDP was conducted between September 1987 and April 1990. It concentrated on energy innovations in homes built to the Super Good Cents specification. All of the test homes have electric heat and mechanical ventilation systems. Seven different types of active ventilation systems are represented in the homes. Three of these system types are equipped with heat recovery devices, and are represented in approximately a quarter of the test homes. The potential for both natural and mechanical ventilation was measured. Potential structural leakage was measured by blower door testing. Flow rate and operating time of mechanical ventilation systems were measured with flow hoods and hour meters. Actual ventilation was measured by using a passive tracer gas technique for several weeks during the heating season and at times of normal occupancy.

  13. Sorafenib in advanced melanoma: a Phase II randomised discontinuation trial analysis.

    PubMed

    Eisen, T; Ahmad, T; Flaherty, K T; Gore, M; Kaye, S; Marais, R; Gibbens, I; Hackett, S; James, M; Schuchter, L M; Nathanson, K L; Xia, C; Simantov, R; Schwartz, B; Poulin-Costello, M; O'Dwyer, P J; Ratain, M J

    2006-09-01

    The effects of sorafenib--an oral multikinase inhibitor targeting the tumour and tumour vasculature--were evaluated in patients with advanced melanoma enrolled in a large multidisease Phase II randomised discontinuation trial (RDT). Enrolled patients received a 12-week run-in of sorafenib 400 mg twice daily (b.i.d.). Patients with changes in bi-dimensional tumour measurements <25% from baseline were then randomised to sorafenib or placebo for a further 12 weeks (ie to week 24). Patients with > or =25% tumour shrinkage after the run-in continued on open-label sorafenib, whereas those with > or =25% tumour growth discontinued treatment. This analysis focussed on secondary RDT end points: changes in bi-dimensional tumour measurements from baseline after 12 weeks and overall tumour responses (WHO criteria) at week 24, progression-free survival (PFS), safety and biomarkers (BRAF, KRAS and NRAS mutational status). Of 37 melanoma patients treated during the run-in phase, 34 were evaluable for response: one had > or =25% tumour shrinkage and remained on open-label sorafenib; six (16%) had <25% tumour growth and were randomised (placebo, n=3; sorafenib, n=3); and 27 had > or =25% tumour growth and discontinued. All three randomised sorafenib patients progressed by week 24; one remained on sorafenib for symptomatic relief. All three placebo patients progressed by week-24 and were re-started on sorafenib; one experienced disease re-stabilisation. Overall, the confirmed best responses for each of the 37 melanoma patients who received sorafenib were 19% stable disease (SD) (ie n=1 open-label; n=6 randomised), 62% (n=23) progressive disease (PD) and 19% (n=7) unevaluable. The overall median PFS was 11 weeks. The six randomised patients with SD had overall PFS values ranging from 16 to 34 weeks. The most common drug-related adverse events were dermatological (eg rash/desquamation, 51%; hand-foot skin reaction, 35%). There was no relationship between V600E BRAF status and disease

  14. Urotensin II((4-11)) Azasulfuryl Peptides: Synthesis and Biological Activity.

    PubMed

    Merlino, Francesco; Yousif, Ali M; Billard, Étienne; Dufour-Gallant, Julien; Turcotte, Stéphane; Grieco, Paolo; Chatenet, David; Lubell, William D

    2016-05-26

    Cyclic azasulfuryl (As) peptide analogs of the urotensin II (UII, 1, H-Glu-Thr-Pro-Asp-c[Cys-Phe-Trp-Lys-Tyr-Cys]-Val-OH) fragment 4-11 were synthesized to explore the influences of backbone structure on biological activity. N-Aminosulfamides were inserted as surrogates of the Trp(7) and Lys(8) residues in the biologically relevant Trp-Lys-Tyr triad. A combination of solution- and solid-phase methods were used to prepare novel UII((4-11)) analogs 6-11 by routes featuring alkylation of azasulfuryl-glycine tripeptide precursors to install various side chains. The pharmacological profiles of derivatives 6-11 were tested in vitro using a competitive binding assay and ex vivo using a rat aortic ring bioassay. Although the analogs exhibited weak affinity for the urotensin II receptor (UT) without agonistic activity, azasulfuryl-UII((4-11)) derivatives 7-9 reduced up to 50% of the effects of UII and urotensin II-related peptide (URP) without affecting their potency. PMID:27140209

  15. 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.

  16. Epigenetic Therapy Using Belinostat for Patients With Unresectable Hepatocellular Carcinoma: A Multicenter Phase I/II Study With Biomarker and Pharmacokinetic Analysis of Tumors From Patients in the Mayo Phase II Consortium and the Cancer Therapeutics Research Group

    PubMed Central

    Yeo, Winnie; Chung, Hyun C.; Chan, Stephen L.; Wang, Ling Z.; Lim, Robert; Picus, Joel; Boyer, Michael; Mo, Frankie K.F.; Koh, Jane; Rha, Sun Y.; Hui, Edwin P.; Jeung, Hei C.; Roh, Jae K.; Yu, Simon C.H.; To, Ka F.; Tao, Qian; Ma, Brigette B.; Chan, Anthony W.H.; Tong, Joanna H.M.; Erlichman, Charles; Chan, Anthony T.C.; Goh, Boon C.

    2012-01-01

    Purpose Epigenetic aberrations have been reported in hepatocellular carcinoma (HCC). In this study of patients with unresectable HCC and chronic liver disease, epigenetic therapy with the histone deacetylase inhibitor belinostat was assessed. The objectives were to determine dose-limiting toxicity and maximum-tolerated dose (MTD), to assess pharmacokinetics in phase I, and to assess activity of and explore potential biomarkers for response in phase II. Patients and Methods Major eligibility criteria included histologically confirmed unresectable HCC, European Cooperative Oncology Group performance score ≤ 2, and adequate organ function. Phase I consisted of 18 patients; belinostat was given intravenously once per day on days 1 to 5 every 3 weeks; dose levels were 600 mg/m2 per day (level 1), 900 mg/m2 per day (level 2), 1,200 mg/m2 per day (level 3), and 1,400 mg/m2 per day (level 4). Phase II consisted of 42 patients. The primary end point was progression-free survival (PFS), and the main secondary end points were response according to Response Evaluation Criteria in Solid Tumors (RECIST) and overall survival (OS). Exploratory analysis was conducted on pretreatment tumor tissues to determine whether HR23B expression is a potential biomarker for response. Results Belinostat pharmacokinetics were linear from 600 to 1,400 mg/m2 without significant accumulation. The MTD was not reached at the maximum dose administered. Dose level 4 was used in phase II. The median number of cycles was two (range, one to 12). The partial response (PR) and stable disease (SD) rates were 2.4% and 45.2%, respectively. The median PFS and OS were 2.64 and 6.60 months, respectively. Exploratory analysis revealed that disease stabilization rate (complete response plus PR plus SD) in tumors having high and low HR23B histoscores were 58% and 14%, respectively (P = .036). Conclusion Epigenetic therapy with belinostat demonstrates tumor stabilization and is generally well-tolerated. HR23B

  17. Gene expression of transporters and phase I/II metabolic enzymes in murine small intestine during fasting

    PubMed Central

    van den Bosch, Heleen M; Bünger, Meike; de Groot, Philip J; van der Meijde, Jolanda; Hooiveld, Guido JEJ; Müller, Michael

    2007-01-01

    Background Fasting has dramatic effects on small intestinal transport function. However, little is known on expression of intestinal transport and phase I/II metabolism genes during fasting and the role the fatty acid-activated transcription factor PPARα may play herein. We therefore investigated the effects of fasting on expression of these genes using Affymetrix GeneChip MOE430A arrays and quantitative RT-PCR. Results After 24 hours of fasting, expression levels of 33 of the 253 analyzed transporter and phase I/II metabolism genes were changed. Upregulated genes were involved in transport of energy-yielding molecules in processes such as glycogenolysis (G6pt1) and mitochondrial and peroxisomal oxidation of fatty acids (Cact, Mrs3/4, Fatp2, Cyp4a10, Cyp4b1). Other induced genes were responsible for the inactivation of the neurotransmitter serotonin (Sert, Sult1d1, Dtd, Papst2), formation of eicosanoids (Cyp2j6, Cyp4a10, Cyp4b1), or for secretion of cholesterol (Abca1 and Abcg8). Cyp3a11, typically known because of its drug metabolizing capacity, was also increased. Fasting had no pronounced effect on expression of phase II metabolic enzymes, except for glutathione S-transferases which were down-regulated. Time course studies revealed that some genes were acutely regulated, whereas expression of other genes was only affected after prolonged fasting. Finally, we identified 8 genes that were PPARα-dependently upregulated upon fasting. Conclusion We have characterized the response to fasting on expression of transporters and phase I/II metabolic enzymes in murine small intestine. Differentially expressed genes are involved in a variety of processes, which functionally can be summarized as a) increased oxidation of fat and xenobiotics, b) increased cholesterol secretion, c) increased susceptibility to electrophilic stressors, and d) reduced intestinal motility. This knowledge increases our understanding of gut physiology, and may be of relevance for e.g. pre

  18. Removal of Ni(II), Zn(II) and Pb(II) ions from single metal aqueous solution using rice husk-based activated carbon

    SciTech Connect

    Taha, Mohd F. Shaharun, Maizatul S.; Shuib, Anis Suhaila Borhan, Azry

    2014-10-24

    An attempt was made to investigate the potential of rice husk-based activated carbon as an alternative low-cost adsorbent for the removal of Ni(II), Zn(II) and Pb(II) ions from single aqueous solution. Rice husk-based activated carbon was prepared via treatment of rice husk with NaOH followed by the carbonization process at 400°C for 2 hours. Three samples, i.e. raw rice husk, rice husk treated with NaOH and rice husk-based activated carbon, were analyzed for their morphological characteristics using field-emission scanning electron microscope/energy dispersive X-ray (FESEM/EDX). These samples were also analyzed for their carbon, hydrogen, nitrogen, oxygen and silica contents using CHN elemental analyzer and FESEM/EDX. The porous properties of rice husk-based activated carbon were determined by Brunauer-Emmett-Teller (BET) surface area analyzer, and its surface area and pore volume were 255 m{sup 2}/g and 0.17 cm{sup 2}/g, respectively. The adsorption studies for the removal of Ni(II), Zn(II) and Pb(II) ions from single metal aqueous solution were carried out at a fixed initial concentration of metal ion (150 ppm) with variation amount of adsorbent (rice husk-based activated carbon) as a function of varied contact time at room temperature. The concentration of each metal ion was analyzed using atomic absorption spectrophotometer (AAS). The results obtained from adsorption studies indicate the potential of rice husk as an economically promising precursor for the preparation of activated carbon for removal of Ni(II), Zn(II) and Pb(II) ions from single aqueous solution. Isotherm and kinetic model analyses suggested that the experimental data of adsorption studies fitted well with Langmuir, Freundlich and second-order kinetic models.

  19. Removal of Ni(II), Zn(II) and Pb(II) ions from single metal aqueous solution using rice husk-based activated carbon

    NASA Astrophysics Data System (ADS)

    Taha, Mohd F.; Shuib, Anis Suhaila; Shaharun, Maizatul S.; Borhan, Azry

    2014-10-01

    An attempt was made to investigate the potential of rice husk-based activated carbon as an alternative low-cost adsorbent for the removal of Ni(II), Zn(II) and Pb(II) ions from single aqueous solution. Rice husk-based activated carbon was prepared via treatment of rice husk with NaOH followed by the carbonization process at 400°C for 2 hours. Three samples, i.e. raw rice husk, rice husk treated with NaOH and rice husk-based activated carbon, were analyzed for their morphological characteristics using field-emission scanning electron microscope/energy dispersive X-ray (FESEM/EDX). These samples were also analyzed for their carbon, hydrogen, nitrogen, oxygen and silica contents using CHN elemental analyzer and FESEM/EDX. The porous properties of rice husk-based activated carbon were determined by Brunauer-Emmett-Teller (BET) surface area analyzer, and its surface area and pore volume were 255 m2/g and 0.17 cm2/g, respectively. The adsorption studies for the removal of Ni(II), Zn(II) and Pb(II) ions from single metal aqueous solution were carried out at a fixed initial concentration of metal ion (150 ppm) with variation amount of adsorbent (rice husk-based activated carbon) as a function of varied contact time at room temperature. The concentration of each metal ion was analyzed using atomic absorption spectrophotometer (AAS). The results obtained from adsorption studies indicate the potential of rice husk as an economically promising precursor for the preparation of activated carbon for removal of Ni(II), Zn(II) and Pb(II) ions from single aqueous solution. Isotherm and kinetic model analyses suggested that the experimental data of adsorption studies fitted well with Langmuir, Freundlich and second-order kinetic models.

  20. A study on retention and release of Zn (II) by mineral and carbonaceous solid phases alone and in a blend.

    PubMed

    Dadhich, Anima Sunil; Bandaru, Padmavathi; Kavitha, Garimella Venkata

    2007-04-01

    The study was carried out to understand the interaction of Zinc (II), which happens to be an essential micronutrient and essential element for all life, with a mineral surface, Montmorillonite Clay which happens to be an important soil constituent and is compared with carbonaceous solid phase such as Activated Carbon. It was found that retention takes place through chemisorptions, ion exchange and probably precipitation also involved at higher pH. The effect of various parameters such as pH, contact time, adsorbent dosage and initial concentration of the metal ion on the kinetics of adsorption was studied. At higher pH of the clay system, zinc becomes less soluble. The adsorption behaviour of zinc using a blend of Montmorillonite Clay, Activated Carbon was also studied. It was found that when the percentage of Activated Carbon in the blend increases, the percentage retention decreases. The release of Zn (II) was studied using different extracting solutions. The desorption was insignificant indicating the possibility of formation of inner sphere complexes. The adsorption data was also applied to the effluent from Zinc Smelting Industry. PMID:18476404

  1. Phase I/II study of sorafenib in combination with temsirolimus for recurrent glioblastoma or gliosarcoma: North American Brain Tumor Consortium study 05-02

    PubMed Central

    Lee, Eudocia Q.; Kuhn, John; Lamborn, Kathleen R.; Abrey, Lauren; DeAngelis, Lisa M.; Lieberman, Frank; Robins, H. Ian; Chang, Susan M.; Yung, W. K. Alfred; Drappatz, Jan; Mehta, Minesh P.; Levin, Victor A.; Aldape, Kenneth; Dancey, Janet E.; Wright, John J.; Prados, Michael D.; Cloughesy, Timothy F.; Gilbert, Mark R.; Wen, Patrick Y.

    2012-01-01

    The activity of single-agent targeted molecular therapies in glioblastoma has been limited to date. The North American Brain Tumor Consortium examined the safety, pharmacokinetics, and efficacy of combination therapy with sorafenib, a small molecule inhibitor of Raf, vascular endothelial growth factor receptor 2, and platelet-derived growth factor receptor–β, and temsirolimus (CCI-779), an inhibitor of mammalian target of rapamycin. This was a phase I/II study. The phase I component used a standard 3 × 3 dose escalation scheme to determine the safety and tolerability of this combination therapy. The phase II component used a 2-stage design; the primary endpoint was 6-month progression-free survival (PFS6) rate. Thirteen patients enrolled in the phase I component. The maximum tolerated dosage (MTD) for combination therapy was sorafenib 800 mg daily and temsirolimus 25 mg once weekly. At the MTD, grade 3 thrombocytopenia was the dose-limiting toxicity. Eighteen patients were treated in the phase II component. At interim analysis, the study was terminated and did not proceed to the second stage. No patients remained progression free at 6 months. Median PFS was 8 weeks. The toxicity of this combination therapy resulted in a maximum tolerated dose of temsirolimus that was only one-tenth of the single-agent dose. Minimal activity in recurrent glioblastoma multiforme was seen at the MTD of the 2 combined agents. PMID:23099651

  2. Phase I/II study of sorafenib in combination with temsirolimus for recurrent glioblastoma or gliosarcoma: North American Brain Tumor Consortium study 05-02.

    PubMed

    Lee, Eudocia Q; Kuhn, John; Lamborn, Kathleen R; Abrey, Lauren; DeAngelis, Lisa M; Lieberman, Frank; Robins, H Ian; Chang, Susan M; Yung, W K Alfred; Drappatz, Jan; Mehta, Minesh P; Levin, Victor A; Aldape, Kenneth; Dancey, Janet E; Wright, John J; Prados, Michael D; Cloughesy, Timothy F; Gilbert, Mark R; Wen, Patrick Y

    2012-12-01

    The activity of single-agent targeted molecular therapies in glioblastoma has been limited to date. The North American Brain Tumor Consortium examined the safety, pharmacokinetics, and efficacy of combination therapy with sorafenib, a small molecule inhibitor of Raf, vascular endothelial growth factor receptor 2, and platelet-derived growth factor receptor-β, and temsirolimus (CCI-779), an inhibitor of mammalian target of rapamycin. This was a phase I/II study. The phase I component used a standard 3 × 3 dose escalation scheme to determine the safety and tolerability of this combination therapy. The phase II component used a 2-stage design; the primary endpoint was 6-month progression-free survival (PFS6) rate. Thirteen patients enrolled in the phase I component. The maximum tolerated dosage (MTD) for combination therapy was sorafenib 800 mg daily and temsirolimus 25 mg once weekly. At the MTD, grade 3 thrombocytopenia was the dose-limiting toxicity. Eighteen patients were treated in the phase II component. At interim analysis, the study was terminated and did not proceed to the second stage. No patients remained progression free at 6 months. Median PFS was 8 weeks. The toxicity of this combination therapy resulted in a maximum tolerated dose of temsirolimus that was only one-tenth of the single-agent dose. Minimal activity in recurrent glioblastoma multiforme was seen at the MTD of the 2 combined agents. PMID:23099651

  3. Nrf2-regulated phase-II detoxification enzymes and phase-III transporters are induced by thyroid hormone in rat liver.

    PubMed

    Cornejo, Pamela; Vargas, Romina; Videla, Luis A

    2013-01-01

    Thyroid hormone (T₃)-induced calorigenesis triggers the hepatic production of reactive oxygen species (ROS) and redox-sensitive nuclear transcription factor erythroid 2-related factor 2 (Nrf2) activation. The aim of this study was to test the hypothesis that in vivo T₃ administration upregulates the expression of phase II and III detoxification proteins that is controlled by Nrf2. Male Sprague-Dawley rats were given a single intraperitoneal dose of 0.1 mg T₃/kg or T₃ vehicle (controls). After treatment, rectal temperature of the animals, liver Nrf2 DNA binding (EMSA), protein levels of epoxide hydrolase 1 (Eh1), NADPH-quinone oxidoreductase 1 (NQO1), glutathione-S-transferases Ya (GST Ya) and Yp (GST Yp), and multidrug resistance-associated proteins 2 (MRP-2) and 4 (MRP-4) (Western blot), and MRP-3 (RT-PCR) were determined at different times. T₃ significantly rose the rectal temperature of the animals in the time period studied, concomitantly with increases (P < 0.05) of liver Nrf2 DNA binding at 1 and 2 h after treatment, which was normalized at 4-12 h. Within 1-2 h after T₃ treatment, liver phase II enzymes Eh1, NQO1, GST Ya, and GST Yp were enhanced (P < 0.05) as did phase III transporters MRP-2 and MRP-3, whereas MRP-4 remained unchanged. In conclusion, enhancement of liver Nrf2 DNA binding elicited by in vivo T₃ administration is associated with upregulation of the expression of detoxification and drug transport proteins. These changes, in addition to antioxidant protein induction previously observed, may represent cytoprotective mechanisms underlying T₃ preconditioning against liver injury mediated by ROS and chemical toxicity. PMID:23554160

  4. Synthesis, characterization and in vitro anticancer activity of 18-membered octaazamacrocyclic complexes of Co(II), Ni(II), Cd(II) and Sn(II)

    NASA Astrophysics Data System (ADS)

    Kareem, Abdul; Zafar, Hina; Sherwani, Asif; Mohammad, Owais; Khan, Tahir Ali

    2014-10-01

    An effective series of 18 membered octaazamacrocyclic complexes of the type [MLX2], where X = Cl or NO3 have been synthesized by template condensation reaction of oxalyl dihydrazide with dibenzoylmethane and metal salt in 2:2:1 molar ratio. The formation of macrocyclic framework, stereochemistry and their overall geometry have been characterized by various physico-chemical studies viz., elemental analysis, electron spray ionization-mass spectrometry (ESI-MS), I.R, UV-Vis, 1H NMR, 13C NMR spectroscopy, X-ray diffraction (XRD) and TGA/DTA studies. These studies suggest formation of octahedral macrocyclic complexes of Co(II), Ni(II), Cd(II) and Sn(II). The molar conductance values suggest nonelectrolytic nature for all the complexes. Thermogravimatric analysis shows that all the complexes are stable up to 600 °C. All these complexes have been tested against different human cancer cell lines i.e. human hepatocellular carcinoma (Hep3B), human cervical carcinoma (HeLa), human breast adenocarcinoma (MCF7) and normal cells (PBMC). The newly synthesized 18-membered octaazamacrocyclic complexes during in vitro anticancer evaluation, displayed moderate to good cytotoxicity on liver (Hep3B), cervical (HeLa) and breast (MCF7) cancer cell lines, respectively. The most effective anticancer cadmium complex (C34H28N10CdO10) was found to be active with IC50 values, 2.44 ± 1.500, 3.55 ± 1.600 and 4.82 ± 1.400 in micro-molar on liver, cervical and breast cancer cell lines, respectively.

  5. Phase II of the demonstration of the Koppelman series C process. Topical report, February 1995--February 1996

    SciTech Connect

    Merriam, N.

    1998-12-31

    A pilot plant using the Koppelman Series C Process was designed, constructed, and operated near Gillette, Wyoming, as part of Phase I of this project. Construction was completed in late fall of 1993, and the shakedown was completed in early 1994. The initial series of tests performed to prove the process and to characterize the effluents was conducted during the first half of 1994. The results of those tests are described in the final report for Phase I. This report describes the activities conducted during Phase II of the project the objective of which was to move the process, which was proven during Phase I, a step closer to commercialization. Specifically, the work was planned to lower the cost of the process by developing a high-capacity processor, increasing the already high efficiency of the process by using a feed coal preheated, increasing the bulk density of the product by using mixed particle size extrudate, and preparing a preliminary scoping design for the water treatment plant for a 500,000 ton per year commercial plant.

  6. The subthalamic nucleus part II: modelling and simulation of activity.

    PubMed

    Heida, Tjitske; Marani, Enrico; Usunoff, Kamen G

    2008-01-01

    Part I of The Subthalamic Nucleus (volume 198) (STN) accentuates the gap between experimental animal and human information concerning subthalamic development, cytology, topography and connections.The light and electron microscopical cytology focuses on the open nucleus concept and the neuronal types present in the STN. The cytochemistry encompasses enzymes, NO, glial fibrillary acidic protein (GFAP), calcium binding proteins, and receptors (dopamine, cannabinoid, opioid, glutamate, gamma-aminobutyric acid (GABA), serotonin, cholinergic, and calcium channels). The ontogeny of the subthalamic cell cord is also reviewed. The topography concerns the rat, cat, baboon and human STN. The descriptions of the connections are also given from a historical point of view. Recent tracer studies on the rat nigro-subthalamic connection revealed contralateral projections. This monograph (Part II of the two volumes) on the subthalamic nucleus (STN) starts with a systemic model of the basal ganglia to evaluate the position of the STN in the direct, indirect and hyperdirect pathways. A summary of in vitro studies is given, describing STN spontaneous activity as well as responses to depolarizing and hyperpolarizing inputs and high-frequency stimulation. STN bursting activity and the underlying ionic mechanisms are investigated. Deep brain stimulation used for symptomatic treatment of Parkinson's disease is discussed in terms of the elements that are influenced and its hypothesized mechanisms. This part of the monograph explores the pedunculopontine-subthalamic connections and summarizes attempts to mimic neurotransmitter actions of the pedunculopontine nucleus in cell cultures and high-frequency stimulation on cultured dissociated rat subthalamic neurons. STN cell models - single- and multi-compartment models and system-level models are discussed in relation to subthalamic function and dysfunction. Parts I and II are compared. PMID:18727495

  7. 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

  8. Phase II trial of biweekly docetaxel, cisplatin, and 5-fluorouracil chemotherapy for advanced esophageal squamous cell carcinoma.

    PubMed

    Tanaka, Yoshihiro; Yoshida, Kazuhiro; Yamada, Atsuko; Tanahashi, Toshiyuki; Okumura, Naoki; Matsuhashi, Nobuhisa; Yamaguchi, Kazuya; Miyazaki, Tatsuhiko

    2016-06-01

    The prognosis of esophageal cancer patients is still unsatisfactory. Although a docetaxel, cisplatin, and 5-Fu (DCF) regimen has been reported, it is often difficult to accomplish because of severe toxicity. Therefore, we developed a new biweekly DCF (Bi-DCF) regimen and previously reported the recommended dose in a phase I dose-escalation study. We then performed a phase II study of Bi-DCF for advanced esophageal squamous cell carcinoma (SCC). Patients with clinical stage II/III were eligible. Patients received 2 courses of chemotherapy: docetaxel 35 mg/m(2) with cisplatin 40 mg/m(2) on days 1 and 15 and 400 mg/m(2) 5-fluorouracil on days 1-5 and 15-19 every 4 weeks. After completion of the chemotherapy, patients received esophagectomy. The primary endpoint was the completion rate of protocol treatment. Thirty-two patients were enrolled. The completion rate of protocol treatment (completion of two courses of preoperative chemotherapy and R0 surgery) was 100 %. During chemotherapy, the most common grade 3 or 4 toxicities were neutropenia (31.3 %). No treatment-related death was observed, and the incidence of operative morbidity was tolerable. The overall response rate after the chemotherapy was 90.3 %. This Bi-DCF regimen was well tolerated and highly active. This trial was registered with the University Hospital Medical Information Network (No. UMIN 000014625). PMID:26896963

  9. Preconcentration of Sn (II) using the methylene blue on the activated carbon and its determination by spectrophotometry method.

    PubMed

    Khodadoust, Saeid; Cham Kouri, Narges

    2014-04-01

    A simple and accurate spectrophotometric method for determination of trace amounts of Sn (II) ion in soil sample was developed by using the methylene blue (MB) in the presence of activated carbon (AC) as the adsorbent Solid Phase Extraction (SPE) of Sn (II) and then determined by UV-Vis. The Beer's law is obeyed over the concentration range of 1-80ngmL(-1) of Sn (II) with the detection limits of 0.34ngmL(-1). The influence of type and volume of eluent, concentration of MB, pH, and amount of AC on sensitivity of spectrophotometric method were optimized. The method has been successfully applied for Sn (II) ion determination in soil sample. PMID:24394524

  10. Adsorption and desorption of Zn(II) and Cu(II) on Ca- alginate immobilized activated rice bran

    NASA Astrophysics Data System (ADS)

    Suratman, A.; Kamalia, N. Z.; Kusumawati, W. A.

    2016-02-01

    Ca-alginate immobilized activated rice bran has been used for adsorption of Zn(II) and Cu(II) from aqueous solution. The effect of the pH, kinetics model, adsorption isotherm and desorption on the adsorption performance was investigated. Activated rice bran was immobilized by the entrapment in alginate beads. The adsorption strength of Ca-alginate immobilized activated rice bran was compared to Ca-alginate and non-immobilized activated rice bran. The concentrations of adsorbed ions were analyzed using Atomic Absorption Spectrophotometer (AAS). The result showed that pH of 4.0 and the contact time of 120 min are the optimum condition for adsorption of Zn(II) and Cu(II). The adsorption kinetic of Zn(II) and Cu(II) followed the pseudo-second-order model with adsorption rate constant 4.9 x 10-2 and 3.14 g.mg-1.min-1, respectively. The both adsorption processes obeyed Langmuir isotherm with adsorption capacity of 2.03 and 2.42 mg.g-1 of adsorbent, respectively. The strength of Zn adsorption on Ca-alginate immobilized activated rice bran (86.63%) was more effective compared to Ca-alginate beads (60.96%) and activated rice bran (43.85%). The strength of Cu adsorption was 80.00%, 61.50% and 22.10%, respectively. The desorption of Zn(II) and Cu(II) showed that recovery percentage of the adsorption was 76.56% and 57.80% with the condition of using HCl 0.1 M as desorption agent for 1 hour.

  11. Msn2p/Msn4p act as a key transcriptional activator of yeast cytoplasmic thiol peroxidase II.

    PubMed

    Hong, Seung-Keun; Cha, Mee-Kyung; Choi, Yong-Soo; Kim, Won-Cheol; Kim, Il-Han

    2002-04-01

    We observed that the transcription of Saccharomyces cerevisiae cytoplasmic thiol peroxidase type II (cTPx II) (YDR453C) is regulated in response to various stresses (e.g. oxidative stress, carbon starvation, and heat-shock). It has been suggested that both transcription-activating proteins, Yap1p and Skn7p, regulate the transcription of cTPx II upon exposure to oxidative stress. However, a dramatic loss of transcriptional response to various stresses in yeast mutant strains lacking both Msn2p and Msn4p suggests that the transcription factors act as a principal transcriptional activator. In addition to two Yap1p response elements (YREs), TTACTAA and TTAGTAA, the presence of two stress response elements (STREs) (CCCCT) in the upstream sequence of cTPx II also suggests that Msn2p/Msn4p could control stress-induced expression of cTPx II. Analysis of the transcriptional activity of site-directed mutagenesis of the putative STREs (STRE1 and STRE2) and YREs (TRE1 and YRE2) in terms of the activity of a lacZ reporter gene under control of the cTPx II promoter indicates that STRE2 acts as a principal binding element essential for transactivation of the cTPx II promoter. The transcriptional activity of the cTPx II promoter was exponentially increased after postdiauxic growth. The transcriptional activity of the cTPx II promoter is greatly increased by rapamycin. Deletion of Tor1, Tor2, Ras1, and Ras2 resulted in a considerable induction when compared with their parent strains, suggesting that the transcription of cTPx II is under negative control of the Ras/cAMP and target of rapamycin signaling pathways. Taken together, these results suggest that cTPx II is a target of Msn2p/Msn4p transcription factors under negative control of the Ras-protein kinase A and target of rapamycin signaling pathways. Furthermore, the accumulation of cTPx II upon exposure to oxidative stress and during the postdiauxic shift suggests an important antioxidant role in stationary phase yeast cells

  12. Large-N Over the Source Physics Experiment (SPE) Phase I and Phase II Test Beds

    NASA Astrophysics Data System (ADS)

    Snelson, C. M.; Carmichael, J. D.; Mellors, R. J.; Abbott, R. E.

    2014-12-01

    One of the current challenges in the field of monitoring and verification is source discrimination of low-yield nuclear explosions from background seismicity, both natural and anthropogenic. Work is underway at the Nevada National Security Site to conduct a series of chemical explosion experiments using a multi-institutional, multi-disciplinary approach. The goal of this series of experiments, called the Source Physics Experiments (SPE), is to refine the understanding of the effect of earth structures on source phenomenology and energy partitioning in the source region, the transition of seismic energy from the near field to the far field, and the development of S waves observed in the far field. To fully explore these problems, the SPE series includes tests in both hard and soft rock geologic environments. The project comprises a number of activities, which range from characterizing the shallow subsurface to acquiring new explosion data from both the near field (<100 m) and the far field (>100 m). SPE includes a series of planned explosions (with different yields and depths of burials), which are conducted in the same hole and monitored by a diverse set of sensors recording characteristics of the explosions, ground-shock, seismo-acoustic energy propagation. This presentation focuses on imaging the full 3D wavefield over hard rock and soft rock test beds using a large number of seismic sensors. This overview presents statistical analyses of optimal sensor layout required to estimate wavefield discriminants and the planned deployment for the upcoming experiments. This work was conducted under Contract No. DE-AC52-06NA25946 with the U.S. Department of Energy. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

  13. Protein kinase a activity is increased in rat heart during late hypodynamic phase of sepsis.

    PubMed

    Yang, S L; Hsu, C; Lue, S I; Hsu, H K; Liu, M S

    1997-07-01

    Changes in the activities of protein kinase A (PKA, or cAMP-dependent protein kinase) in rat heart during different cardiodynamic phases of sepsis were investigated. Sepsis was induced by cecal ligation and puncture. Experiments were divided into three groups: control, early sepsis, and late sepsis. Early and late sepsis refers to those animals killed at 9 and 18 h, respectively, after cecal ligation and puncture. Cardiac PKA was extracted and partially purified by acid precipitation, ammonium sulfate fractionation, and DEAE-cellulose chromatography. PKA was eluted from DEAE-cellulose column with a linear NaCl gradient. Two peaks of PKA, type I (eluted at low ionic strength) and type II (eluted at high ionic strength), were collected and their activities were determined based on the rate of incorporation of [gamma-32P]ATP into histone. Results obtained show that during early sepsis, both type I and type II PKA activities were unaffected. During late sepsis, type I PKA activities were stimulated by 66.7-97.7%, while type II PKA activities remained constant. Kinetic analysis of the data on type I PKA during late sepsis reveals that the Vmax values for ATP, cAMP, and histone were increased by 84.7, 66.7, and 97.7%, respectively; while the Km values for ATP, cAMP, and histone were unaltered. These data indicate that type I PKA is activated in rat heart during late hypodynamic phase of sepsis. Since kinase-mediated phosphorylation plays an important role in regulating myocardial function and metabolism, an activation of type I PKA during late sepsis may contribute to the development of altered myocardial function during hypodynamic phase of sepsis. PMID:9249915

  14. Type-II phase resetting curve is optimal for stochastic synchrony

    NASA Astrophysics Data System (ADS)

    Abouzeid, Aushra; Ermentrout, Bard

    2009-07-01

    The phase-resetting curve (PRC) describes the response of a neural oscillator to small perturbations in membrane potential. Its usefulness for predicting the dynamics of weakly coupled deterministic networks has been well characterized. However, the inputs to real neurons may often be more accurately described as barrages of synaptic noise. Effective connectivity between cells may thus arise in the form of correlations between the noisy input streams. We use constrained optimization and perturbation methods to prove that the PRC shape determines susceptibility to synchrony among otherwise uncoupled noise-driven neural oscillators. PRCs can be placed into two general categories: type-I PRCs are non-negative, while type-II PRCs have a large negative region. Here we show that oscillators with type-II PRCs receiving common noisy input synchronize more readily than those with type-I PRCs.

  15. 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.

  16. 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.

  17. BWR Full Integral Simulation Test (FIST) Phase II test results and TRAC-BWR model qualification

    SciTech Connect

    Sutherland, W A; Alamgir, M; Findlay, J A; Hwang, W S

    1985-10-01

    Eight matrix tests were conducted in the FIST Phase I. These tests investigated the large break, small break and steamline break LOCA's, as well as natural circulation and power transients. There are nine tests in Phase II of the FIST program. They include the following LOCA tests: BWR/6 LPCI line break, BWR/6 intermediate size recirculation break, and a BWR/4 large break. Steady state natural circulation tests with feedwater makeup performed at high and low pressure, and at high pressure with HPCS makeup, are included. Simulation of a transient without rod insertion, and with controlled depressurization, was performed. Also included is a simulation of the Peach Bottom turbine trip test. The final two tests simulated a failure to maintain water level during a postulated accident. A FIST program objective is to assess the TRAC code by comparisons with test data. Two post-test predictions made with TRACB04 are compared with Phase II test data in this report. These are for the BWR/6 LPCI line break LOCA, and the Peach Bottom turbine trip test simulation.

  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. Early Investigational Therapeutics for Gastrointestinal Motility Disorders: From Animal Studies to Phase II Trials

    PubMed Central

    Valentin, Nelson; Acosta, Andres; Camilleri, Michael

    2015-01-01

    Introduction The most common gastrointestinal disorders which include evidence of dysmotility include: gastroparesis, the lower functional gastrointestinal disorders associated with altered bowel function [such as chronic (functional) diarrhea, chronic idiopathic constipation (CIC)], and opioid induced constipation (OIC). These conditions, which are grouped as gastrointestinal motility and functional disorders, are characterized by abnormal motor, sensory, or secretory functions that alter bowel function and result in a significant disease burden, since currently available treatments do not completely alleviate symptoms. New drugs are being developed for these disorders, targeting mechanisms involved in the pathophysiology of these diseases, specifically, motor function, intestinal secretion and bile acid modulation. Areas Covered The article provides a brief overview of motility disorders and the drugs approved and currently available for these indications. It also provides an evaluation of the efficacy, safety and possible mechanisms of the drugs currently under investigation for the treatment of gastroparesis, chronic diarrhea, CIC and OIC, based on animal to phase II studies. Medications with complete phase III trials are excluded from this discussion. Expert opinion Treatment of gastrointestinal motility disorders requires the understanding of the pathophysiological mechanisms, biomarkers to identify subgroups of these disorders, and robust pharmacological studies from animal to phase II studies. These are prerequisites for the development of efficacious medications and individualizing therapy in order to enhance the treatment of these patients. PMID:25971881

  20. Activation analysis of the PULSAR-II fusion power reactor

    SciTech Connect

    Khater, H.Y.

    1995-12-31

    The PULSAR-II pulsed tokamak power plant design utilizes a blanket made of the vanadium alloy, V-5Cr-5Ti, and cooled with liquid lithium. The shield is made of a mixture of the low activation austenitic steel (Tenelon) and vanadium. The blanket is assumed to be replaced every 5.6 full power years (FPY) and the shield is assumed to stay in place for 30 FPY. The activity induced in the blanket at the end of its lifetime is higher than the activity induced in the shield after 30 FPY. At shutdown, the blanket and shield activities are 2678 MCi and 1747 MCi, respectively. One year after shutdown the shield activity drops to 18 MCi compared to 84 MCi for the blanket. The total decay heat generated in the blanket at the end of its lifetime is 34.7 MW and drops to 17.6 MW within an hour. At shutdown, 25.3 MW of decay heat are generated in the shield, dropping to only 0.1 MW within the first year. One week after shutdown, the values of the integrated decay heat are 1770 GJ for the blanket and 469 GJ for the shield. The radwaste classification of the reactor structure is evaluated according to both the NRC 10CFR61 and Fetter waste disposal concentration limits. After 5.6 years of irradiation, the blanket will only qualify for Class C low level waste. After 30 years of operation, the shield will also qualify for disposal as Class C waste. Only remote maintenance will be allowed inside the containment building.

  1. HOPE-X high speed flight demonstration program phase II - A CNES / NAL / NASDA cooperation

    NASA Astrophysics Data System (ADS)

    Venel, S.; Faucon, P.; Yanagihara, M.; Miyazawa, Y.; Akimoto, T.; Sagisaka, M.

    A High Speed Flight Demonstration (HSFD) program is planned as part of the NAL/NASDA joint research for the HOPE-X unmanned re-entry vehicle project. The program consists of two phases. The purpose of HSFD Phase I is to verify the subsystems for the terminal phase of the HOPE-X return flight, using a jet engine powered scaled model. The purpose of HSFD Phase II is to estimate the transonic aerodynamic characteristic of the HOPE-X configuration : a HOPE-X 25% scaled vehicle will be lifted to high altitude by a stratospheric balloon, from where it will be released and accelerate into free fall to a defined Mach Number. The HSFD Phase II is conducted in collaboration with the CNES Balloon Division of France. It is responsible for the balloon system, the launch operation, and the flight service including the site (SSC base in Esrange near Kiruna in Sweden), the TM/TC system, the flight survey, the safety and the helicopter recovery after touch down. Six flights are planned between May and August 2003. CNES has an extensive experience in engineering experiments with balloons. The HSFD flight mission is nevertheless a very unusual one, and CNES has to lead specific development. In particular, the CNES/HSFD interface required CNES to develop a dedicated housekeeping gondola in order to power supply the vehicle during the ground tests and the flight under the balloon. The HSFD vehicle and the CNES gondola are integrated in the flight train through a dedicated mechanical interface piece together with a dedicated release system. The launch procedures have also to be adapted. A flight campaign took place in Kiruna last August 2001, to train the team to launch the vehicle, and to test the release system and the CNES power supply gondola. CNES is now manufacturing all the HOPE-X balloon interface equipment.

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

    PubMed

    Mishra, Kavita K; Squire, Sarah; Lamborn, Kathleen; Banerjee, Anuradha; Gupta, Nalin; Wara, William M; Prados, Michael D; Berger, Mitchel S; Haas-Kogan, Daphne A

    2010-10-01

    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

  4. Final Phase I-Phase II interim report : expedited site characterization, Morrill, Kansas.

    SciTech Connect

    LaFreniere, L. M.

    2005-10-20

    The city of Morrill, Kansas, is located in Brown County, in the northeastern corner of the state. The town lies about 7 mi east of Sabetha and about 10 mi northwest of Hiawatha (Figure 1.1). The population of Morrill as of the 2000 census was approximately 277. The Commodity Credit Corporation (CCC), an agency of the U.S. Department of Agriculture (USDA), operated a grain storage facility in the northwestern section of Morrill from 1950 until 1971. The property continued to be used for grain storage after 1971. Fourteen of the original 21 CCC/USDA circular bin structures remain today. Prior to 1986, commercial grain fumigants containing carbon tetrachloride were commonly used by the CCC/USDA and the grain storage industry to preserve grain. Contamination with carbon tetrachloride, also known as tetrachloromethane, was initially identified in groundwater at Morrill in October 1985 in public water supply well PWS5, during statewide testing of public water supply wells for volatile organic compounds (VOCs). A preliminary assessment was completed by the Kansas Department of Health and Environment (KDHE) in 1989 to obtain background information on the Morrill public water supply and to identify potential sources of the detected carbon tetrachloride contamination (KDHE 1989). Since 1991 the city of Morrill has obtained its water by pipeline from the municipal water supply of Sabetha. Water supplied through the Sabetha system comes from a surface reservoir. Former public wells in Morrill are no longer used for municipal supply. Wells PWS3, PWS4, and PWS5 were plugged in 1993. Wells PWS1 and PWS2 are no longer in active production, but they continue to be available for non-drinking purposes such as bulk hauling for agricultural uses, fire fighting, and road work (Hansen 2001). Because the KDHE found carbon tetrachloride in the groundwater at the former CCC/USDA facility at Morrill that could, in part, be linked to historical use of carbon tetrachloride-based grain

  5. 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.

  6. [Spanish version of the new World Health Organization Disability Assessment Schedule II (WHO-DAS-II): initial phase of development and pilot study. Cantabria disability work group].

    PubMed

    Vázquez-Barquero, J L; Vázquez Bourgón, E; Herrera Castanedo, S; Saiz, J; Uriarte, M; Morales, F; Gaite, L; Herrán, A; Ustün, T B

    2000-01-01

    The aim of the present paper is to present the initial phases of the development of the Spanish version of the "World Health Organization Disablement Assessment Schedule II" WHO-DAS-II and also to describe the quantitative and qualitative methodological strategies used in the elaboration process of an instrument: i) compatible with the new International Classification of Functioning and Disability -ICIDH-2- of the World Health Organisation; ii) with criteria of cross-cultural applicability and; iii) to allow us to assess the disability in all its dimensions. PMID:10937388

  7. Manganese(II) induces cell division and increases in superoxide dismutase and catalase activities in an aging deinococcal culture

    SciTech Connect

    Chou, F.I.; Tan, S.T. )

    1990-04-01

    Addition of Mn(II) at 2.5 microM or higher to stationary-phase cultures of Deinococcus radiodurans IR was found to trigger at least three rounds of cell division. This Mn(II)-induced cell division (Mn-CD) did not occur when the culture was in the exponential or death phase. The Mn-CD effect produced daughter cells proportionally reduced in size, pigmentation, and radioresistance but proportionally increased in activity and amount of the oxygen toxicity defense enzymes superoxide dismutase and catalase. In addition, the concentration of an Mn-CD-induced protein was found to remain high throughout the entire Mn-CD phase. It was also found that an untreated culture exhibited a growth curve characterized by a very rapid exponential-stationary transition and that cells which had just reached the early stationary phase were synchronous. Our results suggest the presence of an Mn(II)-sensitive mechanism for controlling cell division. The Mn-CD effect appears to be specific to the cation Mn(II) and the radioresistant bacteria, deinococci.

  8. Noncollinear parametric amplification in the near-infrared based on type-II phase matching

    NASA Astrophysics Data System (ADS)

    Schmidt, C.; Bühler, J.; Heinrich, A.-C.; Leitenstorfer, A.; Brida, D.

    2015-09-01

    Noncollinear parametric amplification based on type-II phase matching for the generation of ultrabroadband and tunable spectra in the near infrared is investigated. In a noncollinear geometry the group velocity matching condition between signal and idler can be obtained in frequently used crystals such as β-barium borate (BBO) even for wavelengths fully located in the anomalous dispersion region. The extremely broadband operation, peculiar tuning possibilities and straightforward experimental implementation with the standard BBO crystal pave the way for a versatile NIR source in ultrafast spectroscopy.

  9. 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

  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. Benchmark calculations on the phase II problem of uncertainty analyses for criticality safety assessment

    SciTech Connect

    Lee, G. S.; Lee, J.; Kim, G. Y.; Woo, S. W.

    2012-07-01

    The phase II benchmark problem of expert group UACSA includes a configuration of a PWR fuel storage rack and focuses on the uncertainty of criticality from manufacturing tolerance of design parameters such as fuel enrichment, density, diameter, thickness of neutron absorber and structural material, and so on. It provides probability density functions for each design parameter. In this paper, upper limits of k{sub eff} of 95%/95% tolerance with two methods are calculated by sampling design parameters using given probability distributions and compared with the result from traditional approach. (authors)

  12. Orbital phase dependent IUE spectra of the nova like binary II Arietis

    NASA Technical Reports Server (NTRS)

    Guinan, E. F.; Sion, E. M.

    1981-01-01

    Nine low dispersion IUE spectra of the nova like binary TT Ari over its 3h17m orbital period were obtained. Four short wave spectra and five long wave spectra exhibit marked changes in line strength and continuum shape with orbital phase. The short wave spectra show the presence in absorption of C III, Lyman alpha, SiIII, NV, SiIV, CIV, HeII, AlIII, and NIV. The CIV shows a P Cygni profile on two of the spectra. Implications of these spectra for the nature of nova like variables are discussed.

  13. Phase I/II Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Patients With Advanced Melanoma

    PubMed Central

    Ott, Patrick A.; Hamid, Omid; Pavlick, Anna C.; Kluger, Harriet; Kim, Kevin B.; Boasberg, Peter D.; Simantov, Ronit; Crowley, Elizabeth; Green, Jennifer A.; Hawthorne, Thomas; Davis, Thomas A.; Sznol, Mario; Hwu, Patrick

    2014-01-01

    Purpose The antibody-drug conjugate glembatumumab vedotin links a fully human immunoglobulin G2 monoclonal antibody against the melanoma-related glycoprotein NMB (gpNMB) to the potent cytotoxin monomethyl auristatin E. This study evaluated the safety and activity of glembatumumab vedotin in patients with advanced melanoma. Patients and Methods Patients received glembatumumab vedotin every 3 weeks (schedule 1) in a dose escalation and phase II expansion at the maximum-tolerated dose (MTD). Dosing during 2 of 3 weeks (schedule 2) and weekly (schedule 3) was also assessed. The primary end points were safety and pharmacokinetics. The secondary end points included antitumor activity, gpNMB expression, and immunogenicity. Results One hundred seventeen patients were treated using schedule 1 (n = 79), schedule 2 (n = 15), or schedule 3 (n = 23). The MTDs were 1.88, 1.5, and 1.0 mg/kg for schedules 1, 2, and 3, respectively. Grade 3/4 treatment-related toxicities that occurred in two or more patients included rash, neutropenia, fatigue, neuropathy, arthralgia, myalgia, and diarrhea. Three treatment-related deaths (resulting from pneumococcal sepsis, toxic epidermal necrolysis, and renal failure) occurred at doses exceeding the MTDs. In the schedule 1 phase II expansion cohort (n = 34), five patients (15%) had a partial response and eight patients (24%) had stable disease for ≥ 6 months. The objective response rate (ORR) was 2 of 6 (33%) for the schedule 2 MTD and 3 of 12 (25%) for the schedule 3 MTD. Rash was correlated with a greater ORR and improved progression-free survival. Conclusion Glembatumumab vedotin is active in advanced melanoma. The schedule 1 MTD (1.88 mg/kg once every 3 weeks) was associated with a promising ORR and was generally well tolerated. More frequent dosing was potentially associated with a greater ORR but increased toxicity. PMID:25267741

  14. Synthesis, characterization and biological activity of some new VO(IV), Co(II), Ni(II), Cu(II) and Zn(II) complexes of chromone based NNO Schiff base derived from 2-aminothiazole

    NASA Astrophysics Data System (ADS)

    Kalanithi, M.; Kodimunthiri, D.; Rajarajan, M.; Tharmaraj, P.

    2011-11-01

    Coordination compounds of VO(IV), Co(II), Ni(II), Cu(II) and Zn(II) with the Schiff base obtained through the condensation of 2-aminothiazole with 3-formyl chromone were synthesized. The compounds were characterized by 1H, 13C NMR, UV-Vis, IR, Mass, EPR, molar conductance and magnetic susceptibility measurements. The Cu(II) complex possesses tetrahedrally distorted square planar geometry whereas Co(II), Ni(II), and Zn(II) show distorted tetrahedral geometry. The VO(IV) complex shows square pyramidal geometry. The cyclic voltammogram of Cu (II) complex showed a well defined redox couple Cu(II)/Cu(I) with quasireversible nature. The antimicrobial activity against the species Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Candida albigans and Aspergillus niger was screened and compared to the activity of the ligand. Emission spectrum was recorded for the ligand and the metal(II) complexes. The second harmonic generation (SHG) efficiency was measured and found to have one fourth of the activity of urea. The SEM image of the copper(II) complex implies that the size of the particles is 2 μm.

  15. Middeck Active Control Experiment (MACE), phase A

    NASA Technical Reports Server (NTRS)

    Crawley, Edward F.; Deluis, Javier; Miller, David W.

    1989-01-01

    A rationale to determine which structural experiments are sufficient to verify the design of structures employing Controlled Structures Technology was derived. A survey of proposed NASA missions was undertaken to identify candidate test articles for use in the Middeck Active Control Experiment (MACE). The survey revealed that potential test articles could be classified into one of three roles: development, demonstration, and qualification, depending on the maturity of the technology and the mission the structure must fulfill. A set of criteria was derived that allowed determination of which role a potential test article must fulfill. A review of the capabilities and limitations of the STS middeck was conducted. A reference design for the MACE test article was presented. Computing requirements for running typical closed-loop controllers was determined, and various computer configurations were studied. The various components required to manufacture the structure were identified. A management plan was established for the remainder of the program experiment development, flight and ground systems development, and integration to the carrier. Procedures for configuration control, fiscal control, and safety, reliabilty, and quality assurance were developed.

  16. Function of redox-active tyrosine in photosystem II.

    PubMed

    Ishikita, Hiroshi; Knapp, Ernst-Walter

    2006-06-01

    Water oxidation at photosystem II Mn-cluster is mediated by the redox-active tyrosine Y(Z). We calculated the redox potential (E(m)) of Y(Z) and its symmetrical counterpart Y(D), by solving the linearized Poisson-Boltzmann equation. The calculated E(m)(Y( )/Y(-)) were +926 mV/+694 mV for Y(Z)/Y(D) with the Mn-cluster in S2 state. Together with the asymmetric position of the Mn-cluster relative to Y(Z/D), differences in H-bond network between Y(Z) (Y(Z)/D1-His(190)/D1-Asn(298)) and Y(D) (Y(D)/D2-His(189)/D2-Arg(294)/CP47-Glu(364)) are crucial for E(m)(Y(Z/D)). When D1-His(190) is protonated, corresponding to a thermally activated state, the calculated E(m)(Y(Z)) was +1216 mV, which is as high as the E(m) for P(D1/D2). We observed deprotonation at CP43-Arg(357) upon S-state transition, which may suggest its involvement in the proton exit pathway. E(m)(Y(D)) was affected by formation of P(D2)(+) (but not P(D1)(+)) and sensitive to the protonation state of D2-Arg(180). This points to an electrostatic link between Y(D) and P(D2). PMID:16513785

  17. Active transcription and essential role of RNA polymerase II at the centromere during mitosis

    PubMed Central

    Chan, F. Lyn; Marshall, Owen J.; Saffery, Richard; Won Kim, Bo; Earle, Elizabeth; Choo, K. H. Andy; Wong, Lee H.

    2012-01-01

    Transcription of the centromeric regions has been reported to occur in G1 and S phase in different species. Here, we investigate whether transcription also occurs and plays a functional role at the mammalian centromere during mitosis. We show the presence of actively transcribing RNA polymerase II (RNAPII) and its associated transcription factors, coupled with the production of centromere satellite transcripts at the mitotic kinetochore. Specific inhibition of RNAPII activity during mitosis leads to a decrease in centromeric α-satellite transcription and a concomitant increase in anaphase-lagging cells, with the lagging chromosomes showing reduced centromere protein C binding. These findings demonstrate an essential role of RNAPII in the transcription of α-satellite DNA, binding of centromere protein C, and the proper functioning of the mitotic kinetochore. PMID:22308327

  18. He II Liquid/Vapor Phase Separator for Large Dynamic Range Operation

    NASA Technical Reports Server (NTRS)

    Nakano, A.; Petrac, D.

    1995-01-01

    A phase separator, which separates helium vapor from liquid superfluid helium (He II), is an indispensable device for space cryogenics. The most recent approach to the Space Infrared Telescope Facility (SIRTF) uses a new design concept in which only the detector package is cold at launch, the remainder of the telescope being subsequently cooled to operating temperature on orbit. Therefore, a large dynamic operational range is required of the cryogen system. This is a report of initial laboratory test results with candidate porous plugs as phase separators. Mass flow rates and pressure and temperature differences across a porous plug were measured in this experiment. Relatively large mass flow rates were observed even at small pressure differences. In the high mass flow rate region, a hysteresis was observed with increases and decreases of the pressure difference. A linear theory is proposed and compared with experimental data to explain several phenomena observed in this system.

  19. 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.

  20. Effects of polyaromatic hydrocarbons on photosystem II activity in pea leaves.

    PubMed

    Kreslavski, Vladimir D; Lankin, Anton V; Vasilyeva, Galina K; Luybimov, Valery Yu; Semenova, Galina N; Schmitt, Franz-Josef; Friedrich, Thomas; Allakhverdiev, Suleyman I

    2014-08-01

    The acute effects of three typical polyaromatic hydrocarbons (PAHs): naphthalene (Naph), phenanthrene (Phen) and fluoranthene (Flu) on photochemical activity of photosystem II (PSII) in detached leaves of 3-week-old pea plants were studied. The leaves were exposed in water with PAHs under white light for 0.5-72 h. The activity of PSII was examined by prompt and delayed chlorophyll a (Chl a) fluorescence. The effects of PAHs depended on their concentration and exposure time. This dependency was more significant in the presence of chemical stressors (Triton X-100 or acetone) or under high intensity irradiance. Increased content of PAHs and long-term exposure (24-72 h) led to significant reduction of the maximum photochemical quantum efficiency (Fv/Fm) of PS II, changes in the polyphasic fluorescence induction (OJIP), and to decreasing amplitudes of fast and slow components of delayed Chl a fluorescence. The damage of PSII depended on water solubility of a given type of PAHs, their concentration and exposure time. During short-time exposure the compound with highest water-solubility - naphthalene - revealed the strongest effect. During long-time exposure the compounds with low water-solubility -Phen, Flu-revealed the strongest effect as the corresponding PAH accumulates in the thylakoids especially when the solution is oversaturated containing a solid phase. The reduction of PSII activity at the presence of naphthalene (30 mg L(-1)) was accompanied by transient generation of H2O2 as well as swelling of thylakoids and distortion of cell plasma membranes, which was indicated by electron microscopy images. Distortion of thylakoid membranes due to accumulation of PAHs as well as the development of oxidative stress seems to be the main pathways of PAHs influencing the photochemical activity of PS II. PMID:24637130