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Sample records for flinders sensitive line

  1. Olfactory discrimination and memory deficits in the Flinders Sensitive Line rodent model of depression.

    Science.gov (United States)

    Cook, A; Pfeiffer, L-M; Thiele, S; Coenen, V A; Döbrössy, M D

    2017-10-01

    Major Depressive Disorder (MDD) is a heterogeneous psychiatric disorder with broad symptomatic manifestations. The current study examined, for the first time, olfactory memory and discrimination in the Flinders Sensitive Line (FSL) rodent model of depression. Male FSL rats and controls were trained on an Olfactory Discrimination (OD) and a Social Interaction (SI) test. On the OD test, the FSL and controls performed similarly at the shortest inter-trial interval (5min), however, with extended delay of 30min, the FSLs had a recall and odour discrimination deficit. At the longest delay (60min) both groups performed poorly. The FSL rats i.) had a deficit in olfactory discrimination suggesting impairment in olfactory memory and recall; ii.) were less likely to socialize with unfamiliar rats. The data suggests that FSL animals have an impaired olfactory information processing capacity. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Neuropeptide s alters anxiety but not depression-like behaviors in the flinders sensitive line rats, a genetic animal model

    DEFF Research Database (Denmark)

    Mathe, A.; Wegener, Gregers; Finger, B.

    2010-01-01

    Background: Neuropeptide S (NPS) and its receptor (NPSR) have been implicated in the mediation of anxiolytic-like behavior in rodents. However, little knowledge is available to what extent the NPS system is involved in depression-related behaviors. The aim of the present work was to characterize...... the effects of centrally administered NPS on depression- and anxiety-related behaviors, using a well validated animal model of depression, the Flinders Sensitive Line (FSL) rats and their controls the Flinders Resistant Line (FRL). Methods: Male and female were tested. Seven days following insertion....... In selected animals effect of NPS on home cage activity was explored. Finally, brains from separate groups of naive animals were harvested; hippocampi, amygdalae and PVN punched out, and mRNA transcripts measured with the real-time quantitative polymerase chain reaction (rt-qPCR). Results: The most salient...

  3. The brain 5-HT4 receptor binding is down-regulated in the Flinders Sensitive Line depression model and in response to paroxetine administration

    DEFF Research Database (Denmark)

    Licht, Cecilie Löe; Marcussen, Anders Bue; Wegener, Gregers

    2009-01-01

    The 5-hydroxytryptamine (5-HT(4)) receptor may be implicated in depression and is a new potential target for antidepressant treatment. We have investigated the brain 5-HT(4) receptor [(3)H]SB207145 binding in the Flinders Sensitive Line rat depression model by quantitative receptor autoradiography....... In the Flinders Sensitive Line, the 5-HT(4) receptor and 5-HT transporter binding were decreased in the dorsal and ventral hippocampus, and the changes in binding were directly correlated within the dorsal hippocampus. Chronic but not acute paroxetine administration caused a 16-47% down-regulation of 5-HT(4......) receptor binding in all regions evaluated including the basal ganglia and hippocampus, while 5-HT depletion increased the 5-HT(4) receptor binding in the dorsal hippocampus, hypothalamus, and lateral globus pallidus. In comparison, the 5-HT(2A) receptor binding was decreased in the frontal and cingulate...

  4. Effects of Pyridostigmine in Flinders Line Rats Differing in Cholinergic Sensitivity (AIBS GWI 0055)

    National Research Council Canada - National Science Library

    Overstreet, David

    1999-01-01

    .... The second aim was to determine whether pyridostigmine had prophylactic effects against the organophosphates chlorpyrifos and diisopropylfluorophosphate regardless of innate cholinergic sensitivity...

  5. Neuropeptide S alters anxiety, but not depression-like behaviour in Flinders Sensitive Line rats: a genetic animal model of depression.

    Science.gov (United States)

    Wegener, Gregers; Finger, Beate C; Elfving, Betina; Keller, Kirsten; Liebenberg, Nico; Fischer, Christina W; Singewald, Nicolas; Slattery, David A; Neumann, Inga D; Mathé, Aleksander A

    2012-04-01

    Neuropeptide S (NPS) and its receptor (NPSR) have been implicated in the mediation of anxiolytic-like behaviour in rodents. However, little knowledge is available regarding the NPS system in depression-related behaviours, and whether NPS also exerts anxiolytic effects in an animal model of psychopathology. Therefore, the aim of this work was to characterize the effects of NPS on depression- and anxiety-related parameters, using male and female rats in a well-validated animal model of depression: the Flinders Sensitive Line (FSL), their controls, the Flinders Resistant Line (FRL), and Sprague-Dawley (SD) rats. We found that FSL showed greater immobility in the forced swim test (FST) than FRL, confirming their phenotype. However, NPS did not affect depression-related behaviour in any rat line. No significant differences in baseline anxiety levels between the FSL and FRL strains were observed, but FSL and FRL rats displayed less anxiety-like behaviour compared to SD rats. NPS decreased anxiety-like behaviour on the elevated plus-maze in all strains. The expression of the NPSR in the amygdala, periventricular hypothalamic nucleus, and hippocampus was equal in all male strains, although a trend towards reduced expression within the amygdala was observed in FSL rats compared to SD rats. In conclusion, NPS had a marked anxiolytic effect in FSL, FRL and SD rats, but did not modify the depression-related behaviour in any strain, in spite of the significant differences in innate level between the strains. These findings suggest that NPS specifically modifies anxiety behaviour but cannot overcome/reverse a genetically mediated depression phenotype.

  6. Exploring a post-traumatic stress disorder paradigm in Flinders sensitive line rats to model treatment-resistant depression I: bio-behavioural validation and response to imipramine.

    Science.gov (United States)

    Brand, Sarel Jacobus; Harvey, Brian Herbert

    2017-08-01

    Co-morbid depression with post-traumatic stress disorder (PTSD) is often treatment resistant. In developing a preclinical model of treatment-resistant depression (TRD), we combined animal models of depression and PTSD to produce an animal with more severe as well as treatment-resistant depressive-like behaviours. Male Flinders sensitive line (FSL) rats, a genetic animal model of depression, were exposed to a stress re-stress model of PTSD [time-dependent sensitisation (TDS)] and compared with stress-naive controls. Seven days after TDS stress, depressive-like and coping behaviours as well as hippocampal and cortical noradrenaline (NA) and 5-hydroxyindoleacetic acid (5HIAA) levels were analysed. Response to sub-chronic imipramine treatment (IMI; 10 mg/kg s.c.×7 days) was subsequently studied. FSL rats demonstrated bio-behavioural characteristics of depression. Exposure to TDS stress in FSL rats correlated negatively with weight gain, while demonstrating reduced swimming behaviour and increased immobility versus unstressed FSL rats. IMI significantly reversed depressive-like (immobility) behaviour and enhanced active coping behaviour (swimming and climbing) in FSL rats. The latter was significantly attenuated in FSL rats exposed to TDS versus unstressed FSL rats. IMI reversed reduced 5HIAA levels in unstressed FSL rats, whereas exposure to TDS negated this effect. Lowered NA levels in FSL rats were sustained after TDS with IMI significantly reversing this in the hippocampus. Combining a gene-X-environment model of depression with a PTSD paradigm produces exaggerated depressive-like symptoms that display an attenuated response to antidepressant treatment. This work confirms combining FSL rats with TDS exposure as a putative animal model of TRD.

  7. The flinders sensitive line rats, a genetic model of depression, show abnormal serotonin receptor mRNA expression in the brain that is reversed by 17beta-estradiol.

    Science.gov (United States)

    Osterlund, M K; Overstreet, D H; Hurd, Y L

    1999-12-10

    The possible link between estrogen and serotonin (5-HT) in depression was investigated using a genetic animal model of depression, the Flinders Sensitive Line (FSL) rats, in comparison to control Flinders Resistant Line rats. The mRNA levels of the estrogen receptor (ER) alpha and beta subtypes and the 5-HT(1A) and 5-HT(2A) receptors were analyzed in several limbic-related areas of ovariectomized FSL and FRL rats treated with 17beta-estradiol (0.15 microg/g) or vehicle. The FSL animals were shown to express significantly lower levels of the 5-HT(2A) receptor transcripts in the perirhinal cortex, piriform cortex, and medial anterodorsal amygdala and higher levels in the CA 2-3 region of the hippocampus. The only significant difference between the rat lines in ER mRNA expression was found in the medial posterodorsal amygdala, where the FSL rats showed lower ERalpha expression levels. Overall, estradiol treatment increased 5-HT(2A) and decreased 5-HT(1A) receptor mRNA levels in several of the examined regions of both lines. Thus, in many areas, estradiol was found to regulate the 5-HT receptor mRNA expression in the opposite direction to the alterations found in the FSL rats. These findings further support the implication of 5-HT receptors, in particular the 5-HT(2A) subtype, in the etiology of affective disorders. Moreover, the ability of estradiol to regulate the expression of the 5-HT(1A) and 5-HT(2A) receptor genes might account for the reported influence of gonadal hormones in mood and depression.

  8. Garcinia mangostana Linn displays antidepressant-like and pro-cognitive effects in a genetic animal model of depression: a bio-behavioral study in the Flinders Sensitive Line rat.

    Science.gov (United States)

    Oberholzer, Inge; Möller, Marisa; Holland, Brendan; Dean, Olivia M; Berk, Michael; Harvey, Brian H

    2018-04-01

    There is abundant evidence for both disorganized redox balance and cognitive deficits in major depressive disorder (MDD). Garcinia mangostana Linn (GM) has anti-oxidant activity. We studied the antidepressant-like and pro-cognitive effects of raw GM rind in Flinders Sensitive Line (FSL) rats, a genetic model of depression, following acute and chronic treatment compared to a reference antidepressant, imipramine (IMI). The chemical composition of the GM extract was analysed for levels of α- and γ-mangostin. The acute dose-dependent effects of GM (50, 150 and 200 mg/kg po), IMI (20 mg/kg po) and vehicle were determined in the forced swim test (FST) in FSL rats, versus Flinders Resistant Line (FRL) control rats. Locomotor testing was conducted using the open field test (OFT). Using the most effective dose above coupled with behavioral testing in the FST and cognitive assessment in the novel object recognition test (nORT), a fixed dose 14-day treatment study of GM was performed and compared to IMI- (20 mg/kg/day) and vehicle-treated animals. Chronic treated animals were also assessed with respect to frontal cortex and hippocampal monoamine levels and accumulation of malondialdehyde. FSL rats showed significant cognitive deficits and depressive-like behavior, with disordered cortico-hippocampal 5-hydroxyindole acetic acid (5-HIAA) and noradrenaline (NA), as well as elevated hippocampal lipid peroxidation. Acute and chronic IMI treatment evoked pronounced antidepressant-like effects. Raw GM extract contained 117 mg/g and 11 mg/g α- and γ-mangostin, respectively, with acute GM demonstrating antidepressant-like effects at 50 mg/kg/day. Chronic GM (50 mg/kg/d) displayed significant antidepressant- and pro-cognitive effects, while demonstrating parity with IMI. Both behavioral and monoamine assessments suggest a more prominent serotonergic action for GM as opposed to a noradrenergic action for IMI, while both IMI and GM reversed hippocampal lipid peroxidation in

  9. Flinders University Electric Vehicle Project

    Science.gov (United States)

    Atkinson, D. A.

    1973-01-01

    Outlines the specifications and principles involved in the operation of an electric car developed by the Institute of Solar and Electochemical Energy Conversion at Flinders University in South Australia. (JR)

  10. Flinders Petrie and Eugenics at UCL

    Directory of Open Access Journals (Sweden)

    Kathleen L. Sheppard

    2010-05-01

    Full Text Available William Matthew Flinders Petrie is considered the father of scientific archaeology and is credited with developing a chronology of Ancient Egypt using the nondescript artefacts that other archaeologists had ignored. He occupied the first chair of Egyptology in England, and was also well-known for the museum built around his personal collection of Egyptian artifacts at University College London. Petrie's archaeological work has been studied by scholars, from various disciplines, for its scholarly, cultural, and historical value, while Petrie's life and career outside of archaeology have been the subject of relatively little study. Petrie himself wrote two life stories: the first, 'Ten Years Digging in Egypt, 1881–1891' (1892, detailed the years before his professorship at UCL; in 1932 he published his second, more complete autobiography, 'Seventy Years in Archaeology'. After he died in 1942 there were various obituaries and memorials that outlined his life and major achievements in archaeology. There was very little written about Petrie the man until 1985, when Margaret Drower's 'Flinders Petrie: A Life in Archaeology' was published; it remains the most comprehensive work on Petrie's life. A thin volume of the correspondence of Hilda and Flinders Petrie also allows a glimpse into life on excavation. In short, much of what is known about Petrie focuses on his excavations in Egypt, his time as Professor of Egyptology at University College London, or the museum that bears his name. Subsequently, as a historical matter, Petrie's work in the discipline of eugenics has rarely been discussed as part of his career.

  11. The Flinders University inductively driven spherical Tokamak project

    International Nuclear Information System (INIS)

    McCarthy, L.

    1998-01-01

    Full text: The Flinders University inductive start up Spherical Tokamak (ST) program is designed with two major functions: first a target plasma for a definitive test of rotating magnetic field (RMF) current drive, and secondly as a target plasma to be used in development of diagnostics for the collaboration between Flinders University and the Australian National Fusion Facility. A third goal is to maintain an Australian link to the international ST community at a time when this ST approach to plasma fusion is entering a ''second generation'' phase of larger machines, following the demonstration of resilience to major disruptions on START and MEDUSA, and excellent confinement properties, and β. Modelling of the optimum operating regime consistent with power supplies available at Flinders University, and comparisons of plasmas prepared by RMF alone with ohmically heated plasmas such as START, are presented to support the need for the design of this OH hot confined target plasma approach to RMF current drive as an alternative to that of pure RMF current drive at higher powers being attempted elsewhere, should that approach not prove successful. Progress on the experiments, which now includes successful tests of the toroidal field system and the OH coil system, is reported. The RMF facility will not be available till late in 1998. The case is made for retaining the valuable equipment resources of the Flinders University plasma research group and negotiating for the transfer of these to the Australian National Fusion Facility at the completion of this project at the end of 1999

  12. Isolation of two chloroethylnitrosourea-sensitive Chinese hamster cell lines

    International Nuclear Information System (INIS)

    Hata, H.; Numata, M.; Tohda, H.; Yasui, A.; Oikawa, A.

    1991-01-01

    1-[(4-Amino-2-methylpyrimidin-5-yl)methyl]-3-(2-chloroethyl)-3- nitrosourea hydrochloride (ACNU), a cancer chemotherapeutic bifunctional alkylating agent, causes chloroethylation of DNA and subsequent DNA strand cross-linking through an ethylene bridge. We isolated and characterized two ACNU-sensitive mutants from mutagenized Chinese hamster ovary cells and found them to be new drug-sensitive recessive Chinese hamster mutants. Both mutants were sensitive to various monofunctional alkylating agents in a way similar to that of the parental cell lines CHO9. One mutant (UVS1) was cross-sensitive to UV and complemented the UV sensitivity of all Chinese hamster cell lines of 7 established complementation groups. Since UV-induced unscheduled DNA synthesis was very low, a new locus related to excision repair is thought to be defective in this cell line. Another ACNU-sensitive mutant, CNU1, was slightly more sensitive to UV than the parent cell line. CNU1 was cross-sensitive to 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and slightly more sensitive to mitomycin C. No increased accumulation of ACNU and a low level of UV-induced unscheduled DNA synthesis in this cell as compared with the parental cell line suggest that there is abnormality in a repair response of this mutant cell to some types of DNA cross-links

  13. Radiation sensitivity of human lung cancer cell lines

    International Nuclear Information System (INIS)

    Carmichael, J.; Degraff, W.G.; Gamson, J.; Russo, G.; Mitchell, J.B.; Gazdar, A.F.; Minna, J.D.; Levitt, M.L.

    1989-01-01

    X-Ray survival curves were determined using a panel of 17 human lung cancer cell lines, with emphasis on non-small cell lung cancer (NSCLC). In contrast to classic small cell lung cancer (SCLC) cell lines, NSCLC cell lines were generally less sensitive to radiation as evidenced by higher radiation survival curve extrapolation numbers, surviving fraction values following a 2Gy dose (SF2) and the mean inactivation dose values (D) values. The spectrum of in vitro radiation responses observed was similar to that expected in clinical practice, although mesothelioma was unexpectedly sensitive in vitro. Differences in radiosensitivity were best distinguished by comparison of SF2 values. Some NSCLC lines were relatively sensitive, and in view of this demonstrable variability in radiation sensitivity, the SF2 value may be useful for in vitro predictive assay testing of clinical specimens. (author)

  14. Evaluasi Tingkat Kesiapan Organisasi dalam Rangka Preservasi Digital (Studi Kasus Pada Unit Repositori Flinders Academic Commons Of Flinders University Library (FACFUL, Adelaide, Australia Selatan

    Directory of Open Access Journals (Sweden)

    Rattahpinnusa Haresariu Handisa

    2017-12-01

    Full Text Available Penelitian ini bertujuan mengidentifikasi tingkat kesiapan lembaga repositori dalam rangka preservasi digital pada Flinders Academic Commons Flinders University Library (FACFUL dan mengidentifikasi faktor-faktor yang berpengaruh terhadap tingkat kesiapan organisasi. Terdapat tiga aspek yang diteliti meliputi: kesiapan infrastruktur, kesiapan teknologi serta sumber daya yang dibutuhkan bagi preservasi digital. Penelitian ini menggunakan metode studi kasus dengan  intesity sampel. Adapun instrumen pengumpulan data menggunakan Cornell University Survey of Institutional Readiness Checklist. Selanjutnya, tehnik pengambilan data menggunakan tehnik wawancara dengan Ms. Liz-Walkley Hall selaku pustakawati yang bertanggung jawab terhadap unit repositori digital FACFUL. Adapun informasi penunjang diperoleh melalui studi kepustakaan merujuk pada website Perpustakaan Universitas  Flinders. Data yang terkumpul dianalisis secara deskriptif menggunakan indikator kesiapan organisasi Cornel University Model. Hasil penelitian menunjukkan bahwa unit repositori pada FACFUL kurang siap dalam menjalankan preservasi digital. Tingkat kesiapan organisasi Perpustakaan Universitas  Flinders dalam pelestarian digital berapa pada level terbawah yakni Acknowledgement . Pada tingkat tersebut, Perpustakaan Flinders masih dalam tahap pengembangan kesadaran tentang pentingnya preservasi digital. Selanjutnya, faktor-faktor yang mempengaruhi rendahnya tingkat kesiapan organisasi tersebut adalah tidak adanya pernyataan pentingya preservasi digital pada kebijakan pengembangan koleksi; keterbatasan pendanaan dan keterbatasan sumber daya manusia yang kompeten dalam preservasi digital. Penelitian ini merekomendasikan Perpustakaan Universitas Flinders untuk  melakukan uji kelayakan bagi preservasi digital. Salah satu model bisnis yang sesuai dengan kondisi Perpustakaan Universitas  Flinders adalah Meta Archive Model (MAM. Model tersebut berbasis komunitas bagi preservasi digital

  15. Radiation sensitivity of Merkel cell carcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Leonard, J.H.; Ramsay, J.R.; Birrell, G.W. [Queensland Institute of Medical Research (Australia)] [and others

    1995-07-30

    Merkel cell carcinoma (MCC), being a small cell carcinoma, would be expected to be sensitive to radiation. Clinical analysis of patients at our center, especially those with macroscopic disease, would suggest the response is quite variable. We have recently established a number of MCC cell lines from patients prior to radiotherapy, and for the first time are in a position to determine their sensitivity under controlled conditions. Some of the MCC lines grew as suspension cultures and could not be single cell cloned; therefore, it was not possible to use clonogenic survival for all cell lines. A tetrazolium based (MTT) assay was used for these lines, to estimate cell growth after {gamma} irradiation. Control experiments were conducted on lymphoblastoid cell lines (LCL) and the adherent MCC line, MCC13, to demonstrate that the two assays were comparable under the conditions used. We have examined cell lines from MCC, small cell lung cancer (SCLC), malignant melanomas, Epstein Barr virus (EBV) transformed lymphocytes (LCL), and skin fibroblasts for their sensitivity to {gamma} irradiation using both clonogenic cell survival and MTT assays. The results show that the tumor cell lines have a range of sensitivities, with melanoma being more resistant (surviving fraction at 2 Gy (SF2) 0.57 and 0.56) than the small cell carcinoma lines, MCC (SF2 range 0.21-0.45, mean SF2 0.30, n = 8) and SCLC (SF2 0.31). Fibroblasts were the most sensitive (SF2 0.13-0.20, mean 0.16, n = 5). The MTT assay, when compared to clonogenic assay for the MCC13 adherent line and the LCL, gave comparable results under the conditions used. Both assays gave a range of SF2 values for the MCC cell lines, suggesting that these cancers would give a heterogeneous response in vivo. The results with the two derivative clones of MCC14 (SF2 for MCC14/1 0.38, MCC14/2 0.45) would further suggest that some of them may develop resistance during clonogenic evolution. 25 refs., 3 figs., 1 tab.

  16. Radiation sensitivity of Merkell cell carcinoma cell lines

    International Nuclear Information System (INIS)

    Leonard, J. Helen; Ramsay, Jonathan R.; Kearsley, John H.; Birrell, Geoff W.

    1995-01-01

    Purpose: Merkel cell carcinoma (MCC), being a small cell carcinoma, would be expected to be sensitive to radiation. Clinical analysis of patients at our center, especially those with macroscopic disease, would suggest the response is quite variable. We have recently established a number of MCC cell lines from patients prior to radiotherapy, and for the first time are in a position to determine their sensitivity under controlled conditions. Methods and Materials: Some of the MCC lines grew as suspension cultures and could not be single cell cloned; therefore, it was not possible to use clonogenic survival for all cell lines. A tetrazolium based (MTT) assay was used for these lines, to estimate cell growth after γ irradiation. Control experiments were conducted on lymphoblastoid cell lines (LCL) and the adherent MCC line, MCC13, to demonstrate that the two assays were comparable under the conditions used. Results: We have examined cell lines from MCC, small cell lung cancer (SCLC), malignant melanomas, Epstein Barr virus (EBV) transformed lymphocytes (LCL), and skin fibroblasts for their sensitivity to γ irradiation using both clonogenic cell survival and MTT assays. The results show that the tumor cell lines have a range of sensitivities, with melanoma being more resistant (surviving fraction at 2 Gy (SF2) 0.57 and 0.56) than the small cell carcinoma lines, MCC (SF2 range 0.21-0.45, mean SF2 0.30, n = 8) and SCLC (SF2 0.31). Fibroblasts were the most sensitive (SF2 0.13-0.20, mean 0.16, n = 5). The MTT assay, when compared to clonogenic assay for the MCC13 adherent line and the LCL, gave comparable results under the conditions used. Conclusion: Both assays gave a range of SF2 values for the MCC cell lines, suggesting that these cancers would give a heterogeneous response in vivo. The results with the two derivative clones of MCC14 (SF2 for MCC14/1 0.38, MCC14/2 0.45) would further suggest that some of them may develop resistance during clonogenic evolution

  17. The rotamak - contributions from ANSTO and Flinders University

    International Nuclear Information System (INIS)

    Jones, I.R.

    1998-01-01

    Full text: The investigation of plasma/field configurations of the compact torus variety is of current interest in the field of fusion research. Two configurations of this genre are the field reversed configuration (FRC), which does not have an externally applied toroidal magnetic field, and the spherical tokamak (ST) which possesses such a field. Both of these compact torus concepts, as studied outside Australia, suffer from the very serious disadvantage that they are inherently pulsed devices; the toroidal plasma current is not maintained indefinitely. The rotamak is a compact torus configuration having the unique and distinctive feature that the toroidal plasma current is driven in a steady-state, non-inductive fashion by means of the application of a rotating magnetic field. In its basic form, the rotamak is operated as an FRC. However, by means of a simple modification, a steady toroidal magnetic field can be added to the basic rotamak apparatus and the configuration then becomes that of an ST. The rotamak concept was conceived and developed in Australia and the bulk of investigations in this field, both theoretical and experimental, have been undertaken at Flinders University (1979-1998) and AAEC/ANSTO (1982-1988). This talk will cover the history of the project in this country, will dwell on the marvelous interaction which flourished between the two research groups and will finish with the news that the rotamak concept has been enthusiastically embraced by fusion research teams in the United States

  18. Caffeine markedly sensitizes human mesothelioma cell lines to pemetrexed

    Science.gov (United States)

    Min, Sang Hee; Goldman, I. David; Zhao, Rongbao

    2013-01-01

    Pemetrexed is a new generation antifolate approved for the treatment of mesothelioma and non-small cell lung cancer. Caffeine is known to augment radiation or chemotherapeutic drug-induced cell killing. The current study addresses the impact of caffeine on the activity of pemetrexed in mesothelioma cell lines. Caffeine enhanced pemetrexed activity in all four mesothelioma cell lines tested (H2052, H2373, H28 and MSTO-211H). Caffeine sensitized H2052 cells in a dose- and schedule-dependent manner, and was associated with a markedly decreased clonogenic survival. Caffeine sensitization occurred only in cells subjected to pulse, but not continuous, exposure to pemetrexed. Similar pemetrexed sensitization was also observed with the clinically better tolerated caffeine analog, theobromine. Pemetrexed sensitization by caffeine was associated with an increase in pemetrexed-induced phosphorylation of ataxia-telangiectasia-mutated (ATM) and Chk1. These data indicate that caffeine and its analog, theobromine, may be a useful approach to enhance pemetrexed-based chemotherapy. PMID:17594092

  19. Sensitivity of grounding line dynamics to basal conditions

    Science.gov (United States)

    Gagliardini, O.; Brondex, J.; Chauveau, G.; Gillet-chaulet, F.; Durand, G.

    2017-12-01

    In the context of a warming climate, the dynamical contribution of Antarctica to future sea level rise is still tainted by high uncertainties. Among the processes entering these uncertainties is the link between basal hydrology, friction and grounding line dynamics. Recent works have shown how sensitive is the response of the grounding line retreat to the choice of the form of the friction law. Indeed, starting from the same initial state, grounding line retreat rates can range over almost two orders of magnitude depending on the friction law formulation.Here, we use a phenomenological law that depends on the water pressure and allows a continuous transition from a Weertman-type friction at low water pressure to a Coulomb-type friction at high water pressure. This friction law depends on two main parameters that control the Weertman and Coulomb regimes. The range of values for these two parameters is only weakly physically constrained, and it can be shown that, for a given basal shear stress, different couples of parameters can conduct to the same sliding velocity. In addition, we show that close to the grounding line where basal water pressure is high, determining these two parameters might conduct to an ill-posed inverse problem with no solution.The aim of this presentation is to discuss a methodology to guide the choice of the two friction parameters and explore the sensitivity of the grounding line dynamics to this initial choice. We present results obtained both on a synthetic configuration used by the Marine Ice Sheet Model Intercomparison exercise and for the Amundsen sea sector using the experiments proposed by InitMIP-Antarctica, the first exercise in a series of ISMIP6 ice-sheet model intercomparison activities.

  20. Measuring the sensitivity of a boron-lined ion chamber

    International Nuclear Information System (INIS)

    Barton, D.M.

    1992-03-01

    Boron-lined ion chambers are used to monitor external neutron flux from fissionable materials assembled at the Los Alamos Critical Assembly Experiment Facility. The sensitivity of these chambers must be measured periodically in order to detect changes in filling gas and to evaluate other factors that may affect chamber performance. We delineate a procedure to measure ion chamber response using a particular neutron source ( 239 PuBe) in a particular moderating geometry of polyethylene. We also discuss use of the amplifier, high-voltage power supply, recorders, and scram circuits that comprise the complete ion chamber monitoring system

  1. Delay-Line Three-Dimensional Position Sensitive Radiation Detection

    Science.gov (United States)

    Jeong, Manhee

    High-resistivity silicon(Si) in large volumes and with good charge carrier transport properties has been produced and achieved success as a radiation detector material over the past few years due to its relatively low cost as well as the availability of well-established processing technologies. One application of that technology is in the fabrication of various position-sensing topologies from which the incident radiation's direction can be determined. We have succeeded in developing the modeling tools for investigating different position-sensing schemes and used those tools to examine both amplitude-based and time-based methods, an assessment that indicates that fine position-sensing can be achieved with simpler readout designs than are conventionally deployed. This realization can make ubiquitous and inexpensive deployment of special nuclear materials (SNM) detecting technology becomes more feasible because if one can deploy position-sensitive semiconductor detectors with only one or two contacts per side. For this purpose, we have described the delay-line radiation detector and its optimized fabrication. The semiconductor physics were simulated, the results from which guided the fabrication of the guard ring structure and the detector electrode, both of which included metal-field-plates. The measured improvement in the leakage current was confirmed with the fabricated devices, and the structures successfully suppressed soft-breakdown. We also demonstrated that fabricating an asymmetric strip-line structure successfully minimizing the pulse shaping and increases the distance through which one can propagate the information of the deposited charge distribution. With fabricated delay-line detectors we can acquire alpha spectra (Am-241) and gamma spectra (Ba-133, Co-57 and Cd-109). The delay-line detectors can therefore be used to extract the charge information from both ion and gamma-ray interactions. Furthermore, standard charge-sensitive circuits yield high SNR

  2. Sensitivity of the PEP beam transport line to perturbations

    International Nuclear Information System (INIS)

    Peterson, J.M.; Brown, K.L.

    1979-03-01

    The sensitivity of a beam-transport line to various perturbations determines the extent to which one can simplify component design and relax tolerances. For the PEP injection lines, effects of various fabrication errors, magnet misalignments, and residual gas scattering were studied. Using the TURTLE ray-tracing program, it is found that magnetic-field errors corresponding to a relative sextupole strength in the dipoles of 0.5% and/or a relative sextupole or octupole strength in the quadrupoles of 5% are permissible. This allows relatively loose tolerances in magnet fabrication. Transverse misalignment of a quadrupole by a distance x causes the beam centroid to be displaced downstream by as much as 5x. This requires a quadrupole alignment accuracy of +- 0.5 mm or better. No compensation for the earth's field is necessary because an integral number of optical wavelengths and a short wavelength were used for the design. Analysis shows that beam broadening from multiple coulomb scattering is insignificant for pressures of less than 1/10 torr

  3. Flinders Island spotted fever rickettsioses caused by "marmionii" strain of Rickettsia honei, Eastern Australia.

    Science.gov (United States)

    Unsworth, Nathan B; Stenos, John; Graves, Stephen R; Faa, Antony G; Cox, G Erika; Dyer, John R; Boutlis, Craig S; Lane, Amanda M; Shaw, Matthew D; Robson, Jennifer; Nissen, Michael D

    2007-04-01

    Australia has 4 rickettsial diseases: murine typhus, Queensland tick typhus, Flinders Island spotted fever, and scrub typhus. We describe 7 cases of a rickettsiosis with an acute onset and symptoms of fever (100%), headache (71%), arthralgia (43%), myalgia (43%), cough (43%), maculopapular/petechial rash (43%), nausea (29%), pharyngitis (29%), lymphadenopathy (29%), and eschar (29%). Cases were most prevalent in autumn and from eastern Australia, including Queensland, Tasmania, and South Australia. One patient had a history of tick bite (Haemaphysalis novaeguineae). An isolate shared 99.2%, 99.8%, 99.8%, 99.9%, and 100% homology with the 17 kDa, ompA, gltA, 16S rRNA, and Sca4 genes, respectively, of Rickettsia honei. This Australian rickettsiosis has similar symptoms to Flinders Island spotted fever, and the strain is genetically related to R. honei. It has been designated the "marmionii" strain of R. honei, in honor of Australian physician and scientist Barrie Marmion.

  4. Sensitivity of breast cancer cell lines to recombinant thiaminase I.

    Science.gov (United States)

    Liu, Shuqian; Monks, Noel R; Hanes, Jeremiah W; Begley, Tadhg P; Yu, Hui; Moscow, Jeffrey A

    2010-05-01

    We have previously shown that the expression of the thiamine transporter THTR2 is decreased sevenfold in breast cancer, which may leave breast cancer cells vulnerable to acute thiamine starvation. This concept was supported by the observation that MDA231 breast cancer xenografts demonstrated growth inhibition in mice fed a thiamine-free diet. We purified recombinant Bacillus thiaminolyticus thiaminase I enzyme, which digests thiamine, to study acute thiamine starvation in breast cancer. Thiaminase I enzyme was cytotoxic in six breast cancer cell lines with IC(50)s ranging from 0.012 to 0.022 U/ml. The growth inhibitory effects of the combination of thiaminase I with either doxorubicin or paclitaxel were also examined. Over a wide range of drug concentrations, thiaminase 1 was consistently synergistic or additive with doxorubicin and paclitaxel in MCF-7, ZR75, HS578T and T47D cell lines, with most combinations having a calculated combination index (CI) of less than 0.8, indicating synergy. Although thiaminase I exposure did not stimulate the energy-sensing signaling kinases AKT, AMPK and GSK-3beta in MCF-7, ZR75, HS578T and T47D cell lines, thiaminase I exposure did stimulate expression of the ER stress response protein GRP78. In summary, thiaminase I is cytotoxic in breast cancer cell lines and triggers the unfolded protein response. These findings suggest that THTR2 down-regulation in breast tumors may present a nutritional vulnerability that could be exploited by thiaminase I enzyme therapy.

  5. 9-β-arabinofuranosyladenine preferentially sensitizes radioresistant squamous cell carcinoma cell lines to x-rays

    International Nuclear Information System (INIS)

    Heaton, D.

    1992-06-01

    The effect of 9-β-arabinofuranosyladenine (ara-A) on sensitivity to the deleterious effects of x-rays was studied in six squamous cell carcinoma cell lines. Three lines were relatively radioresistant, having D 0 values of 2.31 to 2.89 Gy, and the other three lines were relatively radiosensitive, having D 0 values of between 1.07 and 1.45 Gy. Ara-A (50 or 500 μM) was added to cultures 30 min prior to irradiation and removed 30 min after irradiation, and sensitivity was measured in terms of cell survival. The radiosensitizing effect of ara-A was very dependent on the inherent radiosensitivity of the tumor cell line. Fifty micromolar concentrations of ara-A sensitized only the two most radioresistant lines, SCC-12B.2 and JSQ-3. Five hundred micromolar concentrations of ara-A sensitized the more sensitive cell lines, SQ-20B and SQ-9G, but failed to have any effect on the radiation response of the two most sensitive cell lines, SQ-38 and SCC-61. Concentrations of ara-A as low as 10 μM were equally efficient in inhibiting DNA synthesis in all six cell lines. These results suggest that the target for the radiosensitizing effect of ara-A is probably related to the factor controlling the inherent radiosensitivity of human tumor cells. Therefore, ara-A might be useful in overcoming radiation resistance in vivo

  6. 9-{beta}-arabinofuranosyladenine preferentially sensitizes radioresistant squamous cell carcinoma cell lines to x-rays

    Energy Technology Data Exchange (ETDEWEB)

    Heaton, D. [Rush Univ. Medical Center, Chicago, IL (United States). Therapeutic Radiology; Mustafi, R. [Chicago Univ., IL (United States). Dept. of Radiation and Cellular Oncology; Schwartz, J.L. [Chicago Univ., IL (United States). Dept. of Radiation and Cellular Oncology]|[Argonne National Lab., IL (United States)

    1992-06-01

    The effect of 9-{beta}-arabinofuranosyladenine (ara-A) on sensitivity to the deleterious effects of x-rays was studied in six squamous cell carcinoma cell lines. Three lines were relatively radioresistant, having D{sub 0} values of 2.31 to 2.89 Gy, and the other three lines were relatively radiosensitive, having D{sub 0} values of between 1.07 and 1.45 Gy. Ara-A (50 or 500 {mu}M) was added to cultures 30 min prior to irradiation and removed 30 min after irradiation, and sensitivity was measured in terms of cell survival. The radiosensitizing effect of ara-A was very dependent on the inherent radiosensitivity of the tumor cell line. Fifty micromolar concentrations of ara-A sensitized only the two most radioresistant lines, SCC-12B.2 and JSQ-3. Five hundred micromolar concentrations of ara-A sensitized the more sensitive cell lines, SQ-20B and SQ-9G, but failed to have any effect on the radiation response of the two most sensitive cell lines, SQ-38 and SCC-61. Concentrations of ara-A as low as 10 {mu}M were equally efficient in inhibiting DNA synthesis in all six cell lines. These results suggest that the target for the radiosensitizing effect of ara-A is probably related to the factor controlling the inherent radiosensitivity of human tumor cells. Therefore, ara-A might be useful in overcoming radiation resistance in vivo.

  7. High sensitivity on-line monitor for radioactive effluent

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, Toshimi [Tohoku Electric Power Co. Ltd., Sendai (Japan); Ishizuka, Akira; Abe, Eisuke; Inoue, Yasuhiko; Fujii, Masaaki; Kitaguchi, Hiroshi; Doi, Akira

    1983-04-01

    A new approach for a highly sensitive effluent monitor is presented. The free flow type monitor, which consists of a straightener, nozzle, monitoring section and ..gamma..-ray detector, is demonstrated to be effective in providing long term stability. The 160 start-and-stop cycles of effluent discharge were repeated in a 120-h testing period. Results showed a background increase was not observed for the free flow type monitor. The background count rate was calibrated to the lowest detection limit to be 2.2 x 10/sup -2/ Bq/ml for a 300 s measurement time.

  8. Flinders Island Spotted Fever Rickettsioses Caused by “marmionii” Strain of Rickettsia honei, Eastern Australia

    Science.gov (United States)

    Unsworth, Nathan B.; Graves, Stephen R.; Faa, Antony G.; Cox, G. Erika; Dyer, John R.; Boutlis, Craig S.; Lane, Amanda M.; Shaw, Matthew D.; Robson, Jennifer; Nissen, Michael D.

    2007-01-01

    Australia has 4 rickettsial diseases: murine typhus, Queensland tick typhus, Flinders Island spotted fever, and scrub typhus. We describe 7 cases of a rickettsiosis, with an acute onset and symptoms of fever (100%), headache (71%), arthralgia (43%), myalgia (43%), cough (43%), maculopapular/petechial rash (43%), nausea (29%), pharyngitis (29%), lymphadenopathy (29%), and eschar (29%). Cases were most prevalent in autumn and from eastern Australia, including Queensland, Tasmania, and South Australia. One patient had a history of tick bite (Haemaphysalis novaeguineae). An isolate shared 99.2%, 99.8%, 99.8%, 99.9%, and 100% homology with the 17 kDa, ompA, gltA, 16S rRNA, and Sca4 genes, respectively, of Rickettsia honei. This Australian rickettsiosis has similar symptoms to Flinders Island spotted fever, and the strain is genetically related to R. honei. It has been designated the “marmionii” strain of R. honei, in honor of Australian physician and scientist Barrie Marmion. PMID:17553271

  9. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: Central California: REPTILEL (Reptile and Amphibian Lines)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains sensitive biological resource data for amphibians and reptiles in Central California. Vector lines in this data set represent general stream...

  10. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: South Florida: ESIL (ESI Shoreline Types - Lines)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The ESIL data set contains vector lines representing the shoreline and coastal habitats of South Florida classified according to the Environmental Sensitivity Index...

  11. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: South Florida: HYDRO (Hydrography Lines and Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains vector lines and polygons representing coastal hydrography used in the creation of the Environmental Sensitivity Index (ESI) for South...

  12. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: Southern California: FISHL (Fish Lines)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains sensitive biological resource data for threatened/endandered/rare and/or anadromous fish species in Southern California. Vector lines in this...

  13. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: Central California: FISHL (Fish Lines)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains sensitive biological resource data for anadromous fish and rare fish species occurrences in Central California. Vector lines in this data set...

  14. Virginia ESI: ESI (Environmental Sensitivity Index Shoreline Types - Lines and Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains vector lines and polygons representing the shoreline and coastal habitats for Virginia, classified according to the Environmental Sensitivity...

  15. Maryland ESI: ESI (Environmental Sensitivity Index Shoreline Types - Lines and Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains vector lines and polygons representing the shoreline and coastal habitats for Maryland, classified according to the Environmental Sensitivity...

  16. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: Southern California: HYDRO (Hydrography Lines and Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains vector lines and polygons representing coastal hydrography used in the creation of the Environmental Sensitivity Index (ESI) for Southern...

  17. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: Central California: HYDRO (Hydrography Lines and Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains vector lines and polygons representing coastal hydrography used in the creation of the Environmental Sensitivity Index (ESI) for Central...

  18. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: Northern California: HYDRO (Hydrography Lines and Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains vector lines and polygons representing coastal hydrography used in the creation of the Environmental Sensitivity Index (ESI) for Northern...

  19. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: New Hampshire: HYDRO (Hydrography Lines and Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains vector lines and polygons representing coastal hydrography used in the creation of the Environmental Sensitivity Index (ESI) for New...

  20. Productivity and abundance of large sponge populations on Flinders Reef flats, Coral Sea

    Science.gov (United States)

    Wilkinson, Clive R.

    1987-04-01

    Large populations of flattened sponges with cyanobacterial symbionts were observed on the shallow reef-flats of the Flinders Reefs, Coral Sea. Estimates of these populations indicated as many as 60 individuals with a total wet biomass of 1.2 kg per m2 in some areas. Along a metre wide transect across 1.3 km of reef flat the population was estimated at 530 kg wet weight sponge (mean 411 g m-2). The four prominent species had instantaneous P/R ratios between 1.3 and 1.8 at optimum light such that photosynthetic productivity was calculated to provide between 61 and 80% of sponge energy requirements in summer and 48 to 64% in winter. While such sponge beds are a prominent feature of these reefs, they appear to contribute less than 10% of gross reef-flat productivity.

  1. Establishment of cell lines derived from ataxia telangiectasia and xeroderma pigmentosum patients with high radiation sensitivity

    International Nuclear Information System (INIS)

    Hashimoto, Tomoko; Furuyama, Jun-ichi; Nakano, Yoshiro; Owada, M. Koji; Kakunaga, Takeo

    1986-01-01

    Four human fibroblast cell lines, three of which were derived from a patient with ataxia telangiectasia and the other from a patient with xeroderma pigmentosum, were established after transfection with cloned SV40 DNA. These 4 cell lines showed some phenotypes characteristic of neoplastically transformed cells, and had a human karyotype with heteromorphisms identical to those of the parental fibroblasts. Their sensitivity to the cytotoxic effects of γ-rays or ultraviolet irradiation was as high as those of their parental fibroblasts. (Auth.)

  2. Solar monochromatic images in magneto-sensitive spectral lines and maps of vector magnetic fields

    Science.gov (United States)

    Shihui, Y.; Jiehai, J.; Minhan, J.

    1985-01-01

    A new method which allows by use of the monochromatic images in some magneto-sensitive spectra line to derive both the magnetic field strength as well as the angle between magnetic field lines and line of sight for various places in solar active regions is described. In this way two dimensional maps of vector magnetic fields may be constructed. This method was applied to some observational material and reasonable results were obtained. In addition, a project for constructing the three dimensional maps of vector magnetic fields was worked out.

  3. Expression of Ku correlates with radiation sensitivities in the head and neck cancer cell lines

    International Nuclear Information System (INIS)

    Lee, Sang Wook; Yu, Eun Sil; Yi, So Lyoung; Son, Se Hee; Kim, Jong Hoon; Ahn, Seung Do; Shin, Seong Soo; Choi, Eun Kyung

    2004-01-01

    DNA-dependent protein kinase (DNA-PK) is a serine/threonine kinase consisting of a 470 kDa catalytic subunit (DNA-PKcs) and a heterodimeric regulatory complex, called Ku, which is composed of 70 kDa (Ku 70) and 86 kDa (Ku 80) proteins. The DNA-PK has been shown to play a pivotal role in rejoining DNA double-strand-breaks (dsb) in mammalian cells. The purpose of this study is to examine the relationship between the level of Ku expression and radiation sensitivity. Nine head and neck, cancer cell lines showed various intrinsic radiation sensitivities. Among the nine, AMC-HN-3 cell was the most sensitive for X-ray irradiation and AMC-HN-9 cell was the most resistance. The most sensitive and resistant cell lines were selected and the test sensitivity of radiation and expression of Ku were measured. Radiation sensitivity was obtained by colony forming assay and Ku protein expression using Western blot analysis. Ku80 increased expression by radiation, wheras Ku70 did not. Overexpression of Ku80 protein increased radiation resistance in AMC-HN9 cell line. There was a correlation between Ku80 expression and radiation resistance. Ku80 was shown to play an important role in radiation damage response. Induction of Ku80 expression had an important role in DNA damage repair by radiation. Ku80 expression may be an effective predictive assay of radiosensitivity on head and neck cancer

  4. Chicken lines divergently selected for antibody responses to sheep red blood cells show line-specific differences in sensitivity to immunomodulation by diet. Part I: Humoral parameters

    NARCIS (Netherlands)

    Adriaansen-Tennekes, R.; Vries Reilingh, de G.; Nieuwland, M.G.B.; Parmentier, H.K.; Savelkoul, H.F.J.

    2009-01-01

    Individual differences in nutrient sensitivity have been suggested to be related with differences in stress sensitivity. Here we used layer hens divergently selected for high and low specific antibody responses to SRBC (i.e., low line hens and high line hens), reflecting a genetically based

  5. 3-Bromopyruvate induces necrotic cell death in sensitive melanoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Qin, J.-Z.; Xin, H. [Oncology Institute, Cardinal Bernardin Cancer Center, Loyola University of Chicago Medical Center (United States); Nickoloff, B.J., E-mail: bnickol@lumc.edu [Oncology Institute, Cardinal Bernardin Cancer Center, Loyola University of Chicago Medical Center (United States)

    2010-05-28

    Clinicians successfully utilize high uptake of radiolabeled glucose via PET scanning to localize metastases in melanoma patients. To take advantage of this altered metabolome, 3-bromopyruvate (BrPA) was used to overcome the notorious resistance of melanoma to cell death. Using four melanoma cell lines, BrPA triggered caspase independent necrosis in two lines, whilst the other two lines were resistant to killing. Mechanistically, sensitive cells differed from resistant cells by; constitutively lower levels of glutathione, reduction of glutathione by BrPA only in sensitive cells; increased superoxide anion reactive oxygen species, loss of outer mitochondrial membrane permeability, and rapid ATP depletion. Sensitive cell killing was blocked by N-acetylcysteine or glutathione. When glutathione levels were reduced in resistant cell lines, they became sensitive to killing by BrPA. Taken together, these results identify a metabolic-based Achilles' heel in melanoma cells to be exploited by use of BrPA. Future pre-clinical and clinical trials are warranted to translate these results into improved patient care for individuals suffering from metastatic melanoma.

  6. 3-Bromopyruvate induces necrotic cell death in sensitive melanoma cell lines.

    Science.gov (United States)

    Qin, J-Z; Xin, H; Nickoloff, B J

    2010-05-28

    Clinicians successfully utilize high uptake of radiolabeled glucose via PET scanning to localize metastases in melanoma patients. To take advantage of this altered metabolome, 3-bromopyruvate (BrPA) was used to overcome the notorious resistance of melanoma to cell death. Using four melanoma cell lines, BrPA triggered caspase independent necrosis in two lines, whilst the other two lines were resistant to killing. Mechanistically, sensitive cells differed from resistant cells by; constitutively lower levels of glutathione, reduction of glutathione by BrPA only in sensitive cells; increased superoxide anion reactive oxygen species, loss of outer mitochondrial membrane permeability, and rapid ATP depletion. Sensitive cell killing was blocked by N-acetylcysteine or glutathione. When glutathione levels were reduced in resistant cell lines, they became sensitive to killing by BrPA. Taken together, these results identify a metabolic-based Achilles' heel in melanoma cells to be exploited by use of BrPA. Future pre-clinical and clinical trials are warranted to translate these results into improved patient care for individuals suffering from metastatic melanoma. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  7. 3-Bromopyruvate induces necrotic cell death in sensitive melanoma cell lines

    International Nuclear Information System (INIS)

    Qin, J.-Z.; Xin, H.; Nickoloff, B.J.

    2010-01-01

    Clinicians successfully utilize high uptake of radiolabeled glucose via PET scanning to localize metastases in melanoma patients. To take advantage of this altered metabolome, 3-bromopyruvate (BrPA) was used to overcome the notorious resistance of melanoma to cell death. Using four melanoma cell lines, BrPA triggered caspase independent necrosis in two lines, whilst the other two lines were resistant to killing. Mechanistically, sensitive cells differed from resistant cells by; constitutively lower levels of glutathione, reduction of glutathione by BrPA only in sensitive cells; increased superoxide anion reactive oxygen species, loss of outer mitochondrial membrane permeability, and rapid ATP depletion. Sensitive cell killing was blocked by N-acetylcysteine or glutathione. When glutathione levels were reduced in resistant cell lines, they became sensitive to killing by BrPA. Taken together, these results identify a metabolic-based Achilles' heel in melanoma cells to be exploited by use of BrPA. Future pre-clinical and clinical trials are warranted to translate these results into improved patient care for individuals suffering from metastatic melanoma.

  8. Structure sensitivity of methanol electrooxidation pathways on platinum : an on-line electrochemical mass spectrometry study

    NARCIS (Netherlands)

    Housmans, T.H.M.; Wonders, A.H.; Koper, M.T.M.

    2006-01-01

    By monitoring the mass fractions of CO2 (m/z 44) and methylformate (m/z 60, formed from CH3OH + HCOOH) with on-line electrochemical mass spectrometry (OLEMS), the selectivity and structure sensitivity of the methanol oxidation pathways were investigated on the basal planesPt(111), Pt(110), and

  9. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity.

    Science.gov (United States)

    Barretina, Jordi; Caponigro, Giordano; Stransky, Nicolas; Venkatesan, Kavitha; Margolin, Adam A; Kim, Sungjoon; Wilson, Christopher J; Lehár, Joseph; Kryukov, Gregory V; Sonkin, Dmitriy; Reddy, Anupama; Liu, Manway; Murray, Lauren; Berger, Michael F; Monahan, John E; Morais, Paula; Meltzer, Jodi; Korejwa, Adam; Jané-Valbuena, Judit; Mapa, Felipa A; Thibault, Joseph; Bric-Furlong, Eva; Raman, Pichai; Shipway, Aaron; Engels, Ingo H; Cheng, Jill; Yu, Guoying K; Yu, Jianjun; Aspesi, Peter; de Silva, Melanie; Jagtap, Kalpana; Jones, Michael D; Wang, Li; Hatton, Charles; Palescandolo, Emanuele; Gupta, Supriya; Mahan, Scott; Sougnez, Carrie; Onofrio, Robert C; Liefeld, Ted; MacConaill, Laura; Winckler, Wendy; Reich, Michael; Li, Nanxin; Mesirov, Jill P; Gabriel, Stacey B; Getz, Gad; Ardlie, Kristin; Chan, Vivien; Myer, Vic E; Weber, Barbara L; Porter, Jeff; Warmuth, Markus; Finan, Peter; Harris, Jennifer L; Meyerson, Matthew; Golub, Todd R; Morrissey, Michael P; Sellers, William R; Schlegel, Robert; Garraway, Levi A

    2012-03-28

    The systematic translation of cancer genomic data into knowledge of tumour biology and therapeutic possibilities remains challenging. Such efforts should be greatly aided by robust preclinical model systems that reflect the genomic diversity of human cancers and for which detailed genetic and pharmacological annotation is available. Here we describe the Cancer Cell Line Encyclopedia (CCLE): a compilation of gene expression, chromosomal copy number and massively parallel sequencing data from 947 human cancer cell lines. When coupled with pharmacological profiles for 24 anticancer drugs across 479 of the cell lines, this collection allowed identification of genetic, lineage, and gene-expression-based predictors of drug sensitivity. In addition to known predictors, we found that plasma cell lineage correlated with sensitivity to IGF1 receptor inhibitors; AHR expression was associated with MEK inhibitor efficacy in NRAS-mutant lines; and SLFN11 expression predicted sensitivity to topoisomerase inhibitors. Together, our results indicate that large, annotated cell-line collections may help to enable preclinical stratification schemata for anticancer agents. The generation of genetic predictions of drug response in the preclinical setting and their incorporation into cancer clinical trial design could speed the emergence of 'personalized' therapeutic regimens.

  10. The Cancer Cell Line Encyclopedia enables predictive modeling of anticancer drug sensitivity

    Science.gov (United States)

    Barretina, Jordi; Caponigro, Giordano; Stransky, Nicolas; Venkatesan, Kavitha; Margolin, Adam A.; Kim, Sungjoon; Wilson, Christopher J.; Lehár, Joseph; Kryukov, Gregory V.; Sonkin, Dmitriy; Reddy, Anupama; Liu, Manway; Murray, Lauren; Berger, Michael F.; Monahan, John E.; Morais, Paula; Meltzer, Jodi; Korejwa, Adam; Jané-Valbuena, Judit; Mapa, Felipa A.; Thibault, Joseph; Bric-Furlong, Eva; Raman, Pichai; Shipway, Aaron; Engels, Ingo H.; Cheng, Jill; Yu, Guoying K.; Yu, Jianjun; Aspesi, Peter; de Silva, Melanie; Jagtap, Kalpana; Jones, Michael D.; Wang, Li; Hatton, Charles; Palescandolo, Emanuele; Gupta, Supriya; Mahan, Scott; Sougnez, Carrie; Onofrio, Robert C.; Liefeld, Ted; MacConaill, Laura; Winckler, Wendy; Reich, Michael; Li, Nanxin; Mesirov, Jill P.; Gabriel, Stacey B.; Getz, Gad; Ardlie, Kristin; Chan, Vivien; Myer, Vic E.; Weber, Barbara L.; Porter, Jeff; Warmuth, Markus; Finan, Peter; Harris, Jennifer L.; Meyerson, Matthew; Golub, Todd R.; Morrissey, Michael P.; Sellers, William R.; Schlegel, Robert; Garraway, Levi A.

    2012-01-01

    The systematic translation of cancer genomic data into knowledge of tumor biology and therapeutic avenues remains challenging. Such efforts should be greatly aided by robust preclinical model systems that reflect the genomic diversity of human cancers and for which detailed genetic and pharmacologic annotation is available1. Here we describe the Cancer Cell Line Encyclopedia (CCLE): a compilation of gene expression, chromosomal copy number, and massively parallel sequencing data from 947 human cancer cell lines. When coupled with pharmacologic profiles for 24 anticancer drugs across 479 of the lines, this collection allowed identification of genetic, lineage, and gene expression-based predictors of drug sensitivity. In addition to known predictors, we found that plasma cell lineage correlated with sensitivity to IGF1 receptor inhibitors; AHR expression was associated with MEK inhibitor efficacy in NRAS-mutant lines; and SLFN11 expression predicted sensitivity to topoisomerase inhibitors. Altogether, our results suggest that large, annotated cell line collections may help to enable preclinical stratification schemata for anticancer agents. The generation of genetic predictions of drug response in the preclinical setting and their incorporation into cancer clinical trial design could speed the emergence of “personalized” therapeutic regimens2. PMID:22460905

  11. X-ray-sensitive mutants of Chinese hamster ovary cell line

    International Nuclear Information System (INIS)

    Jeggo, P.A.; Kemp, L.M.

    1983-01-01

    A standard technique of microbial genetics, which involves the transfer of cells from single colonies by means of sterile toothpicks, has been adapted to somatic cell genetics. Its use has been demonstrated in the isolation of X-ray-sensitive mutants of CHO cells. 9000 colonies have been tested and 6 appreciably X-ray-sensitive mutants were isolated. (D 10 values 5-10-fold of wild-type D 10 value.) A further 6 mutants were obtained which showed a slight level of sensitivity (D 10 values less than 2-fold of wild-type D 10 value). The 6 more sensitive mutants were also sensitive to bleomycin, a chemotherapeutic agent inducing X-ray-like damage. Cross-sensitivity to UV-irradiation and treatment with the alkylating agents, MMS, EMS and MNNG, was investigated for these mutants. Some sensitivity to these other agents was observed, but in all cases it was less severe than the level of sensitivity to X-irradiation. Each mutant showed a different overall response to the spectrum of agents examined and these appear to represent new mutant phenotypes derived from cultured mammalian cell lines. One mutant strain, xrs-7, was cross-sensitive to all the DNA-damaging agents, but was proficient in the repair of single-strand breaks. (Auth.)

  12. FlindersTechnology Associates (FTA) filter paper-based DNA extraction with polymerase chain reaction (PCR) for detection of Pneumocystis jirovecii from respiratory specimens of immunocompromised patients.

    Science.gov (United States)

    Nuchprayoon, Surang; Saksirisampant, Wilai; Jaijakul, Siraya; Nuchprayoon, Issarang

    2007-01-01

    We evaluated the diagnostic value of Flinders Technology Associates (FTA) filter paper together with polymerase chain reaction (PCR) for detection of Pneumocystis jirovecii (carinii) from induced sputum (IS) and bronchoalveolar lavage fluid (BALF) samples. The study involved 162 patients with clinical diagnosis of pneumocystis pneumonia (PcP) of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) patients and other immunocompromised patients. P. jirovecii cysts or trophozoites were detected in IS and BALF by cytological method. The mitochondrial 5S ribosomal ribonucleic acid (rRNA) gene of P. jirovecii was amplified from these samples by using FTA filters together with a one-step PCR method (FTA-PCR). With the FTA-PCR method, the sensitivity and specificity of the test compared to microscopic examination were 67% and 90% for IS, while they were 67% and 91% for BALF, respectively. The sensitivity and specificity of the FTA-PCR test was also comparable to PCR with the conventional deoxyribonucleic acid (DNA) extraction method. We concluded that FTA-PCR is useful to detect P. jirovecii in noninvasive IS.

  13. γ-radiation induces cellular sensitivity and aberrant methylation in human tumor cell lines.

    Science.gov (United States)

    Kumar, Ashok; Rai, Padmalatha S; Upadhya, Raghavendra; Vishwanatha; Prasada, K Shama; Rao, B S Satish; Satyamoorthy, Kapettu

    2011-11-01

    Ionizing radiation induces cellular damage through both direct and indirect mechanisms, which may include effects from epigenetic changes. The purpose of this study was to determine the effect of ionizing radiation on DNA methylation patterns that may be associated with altered gene expression. Sixteen human tumor cell lines originating from various cancers were initially tested for radiation sensitivity by irradiating them with γ-radiation in vitro and subsequently, radiation sensitive and resistant cell lines were treated with different doses of a demethylating agent, 5-Aza-2'-Deoxycytidine (5-aza-dC) and a chromatin modifier, Trichostatin-A (TSA). Survival of these cell lines was measured using 3-(4, 5-Dimethylthiazol- 2-yl)-2, 5-diphenyltetrazolium (MTT) and clonogenic assays. The effect of radiation on global DNA methylation was measured using reverse phase high performance liquid chromatography (RP-HPLC). The transcription response of methylated gene promoters, from cyclin-dependent kinase inhibitor 2A (p16(INK4a)) and ataxia telangiectasia mutated (ATM) genes, to radiation was measured using a luciferase reporter assay. γ-radiation resistant (SiHa and MDAMB453) and sensitive (SaOS2 and WM115) tumor cell lines were examined for the relationship between radiation sensitivity and DNA methylation. Treatment of cells with 5-aza-dC and TSA prior to irradiation enhanced DNA strand breaks, G2/M phase arrest, apoptosis and cell death. Exposure to γ-radiation led to global demethylation in a time-dependent manner in tumor cells in relation to resistance and sensitivity to radiation with concomitant activation of p16(INK4a) and ATM gene promoters. These results provide important information on alterations in DNA methylation as one of the determinants of radiation effects, which may be associated with altered gene expression. Our results may help in delineating the mechanisms of radiation resistance in tumor cells, which can influence diagnosis, prognosis and

  14. O6-alkylguanine-DNA-alkyltransferase activity and nitrosourea sensitivity in human cancer cell lines.

    OpenAIRE

    Walker, M. C.; Masters, J. R.; Margison, G. P.

    1992-01-01

    The DNA repair enzyme, O6-alkylguanine-DNA-alkyltransferase (ATase), is thought to be the principal mechanism controlling resistance to nitrosoureas and related alkylating agents. We compared the sensitivities of five human testis and five bladder tumour cell lines to two nitrosoureas (N-nitroso-N-methylurea (MNU) and mitozolomide) with cellular levels of ATase. Enzyme levels ranged from 3 to 206 fmol mg-1 protein (0.1 x 10(4) to 5.1 x 10(4) molecules/cell) in the testis lines and from 11 to ...

  15. Interferon-gamma sensitizes colonic epithelial cell lines to physiological and therapeutic inducers of colonocyte apoptosis.

    LENUS (Irish Health Repository)

    O'Connell, J

    2012-02-03

    Homeostasis in the colonic epithelium is achieved by a continuous cycle of proliferation and apoptosis, in which imbalances are associated with disease. Inflammatory bowel disease (IBD) and colon cancer are associated with either excessive or insufficient apoptosis of colonic epithelial cells, respectively. By using two colonic epithelial cell lines, HT29 and SW620, we investigated how the epithelial cell\\'s sensitivity to apoptosis was regulated by the proinflammatory cytokine interferon-gamma (IFN-gamma). We found that IFN-gamma sensitized HT29 cells, and to a lesser extent SW620, to diverse inducers of apoptosis of physiologic or therapeutic relevance to the colon. These apoptosis inducers included Fas (CD95\\/APO-1) ligand (FasL), short-chain fatty acids, and chemotherapeutic drugs. The extent of IFN-gamma-mediated apoptosis sensitization in these two cell lines correlated well with the degree of IFN-gamma-mediated upregulation of the proapoptotic protease caspase-1. Although IFN-gamma alone effectively sensitized HT29 cells to apoptosis, inclusion of the protein synthesis inhibitor cyclohexamide (CHX) during apoptotic challenge was necessary for maximal sensitization of SW620. The requirement of CHX to sensitize SW620 cells to apoptosis implies a need to inhibit translation of antiapoptotic proteins absent from HT29. In particular, the antiapoptotic protein Bcl-2 was strongly expressed in SW620 cells but absent from HT29. Our results indicate that IFN-gamma increases the sensitivity of colonic epithelial cells to diverse apoptotic stimuli in concert, via upregulation of caspase-1. Our findings implicate caspase-1 and Bcl-2 as important central points of control determining the general sensitivity of colonic epithelial cells to apoptosis.

  16. Evaluation of Flinders Technology Associates cards for storage and molecular detection of avian metapneumoviruses.

    Science.gov (United States)

    Awad, Faez; Baylis, Matthew; Jones, Richard C; Ganapathy, Kannan

    2014-01-01

    The feasibility of using Flinders Technology Associates (FTA) cards for the molecular detection of avian metapneumovirus (aMPV) by reverse transcriptase-polymerase chain reaction (RT-PCR) was investigated. Findings showed that no virus isolation was possible from aMPV-inoculated FTA cards, confirming viral inactivation upon contact with the cards. The detection limits of aMPV from the FTA card and tracheal organ culture medium were 10(1.5) median ciliostatic doses/ml and 10(0.75) median ciliostatic doses/ml respectively. It was possible to perform molecular characterization of both subtypes A and B aMPV using inoculated FTA cards stored for up to 60 days at 4 to 6°C. Tissues of the turbinate, trachea and lung of aMPV-infected chicks sampled either by direct impression smears or by inoculation of the tissue homogenate supernatants onto the FTA cards were positive by RT-PCR. However, the latter yielded more detections. FTA cards are suitable for collecting and transporting aMPV-positive samples, providing a reliable and hazard-free source of RNA for molecular characterization.

  17. Differential biological effects of iodoacetate in mammalian cell lines; radio sensitization and radio protection

    International Nuclear Information System (INIS)

    Yadav, Usha; Anjaria, K.B.; Desai, Utkarsha N.; Chaurasia, Rajesh K.; Shirsath, K.B.; Bhat, Nagesh N.; Balakrishnan, Sreedevi; Sapra, B.K.; Nairy, Rajesha

    2014-01-01

    There are several studies where it has been shown that Iodoacetate (IA) possesses in vivo anti-tumor activity. The fact that it is a model glycolytic inhibitor makes it more interesting. As seen in recent trends, glycolytic inhibitors are emerging as new strategy for cancer therapeutic research taking advantage of glycolytic phenotype of cancerous tissues. IA has been reported to have radioprotective effects in yeast cells and human lymphocytes. Biological effects of IA in response to radiation in mammalian cell lines are not well documented. We screened IA for cytotoxicity using clonogenic assay at different concentrations ranging from 0.1 to 2.5 μg/ml using three different mammalian cell lines; A-549 (human lung carcinoma cell line), MCF-7 (human mammary cancer cell line) and a noncancerous CHO (Chinese hamster ovary cell line). For studying radioprotective/radio sensitizing efficacy, cells were exposed to 4 Gy of 60 Co-γ radiation using a teletherapy source at a dose rate of 1 Gy/min, following which IA post-treatment was carried out. Clonogenic and micronucleus assay were performed to assess radioprotection/sensitization. The results indicated that IA was highly cytotoxic in cancerous cell lines A-549 (IC 50 =1.25 μg/ml) and MCF-7 (IC 50 = 1.9 μg/ml). In contrast, it was totally non-toxic in non-cancerous cell line, viz. CHO, in the same concentration range. In addition, IA exhibited radio protective effect in CHO cell line, whereas in other two cancer cell lines, viz. A-549 and MCF-7, radio sensitizing effect was seen as judged by induction of cell killing and micronuclei. In conclusion, lA, a model glycolytic inhibitor, was found to be selectively cytotoxic in cancer cells as compared to normal cells. Further, it reduced radiation induced damage (micronuclei and cell killing) in normal cells but increased it in cancer cells indicating its potential use in cancer therapy. (author)

  18. Spectrometer sensitivity calibration in the extreme uv by means of branching ratios of magnetic dipole lines

    International Nuclear Information System (INIS)

    Denne, B.; Hinnov, E.

    1984-04-01

    Relative intensity measurements of various line pairs resulting from magnetic dipole transitions within the configurations s 2 p 2 and s 2 p 4 , in conjunction with calculated transition probabilities, have been used to determine the wavelength dependence of the sensitivity of a grazing incidence spectrometer, in the range 400 to 1000 A. Emissions from Cr XIX, Fe XXI, Ni XXI and XXIII, Cu XXIV, and Zr XXVII ions in PLT tokamak discharges were used for this purpose. Absolute sensitivity of the spectrometer at selected wavelengths had been determined by the traditional hydrogen, helium, carbon, and oxygen electric-dipole line pairs from the same discharges. Similar attempts to use transitions in the s 2 p 3 configurations in Cr XVIII, Zr XXVI, and Mo XXVIII ions resulted in significant discrepancies that are ascribed to uncertainties in the corresponding calculated transition probabilities

  19. Sensitivity to ionizing radiation and chemotherapeutic agents in gemcitabine-resistant human tumor cell lines

    International Nuclear Information System (INIS)

    Bree, Chris van; Kreder, Natasja Castro; Loves, Willem J.P.; Franken, Nicolaas A.P.; Peters, Godefridus J.; Haveman, Jaap

    2002-01-01

    Purpose: To determine cross-resistance to anti-tumor treatments in 2',2'difluorodeoxycytidine (dFdC, gemcitabine)-resistant human tumor cells. Methods and Materials: Human lung carcinoma cells SW-1573 (SWp) were made resistant to dFdC (SWg). Sensitivity to cisplatin (cDDP), paclitaxel, 5-fluorouracil (5-FU), methotrexate (MTX), cytarabine (ara-C), and dFdC was measured by a proliferation assay. Radiosensitivity and radioenhancement by dFdC of this cell panel and the human ovarian carcinoma cell line A2780 and its dFdC-resistant variant AG6000 were determined by clonogenic assay. Bivariate flowcytometry was performed to study cell cycle changes. Results: In the SWg, a complete deoxycytidine kinase (dCK) deficiency was found on mRNA and protein level. This was accompanied by a 10-fold decrease in dCK activity which resulted in the >1000-fold resistance to dFdC. Sensitivity to other anti-tumor drugs was not altered, except for ara-C (>100-fold resistance). Radiosensitivity was not altered in the dFdC-resistant cell lines SWg and AG6000. High concentrations (50-100 μM dFdC) induced radioenhancement in the dFdC-resistant cell lines similar to the radioenhancement obtained at lower concentrations (10 nM dFdC) in the parental lines. An early S-phase arrest was found in all cell lines after dFdC treatment where radioenhancement was achieved. Conclusions: In the dFdC-resistant lung tumor cell line SWg, the deficiency in dCK is related to the resistance to dFdC and ara-C. No cross-resistance was observed to other anti-tumor drugs used for the treatment in lung cancer. Sensitivity to ionizing radiation was not altered in two different dFdC-resistant cell lines. Resistance to dFdC does not eliminate the ability of dFdC to sensitize cells to radiation

  20. Inhibition of iron uptake is responsible for differential sensitivity to V-ATPase inhibitors in several cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Sarah Straud

    2010-07-01

    Full Text Available Many cell lines derived from tumors as well as transformed cell lines are far more sensitive to V-ATPase inhibitors than normal counterparts. The molecular mechanisms underlying these differences in sensitivity are not known. Using global gene expression data, we show that the most sensitive responses to HeLa cells to low doses of V-ATPase inhibitors involve genes responsive to decreasing intracellular iron or decreasing cholesterol and that sensitivity to iron uptake is an important determinant of V-ATPase sensitivity in several cancer cell lines. One of the most sensitive cell lines, melanoma derived SK-Mel-5, over-expresses the iron efflux transporter ferroportin and has decreased expression of proteins involved in iron uptake, suggesting that it actively suppresses cytoplasmic iron. SK-Mel-5 cells have increased production of reactive oxygen species and may be seeking to limit additional production of ROS by iron.

  1. Raman spectroscopy differentiates between sensitive and resistant multiple myeloma cell lines

    Science.gov (United States)

    Franco, Domenico; Trusso, Sebastiano; Fazio, Enza; Allegra, Alessandro; Musolino, Caterina; Speciale, Antonio; Cimino, Francesco; Saija, Antonella; Neri, Fortunato; Nicolò, Marco S.; Guglielmino, Salvatore P. P.

    2017-12-01

    Current methods for identifying neoplastic cells and discerning them from their normal counterparts are often nonspecific and biologically perturbing. Here, we show that single-cell micro-Raman spectroscopy can be used to discriminate between resistant and sensitive multiple myeloma cell lines based on their highly reproducible biomolecular spectral signatures. In order to demonstrate robustness of the proposed approach, we used two different cell lines of multiple myeloma, namely MM.1S and U266B1, and their counterparts MM.1R and U266/BTZ-R subtypes, resistant to dexamethasone and bortezomib, respectively. Then, micro-Raman spectroscopy provides an easily accurate and noninvasive method for cancer detection for both research and clinical environments. Characteristic peaks, mostly due to different DNA/RNA ratio, nucleic acids, lipids and protein concentrations, allow for discerning the sensitive and resistant subtypes. We also explored principal component analysis (PCA) for resistant cell identification and classification. Sensitive and resistant cells form distinct clusters that can be defined using just two principal components. The identification of drug-resistant cells by confocal micro-Raman spectroscopy is thus proposed as a clinical tool to assess the development of resistance to glucocorticoids and proteasome inhibitors in myeloma cells.

  2. Line-robust statistics for continuous gravitational waves: safety in the case of unequal detector sensitivities

    International Nuclear Information System (INIS)

    Keitel, David; Prix, Reinhard

    2015-01-01

    The multi-detector F-statistic is close to optimal for detecting continuous gravitational waves (CWs) in Gaussian noise. However, it is susceptible to false alarms from instrumental artefacts, for example quasi-monochromatic disturbances (‘lines’), which resemble a CW signal more than Gaussian noise. In a recent paper (Keitel et al 2014 Phys. Rev. D 89 064023), a Bayesian model selection approach was used to derive line-robust detection statistics for CW signals, generalizing both the F-statistic and the F-statistic consistency veto technique and yielding improved performance in line-affected data. Here we investigate a generalization of the assumptions made in that paper: if a CW analysis uses data from two or more detectors with very different sensitivities, the line-robust statistics could be less effective. We investigate the boundaries within which they are still safe to use, in comparison with the F-statistic. Tests using synthetic draws show that the optimally-tuned version of the original line-robust statistic remains safe in most cases of practical interest. We also explore a simple idea on further improving the detection power and safety of these statistics, which we, however, find to be of limited practical use. (paper)

  3. Minimizing new tritium line sensitivity by a quality process implemented at Madagascar-INSTN

    International Nuclear Information System (INIS)

    Rajaobelison, J.; Raoelina Andriambololona; Ramaroson, V.; Andriamiharitsoa, G.; Fareze, L.P.; Razafintsalama, F.F.A.; Marah, H.

    2009-01-01

    A quality process rigorously implemented in the Isotope Hydrology Laboratory of Madagascar-I.N.S.T.N has significantly contributed to minimize the sensitivity of a recently installed tritium line used for groundwater dating. The ISO/CEI 17025 standard has been applied to fifteen (15) groundwater samples collected from different boreholes in the semi-arid South of Madagascar. The results are in agreement with the spikes analyses results which show that the mean value of the enrichment factor is 23.78 and the enrichment parameter is 0.88 for a preliminary test. Such values are much higher than the usual ones (approximately of 18) for a first enrichment, indicating electrolytic cells optimised work. In addition, the standard deviations are respectively 1.6 and 0.02 for the enrichment factor and parameter, meaning therefore that the cells performances are relatively good. In addition, background measurement was carried out on a dead water sample and produced a relatively low value of 1.07cpm, them simultaneous activities measurement of indoor and outdoor control water samples gave approximately the same values. The latter results prove that there is no indoor contamination of the samples. Finally, the groundwater samples analysis results show that the water activities vary from 0.27 TU to 2.97 TU confirming that the tritium line sensitivity is lower than 0.30 TU and that the system is able to determine groundwater ages up to one thousand years (1000 a), whereas usual tritium lines sensitivities are around 0.80 TU.

  4. Nuclear scaffold organization in the X-ray sensitive Chinese hamster mutant cell line, xrs-5

    International Nuclear Information System (INIS)

    Yasui, L.S.; Fink, T.J.; Enrique, A.M.

    1994-01-01

    Nuclear organization was probed in the radiation-sensitive Chinese hamster ovary (CHO) cell line, xrs-5, and compared with parental CHO K1 cells using the resinless section technique and DNase I digestions. The resinless section data showed no gross morphological differences in core filaments from the nuclear scaffolds of unirradiated CHO K1 and xrs-5 cells. However, the nuclear scaffolds of irradiated xrs-5 cells (1 Gy) had significantly increased ground substance. Irradiated and unirradiated CHO K1 cell nuclear scaffolds were morphologically identical. These data suggest that both CHO K1 and xrs-5 cell nuclear scaffolds had internal nuclear scaffolding networks that could provide DNA attachment sites. (author)

  5. A high-sensitive and quantitative in-line monitoring method for transplutonium elements separation processes

    International Nuclear Information System (INIS)

    Zhu Rongbao; Wang Shiju; Xu Yingpu; Zhang Zengrui

    1986-04-01

    A high-sensitive monitoring device and a quantitative analys technigue for transplutonium elements separation processes are described. X-ray and low energy γ-ray are measured by means of a scintillation monitor with two NaI(Tl) thin crystals. The α spectra of the fluents of ion-exchange column is measured by means of Si(Au) surface barrier in-line monitor. The construction of the monitors, auxiliary electronics, investigation result for the α spectra character of thick source and the calibration method were described. The determination results for extracting process of 243 Am and 244 Cm by ion-exchange chromatography were given. The sensitivity of total adding amount for 243 Am using the 4π scintillation monitor is better than 0.1 μCi. The precision of 243 Am and 244 Cm concentration determination using Si(Au) monitor is +- 5%. The precision of the two metals contents in containers is about +- 10%

  6. A UV-sensitive human clonal cell line, RSa, which has low repair activity

    International Nuclear Information System (INIS)

    Suzuki, N.; Fuse, A.

    1981-01-01

    The repair activity of a human transformed cell line, RSa, which was found to be highly sensitive to the lethal effects of 254 mm far-ultraviolet radiation, was compared with that of HeLa cells by evaluating the range of UV-induced incorporation of [methyl- 3 H]thymidine ([ 3 H]dThd) or 5-[6- 3 H]bromodeoxyuridine ([ 3 H]BrdUrd) into deoxyribonucleic acid. Direct scintillation counting was used for measuring the extent of unscheduled DNA synthesis (UDS) in UV-irradiated cells, which were treated with hydroxyurea or with arginine deprivation. More quantitative measurements were made by using the density labeling and equilibrium centrifugation method for assaying repair replication. All the amounts of UDS and repair replication in RSa cells were markedly below those in HeLa cells. The possible relationships of the low repair activity to abnormally high UV sensitivity in RSa cells are discussed. (orig.)

  7. Performance of a novel keratinocyte-based reporter cell line to screen skin sensitizers in vitro

    International Nuclear Information System (INIS)

    Emter, Roger; Ellis, Graham; Natsch, Andreas

    2010-01-01

    In vitro tests are needed to replace animal tests to screen for the skin sensitization potential of chemicals. Skin sensitizers are electrophilic molecules and the Nrf2-electrophile-sensing pathway comprising the repressor protein Keap1, the transcription factor Nrf2 and the antioxidant response element (ARE) is emerging as a toxicity pathway induced by skin sensitizers. Previously, we screened a large set of chemicals in the reporter cell line AREc32, which contains an eight-fold repeat of the rat GSTA2 ARE-sequence upstream of a luciferase reporter gene in the human breast cancer cell line MCF7. This approach was now further developed to bring it closer to the conditions in the human skin and to propose a fully standardized assay. To this end, a luciferase reporter gene under control of a single copy of the ARE-element of the human AKR1C2 gene was stably inserted into HaCaT keratinocytes. A standard operating procedure was developed whereby chemicals are routinely tested at 12 concentrations in triplicate for significant induction of gene activity. We report results from this novel assay on (i) a list of reference chemicals published by ECVAM, (ii) the ICCVAM list of chemicals for validation of alternative endpoints in the LLNA and (iii) on a more general list of 67 chemicals derived from the ICCVAM database. For comparison, peptide reactivity data are presented for the same chemicals. The results indicate a good predictive value of this approach for hazard identification. Its technical simplicity, the high-throughput format and the good predictivity may make this assay a candidate for rapid validation to meet the tight deadline to replace animal tests for skin sensitization by 2013 set by the European authorities.

  8. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: Upper Coast of Texas: ESIL (ESI Shoreline Types - Lines)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The ESIL data set contains lines representing the shoreline and coastal habitats of the Upper Coast of Texas, classified according to the Environmental Sensitivity...

  9. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: Upper Coast of Texas: HYDRO (Hydrography Lines and Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains vector lines and polygons representing coastal hydrography used in the creation of the Environmental Sensitivity Index (ESI) for the Upper...

  10. Chicken lines divergently selected for antibody responses to sheep red blood cells show line-specific differences in sensitivity to immunomodulation by diet. Part I: Humoral parameters.

    Science.gov (United States)

    Adriaansen-Tennekes, R; de Vries Reilingh, G; Nieuwland, M G B; Parmentier, H K; Savelkoul, H F J

    2009-09-01

    Individual differences in nutrient sensitivity have been suggested to be related with differences in stress sensitivity. Here we used layer hens divergently selected for high and low specific antibody responses to SRBC (i.e., low line hens and high line hens), reflecting a genetically based differential immune competence. The parental line of these hens was randomly bred as the control line and was used as well. Recently, we showed that these selection lines differ in their stress reactivity; the low line birds show a higher hypothalamic-pituitary-adrenal (HPA) axis reactivity. To examine maternal effects and neonatal nutritional exposure on nutrient sensitivity, we studied 2 subsequent generations. This also created the opportunity to examine egg production in these birds. The 3 lines were fed 2 different nutritionally complete layer feeds for a period of 22 wk in the first generation. The second generation was fed from hatch with the experimental diets. At several time intervals, parameters reflecting humoral immunity were determined such as specific antibody to Newcastle disease and infectious bursal disease vaccines; levels of natural antibodies binding lipopolysaccharide, lipoteichoic acid, and keyhole limpet hemocyanin; and classical and alternative complement activity. The most pronounced dietary-induced effects were found in the low line birds of the first generation: specific antibody titers to Newcastle disease vaccine were significantly elevated by 1 of the 2 diets. In the second generation, significant differences were found in lipoteichoic acid natural antibodies of the control and low line hens. At the end of the observation period of egg parameters, a significant difference in egg weight was found in birds of the high line. Our results suggest that nutritional differences have immunomodulatory effects on innate and adaptive humoral immune parameters in birds with high HPA axis reactivity and affect egg production in birds with low HPA axis reactivity.

  11. Paris Saponin I Sensitizes Gastric Cancer Cell Lines to Cisplatin via Cell Cycle Arrest and Apoptosis.

    Science.gov (United States)

    Song, Shuichuan; Du, Leiwen; Jiang, Hao; Zhu, Xinhai; Li, Jinhui; Xu, Ji

    2016-10-18

    BACKGROUND Dose-related toxicity is the major restriction of cisplatin and cisplatin-combination chemotherapy, and is a challenge for advanced gastric cancer treatment. We explored the possibility of using Paris saponin I as an agent to sensitize gastric cancer cells to cisplatin, and examined the underlying mechanism. MATERIAL AND METHODS Growth inhibition was detected by MTT assay. The cell cycle and apoptosis were detected using flow cytometry and Annexin V/PI staining. The P21waf1/cip1, Bcl-2, Bax, and caspase-3 protein expression were detected using Western blot analysis. RESULTS The results revealed that PSI sensitized gastric cancer cells to cisplatin, with low toxicity. The IC50 value of cisplatin in SGC-7901 cell lines was decreased when combined with PSI. PSI promoted cisplatin-induced G2/M phase arrest and apoptosis in a cisplatin concentration-dependent manner. Bcl-2 protein expression decreased, but Bax, caspase-3, and P21waf1/cip1 protein expression increased with PSI treatment. CONCLUSIONS The underlying mechanism of Paris saponin I may be related to targeting the apoptosis pathway and cell cycle blocking, which suggests that PSI is a potential therapeutic sensitizer for cisplatin in treating gastric cancer.

  12. First Complete Genomic Sequence of a Rabies Virus from the Republic of Tajikistan Obtained Directly from a Flinders Technology Associates Card

    OpenAIRE

    Goharriz, H.; Marston, D. A.; Sharifzoda, F.; Ellis, R. J.; Horton, D. L.; Khakimov, T.; Whatmore, A.; Khamroev, K.; Makhmadshoev, A. N.; Bazarov, M.; Fooks, A. R.; Banyard, A. C.

    2017-01-01

    ABSTRACT A brain homogenate derived from a rabid dog in the district of Tojikobod, Republic of Tajikistan, was applied to a Flinders Technology Associates (FTA) card. A full-genome sequence of rabies virus (RABV) was generated from the FTA card directly without extraction, demonstrating the utility of these cards for readily obtaining genetic data.

  13. A randomised trial of the Flinders Program to improve patient self-management competencies in a range of chronic conditions: study rationale and protocol

    Directory of Open Access Journals (Sweden)

    Malcolm W. Battersby

    2010-03-01

    Full Text Available BackgroundSupporting self management is seen as an important healthservice strategy in dealing with the large and increasing healthburden of chronic conditions. Several types of selfmanagementprograms are available. Evidence to datesuggests that disease-specific and lay-led self managementprograms provide only part of the support needed forimproved outcomes. The Flinders Program is promising as ageneric self management intervention, which can becombined with targeted disease-specific and lay-ledinterventions, but it has yet to be evaluated for a range ofchronic conditions using a rigorous controlled trial design. Thispaper gives the rationale for a randomised controlled trial andprocess evaluation of the Flinders Program of chroniccondition self-management in community practice, and detailsand justifies the design of such a study.MethodThe design for a randomised trial and associated processevaluation, suited to evaluation of a complex and behaviouralintervention as it is applied in actual practice, is presented andjustified.ConclusionA randomised trial of the Flinders Program is required and afunctional design is presented. Results from this trial,currently underway, will test the effectiveness of the FlindersProgram in improving patient competencies in selfmanagementof chronic conditions in practice conditions.A process evaluation alongside the trial will exploresystem, provider and patient factors associated withgreater and lesser Program effectiveness.

  14. First Complete Genomic Sequence of a Rabies Virus from the Republic of Tajikistan Obtained Directly from a Flinders Technology Associates Card.

    Science.gov (United States)

    Goharriz, H; Marston, D A; Sharifzoda, F; Ellis, R J; Horton, D L; Khakimov, T; Whatmore, A; Khamroev, K; Makhmadshoev, A N; Bazarov, M; Fooks, A R; Banyard, A C

    2017-07-06

    A brain homogenate derived from a rabid dog in the district of Tojikobod, Republic of Tajikistan, was applied to a Flinders Technology Associates (FTA) card. A full-genome sequence of rabies virus (RABV) was generated from the FTA card directly without extraction, demonstrating the utility of these cards for readily obtaining genetic data. © Crown copyright 2017.

  15. Screening the Drug Sensitivity Genes Related to GEM and CDDP in the Lung Cancer Cell-lines

    Directory of Open Access Journals (Sweden)

    Chunyu YANG

    2009-10-01

    Full Text Available Background and objective Screening of small-cell lung cancer (SCLC and non-small cell lung cancer (NSCLC cell lines with gemcitabine hydrochloride (GEM and cisplatin (CDDP related to drug sensitivity gene might clarify the action mechanism of anti-cancer drugs and provide a new clue for overcoming drug resistance and the development of new anti-cancer drugs, and also provide theoretical basis for the clinical treatment of individual. Methods The drug sensitivity of CDDP and GEM in 4 SCLC cell lines and 6 NSCLC cell lines was determined using MTT colorimetric assay, while the cDNA macroarray was applied to detect the gene expression state related to drug sensitivity of 10 lung cancer cell line in 1 291, and the correlation between the two was analysized. Results There were 6 genes showing significant positive correlation (r≥0.632, P < 0.05 with GEM sensitivity; 45 genes positively related to CDDP; another 41 genes related to both GEM and CDDP (r≥± 0.4. Lung cancer with GEM and CDDP sensitivity of two types of drugs significantly related genes were Metallothinein (Signal transduction molecules, Cathepsin B (Organization protease B and TIMP1 (Growth factor; the GEM, CDDP sensitivity associated genes of lung cancer cell lines mainly distributed in Metallothinein, Cathepsin B, growth factor TIMP1 categories. Conclusion There existed drug-related sensitive genes of GEM, CDDP in SCLC and NSCLC cell lines; of these genes, Metallothinein, Cathepsin B and TIMP1 genes presented a significant positive correlation with GEM drug sensitivity, a significant negative correlation with CDDP drug sensitivity.

  16. On-line evaluation of position-sensitive detector (PSD) diffraction data

    International Nuclear Information System (INIS)

    Stansfield, R.F.D.; McIntyre, G.J.

    1985-01-01

    The amount of raw data accumulated in a single-crystal diffraction experiment using a two-dimensional Position Sensitive Detector is usually so large that it is impracticable to store it. It is therefore necessary to reduce each local three-dimensional array of counts to a Bragg intensity, in a time not longer than the average time that one reflection is active. The statistically optimum procedure comprises an estimation of the background from a large number of counts, and an integration of peak intensity within a suitable three-dimensional envelope. A typical on-line method is described, using as an example the D19 diffractometer at the Institut Max von Laue - Paul Langevin (ILL) high-flux reactor. Current methods of PSD data reduction are reviewed. These fall into three groups according to the basis of the method used to find the integration envelope: (a) statistical criteria, (b) three-dimensional sigma(I)/I analysis, and (c) pre-calculation of the resolution function. On-line data reduction imposes special requirements on diagnostics to check the precision of the reduced data, especially at the start of an experiment, when any peculiarities must be identified and allowed for in the data-reduction procedure. The diagnostic possibilities resulting from the comparison of local with global characteristics of the background and the integration envelope are discussed. (author)

  17. Widespread molecular patterns associated with drug sensitivity in breast cancer cell lines, with implications for human tumors.

    Directory of Open Access Journals (Sweden)

    Chad J Creighton

    Full Text Available BACKGROUND: Recent landmark studies have profiled cancer cell lines for molecular features, along with measuring the corresponding growth inhibitory effects for specific drug compounds. These data present a tool for determining which subsets of human cancer might be more responsive to particular drugs. To this end, the NCI-DREAM-sponsored DREAM7: Drug Sensitivity Prediction Challenge (sub-challenge 1 set out to predict the sensitivities of 18 breast cancer cell lines to 31 previously untested compounds, on the basis of molecular profiling data and a training subset of cell lines. METHODS AND RESULTS: With 47 teams submitting blinded predictions, team Creighton scored third in terms of overall accuracy. Team Creighton's method was simple and straightforward, incorporated multiple expression data types (RNA-seq, gene array, RPPA, and incorporated all profiled features (not only the "best" predictive ones. As an extension of the approach, cell line data, from public datasets of expression profiling coupled with drug sensitivities (Barretina, Garnett, Heiser were used to "predict" the drug sensitivities in human breast tumors (using data from The Cancer Genome Atlas. Drug sensitivity correlations within human breast tumors showed differences by expression-based subtype, with many associations in line with the expected (e.g. Lapatinib sensitivity in HER2-enriched cancers and others inviting further study (e.g. relative resistance to PI3K inhibitors in basal-like cancers. CONCLUSIONS: Molecular patterns associated with drug sensitivity are widespread, with potentially hundreds of genes that could be incorporated into making predictions, as well as offering biological clues as to the mechanisms involved. Applying the cell line patterns to human tumor data may help generate hypotheses on what tumor subsets might be more responsive to therapies, where multiple cell line datasets representing various drugs may be used, in order to assess consistency of

  18. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: Hudson River: ESI (Environmental Sensitivity Index Shoreline Types - Lines and Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains vector lines and polygons representing the shoreline and coastal habitats for the Hudson River, classified according to the Environmental...

  19. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: Northern California: ESI (Environmental Sensitivity Index Shoreline Types - Lines and Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains vector lines and polygons representing the shoreline and coastal habitats of Northern California, classified according to the Environmental...

  20. SU-F-T-678: Clotrimazole Sensitizes MCF-7 Breast Cancer Cell Line to Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, L; Tambasco, M [San Diego State University, San Diego, CA (United States)

    2016-06-15

    Purpose: To study the effects of Clotrimazole (CLT) on radiosensitivity of MCF-7 Cells in correlation to detachment of Hexokinase II from the Voltage Dependent Anion Channel on the outer membrane of the mitochondria. Apoptotic fractions were also analyzed in relation to the detachment of Hexokinase. Methods: This study focused on the mammary adenocarcinoma cell line, MCF-7. Colony forming assays were used to analyze radiosensitization by CLT. Flow cytometry methods were used to analyze apoptotic vs necrotic fractions after treatment with CLT. Spectrophotometery was used to analyze the mitochondrial bound and soluble fraction of Hexokinase by means of relative enzymatic activity. Results: Our preliminary data have shown that CLT sensitizes MCF-7 cells to radiation in a dose and incubation time dependent manner up. We have also demonstrated that there are two radiosensitizing periods in MCF-7 cells with the first corresponding to the cycle arrest after 24 hours observed in other cell lines. The second radiosensitizing period occurs with incubation in CLT after irradiation which reaches maximum effect around 24 hours of incubation time. Preliminary data from our Hexokinase detachment assay show a factor of two increase in the ratio of unbound to bound Hexokinase when comparing incubation for 24 hours in media containing 0 and 20 µM CLT. Conclusion: This study and others indicate CLT as a possible radiosensitizing agent in cancer therapies. While CLT itself shows toxicity to the liver in high doses, this study further demonstrates that disruption of the Warburg Effect and unbinding of mitochondrial bound Hexokinase as a possible pathway for cancer treatment.

  1. SU-F-T-678: Clotrimazole Sensitizes MCF-7 Breast Cancer Cell Line to Radiation

    International Nuclear Information System (INIS)

    Garcia, L; Tambasco, M

    2016-01-01

    Purpose: To study the effects of Clotrimazole (CLT) on radiosensitivity of MCF-7 Cells in correlation to detachment of Hexokinase II from the Voltage Dependent Anion Channel on the outer membrane of the mitochondria. Apoptotic fractions were also analyzed in relation to the detachment of Hexokinase. Methods: This study focused on the mammary adenocarcinoma cell line, MCF-7. Colony forming assays were used to analyze radiosensitization by CLT. Flow cytometry methods were used to analyze apoptotic vs necrotic fractions after treatment with CLT. Spectrophotometery was used to analyze the mitochondrial bound and soluble fraction of Hexokinase by means of relative enzymatic activity. Results: Our preliminary data have shown that CLT sensitizes MCF-7 cells to radiation in a dose and incubation time dependent manner up. We have also demonstrated that there are two radiosensitizing periods in MCF-7 cells with the first corresponding to the cycle arrest after 24 hours observed in other cell lines. The second radiosensitizing period occurs with incubation in CLT after irradiation which reaches maximum effect around 24 hours of incubation time. Preliminary data from our Hexokinase detachment assay show a factor of two increase in the ratio of unbound to bound Hexokinase when comparing incubation for 24 hours in media containing 0 and 20 µM CLT. Conclusion: This study and others indicate CLT as a possible radiosensitizing agent in cancer therapies. While CLT itself shows toxicity to the liver in high doses, this study further demonstrates that disruption of the Warburg Effect and unbinding of mitochondrial bound Hexokinase as a possible pathway for cancer treatment.

  2. Quantitative analysis of genes regulating sensitivity to heavy ion irradiation in cultured cell lines of malignant choroid melanoma

    International Nuclear Information System (INIS)

    Kumagai, Ken; Adachi, Nanao; Nimura, Yoshinori

    2004-01-01

    As a treatment strategy for malignant melanoma, heavy ion irradiation has been planned in National Institute of Radiological Sciences (NIRS). However, the molecular biology of the malignant melanoma cell after irradiation of heavy ion is still unknown. In this study, we used resistant and sensitive cell lines of malignant melanoma to study the effects of heavy ion irradiation. Furthermore, gene expression profiling of early response genes for heavy ion irradiation was carried out on these cell lines using microarray technology. (author)

  3. Quantitative analysis of genes regulating sensitivity to heavy ion irradiation in cultured cell lines of malignant choroid melanoma

    International Nuclear Information System (INIS)

    Kumagai, Ken; Nimura, Yoshinori; Kato, Masaki; Seki, Naohiko; Miyahara, Nobuyuki; Aoki, Mizuho; Shino, Yayoi; Furusawa, Yoshiya; Mizota, Atsushi

    2005-01-01

    As a treatment strategy for malignant melanoma, heavy ion irradiation has been planned in National Institute of Radiological Sciences (NIRS). However, the molecular biology of the malignant melanoma cell after irradiation of heavy ion is still unknown. In this study, we used resistant and sensitive cell lines of malignant melanoma to study the effects of heavy ion irradiation. Furthermore, gene expression profiling of early response genes for heavy ion irradiation was carried out on these cell lines using microarray technology. (author)

  4. Effects of extra virgin olive oil phenols on HL60 cell lines sensitive and resistant to anthracyclines

    Directory of Open Access Journals (Sweden)

    M. Crescimanno

    2009-01-01

    Full Text Available The aim of our study was to evaluate the capability of a crude extract of phenols from extra virgin olive oil of Moraiolo cultivar to induce apoptosis and/or differentiation in sensitive and resistant HL60 cell lines to anticancer drugs (Typical Multidrug Resistance. Our data highlight that the crude extract is able to induce apoptosis on both sensitive and resistant cells, whereas the exposure to a number of anticancer drugs does not induce apoptosis in resistant cells. In differentiation experiments we investigated the capability of crude extract of phenols to induce the expression of CD11 granulocytic or CD14 monocytic cell surface antigen in sensitive and resistant HL60 cell lines. At IC50 dose level (17 ug/ml and 32 ug/ml respectively for sensitive and resistant cell lines, the crude extract induced differentiation associated with the expression of CD14 monocytic cell lines but not that of CD11 granulocityc cell surface antigen. Further investigations are in progress to better clarify the mechanism by which olive oil phenols induce diffentiation on this cell line.

  5. Recent improvements to RC-line encoded position-sensitive proportional counters

    International Nuclear Information System (INIS)

    Borkowski, C.J.; Kopp, M.K.

    1977-01-01

    Continuing research on the principles of position encoding with RC lines has advanced the design of position-sensitive proportional counters (PSPCs) to meet the requirements for high count rates (>10 5 counts/sec) and good spatial resolution (>10 4 spatial elements) in small-angle scattering experiments with x rays and neutrons. Low-noise preamplifiers were developed with pole-zero cancellation in the feedback circuit and modular linear amplifiers with passive RCL shaping which, compared to previous designs, reduce output saturation at high count rates approx.20 times and shorten the position signal processing time to 2 ) for low-energy ( 800 x 800 mm 2 ) for the measurement of small-angle scattering with neutrons. The method of electronic thickness discrimination was applied to change the effective thickness of an area PSPC from 12 to 2 cm whenever the molybdenum target of an x-ray generator was changed to a copper target. This thickness adjustment increased the signal-to-background ratio by a factor of approx.6 for the 8-keV photons from the copper target, while maintaining a >90% detection efficiency

  6. Managing chronic conditions care across primary care and hospital systems: lessons from an Australian Hospital Avoidance Risk Program using the Flinders Chronic Condition Management Program.

    Science.gov (United States)

    Lawn, Sharon; Zabeen, Sara; Smith, David; Wilson, Ellen; Miller, Cathie; Battersby, Malcolm; Masman, Kevin

    2017-08-24

    Objective The study aimed to determine the impact of the Flinders Chronic Condition Management Program for chronic condition self-management care planning and how to improve its use with Bendigo Health's Hospital Admission Risk Program (HARP). Methods A retrospective analysis of hospital admission data collected by Bendigo Health from July 2012 to September 2013 was undertaken. Length of stay during admission and total contacts post-discharge by hospital staff for 253 patients with 644 admissions were considered as outcome variables. For statistical modelling we used the generalised linear model. Results The combination of the HARP and Flinders Program was able to achieve significant reductions in hospital admissions and non-significant reduction in emergency department presentations and length of stay. The generalised linear model predicted that vulnerable patient groups such as those with heart disease (P=0.037) and complex needs (Pmanage chronic conditions through a greater focus on coordination and integration of care across primary care and hospital systems. In support of HARP, self-management interventions such as the Flinders Program aim to help individuals better manage their medical treatment and cope with the impact of the condition on their physical and mental wellbeing and thus reduce health services utilisation. What does this paper add? This paper sheds light on which patients might be more or less likely to benefit from the combination of the HARP and Flinders Program, with regard to their impact on reductions in hospital admissions, emergency department presentations and length of stay. This study also sheds light on how the Flinders Program could be better targeted towards and implemented among high-need and high-cost patients to lessen chronic disease burden on Australia's health system. What are the implications for practitioners? Programs targeting vulnerable populations and applying evidence-based chronic condition management and self

  7. Velocity- and acceleration-sensitive units in the trunk lateral line of the trout

    NARCIS (Netherlands)

    Kroese, A. B.; Schellart, N. A.

    1992-01-01

    1. The two main types of lateral line organs of lower vertebrates are the superficial neuromasts (SN), with a cupula that protrudes in the surrounding water, and the canal neuromasts (CN), located in the lateral line canal. The scales of the trunk lateral line canal of fish contain SNs as well as

  8. Comparison of radiation sensitivity for three cell lines as measured by the cloning assay and the micro-nucleus test

    NARCIS (Netherlands)

    Stap, J.; Aten, J. A.

    1990-01-01

    The correlation between cell killing and the induction of micro-nuclei was studied for three cell lines after treatment with gamma radiation to investigate whether the frequency of micro-nucleated cells can be used to determine the radiation sensitivity of a cell type. R1 rat rhabdomyosarcoma cells

  9. The cytokine-dependent MUTZ-3 cell line as an in vitro model for the screening of contact sensitizers

    International Nuclear Information System (INIS)

    Azam, Philippe; Peiffer, Jean-Luc; Chamousset, Delphine; Tissier, Marie-Helene; Bonnet, Pierre-Antoine; Vian, Laurence; Fabre, Isabelle; Ourlin, Jean-Claude

    2006-01-01

    Langerhans cells (LC) are key mediators of contact allergenicity in the skin. However, no in vitro methods exist which are based on the activation process of LC to predict the sensitization potential of chemicals. In this study, we have evaluated the performances of MUTZ-3, a cytokine-dependent human monocytic cell line, in its response to sensitizers. First, we compared undifferentiated MUTZ-3 cells with several standard human cells such as THP-1, KG-1, HL-60, K-562, and U-937 in their response to the strong sensitizer DNCB and the irritant SDS by monitoring the expression levels of HLA-DR, CD54, and CD86 by flow cytometry. Only MUTZ-3 and THP-1 cells show a strong and specific response to sensitizer, while other cell lines showed very variable responses. Then, we tested MUTZ-3 cells against a wider panel of sensitizers and irritants on a broader spectrum of cell surface markers (HLA-DR, CD40, CD54, CD80, CD86, B7-H1, B7-H2, B7-DC). Of these markers, CD86 proved to be the most reliable since it detected all sensitizers, including benzocaine, a classical false negative in local lymph node assay (LLNA) but not irritants. We confirmed the MUTZ-3 response to DNCB by real-time PCR analysis. Taken together, our data suggest that undifferentiated MUTZ-3 cells may represent a valuable in vitro model for the screening of potential sensitizers

  10. LINES

    Directory of Open Access Journals (Sweden)

    Minas Bakalchev

    2015-10-01

    Full Text Available The perception of elements in a system often creates their interdependence, interconditionality, and suppression. The lines from a basic geometrical element have become the model of a reductive world based on isolation according to certain criteria such as function, structure, and social organization. Their traces are experienced in the contemporary world as fragments or ruins of a system of domination of an assumed hierarchical unity. How can one release oneself from such dependence or determinism? How can the lines become less “systematic” and forms more autonomous, and less reductive? How is a form released from modernistic determinism on the new controversial ground? How can these elements or forms of representation become forms of action in the present complex world? In this paper, the meaning of lines through the ideas of Le Corbusier, Leonidov, Picasso, and Hitchcock is presented. Spatial research was made through a series of examples arising from the projects of the architectural studio “Residential Transformations”, which was a backbone for mapping the possibilities ranging from playfulness to exactness, as tactics of transformation in the different contexts of the contemporary world.

  11. 'PSA-SPN' - A Parameter Sensitivity Analysis Method Using Stochastic Petri Nets: Application to a Production Line System

    International Nuclear Information System (INIS)

    Labadi, Karim; Saggadi, Samira; Amodeo, Lionel

    2009-01-01

    The dynamic behavior of a discrete event dynamic system can be significantly affected for some uncertain changes in its decision parameters. So, parameter sensitivity analysis would be a useful way in studying the effects of these changes on the system performance. In the past, the sensitivity analysis approaches are frequently based on simulation models. In recent years, formal methods based on stochastic process including Markov process are proposed in the literature. In this paper, we are interested in the parameter sensitivity analysis of discrete event dynamic systems by using stochastic Petri nets models as a tool for modelling and performance evaluation. A sensitivity analysis approach based on stochastic Petri nets, called PSA-SPN method, will be proposed with an application to a production line system.

  12. Multiple kinase pathways involved in the different de novo sensitivity of pancreatic cancer cell lines to 17-AAG.

    Science.gov (United States)

    Liu, Heping; Zhang, Ti; Chen, Rong; McConkey, David J; Ward, John F; Curley, Steven A

    2012-07-01

    17-Allylamino-17-demethoxygeldanamycin (17-AAG) specifically targets heat shock protein (HSP)90 and inhibits its chaperoning functions for multiple kinases involved in cancer cell growth and survival. To select responsive patients, the molecular mechanisms underlying the sensitivity of cancer cells to 17-AAG must be elucidated. We used cytotoxicity assays and Western blotting to explore the effects of 17-AAG and sorafenib on cell survival and expression of multiple kinases in the pancreatic cancer cell lines AsPC-1 and Panc-1. Gene cloning and transfection, siRNA silencing, and immunohistochemistry were used to evaluate the effects of mutant p53 protein on 17-AAG sensitivity. AsPC-1 and Panc-1 responded differently to 17-AAG, with half maximal inhibitory concentration (IC(50)) values of 0.12 and 3.18 μM, respectively. Comparable expression of HSP90, HSP70, and HSP27 was induced by 17-AAG in AsPC-1 and Panc-1 cells. P-glycoprotein and mutant p53 did not affect 17-AAG sensitivity in these cell lines. Multiple kinases are more sensitive to HSP90 inhibition in AsPC-1 than in Panc-1 cells. After 17-AAG treatment, p-Bad (S112) decreased in AsPC-1 cells and increased in Panc-1 cells. Sorafenib markedly increased p-Akt, p-ERK1/2, p-GSK-3β, and p-S6 in both cell lines. Accordingly, 17-AAG and sorafenib acted antagonistically in AsPC-1 and Panc-1 cells, except at high concentrations in AsPC-1 cells. Differential inhibition of multiple kinases is responsible for the different de novo sensitivity of AsPC-1 and Panc-1 cells to HSP90 inhibition. P-glycoprotein and mutant p53 protein did not play a role in the sensitivity of pancreatic cancer cells to 17-AAG. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Sensitivity Pattern of Second Line Anti-Tuberculosis Drugs against Clinical Isolates of Multidrug Resistant Mycobacterium Tuberculosis

    International Nuclear Information System (INIS)

    Ghafoor, T.; Ikram, A.; Abbasi, S. A.; Zaman, G.; Ayyub, M.; Palomino, J. C.; Vandamme, P.; Martin, A.

    2015-01-01

    Objective:To determine the current sensitivity pattern of second line anti-tuberculosis drugs against clinical isolates of Multidrug Resistant Mycobacterium tuberculosis (MDR-TB). Study Design: A cross-sectional study. Place and Duration of Study: Department of Microbiology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from November 2011 to April 2013. Methodology: Samples received during the study period were processed on BACTEC MGIT 960 system for Mycobacterium tuberculosis (MTB) culture followed by first line drugs susceptibility testing of culture proven MTB isolates. On the basis of resistance to rifampicin and isoniazid, 100 clinical isolates of MDR-TB were further subjected to susceptibility testing against amikacin (AMK), capreomycin (CAP), ofloxacin (OFL) and ethionamide (ETH) as per standard BACTEC MGIT 960 instructions. Results: Out of 100 MDR-TB isolates, 62% were from male patients and 38% from female patients. 97% were sensitive to AMK, 53% to OFL, 87% to CAP; and 87% were sensitive to ETH. Conclusion: The majority of the MDR-TB isolates showed excellent sensitivity against AMK, CAP and ETH. However, sensitivity of MDR-TB isolates against fluoroquinolones like OFL was not encouraging. (author)

  14. Guam and the Northern Mariana Islands ESI: ESI (Environmental Sensitivity Index Shoreline Types - Lines)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains vector lines representing the shoreline and coastal habitats for Guam and the Northern Mariana Islands, classified according to the...

  15. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: Florida Panhandle: ESIL (ESI Shoreline Types - Lines)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The ESIL data set contains vector lines representing the shoreline and coastal habitats of the Florida Panhandle, classified according to the Environmental...

  16. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: Hudson River: RVRMILES (River Mile Marker Lines)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains human-use resource data for river miles along the Hudson River. Vector lines in this data set represent river mile markers. This data set...

  17. Cook Inlet and Kenai Peninsula, Alaska ESI: ESI (Environmental Sensitivity Index Shoreline Types - Polygons and Lines)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains vector lines and polygons representing the shoreline and coastal habitats of Cook Inlet and Kenai Peninsula, Alaska, classified according to...

  18. Improved phase sensitivity in spectral domain phase microscopy using line-field illumination and self phase-referencing

    Science.gov (United States)

    Yaqoob, Zahid; Choi, Wonshik; Oh, Seungeun; Lue, Niyom; Park, Yongkeun; Fang-Yen, Christopher; Dasari, Ramachandra R.; Badizadegan, Kamran; Feld, Michael S.

    2010-01-01

    We report a quantitative phase microscope based on spectral domain optical coherence tomography and line-field illumination. The line illumination allows self phase-referencing method to reject common-mode phase noise. The quantitative phase microscope also features a separate reference arm, permitting the use of high numerical aperture (NA > 1) microscope objectives for high resolution phase measurement at multiple points along the line of illumination. We demonstrate that the path-length sensitivity of the instrument can be as good as 41 pm/Hz, which makes it suitable for nanometer scale study of cell motility. We present the detection of natural motions of cell surface and two-dimensional surface profiling of a HeLa cell. PMID:19550464

  19. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: Northwest Arctic, Alaska: FISHL (Fish Lines)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains sensitive biological resource data for anadromous fish species in Northwest Arctic, Alaska. Vector arcs in this data set represent species...

  20. Low ATM protein expression and depletion of p53 correlates with olaparib sensitivity in gastric cancer cell lines

    Science.gov (United States)

    Kubota, Eiji; Williamson, Christopher T; Ye, Ruiqiong; Elegbede, Anifat; Peterson, Lars; Lees-Miller, Susan P; Bebb, D Gwyn

    2014-01-01

    Small-molecule inhibitors of poly (ADP-ribose) polymerase (PARP) have shown considerable promise in the treatment of homologous recombination (HR)-defective tumors, such as BRCA1- and BRCA2-deficient breast and ovarian cancers. We previously reported that mantle cell lymphoma cells with deficiency in ataxia telangiectasia mutated (ATM) are sensitive to PARP-1 inhibitors in vitro and in vivo. Here, we report that PARP inhibitors can potentially target ATM deficiency arising in a solid malignancy. We show that ATM protein expression varies between gastric cancer cell lines, with NUGC4 having significantly reduced protein levels. Significant correlation was found between ATM protein expression and sensitivity to the PARP inhibitor olaparib, with NUGC4 being the most sensitive. Moreover, reducing ATM kinase activity using a small-molecule inhibitor (KU55933) or shRNA-mediated depletion of ATM protein enhanced olaparib sensitivity in gastric cancer cell lines with depletion or inactivation of p53. Our results demonstrate that ATM is a potential predictive biomarker for PARP-1 inhibitor activity in gastric cancer harboring disruption of p53, and that combined inhibition of ATM and PARP-1 is a rational strategy for expanding the utility of PARP-1 inhibitors to gastric cancer with p53 disruption. PMID:24841718

  1. Selective breeding of two lines of guinea pigs differing in bronchial sensitivity to acetylcholine and histamine exposure.

    Science.gov (United States)

    Mikami, H; Nishibata, R; Kawamoto, Y; Ino, T

    1991-04-01

    We developed two lines of guinea pigs, one as model animals for bronchial asthma with bronchial hypersensitivity and the other with hyposensitivity as a control. In the last four years, the bronchial hypersensitive line (BHS) and hyposensitive line (BHR), both derived from Hartley strain guinea pigs, have been selected by using bronchial reactivity to acetylcholine and to histamine as parameters. Both lines have reached the F6 generation. The following results were obtained with the two lines: 1) Sib and cous in matings, and mating of selected consanguineous individuals were adopted in breeding BHS and BHR. The breeding started with six families, each, but in the F6 generation the number of families decreased to two in each line. 2) Appearance rates of hyper- or hyposensitivity to acetylcholine and histamine increased with successive generations in both lines, which had been completely separated by the F6 generation. 3) Coefficients of inbreeding in BHS and BHR in the F6 generation ranged from 42% to 45% in the former and 42% in the latter. 4) Heritabilities (h2) of BHS and BHR for the appearance rates of sensitivity to acetylcholine were presumed to be 0.54 in the former and 0.69 in the latter. 5) No difference in the body weight of 0, 20, and 40 day-old BHS was observed in any generation. On the other hand, the body weight of 20 and 40 day-old BHR tended to decrease with successive generations. 6) Mean litter sizes of BHS and BHR in each of the generations ranged from 2.24 to 3.47 animals in the former and from 2.63 to 3.38 animals in the latter.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Sensitivity to ionizing radiation and chemotherapeutic agents in gemcitabine-resistant human tumor cell lines

    NARCIS (Netherlands)

    van Bree, Chris; Castro Kreder, Natasja; Loves, Willem J. P.; Franken, Nicolaas A. P.; Peters, Godefridus J.; Haveman, Jaap

    2002-01-01

    Purpose: To determine cross-resistance to anti-tumor treatments in 2',2'difluorodeoxycytidine (dFdC, gemcitabine)-resistant human tumor cells. Methods and Materials: Human lung carcinoma cells SW-1573 (SWp) were made resistant to dFdC (SWg). Sensitivity to cisplatin (cDDP), paclitaxel,

  3. Characterising alluvial aquifers in a remote ephemeral catchment (Flinders River, Queensland) using a direct push tracer approach

    Science.gov (United States)

    Taylor, Andrew R.; Smith, Stanley D.; Lamontagne, Sébastien; Suckow, Axel

    2018-01-01

    The availability of reliable water supplies is a key factor limiting development in northern Australia. However, characterising groundwater resources in this remote part of Australia is challenging due to a lack of existing infrastructure and data. Here, direct push technology (DPT) was used to characterise shallow alluvial aquifers at two locations in the semiarid Flinders River catchment. DPT was used to evaluate the saturated thickness of the aquifer and estimate recharge rates by sampling for environmental tracers in groundwater (major ions, 2H, 18O, 3H and 14C). The alluvium at Fifteen Mile Reserve and Glendalough Station consisted of a mixture of permeable coarse sandy and gravely sediments and less permeable clays and silts. The alluvium was relatively thin (i.e. < 20 m) and, at the time of the investigation, was only partially saturated. Tritium (3H) concentrations in groundwater was ∼1 Tritium Unit (TU), corresponding to a mean residence time for groundwater of about 12 years. The lack of an evaporation signal for the 2H and 18O of groundwater suggests rapid localised recharge from overbank flood events as the primary recharge mechanism. Using the chloride mass balance technique (CMB) and lumped parameter models to interpret patterns in 3H in the aquifer, the mean annual recharge rate varied between 21 and 240 mm/yr. Whilst this recharge rate is relatively high for a semiarid climate, the alluvium is thin and heterogeneous hosting numerous alluvial aquifers with varied connectivity and limited storage capacity. Combining DPT and environmental tracers is a cost-effective strategy to characterise shallow groundwater resources in unconsolidated sedimentary aquifers in remote data sparse areas.

  4. Cultural differences in on-line sensitivity to emotional voices: comparing East and West

    OpenAIRE

    Liu, Pan; Rigoulot, Simon; Pell, Marc D.

    2015-01-01

    Evidence that culture modulates on-line neural responses to the emotional meanings encoded by vocal and facial expressions was demonstrated recently in a study comparing English North Americans and Chinese (Liu et al., 2015). Here, we compared how individuals from these two cultures passively respond to emotional cues from faces and voices using an Oddball task. Participants viewed in-group emotional faces, with or without simultaneous vocal expressions, while performing a face-irrelevant vis...

  5. MicroRNA signature of cis-platin resistant vs. cis-platin sensitive ovarian cancer cell lines

    Directory of Open Access Journals (Sweden)

    Kumar Smriti

    2011-09-01

    Full Text Available Abstract Background Ovarian cancer is the leading cause of death from gynecologic cancer in women worldwide. According to the National Cancer Institute, ovarian cancer has the highest mortality rate among all the reproductive cancers in women. Advanced stage diagnosis and chemo/radio-resistance is a major obstacle in treating advanced ovarian cancer. The most commonly employed chemotherapeutic drug for ovarian cancer treatment is cis-platin. As with most chemotherapeutic drugs, many patients eventually become resistant to cis-platin and therefore, diminishing its effect. The efficacy of current treatments may be improved by increasing the sensitivity of cancer cells to chemo/radiation therapies. Methods The present study is focused on identifying the differential expression of regulatory microRNAs (miRNAs between cis-platin sensitive (A2780, and cis-platin resistant (A2780/CP70 cell lines. Cell proliferation assays were conducted to test the sensitivity of the two cell lines to cis-platin. Differential expression patterns of miRNA between cis-platin sensitive and cis-platin resistant cell lines were analyzed using novel LNA technology. Results Our results revealed changes in expression of 11 miRNAs out of 1,500 miRNAs analyzed. Out of the 11 miRNAs identified, 5 were up-regulated in the A2780/CP70 cell line and 6 were down regulated as compared to cis-platin sensitive A2780 cells. Our microRNA data was further validated by quantitative real-time PCR for these selected miRNAs. Ingenuity Pathway Analysis (IPA and Kyoto Encyclopedia of Genes and Genomes (KEGG analysis was performed for the selected miRNAs and their putative targets to identify the potential pathways and networks involved in cis-platin resistance. Conclusions Our data clearly showed the differential expression of 11 miRNAs in cis-platin resistant cells, which could potentially target many important pathways including MAPK, TGF-β signaling, actin cytoskeleton, ubiquitin mediated

  6. TERRA Expression Levels Do Not Correlate With Telomere Length and Radiation Sensitivity in Human Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Alexandra eSmirnova

    2013-05-01

    Full Text Available Mammalian telomeres are transcribed into long non-coding telomeric RNA molecules (TERRA that seem to play a role in the maintenance of telomere stability. In human cells, CpG island promoters drive TERRA transcription and are regulated by methylation. It was suggested that the amount of TERRA may be related to telomere length. To test this hypothesis we measured telomere length and TERRA levels in single clones isolated from five human cell lines: HeLa (cervical carcinoma, BRC-230 (breast cancer, AKG and GK2 (gastric cancers and GM847 (SV40 immortalized skin fibroblasts. We observed great clonal heterogeneity both in TRF (Terminal Restriction Fragment length and in TERRA levels. However, these two parameters did not correlate with each other. Moreover, cell survival to γ-rays did not show a significant variation among the clones, suggesting that, in this cellular system, the intra-population variability in telomere length and TERRA levels does not influence sensitivity to ionizing radiation. This conclusion was supported by the observation that in a cell line in which telomeres were greatly elongated by the ectopic expression of telomerase, TERRA expression levels and radiation sensitivity were similar to the parental HeLa cell line.

  7. Response of sensitive human ataxia and resistant T-1 cell lines to accelerated heavy ions

    International Nuclear Information System (INIS)

    Tobias, C.A.; Blakely, E.A.; Chang, P.Y.; Lommel, L.; Roots, R.

    1983-07-01

    The radiation dose responses of fibroblast from a patient with Ataxia telangiectasis (AT-2SF) and an established line of human T-1 cells were studied. Nearly monoenergetic accelerated neon and argon ions were used at the Berkeley Bevalac with various residual range values. The LET of the particles varied from 30 keV/μm to over 1000 keV/μm. All Ataxia survival curves were exponential functions of the dose. Their radiosensitivity reached peak values at 100 to 200 keV/μm. Human T-1 cells have effective sublethal damage repair as has been evidenced by split dose experiments, and they are much more resistant to low LET than to high LET radiation. The repair-misrepair model has been used to interpret these results. We have obtained mathematical expressions that describe the cross sections and inactivation coefficients for both human cell lines as a function of the LET and the type of particle used. The results suggest either that high-LET particles induce a greater number of radiolesions per track or that heavy-ions at high LET induce lesions that kill cells more effectively and that are different from those produced at low LET. We assume that the lesions induced in T-1 and Ataxia cells are qualitatively similar and that each cell line attempts to repair these lesions. The result in most irradiated Ataxia cells, however, is either lethal misrepair or incomplete repair leading to cell death. 63 references, 10 figures, 1 table

  8. Proteomic Differences in Feline Fibrosarcomas Grown Using Doxorubicin-Sensitive and -Resistant Cell Lines in the Chick Embryo Model

    Directory of Open Access Journals (Sweden)

    Katarzyna Zabielska-Koczywąs

    2018-02-01

    Full Text Available Proteomic analyses are rapid and powerful tools that are used to increase the understanding of cancer pathogenesis, discover cancer biomarkers and predictive markers, and select and monitor novel targets for cancer therapy. Feline injection-site sarcomas (FISS are aggressive skin tumours with high recurrence rates, despite treatment with surgery, radiotherapy, and chemotherapy. Doxorubicin is a drug of choice for soft tissue sarcomas, including FISS. However, multidrug resistance is one of the major causes of chemotherapy failure. The main aim of the present study was to identify proteins that differentiate doxorubicin-resistant from doxorubicin-sensitive FISS using two-dimensional gel electrophoresis (2DE, followed by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS analysis. Using the three-dimensional (3D preclinical in ovo model, which resembles features of spontaneous fibrosarcomas, three significantly (p ≤ 0.05 differentially expressed proteins were identified in tumours grown from doxorubicin-resistant fibrosarcoma cell lines (FFS1 and FFS3 in comparison to the doxorubicin-sensitive one (FFS5: Annexin A5 (ANXA5, Annexin A3 (ANXA3, and meiosis-specific nuclear structural protein 1 (MNS1. Moreover, nine other proteins were significantly differentially expressed in tumours grown from the high doxorubicin-resistant cell line (FFS1 in comparison to sensitive one (FFS5. This study may be the first proteomic fingerprinting of FISS reported, identifying potential candidates for specific predictive biomarkers and research targets for doxorubicin-resistant FISS.

  9. Photographic but not line-drawn faces show early perceptual neural sensitivity to eye gaze direction

    Directory of Open Access Journals (Sweden)

    Alejandra eRossi

    2015-04-01

    Full Text Available Our brains readily decode facial movements and changes in social attention, reflected in earlier and larger N170 event-related potentials (ERPs to viewing gaze aversions vs. direct gaze in real faces (Puce et al. 2000. In contrast, gaze aversions in line-drawn faces do not produce these N170 differences (Rossi et al., 2014, suggesting that physical stimulus properties or experimental context may drive these effects. Here we investigated the role of stimulus-induced context on neurophysiological responses to dynamic gaze. Sixteen healthy adults viewed line-drawn and real faces, with dynamic eye aversion and direct gaze transitions, and control stimuli (scrambled arrays and checkerboards while continuous electroencephalographic (EEG activity was recorded. EEG data from 2 temporo-occipital clusters of 9 electrodes in each hemisphere where N170 activity is known to be maximal were selected for analysis. N170 peak amplitude and latency, and temporal dynamics from event-related spectral perturbations (ERSPs were measured in 16 healthy subjects. Real faces generated larger N170s for averted vs. direct gaze motion, however, N170s to real and direct gaze were as large as those to respective controls. N170 amplitude did not differ across line-drawn gaze changes. Overall, bilateral mean gamma power changes for faces relative to control stimuli occurred between 150-350 ms, potentially reflecting signal detection of facial motion.Our data indicate that experimental context does not drive N170 differences to viewed gaze changes. Low-level stimulus properties, such as the high sclera/iris contrast change in real eyes likely drive the N170 changes to viewed aversive movements.

  10. Integrated Cantilever-Based Flow Sensors with Tunable Sensitivity for In-Line Monitoring of Flow Fluctuations in Microfluidic Systems

    Directory of Open Access Journals (Sweden)

    Nadine Noeth

    2013-12-01

    Full Text Available For devices such as bio-/chemical sensors in microfluidic systems, flow fluctuations result in noise in the sensor output. Here, we demonstrate in-line monitoring of flow fluctuations with a cantilever-like sensor integrated in a microfluidic channel. The cantilevers are fabricated in different materials (SU-8 and SiN and with different thicknesses. The integration of arrays of holes with different hole size and number of holes allows the modification of device sensitivity, theoretical detection limit and measurement range. For an average flow in the microliter range, the cantilever deflection is directly proportional to the flow rate fluctuations in the microfluidic channel. The SiN cantilevers show a detection limit below 1 nL/min and the thinnest SU-8 cantilevers a detection limit below 5 nL/min. Finally, the sensor is applied for in-line monitoring of flow fluctuations generated by external pumps connected to the microfluidic system.

  11. A Neutron Sensitive Microchannel Plate Detector with Cross Delay Line Readout

    International Nuclear Information System (INIS)

    Berry, Kevin D.; Bilheux, Hassina Z.; Crow, Lowell; Diawara, Yacouba; Feller, W. Bruce; Iverson, Erik B.; Martin, Adrian; Robertson, J. Lee

    2012-01-01

    Microchannel plates containing neutron absorbing elements such as boron and gadolinium in the bulk glass are used as the sensing element in high spatial resolution, high rate neutron imaging systems. In this paper we describe one such device, using both 10 B and natural Gd, which employs cross delay line signal readout, with time-of-flight capability. This detector has a measured spatial resolution under 40 m FWHM, thermal neutron efficiency of 19%, and has recorded rates in excess of 500 kHz. A physical and functional description is presented, followed by a discussion of measurements of detector performance and a brief survey of some practical applications.

  12. Chromatin status of apoptosis genes correlates with sensitivity to chemo-, immune- and radiation therapy in colorectal cancer cell lines.

    Science.gov (United States)

    Benard, Anne; Janssen, Connie M; van den Elsen, Peter J; van Eggermond, Marja C J A; Hoon, Dave S B; van de Velde, Cornelis J H; Kuppen, Peter J K

    2014-12-01

    The apoptosis pathway of programmed cell death is frequently deregulated in cancer. An intact apoptosis pathway is required for proper response to anti-cancer treatment. We investigated the chromatin status of key apoptosis genes in the apoptosis pathway in colorectal cancer cell lines in relation to apoptosis induced by chemo-, immune- or radiation therapy. Using chromatin immunoprecipitation (ChIP), we measured the presence of transcription-activating histone modifications H3Ac and H3K4me3 and silencing modifications H3K9me3 and H3K27me3 at the gene promoter regions of key apoptosis genes Bax, Bcl2, Caspase-9, Fas (CD95) and p53. Cell lines DLD1, SW620, Colo320, Caco2, Lovo and HT29 were treated with cisplatin, anti-Fas or radiation. The apoptotic response was measured by flow cytometry using propidium iodide and annexin V-FITC. The chromatin status of the apoptosis genes reflected the activation status of the intrinsic (Bax, Bcl2, Caspase-9 and p53) and extrinsic (Fas) pathways. An active intrinsic apoptotic pathway corresponded to sensitivity to cisplatin and radiation treatment of cell lines DLD1, SW620 and Colo320. An active Fas promoter corresponded to an active extrinsic apoptotic pathway in cell line DLD1. mRNA expression data correlated with the chromatin status of the apoptosis genes as measured by ChIP. In conclusion, the results presented in this study indicate that the balance between activating and silencing histone modifications, reflecting the chromatin status of apoptosis genes, can be used to predict the response of tumor cells to different anti-cancer therapies and could provide a novel target to sensitize tumors to obtain adequate treatment responses.

  13. A very sensitive nonintercepting beam average velocity monitoring system for the TRIUMF 300-keV injection line

    International Nuclear Information System (INIS)

    Yin, Y.; Laxdal, R.E.; Zelenski, A.; Ostroumov, P.

    1997-01-01

    A nonintercepting beam velocity monitoring system has been installed in the 300-keV injection line of the TRIUMF cyclotron to reproduce the injection energy for beam from different ion sources and to monitor any beam energy fluctuations. By using a programmable beam signal leveling method the system can work with a beam current dynamic range of 50 dB. Using synchronous detection, the system can detect 0.5 eV peak-to-peak energy modulation of the beam, sensitivity is 1.7x10 -6 . The paper will describe the principle and beam measurement results. copyright 1997 American Institute of Physics

  14. The CO_2 absorption spectrum in the 2.3 µm transparency window by high sensitivity CRDS: (I) Rovibrational lines

    International Nuclear Information System (INIS)

    Vasilchenko, S.; Konefal, M.; Mondelain, D.; Kassi, S.; Čermák, P.; Tashkun, S.A.; Perevalov, V.I.; Campargue, A.

    2016-01-01

    The absorption of carbon dioxide is very weak near 2.3 µm which makes this transparency window of particular interest for the study of Venus’ lower atmosphere. As a consequence of the weakness of the transitions located in this region, previous experimental data are very scarce and spectroscopic databases provide calculated line lists which should be tested and validated by experiment. In this work, we use the Cavity Ring Down Spectroscopy (CRDS) technique for a high sensitivity characterization of the CO_2 absorption spectrum in two spectral intervals of the 2.3 µm window: 4248–4257 and 4295–4380 cm"−"1 which were accessed using a Distributed Feed Back (DFB) diode laser and a Vertical External Cavity Surface Emitting Laser (VECSEL) as light sources, respectively. The achieved sensitivity (noise equivalent absorption, α_m_i_n, on the order of 5×10"−"1"0 cm"−"1) allowed detecting numerous new transitions with intensity values down to 5×10"−"3"0 cm/molecule. The rovibrational assignments were performed by comparison with available theoretical line lists in particular those obtained at IAO Tomsk using the global effective operator approach. Hot bands of the main isotopologue and "1"6O"1"2C"1"8O bands were found to be missing in the HITRAN database while they contribute importantly to the absorption in the region. Additional CRDS spectra of a CO_2 sample highly enriched in "1"8O were recorded in order to improve the spectroscopy of this isotopologue. As a result about 700 lines of "1"6O"1"2C"1"8O, "1"6O"1"2C"1"7O, "1"7O"1"2C"1"8O, "1"2C"1"8O_2 and "1"3C"1"8O_2 were newly measured. The status of the different databases (HITRAN, CDSD, variational calculations) in the important 2.3 µm transparency window is discussed. Possible improvements to correct evidenced deficiencies are suggested. - Highlights: • High sensitivity CRDS with a VECSEL in the 2.3 µm transparency window of CO_2. • Natural and "1"8O enriched CO_2 spectra recorded with

  15. Identification of proteins sensitive to thermal stress in human neuroblastoma and glioma cell lines.

    Directory of Open Access Journals (Sweden)

    Guilian Xu

    Full Text Available Heat-shock is an acute insult to the mammalian proteome. The sudden elevation in temperature has far-reaching effects on protein metabolism, leads to a rapid inhibition of most protein synthesis, and the induction of protein chaperones. Using heat-shock in cells of neuronal (SH-SY5Y and glial (CCF-STTG1 lineage, in conjunction with detergent extraction and sedimentation followed by LC-MS/MS proteomic approaches, we sought to identify human proteins that lose solubility upon heat-shock. The two cell lines showed largely overlapping profiles of proteins detected by LC-MS/MS. We identified 58 proteins in detergent insoluble fractions as losing solubility in after heat shock; 10 were common between the 2 cell lines. A subset of the proteins identified by LC-MS/MS was validated by immunoblotting of similarly prepared fractions. Ultimately, we were able to definitively identify 3 proteins as putatively metastable neural proteins; FEN1, CDK1, and TDP-43. We also determined that after heat-shock these cells accumulate insoluble polyubiquitin chains largely linked via lysine 48 (K-48 residues. Collectively, this study identifies human neural proteins that lose solubility upon heat-shock. These proteins may represent components of the human proteome that are vulnerable to misfolding in settings of proteostasis stress.

  16. The human cyclin B1 protein modulates sensitivity of DNA mismatch repair deficient prostate cancer cell lines to alkylating agents.

    Science.gov (United States)

    Rasmussen, L J; Rasmussen, M; Lützen, A; Bisgaard, H C; Singh, K K

    2000-05-25

    DNA damage caused by alkylating agents results in a G2 checkpoint arrest. DNA mismatch repair (MMR) deficient cells are resistant to killing by alkylating agents and are unable to arrest the cell cycle in G2 phase after alkylation damage. We investigated the response of two MMR-deficient prostate cancer cell lines DU145 and LNCaP to the alkylating agent MNNG. Our studies reveal that DU145 cancer cells are more sensitive to killing by MNNG than LNCaP. Investigation of the underlying reasons for lower resistance revealed that the DU145 cells contain low endogenous levels of cyclin B1. We provide direct evidence that the endogenous level of cyclin B1 modulates the sensitivity of MMR-deficient prostate cancer cells to alkylating agents.

  17. Hybridization approach to in-line and off-axis (electron) holography for superior resolution and phase sensitivity

    Science.gov (United States)

    Ozsoy-Keskinbora, C.; Boothroyd, C. B.; Dunin-Borkowski, R. E.; van Aken, P. A.; Koch, C. T.

    2014-01-01

    Holography - originally developed for correcting spherical aberration in transmission electron microscopes - is now used in a wide range of disciplines that involve the propagation of waves, including light optics, electron microscopy, acoustics and seismology. In electron microscopy, the two primary modes of holography are Gabor's original in-line setup and an off-axis approach that was developed subsequently. These two techniques are highly complementary, offering superior phase sensitivity at high and low spatial resolution, respectively. All previous investigations have focused on improving each method individually. Here, we show how the two approaches can be combined in a synergetic fashion to provide phase information with excellent sensitivity across all spatial frequencies, low noise and an efficient use of electron dose. The principle is also expected to be widely to applications of holography in light optics, X-ray optics, acoustics, ultra-sound, terahertz imaging, etc. PMID:25387480

  18. arXiv Wilson lines and UV sensitivity in magnetic compactifications

    CERN Document Server

    Ghilencea, D.M.

    2017-06-07

    We investigate the ultraviolet (UV) behaviour of 6D N=1 supersymmetric effective (Abelian) gauge theories compactified on a two-torus (T$_{2}$) with magnetic flux. To this purpose we compute offshell the one-loop correction to the Wilson line state self-energy. The offshell calculation is actually necessary to capture the usual effective field theory expansion in powers of (∂/Λ). Particular care is paid to the regularization of the (divergent) momentum integrals, which is relevant for identifying the corresponding counterterm(s). We find a counterterm which is a new higher dimensional effective operator of dimension d=6, that is enhanced for a larger compactification area (where the effective theory applies) and is consistent with the symmetries of the theory. Its consequences are briefly discussed and comparison is made with orbifold compactifications without flux.

  19. Variation in sensitizing effect of caffeine in human tumour cell lines after γ-irradiation

    International Nuclear Information System (INIS)

    Valenzuela, M.T.; Almodovar, M.R. de; Mateos, S.; McMillan, T.J.

    2000-01-01

    We have investigated whether the protective role of the G2 checkpoint has increasing importance when the p53-dependent G1 checkpoint is inactivated. We have studied the differential effect of caffeine by clonogenic assays and flow cytometry in three human tumour cell lines with different functionality of p53 protein. The radiosensitizing effect of caffeine (2 mM) expressed itself as a significant decrease in surviving fraction at 2 Gy and a significant increase in α-values in RT112 and TE671, both with non-functional p53. However, no radiosensitizing effect was seen in cells with a normal p53 function (MCF-7 BUS). Two millimoles of caffeine also caused important changes in the cell cycle progression after irradiation. MCF-7 BUS showed a G1 arrest after irradiation and an early G2 arrest but those cells that reached the second G2 did not arrest significantly. In contrast, TE671 exhibited radiosensitization by caffeine, no G1 arrest, a G2 arrest in those cells irradiated in G2, no significant accumulation in the second G2 but an overall delay in release from the first cell cycle, which could be abrogated by caffeine. RT112 was similar to TE671 except that the emphasis in a G2 arrest was shifted from the block in cells irradiated in G2 to those irradiated at other cell cycle phases. The data presented confirm that p53 status can be a significant determinant of the efficacy of caffeine as radiosensitizer in these tumour cell lines, and document the importance of the G2 checkpoint in this effect. (author)

  20. Sensitivity Studies for Main Steam Line Break Exercises 2 and 3 with RELAP5/PANBOX

    International Nuclear Information System (INIS)

    Boeer, Rainer; Knoll, Alfred

    2003-01-01

    This paper presents and discusses results obtained with the nuclear plant safety analysis code system RELAP5/PANBOX (R/P/C) for the return-to-power scenario of exercises 2 and 3 of the Organization for Economic Cooperation and Development/Nuclear Energy Agency Main Steam Line Break (MSLB) Benchmark. Both the external and internal coupling options of R/P/C have been considered for exercise 3; i.e., the COBRA module of PANBOX was used to calculate the core thermal hydraulics in the external coupling option, whereas the core thermal hydraulics of RELAP5 was used in the internal coupling option. For the representation of thermal-hydraulic channels, a fine channel geometry based on the 177 fuel assemblies was selected for the external coupling option, and a coarse channel geometry based on 19 coarse channels has been investigated for the internal coupling option. The comparison of the results shows very good agreement of important core parameters between the considered coupling variants. Both exercises 2 and 3 have been investigated with respect to local safety parameters like fuel centerline temperatures and minimum departure from nucleate boiling ratios using the on-line hot subchannel analysis capability of R/P/C in the external coupling option. The results show that both quantities are far from the safety-related limits.The benchmark demonstrates, that R/P/C - as part of the integrated CASCADE-3D core analysis system of Framatome ANP GmbH - has proven to be a powerful tool for detailed analyses of an MSLB accident

  1. Cultural differences in on-line sensitivity to emotional voices: Comparing East and West

    Directory of Open Access Journals (Sweden)

    Pan eLiu

    2015-05-01

    Full Text Available Evidence that culture modulates on-line neural responses to the emotional meanings encoded by vocal and facial expressions was demonstrated recently in a study comparing English North Americans and Chinese (Liu et al., 2015. Here, we compared how individuals from these two cultures passively respond to emotional cues from faces and voices using an Oddball task. Participants viewed in-group emotional faces, with or without simultaneous vocal expressions, while performing a face-irrelevant visual task as the EEG was recorded. A significantly larger visual MMN was observed for Chinese versus English participants when faces were accompanied by voices, suggesting that Chinese were influenced to a larger extent by task-irrelevant vocal cues. These data highlight further differences in how adults from East Asian versus Western cultures process socio-emotional cues, arguing that distinct cultural practices in communication (e.g., display rules shape neurocognitive activity associated with the early perception and integration of multi-sensory emotional cues.

  2. Mycoplasma hyorhinis-Contaminated Cell Lines Activate Primary Innate Immune Cells via a Protease-Sensitive Factor.

    Directory of Open Access Journals (Sweden)

    Simon Heidegger

    Full Text Available Mycoplasma are a frequent and occult contaminant of cell cultures, whereby these prokaryotic organisms can modify many aspects of cell physiology, rendering experiments that are conducted with such contaminated cells problematic. Chronic Mycoplasma contamination in human monocytic cells lines has been associated with suppressed Toll-like receptor (TLR function. In contrast, we show here that components derived from a Mycoplasma hyorhinis-infected cell line can activate innate immunity in non-infected primary immune cells. Release of pro-inflammatory cytokines such as IL-6 by dendritic cells in response to Mycoplasma hyorhinis-infected cell components was critically dependent on the adapter protein MyD88 but only partially on TLR2. Unlike canonical TLR2 signaling that is triggered in response to the detection of Mycoplasma infection, innate immune activation by components of Mycoplasma-infected cells was inhibited by chloroquine treatment and sensitive to protease treatment. We further show that in plasmacytoid dendritic cells, soluble factors from Mycoplasma hyorhinis-infected cells induce the production of large amounts of IFN-α. We conclude that Mycoplasma hyorhinis-infected cell lines release protein factors that can potently activate co-cultured innate immune cells via a previously unrecognized mechanism, thus limiting the validity of such co-culture experiments.

  3. Factors determining sensitivity or resistance of tumor cell lines towards artesunate.

    Science.gov (United States)

    Sertel, Serkan; Eichhorn, Tolga; Sieber, Sebastian; Sauer, Alexandra; Weiss, Johanna; Plinkert, Peter K; Efferth, Thomas

    2010-04-15

    Clinical oncology is still challenged by the development of drug resistance of tumors that result in poor prognosis for patients. There is an urgent necessity to understand the molecular mechanisms of resistance and to develop novel therapy strategies. Artesunate (ART) is an anti-malarial drug, which also exerts profound cytotoxic activity towards cancer cells. We first applied a gene-hunting approach using cluster and COMPARE analyses of microarray-based transcriptome-wide mRNA expression profiles. Among the genes identified by this approach were genes from diverse functional groups such as structural constituents of ribosomes (RPL6, RPL7, RPS12, RPS15A), kinases (CABC1, CCT2, RPL41), transcriptional and translational regulators (SFRS2, TUFM, ZBTB4), signal transducers (FLNA), control of cell growth and proliferation (RPS6), angiogenesis promoting factors (ITGB1), and others (SLC25A19, NCKAP1, BST1, DBH, FZD7, NACA, MTHFD2). Furthermore, we applied a candidate gene approach and tested the role of resistance mechanisms towards established anti-cancer drugs for ART resistance. By using transfected or knockout cell models we found that the tumor suppressor p16(INK4A) and the anti-oxidant protein, catalase, conferred resistance towards ART, while the oncogene HPV-E6 conferred sensitivity towards ART. The tumor suppressor p53 and its downstream protein, p21, as well as the anti-oxidant manganese-dependent superoxide dismutase did not affect cellular response to ART. In conclusion, our pharmacogenomic approach revealed that response of tumor cells towards ART is multi-factorial and is determined by gene expression associated with either ART sensitivity or resistance. At least some of the functional groups of genes (e.g. angiogenesis promoting factors, cell growth and proliferation-associated genes signal transducers and kinases) are also implicated in clinical responsiveness of tumors towards chemotherapy. It merits further investigation, whether ART is responsive in

  4. A Sensitive Sensor Cell Line for the Detection of Oxidative Stress Responses in Cultured Human Keratinocytes

    Directory of Open Access Journals (Sweden)

    Ute Hofmann

    2014-06-01

    Full Text Available In the progress of allergic and irritant contact dermatitis, chemicals that cause the generation of reactive oxygen species trigger a heat shock response in keratinocytes. In this study, an optical sensor cell line based on cultured human keratinocytes (HaCaT cells expressing green fluorescent protein (GFP under the control of the stress-inducible HSP70B’ promoter were constructed. Exposure of HaCaT sensor cells to 25 µM cadmium, a model substance for oxidative stress induction, provoked a 1.7-fold increase in total glutathione and a ~300-fold induction of transcript level of the gene coding for heat shock protein HSP70B’. An extract of Arnica montana flowers resulted in a strong induction of the HSP70B’ gene and a pronounced decrease of total glutathione in keratinocytes. The HSP70B’ promoter-based sensor cells conveniently detected cadmium-induced stress using GFP fluorescence as read-out with a limit of detection of 6 µM cadmium. In addition the sensor cells responded to exposure of cells to A. montana extract with induction of GFP fluorescence. Thus, the HaCaT sensor cells provide a means for the automated detection of the compromised redox status of keratinocytes as an early indicator of the development of human skin disorders and could be applied for the prediction of skin irritation in more complex in vitro 3D human skin models and in the development of micro-total analysis systems (µTAS that may be utilized in dermatology, toxicology, pharmacology and drug screenings.

  5. Protein Profiles Reveal Diverse Responsive Signaling Pathways in Kernels of Two Maize Inbred Lines with Contrasting Drought Sensitivity

    Directory of Open Access Journals (Sweden)

    Liming Yang

    2014-10-01

    Full Text Available Drought stress is a major factor that contributes to disease susceptibility and yield loss in agricultural crops. To identify drought responsive proteins and explore metabolic pathways involved in maize tolerance to drought stress, two maize lines (B73 and Lo964 with contrasting drought sensitivity were examined. The treatments of drought and well water were applied at 14 days after pollination (DAP, and protein profiles were investigated in developing kernels (35 DAP using iTRAQ (isobaric tags for relative and absolute quantitation. Proteomic analysis showed that 70 and 36 proteins were significantly altered in their expression under drought treatments in B73 and Lo964, respectively. The numbers and levels of differentially expressed proteins were generally higher in the sensitive genotype, B73, implying an increased sensitivity to drought given the function of the observed differentially expressed proteins, such as redox homeostasis, cell rescue/defense, hormone regulation and protein biosynthesis and degradation. Lo964 possessed a more stable status with fewer differentially expressed proteins. However, B73 seems to rapidly initiate signaling pathways in response to drought through adjusting diverse defense pathways. These changes in protein expression allow for the production of a drought stress-responsive network in maize kernels.

  6. Response to dexamethasone is glucose-sensitive in multiple myeloma cell lines

    Directory of Open Access Journals (Sweden)

    Turturro Francesco

    2011-09-01

    Full Text Available Abstract Background Hyperglycemia is among the major side effects of dexamethasone (DEX. Glucose or glucocorticoid (GC regulates the expression of thioredoxin-interacting protein (TXNIP that controls the production of reactive oxygen species (ROS through the modulation of thioredoxin (TRX activity. Methods Multiple myeloma (MM cells were grown in 5 or 20 mM/L glucose with or without 25 μM DEX. Semiquantitative reverse transcription-PCR (RT-PCR was used to assess TXNIP RNA expression in response to glucose and DEX. ROS were detected by 5-6-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (CM-H2DCFDA. TRX activity was assayed by the insulin disulfide-reducing assay. Proliferation was evaluated using CellTiter96 reagent with 490-nm absorbtion and used to calculate the DEX IC50 in 20 mM/L glucose using the Chou's dose effect equation. Results TXNIP RNA level responded to glucose or DEX with the same order of magnitude ARH77 > NCIH929 > U266B1 in these cells. MC/CAR cells were resistant to the regulation. ROS level increased concurrently with reduced TRX activity. Surprisingly glucose increased TRX activity in MC/CAR cells keeping ROS level low. DEX and glucose were lacking the expected additive effect on TXNIP RNA regulation when used concurrently in sensitive cells. ROS level was significantly lower when DEX was used in conditions of hyperglycemia in ARH77/NCIH9292 cells but not in U266B1 cells. Dex-IC50 increased 10-fold when the dose response effect of DEX was evaluated with glucose in ARH && and MC/Car cells Conclusions Our study shows for the first time that glucose or DEX regulates important components of ROS production through TXNIP modulation or direct interference with TRX activity in MM cells. We show that glucose modulates the activity of DEX through ROS regualtion in MM cells. A better understanding of these pathways may help in improving the efficacy and reducing the toxicity of DEX, a drug still highly used in the treatment of

  7. Cadmium induced changes in cell organelles: An ultrastructural study using cadmium sensitive and resistant muntjac fibroblast cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Ord, M.J.; Chibber, R.; Bouffler, S.D.

    1988-09-01

    A detailed electron microscopy study of cadmium sensitive and resistant muntjac fibroblast cell lines has identified a wide range of intracellular damage following exposure to cadmium. Damaged organelles included cell membrane, mitochondria, Golgi cisternae and tubular network, chromatin, nucleoli, microfilaments and ribosomes. Although cell membrane damage was generally the earliest indication of adverse cadmium action, particularly with continuous cadmium exposures, cells could tolerate extensive membrane loss. Mitochondrial distortion and some damage to Golgi was also tolerated. The turning point at which cadmium became lethal was generally marked by a cascade of events which included damage to both nuclear and cytoplasmic components. These results for fibroblasts are discussed and compared with damage reported in other types of cells.

  8. Recombination activating activity of XRCC1 analogous genes in X-ray sensitive and resistant CHO cell lines

    International Nuclear Information System (INIS)

    Golubnitchaya-Labudova, O.; Hoefer, M.; Portele, A.; Vacata, V.; Rink, H.; Lubec, G.

    1997-01-01

    The XRCC1 gene (X-ray repair cross complementing) complements the DNA repair deficiency of the radiation sensitive Chinese hamster ovary (CHO) mutant cell line EM9 but the mechanism of the correction is not elucidated yet. XRCC1 shows substantial homology to the RAG2 gene (recombination activating gene) and we therefore tried to answer the question, whether structural similarities (sequence of a putative recombination activating domain, aa 332-362 for XRCC1 and aa 286-316 in RAG2) would reflect similar functions of the homologous, putative recombination activating domain. PCR experiments revealed that no sequence homologous to the structural part of human XRCC1 was present in cDNA of CHO. Differential display demonstrated two putative recombination activating in the parental CHO line AA8 and one in the radiosensitive mutant EM9. Southern blot experiments showed the presence of several genes with partial homology to human XRCC1. Recombination studies consisted of expressing amplified target domains within chimeric proteins in recA - bacteria and subsequent detection of recombination events by sequencing the recombinant plasmids. Recombination experiments demonstrated recombination activating activity of all putative recombination activating domains amplified from AA8 and EM9 genomes as reflected by deletions within the inserts of the recombinant plasmids. The recombination activating activity of XRCC1 analogues could explain a mechanism responsible for the correction of the DNA repair defect in EM9. (author)

  9. Ribavirin restores ESR1 gene expression and tamoxifen sensitivity in ESR1 negative breast cancer cell lines

    Directory of Open Access Journals (Sweden)

    Sappok Anne

    2011-12-01

    Full Text Available Abstract Tumor growth is estrogen independent in approximately one-third of all breast cancers, which makes these patients unresponsive to hormonal treatment. This unresponsiveness to hormonal treatment may be explained through the absence of the estrogen receptor alpha (ESR1. The ESR1 gene re-expression through epigenetic modulators such as DNA methyltransferase inhibitors and/or histone deacetylase inhibitors restores tamoxifen sensitivity in ESR1 negative breast cancer cell lines and opens new treatment horizons in patients who were previously associated with a poor prognosis. In the study presented herein, we tested the ability of ribavirin, which shares some structural similarities with the DNA-methyltransferase inhibitor 5-azacytidine and which is widely known as an anti-viral agent in the treatment of hepatitis C, to restore ESR1 gene re-expression in ESR1 negative breast cancer cell lines. In our study we identified ribavirin to restore ESR1 gene re-expression alone and even more in combination with suberoylanilide hydroxamic acid (SAHA - up to 276 fold induction. Ribavirin and analogs could pave the way to novel translational research projects that aim to restore ESR1 gene re-expression and thus the susceptibility to tamoxifen-based endocrine treatment strategies.

  10. Comparative proteome analysis of drought-sensitive and drought-tolerant rapeseed roots and their hybrid F1 line under drought stress.

    Science.gov (United States)

    Mohammadi, Payam Pour; Moieni, Ahmad; Komatsu, Setsuko

    2012-11-01

    Rapeseed (Brassica napus L.), which is the third leading source of vegetable oil, is sensitive to drought stress during the early vegetative growth stage. To investigate the initial response of rapeseed to drought stress, changes in the protein expression profiles of drought-sensitive (RGS-003) and drought-tolerant lines (SLM-003), and their F1 hybrid, were analyzed using a proteomics approach. Seven-day-old rapeseed seedlings were treated with drought stress by restricting water for 7 days, and proteins were extracted from roots and separated by two-dimensional polyacrylamide gel electrophoresis. In the sensitive rapeseed line, 35 protein spots were differentially expressed under drought stress, and proteins related to metabolism, energy, disease/defense, and transport were decreased. In the tolerant line, 32 protein spots were differentially expressed under drought stress, and proteins involved in metabolism, disease/defense, and transport were increased, while energy-related proteins were decreased. Six protein spots in F1 hybrid were common among expressed proteins in the drought-sensitive and -tolerant lines. Notably, tubulin beta-2 and heat shock protein 70 were decreased in the drought-sensitive line and hybrid F1 plants, while jasmonate-inducible protein and 20S proteasome subunit PAF1 were increased in the F1 hybrids and drought-tolerant line. These results indicate that (1) V-type H(+) ATPase, plasma-membrane associated cation-binding protein, HSP 90, and elongation factor EF-2 have a role in the drought tolerance of rapeseed; (2) The decreased levels of heat shock protein 70 and tubulin beta-2 in the drought-sensitive and hybrid F1 lines might explain the reduced growth of these lines in drought conditions.

  11. The sensitivity of diffuse large B-cell lymphoma cell lines to histone deacetylase inhibitor-induced apoptosis is modulated by BCL-2 family protein activity.

    Directory of Open Access Journals (Sweden)

    Ryan C Thompson

    Full Text Available BACKGROUND: Diffuse large B-cell lymphoma (DLBCL is a genetically heterogeneous disease and this variation can often be used to explain the response of individual patients to chemotherapy. One cancer therapeutic approach currently in clinical trials uses histone deacetylase inhibitors (HDACi's as monotherapy or in combination with other agents. METHODOLOGY/PRINCIPAL FINDINGS: We have used a variety of cell-based and molecular/biochemical assays to show that two pan-HDAC inhibitors, trichostatin A and vorinostat, induce apoptosis in seven of eight human DLBCL cell lines. Consistent with previous reports implicating the BCL-2 family in regulating HDACi-induced apoptosis, ectopic over-expression of anti-apoptotic proteins BCL-2 and BCL-XL or pro-apoptotic protein BIM in these cell lines conferred further resistance or sensitivity, respectively, to HDACi treatment. Additionally, BCL-2 family antgonist ABT-737 increased the sensitivity of several DLBCL cell lines to vorinostat-induced apoptosis, including one cell line (SUDHL6 that is resistant to vorinostat alone. Moreover, two variants of the HDACi-sensitive SUDHL4 cell line that have decreased sensitivity to vorinostat showed up-regulation of BCL-2 family anti-apoptotic proteins such as BCL-XL and MCL-1, as well as decreased sensitivity to ABT-737. These results suggest that the regulation and overall balance of anti- to pro-apoptotic BCL-2 family protein expression is important in defining the sensitivity of DLBCL to HDACi-induced apoptosis. However, the sensitivity of DLBCL cell lines to HDACi treatment does not correlate with expression of any individual BCL-2 family member. CONCLUSIONS/SIGNIFICANCE: These studies indicate that the sensitivity of DLBCL to treatment with HDACi's is dependent on the complex regulation of BCL-2 family members and that BCL-2 antagonists may enhance the response of a subset of DLBCL patients to HDACi treatment.

  12. Cell lines derived from a Medaka radiation-sensitive mutant have defects in DNA double-strand break responses

    International Nuclear Information System (INIS)

    Hidaka, Masayuki; Oda, Shoji; Mitani, Hiroshi; Kuwahara, Yoshikazu; Fukumoto, Manabu

    2010-01-01

    It was reported that the radiation-sensitive Medaka mutant 'ric1' has a defect in the repair of DNA double-strand breaks (DSBs) induced by γ-rays during early embryogenesis. To study the cellular response of a ric1 mutant to ionizing radiation (IR), we established the mutant embryonic cell lines RIC1-e9, RIC1-e42, RIC1-e43. Following exposure to γ-irradiation, the DSBs in wild-type cells were repaired within 1 h, while those in RIC1 cells were not rejoined even after 2 h. Cell death was induced in the wild-type cells with cell fragmentation, but only a small proportion of the RIC1 cells underwent cell death, and without cell fragmentation. Although both wild-type and RIC1 cells showed mitotic inhibition immediately after γ-irradiation, cell division was much slower to resume in the wild-type cells (20 h versus 12 h). In both wild-type and RIC1 cells, Ser139 phosphorylated H2AX (γH2AX) foci were formed after γ-irradiation, however, the γH2AX foci disappeared more quickly in the RIC1 cell lines. These results suggest that the instability of γH2AX foci in RIC1 cells cause an aberration of the DNA damage response. As RIC1 cultured cells showed similar defective DNA repair as ric1 embryos and RIC1 cells revealed defective cell death and cell cycle checkpoint, they are useful for investigating DNA damage responses in vitro. (author)

  13. Physiological joint line total knee arthroplasty designs are especially sensitive to rotational placement - A finite element analysis.

    Science.gov (United States)

    Moewis, Philippe; Checa, Sara; Kutzner, Ines; Hommel, Hagen; Duda, Georg N

    2018-01-01

    Mechanical and kinematical aligning techniques are the usual positioning methods during total knee arthroplasty. However, alteration of the physiological joint line and unbalanced medio-lateral load distribution are considered disadvantages in the mechanical and kinematical techniques, respectively. The aim of this study was to analyse the influence of the joint line on the strain and stress distributions in an implanted knee and their sensitivity to rotational mal-alignment. Finite element calculations were conducted to analyse the stresses in the PE-Inlay and the mechanical strains at the bone side of the tibia component-tibia bone interface during normal positioning of the components and internal and external mal-rotation of the tibial component. Two designs were included, a horizontal and a physiological implant. The loading conditions are based on internal knee joint loads during walking. A medialization of the stresses on the PE-Inlay was observed in the physiological implant in a normal position, accompanied by higher stresses in the mal-rotated positions. Within the tibia component-tibia bone interface, similar strain distributions were observed in both implant geometries in the normal position. However, a medialization of the strains was observed in the physiological implant in both mal-rotated conditions with greater bone volume affected by higher strains. Although evident changes due to mal-rotation were observed, the stresses do not suggest a local plastic deformation of the PE-Inlay. The strains values within most of the tibia component-tibia bone interface were in the physiological strain zone and no significant bone changes would be expected. The physiological cut on the articular aspect showed no detrimental effect compared to the horizontal implant.

  14. Effects of Smac gene over-expression on radiotherapeutic sensitivity of cervical cancer cell line HeLa

    International Nuclear Information System (INIS)

    Zheng Liduan; Wang Liang; Tong Qiangsong; Fei Shihong; Xiong Yufang; Wu Gang

    2005-01-01

    Objective: To study the effects of extrinsic Smac gene transfection and its over-expression on radiotherapeutic sensitivity of cervical cancer cells, in order to explore a novel strategy for ameliorating radiotherapy of cervical cancer. Methods: After Smac gene was transferred into cells of cervical cancer cell line HeLa, the subclone cells were obtained by persistent G 418 selection. Cellular Smac gene expression was determined by RT-PCR and Western blot. After treatment with X-ray irradiation, cellular growth activity in vitro was investigated by MTT colorimetry. Cellular apoptosis and its rate were determined by electron microscopy, Annexin V-FITC and propidium iodide staining flow cytometry. Cellular Caspase-3 protein expression and its activity were assayed by Western blot and colorimetry. Results: RT-PCR and Western blot demonstrated that Smac mRNA and protein levels of HeLa/Smac cells, the selected subclone cells of cervical cancer cell line, were significantly higher than those of HeLa cells (P<0.01). After treated with 8 Gy X-ray irradiation, growth activity of HeLa/Smac cells reduced by 10.19%(P<0.01), as compared with that of HeLa cells. Partial HeLa/Smac cancer cells presented characteristic morphological changes of apoptosis under electron microscope, with an apoptosis rate of 16.4%, which was significantly higher than that of HeLa cells(6.2%, P<0.01). Compared with HeLa cells, Caspase-3 expression level in HeLa/Smac was improved significantly (P<0.01), while its activity was 3.42 times as much as that of HeLa cells (P<0.01). Conclusion: Stable transfection of extrinsic Smac gene and its over-expression in cervical cancer cell line could significantly enhance cellular caspase-3 expression and activity, ameliorate apoptosis-inducing effects of radiation on cancer cells, which would be a novel strategy to improve radiotherapeutic effects for cervical cancer. (authors)

  15. Specific down-regulation of XIAP with RNA interference enhances the sensitivity of canine tumor cell-lines to TRAIL and doxorubicin

    Directory of Open Access Journals (Sweden)

    Rothuizen Jan

    2006-09-01

    Full Text Available Abstract Background Apoptosis resistance occurs in various tumors. The anti-apoptotic XIAP protein is responsible for inhibiting apoptosis by reducing caspase-3 activation. Our aim is to evaluate whether RNA inhibition against XIAP increases the sensitivity of canine cell-lines for chemotherapeutics such as TRAIL and doxorubicin. We used small interfering RNA's (siRNA directed against XIAP in three cell-lines derived from bile-duct epithelia (BDE, mammary carcinoma (P114, and osteosarcoma (D17. These cell-lines represent frequently occurring canine cancers and are highly comparable to their human counterparts. XIAP down-regulation was measured by means of quantitative PCR (Q-PCR and Western blotting. The XIAP depleted cells were treated with a serial dilution of TRAIL or doxorubicin and compared to mock- and nonsense-treated controls. Viability was measured with a MTT assay. Results All XIAP siRNA treated cell-lines showed a mRNA down-regulation over 80 percent. Western blot analysis confirmed mRNA measurements. No compensatory effect of IAP family members was seen in XIAP depleted cells. The sensitivity of XIAP depleted cells for TRAIL was highest in BDE cells with an increase in the ED50 of 14-fold, compared to mock- and nonsense-treated controls. The sensitivity of P114 and D17 cell-lines increased six- and five-fold, respectively. Doxorubicin treatment in XIAP depleted cells increased sensitivity in BDE cells more than eight-fold, whereas P114 and D17 cell-lines showed an increase in sensitivity of three- and five-fold, respectively. Conclusion XIAP directed siRNA's have a strong sensitizing effect on TRAIL-reduced cell-viability and a smaller but significant effect with the DNA damaging drug doxorubicin. The increase in efficacy of chemotherapeutics with XIAP depletion provides the rationale for the use of XIAP siRNA's in insensitive canine tumors.

  16. Influence of Mesenchymal Stem Cells Conditioned Media on Proliferation of Urinary Tract Cancer Cell Lines and Their Sensitivity to Ciprofloxacin.

    Science.gov (United States)

    Maj, Malgorzata; Bajek, Anna; Nalejska, Ewelina; Porowinska, Dorota; Kloskowski, Tomasz; Gackowska, Lidia; Drewa, Tomasz

    2017-06-01

    Mesenchymal stem cells (MSCs) are known to interact with cancer cells through direct cell-to-cell contact and secretion of paracrine factors, although their exact influence on tumor progression in vivo remains unclear. To better understand how fetal and adult stem cells affect tumors, we analyzed viability of human renal (786-0) and bladder (T24) carcinoma cell lines cultured in conditioned media harvested from amniotic fluid-derived stem cells (AFSCs) and adipose-derived stem cells (ASCs). Both media reduced metabolic activity of 786-0 cells, however, decreased viability of T24 cells was noted only after incubation with conditioned medium from ASCs. To test the hypothesis that MSCs-secreted factors might be involved in chemoresistance acquisition, we further analyzed influence of mesenchymal stem cell conditioned media (MSC-CM) on cancer cells sensitivity to ciprofloxacin, that is considered as potential candidate agent for urinary tract cancers treatment. Significantly increased resistance to tested drug indicates that MSCs may protect cancer cells from chemotherapy. J. Cell. Biochem. 118: 1361-1368, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Cell Penetrating Capacity and Internalization Mechanisms Used by the Synthetic Peptide CIGB-552 and Its Relationship with Tumor Cell Line Sensitivity.

    Science.gov (United States)

    Astrada, Soledad; Fernández Massó, Julio Raúl; Vallespí, Maribel G; Bollati-Fogolín, Mariela

    2018-03-30

    CIGB-552 is a twenty-amino-acid novel synthetic peptide that has proven to be effective in reducing tumor size and increasing lifespan in tumor-bearing mice. Such capability is conferred by its cell-penetrating peptide character, which allows it to enter cells and elicit a pro-apoptotic effect through its major mediator, COMMD1 protein. Cell-penetrating peptides are able to use different internalization mechanisms, such as endocytosis or direct transduction through the plasma membrane. Although CIGB-552 cytotoxicity has been evaluated in several non-tumor- and tumor-derived cell lines, no data regarding the relationship between cell line sensitivity, cell penetrating capacity, the internalization mechanisms involved, COMMD1 expression levels, or its subcellular localization has yet been produced. Here, we present the results obtained from a comparative analysis of CIGB-552 sensitivity, internalization capacity and the mechanisms involved in three human tumor-derived cell lines from different origins: mammary gland, colon and lung (MCF-7, HT-29 and H460, respectively). Furthermore, cell surface markers relevant for internalization processes such as phosphatidylserine, as well as CIGB-552 target COMMD1 expression/localization, were also evaluated. We found that both endocytosis and transduction are involved in CIGB-552 internalization in the three cell lines evaluated. However, CIGB-552 incorporation efficiency and contribution of each mechanism is cell-line dependent. Finally, sensitivity was directly correlated with high internalization capacity in those cell lines where endocytosis had a major contribution on CIGB-552 internalization.

  18. Improving Blast Resistance of a Thermo-Sensitive Genic Male Sterile Rice Line GD-8S by Molecular Marker-Assisted Selection

    Directory of Open Access Journals (Sweden)

    Wu-ge LIU

    2008-09-01

    Full Text Available The broad-spectrum blast resistance gene Pi-1, from donor line BL122, was introduced into a thermo-sensitive genic male sterile rice line GD-8S, which possessed good grain quality but high susceptibility to rice blast, by using backcross breeding and molecular marker-assisted selection. Five elite improved male sterile lines, RGD8S-1, RGD8S-2, RGD8S-3, RGD8S-4 and RGD8S-5, were selected based on the results of molecular marker analysis, spikelet sterility, recovery rate of genetic background and agronomic traits. Thirty-three representative blast isolates collected from Guangdong Province, China were used to inoculate the improved lines and the original line GD-8S artificially. The resistance frequencies of the improved lines ranged from 76.47% to 100%, much higher than that of the original line GD-8S (9.09%. On the agronomic characters, there were no significant differences between the improved lines and GD-8S except for flag leaf length and panicle number per plant. The improved lines could be used for breeding hybrid rice with high blast resistance.

  19. Loss in MCL-1 function sensitizes non-Hodgkin's lymphoma cell lines to the BCL-2-selective inhibitor venetoclax (ABT-199)

    International Nuclear Information System (INIS)

    Phillips, D C; Xiao, Y; Lam, L T; Litvinovich, E; Roberts-Rapp, L; Souers, A J; Leverson, J D

    2015-01-01

    As a population, non-Hodgkin's lymphoma (NHL) cell lines positive for the t(14;18) translocation and/or possessing elevated BCL2 copy number (CN; BCL2 High ) are exquisitely sensitive to navitoclax or the B-cell lymphoma protein-2 (BCL-2)-selective inhibitor venetoclax. Despite this, some BCL2 High cell lines remain resistant to either agent. Here we show that the MCL-1-specific inhibitor A-1210477 sensitizes these cell lines to navitoclax. Chemical segregation of this synergy with the BCL-2-selective inhibitor venetoclax or BCL-X L -selective inhibitor A-1155463 indicated that MCL-1 and BCL-2 are the two key anti-apoptotic targets for sensitization. Similarly, the CDK inhibitor flavopiridol downregulated MCL-1 expression and synergized with venetoclax in BCL2 High NHL cell lines to a similar extent as A-1210477. A-1210477 also synergized with navitoclax in the majority of BCL2 Low NHL cell lines. However, chemical segregation with venetoclax or A-1155463 revealed that synergy was driven by BCL-X L inhibition in this population. Collectively these data emphasize that BCL2 status is predictive of venetoclax potency in NHL not only as a single agent, but also in the adjuvant setting with anti-tumorigenic agents that inhibit MCL-1 function. These studies also potentially identify a patient population (BCL2 Low ) that could benefit from BCL-X L (navitoclax)-driven combination therapy

  20. Cytoskeletal Regulation Dominates Temperature-Sensitive Proteomic Changes of Hibernation in Forebrain of 13-Lined Ground Squirrels

    Science.gov (United States)

    Hindle, Allyson G.; Martin, Sandra L.

    2013-01-01

    13-lined ground squirrels, Ictidomys tridecemlineatus, are obligate hibernators that transition annually between summer homeothermy and winter heterothermy – wherein they exploit episodic torpor bouts. Despite cerebral ischemia during torpor and rapid reperfusion during arousal, hibernator brains resist damage and the animals emerge neurologically intact each spring. We hypothesized that protein changes in the brain underlie winter neuroprotection. To identify candidate proteins, we applied a sensitive 2D gel electrophoresis method to quantify protein differences among forebrain extracts prepared from ground squirrels in two summer, four winter and fall transition states. Proteins that differed among groups were identified using LC-MS/MS. Only 84 protein spots varied significantly among the defined states of hibernation. Protein changes in the forebrain proteome fell largely into two reciprocal patterns with a strong body temperature dependence. The importance of body temperature was tested in animals from the fall; these fall animals use torpor sporadically with body temperatures mirroring ambient temperatures between 4 and 21°C as they navigate the transition between summer homeothermy and winter heterothermy. Unlike cold-torpid fall ground squirrels, warm-torpid individuals strongly resembled the homeotherms, indicating that the changes observed in torpid hibernators are defined by body temperature, not torpor per se. Metabolic enzymes were largely unchanged despite varied metabolic activity across annual and torpor-arousal cycles. Instead, the majority of the observed changes were cytoskeletal proteins and their regulators. While cytoskeletal structural proteins tended to differ seasonally, i.e., between summer homeothermy and winter heterothermy, their regulatory proteins were more strongly affected by body temperature. Changes in the abundance of various isoforms of the microtubule assembly and disassembly regulatory proteins dihydropyrimidinase

  1. Cytoskeletal regulation dominates temperature-sensitive proteomic changes of hibernation in forebrain of 13-lined ground squirrels.

    Directory of Open Access Journals (Sweden)

    Allyson G Hindle

    Full Text Available 13-lined ground squirrels, Ictidomys tridecemlineatus, are obligate hibernators that transition annually between summer homeothermy and winter heterothermy - wherein they exploit episodic torpor bouts. Despite cerebral ischemia during torpor and rapid reperfusion during arousal, hibernator brains resist damage and the animals emerge neurologically intact each spring. We hypothesized that protein changes in the brain underlie winter neuroprotection. To identify candidate proteins, we applied a sensitive 2D gel electrophoresis method to quantify protein differences among forebrain extracts prepared from ground squirrels in two summer, four winter and fall transition states. Proteins that differed among groups were identified using LC-MS/MS. Only 84 protein spots varied significantly among the defined states of hibernation. Protein changes in the forebrain proteome fell largely into two reciprocal patterns with a strong body temperature dependence. The importance of body temperature was tested in animals from the fall; these fall animals use torpor sporadically with body temperatures mirroring ambient temperatures between 4 and 21°C as they navigate the transition between summer homeothermy and winter heterothermy. Unlike cold-torpid fall ground squirrels, warm-torpid individuals strongly resembled the homeotherms, indicating that the changes observed in torpid hibernators are defined by body temperature, not torpor per se. Metabolic enzymes were largely unchanged despite varied metabolic activity across annual and torpor-arousal cycles. Instead, the majority of the observed changes were cytoskeletal proteins and their regulators. While cytoskeletal structural proteins tended to differ seasonally, i.e., between summer homeothermy and winter heterothermy, their regulatory proteins were more strongly affected by body temperature. Changes in the abundance of various isoforms of the microtubule assembly and disassembly regulatory proteins

  2. Trichostatin A (TSA) sensitizes the human prostatic cancer cell line DU145 to death receptor ligands treatment.

    Science.gov (United States)

    Taghiyev, Agshin F; Guseva, Natalya V; Sturm, Mary T; Rokhlin, Oskar W; Cohen, Michael B

    2005-04-01

    The human prostatic carcinoma cell line DU145 has previously been found to be resistant to treatment with TNF-family ligands. However, TRAIL, TNF-alpha and anti-Fas antibodies (Ab) treatment in combination with the histone deacetylase inhibitor Trichostatin A (TSA) converted the phenotype of DU145 from resistant to sensitive. TSA induced 15% cell death but simultaneous treatment with TRAIL, TNF-alpha and anti-Fas Ab resulted in 55%, 70% and 40% cell death, respectively. Simultaneous treatment did not increase the level of TSA-induced histone acetylation, but induced the release of acetylated histones from chromatin into the cytosol. This release was caspase dependent since it was abrogated by Z-VAD-fmk. In addition, treatment with TSA induced caspase-9 activation and resulted in the release of cytochrome c and Smac/DIABLO from mitochondria. To further investigate the role of caspase-9 in TSA-mediated apoptosis we used two different approaches: (1) cells were pretreated with the caspase-9 inhibitor Z-LEHD-fmk, and (2) cells were transfected with a dominant-negative form of caspase-9. Both approaches gave similar results: cells became resistant to treatment with TSA. These data indicate that TSA mediates its effect via the mitochondrial pathway. This was confirmed by examining DU145 overexpressing Bcl-2. These transfectants were resistant to TSA treatment. Taken together, our data shows that only simultaneous treatment with TNF-family ligands and TSA in DU145 resulted in caspase activity sufficient to induce apoptosis. The combination of TSA and TNF-family ligands could potentially be the basis for the treatment of prostate cancer.

  3. Relationship between line spread function (LSF), or slice sensitivity profile (SSP), and point spread function (PSF) in CT image system

    International Nuclear Information System (INIS)

    Ohkubo, Masaki; Wada, Shinichi; Kobayashi, Teiji; Lee, Yongbum; Tsai, Du-Yih

    2004-01-01

    In the CT image system, we revealed the relationship between line spread function (LSF), or slice sensitivity profile (SSP), and point spread function (PSF). In the system, the following equation has been reported; I(x,y)=O(x,y) ** PSF(x,y), in which I(x,y) and O(x,y) are CT image and object function, respectively, and ** is 2-dimensional convolution. In the same way, the following 3-dimensional expression applies; I'(x,y,z)=O'(x,y,z) *** PSF'(x,y,z), in which z-axis is the direction perpendicular to the x/y-scan plane. We defined that the CT image system was separable, when the above two equations could be transformed into following equations; I(x,y)=[O(x,y) * LSF x (x)] * LSF y (y) and I'(x,y,z) =[O'(x,y,z) * SSP(z)] ** PSF(x,y), respectively, in which LSF x (x) and LSF y (y) are LSFs in x- and y-direction, respectively. Previous reports for the LSF and SSP are considered to assume the separable-system. Under the condition of separable-system, we derived following equations; PSF(x,y)=LSF x (x) ·LSF y (y) and PSF'(x,y,z)=PSF(x,y)·SSP(z). They were validated by the computer-simulations. When the study based on 1-dimensional functions of LSF and SSP are expanded to that based on 2- or 3-dimensional functions of PSF, derived equations must be required. (author)

  4. Gefitinib upregulates death receptor 5 expression to mediate rmhTRAIL-induced apoptosis in Gefitinib-sensitive NSCLC cell line

    Directory of Open Access Journals (Sweden)

    Yan D

    2015-07-01

    Full Text Available Dong Yan,1,2 Yang Ge,1 Haiteng Deng,3 Wenming Chen,4 Guangyu An1 1Department of Oncology, Beijing Chao-yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Translational Molecular pathology, M.D Anderson Cancer Center, Houston, TX, USA; 3School of Sciences, Tsinghua University, 4Department of Hematology, Beijing Chao-yang Hospital, Capital Medical University, Beijing, People’s Republic of China Background: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL triggers apoptosis in tumor cells, but when used alone, it is not effective in the treatment of TRAIL-resistant tumors. Some studies have shown that gefitinib interacts with recombinant mutant human TRAIL (rmhTRAIL to induce high levels of apoptosis in gefitinib-responsive bladder cancer cell lines; however, the molecular mechanisms underlying the anticancer effects are not fully understood. Several reports have shown that the death receptor 5 (DR5 plays an important role in sensitizing cancer cells to apoptosis induced by TRAIL. Therefore, we investigated the effects of the combination of drugs and the expression of the DR5 to analyze the growth of a gefitinib-responsive non-small cell lung cancer cell line PC9, which was treated with rmhTRAIL and gefitinib individually or in combination.Methods: Human PC9 non-small cell lung cancer cells harboring an epidermal growth factor receptor mutation were used as a model for the identification of the therapeutic effects of gefitinib alone or in combination with rmhTRAIL, and cytotoxicity was assessed by MTT assays. Cell cycle and apoptosis were investigated using flow cytometry. Moreover, the effects of drugs on DR5, BAX, FLIP, and cleaved-caspase3 proteins expressions were analyzed using Western blot analyses. Finally, quantitative polymerase chain reaction analysis was carried out to assess whether rmhTRAIL and gefitinib modulate the expression of genes related to drug activity.Results: Gefitinib and rmh

  5. Chemo-sensitivity in a panel of B-cell precursor acute lymphoblastic leukemia cell lines, YCUB series, derived from children.

    Science.gov (United States)

    Goto, Hiroaki; Naruto, Takuya; Tanoshima, Reo; Kato, Hiromi; Yokosuka, Tomoko; Yanagimachi, Masakatsu; Fujii, Hisaki; Yokota, Shumpei; Komine, Hiromi

    2009-10-01

    Sensitivity to 10 anticancer drugs was evaluated in 6 childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cell lines. Authenticity of newly established cell lines was confirmed by genomic fingerprinting. The line YCUB-5R established at relapse was more resistant to 4-hydroperoxy-cyclophosphamide, cytarabine, L-asparaginase, topotecan, fludarabine, and etoposide than YCUB-5 from the same patient at diagnosis. Of the drugs tested, etoposide and SN-38 (irinotecan) showed highest efficacy in the panel, with 50% growth inhibition at 0.22-1.8 microg/ml and 0.57-3.6 ng/ml, respectively. This cell line panel offers an in vitro model for the development of new therapies for childhood BCP-ALL.

  6. Ecdysteroids Sensitize MDR and Non-MDR Cancer Cell Lines to Doxorubicin, Paclitaxel, and Vincristine but Tend to Protect Them from Cisplatin

    Directory of Open Access Journals (Sweden)

    Ana Martins

    2015-01-01

    Full Text Available Ecdysteroids, analogs of the insect molting hormone, are known for their various mild, nonhormonal bioactivities in mammals. Previously, we reported that less-polar ecdysteroids can modulate the doxorubicin resistance of a multidrug resistant (MDR mouse lymphoma cell line expressing the human ABCB1 transporter. Here, we describe the ability of 20-hydroxyecdysone (1 and its mono- (2 and diacetonide (3 derivatives to sensitize various MDR and non-MDR cancer cell lines towards doxorubicin, paclitaxel, vincristine, or cisplatin. Drug IC50 values with or without ecdysteroid were determined by MTT assay. Compound 3 significantly sensitized all cell lines to each chemotherapeutic except for cisplatin, whose activity was decreased. In order to overcome solubility and stability issues for the future in vivo administration of compound 3, liposomal formulations were developed. By means of their combination index values obtained via checkerboard microplate method, a formulation showed superior activity to that of compound 3 alone. Because ecdysteroids act also on non-ABCB1 expressing (sensitive cell lines, our results demonstrate that they do not or not exclusively exert their adjuvant anticancer activity as ABCB1 inhibitors, but other mechanisms must be involved, and they opened the way towards their in vivo bioactivity testing against various cancer xenografts.

  7. Evaluation of the skin sensitization potential of chemicals using expression of co-stimulatory molecules, CD54 and CD86, on the naive THP-1 cell line.

    Science.gov (United States)

    Yoshida, Y; Sakaguchi, H; Ito, Y; Okuda, M; Suzuki, H

    2003-04-01

    It has been known that dendritic cells (DCs) including Langerhans cells (LCs) play a critical role in the skin sensitization process. Many attempts have been made to develop in vitro sensitization tests that employ DCs derived from peripheral blood mononuclear cells (PBMC-DC) or CD34+ hematopoietic progenitor cells (CD34+ HPC) purified from cord blood or bone marrow. However, the use of the DCs in in vitro methods has been difficult due to the nature of these cells such as low levels in the source and/or donor-to-donor variability. In our studies, we employed the human monocytic leukemia cell line, THP-1, in order to avoid some of these difficulties. At the start, we examined whether treatment of the cells with various cytokines could produce DCs from THP-1. Treatment of THP-1 cells with cytokines such as GM-CSF, IL-4, TNF-alpha, and/or PMA did induce some phenotypic changes in THP-1 cells that were characteristic of DCs. Subsequently, responses to a known sensitizer, dinitrochlorobenzene (DNCB), and a non-sensitizer, dimethyl sulfoxide (DMSO) or sodium lauryl sulfate (SLS), on the expression of co-stimulatory molecules, CD54 and CD86, were examined between the naive cells and the cytokine-treated cells. Interestingly, the naive THP-1 cells responded only to DNCB and the response to the sensitizer was more distinct than cytokine-treated THP-1 cells. Similar phenomena were also observed in the human myeloid leukemia cell line, KG-1. Furthermore, with treatment of DNCB, naive THP-1 cells showed augmented expression of HLA, CD80 and secretion of IL-1 beta. The response of THP-1 cells to a sensitizer was similar to that of LCs/DCs. Upon demonstrating the differentiation of monocyte cells in our system, we then evaluated a series of chemicals, including known sensitizers and non-sensitizers, for their potential to augment CD54 and CD86 expression on naive THP-1 cells. Indeed, known sensitizers such as PPD and 2-MBT significantly augmented CD54 and CD86 expression in a

  8. A uv-sensitive Chinese hamster lung fibroblast cell line (V79/UC) with a possible defect in DNA polymerase activity is deficient in DNA repair

    International Nuclear Information System (INIS)

    Creissen, D.M.; Hill, C.K.

    1991-01-01

    Studies of repair enzyme activities in a uv-sensitive cell line (V79/UC) derived from Chinese hamster V79 cells have revealed levels of total DNA polymerase that are about 50% of the levels in the parental cell line. There are a number of DNA polymerase inhibitors available which allow us to distinguish between the major forms of DNA polymerase (alpha, beta, gamma, and delta) identified in mammalian cells. Enzyme assays with these inhibitors indicate that the aphidicolin-sensitive DNA polymerase is defective in the V79/UC cell line. This could be either polymerase alpha or delta, or both. The V79/UC cells do not express resistance to aphidicolin in standard toxicity studies. However, when aphidicolin is added postirradiation in survival assays designed to measure the extent of inhibitable repair, V79/UC cells do not respond with the further decrease in survival seen in the parental line. Further evidence of a polymerase-dependent repair defect is evident from alkaline elution data. In this case the V79/UC cells show the appearance of single-strand breaks following uv irradiation in the absence of any added inhibitor. Cells of the V79/M12G parental line, on the other hand, show the appearance of single-strand breaks only when aphidicolin is present

  9. Higher Levels of c-Met Expression and Phosphorylation Identify Cell Lines With Increased Sensitivity to AMG-458, a Novel Selective c-Met Inhibitor With Radiosensitizing Effects

    International Nuclear Information System (INIS)

    Li Bo; Torossian, Artour; Sun, Yunguang; Du, Ruihong; Dicker, Adam P.; Lu Bo

    2012-01-01

    Purpose: c-Met is overexpressed in some non-small cell lung cancer (NSCLC) cell lines and tissues. Cell lines with higher levels of c-Met expression and phosphorylation depend on this receptor for survival. We studied the effects of AMG-458 on 2 NSCLC cell lines. Methods and Materials: 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl) -2H-tetrazolium assays assessed the sensitivities of the cells to AMG-458. Clonogenic survival assays illustrated the radiosensitizing effects of AMG-458. Western blot for cleaved caspase 3 measured apoptosis. Immunoblotting for c-Met, phospho-Met (p-Met), Akt/p-Akt, and Erk/p-Erk was performed to observe downstream signaling. Results: AMG-458 enhanced radiosensitivity in H441 but not in A549. H441 showed constitutive phosphorylation of c-Met. A549 expressed low levels of c-Met, which were phosphorylated only in the presence of exogenous hepatocyte growth factor. The combination of radiation therapy and AMG-458 treatment was found to synergistically increase apoptosis in the H441 cell line but not in A549. Radiation therapy, AMG-458, and combination treatment were found to reduce p-Akt and p-Erk levels in H441 but not in A549. H441 became less sensitive to AMG-458 after small interfering RNA knockdown of c-Met; there was no change in A549. After overexpression of c-Met, A549 became more sensitive, while H441 became less sensitive to AMG-458. Conclusions: AMG-458 was more effective in cells that expressed higher levels of c-Met/p-Met, suggesting that higher levels of c-Met and p-Met in NSCLC tissue may classify a subset of tumors that are more sensitive to molecular therapies against this receptor.

  10. Insulin sensitivity and beta-cell function in the offspring of type 2 diabetic patients: impact of line of inheritance.

    LENUS (Irish Health Repository)

    Natali, Andrea

    2010-10-01

    What defects in glucose metabolism are present in offspring of type 2 diabetic patients (FHD(+) with a positive family history of diabetes) and to what extent they depend on line of inheritance are uncertain.

  11. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: Northwest Arctic, Alaska: SOCECON (Socioeconomic Resource Points and Lines)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains vector points and lines representing human-use resource data for airports, marinas, and mining sites in Northwest Arctic, Alaska....

  12. Expression of surface markers on the human monocytic leukaemia cell line, THP-1, as indicators for the sensitizing potential of chemicals.

    Science.gov (United States)

    An, Susun; Kim, Seoyoung; Huh, Yong; Lee, Tae Ryong; Kim, Han-Kon; Park, Kui-Lea; Eun, Hee Chul

    2009-04-01

    Evaluation of skin sensitization potential is an important part of the safety assessment of cosmetic ingredients and topical drugs. Recently, evaluation of changes in surface marker expression induced in dendritic cells (DC) or DC surrogate cell lines following exposure to chemicals represents one approach for in vitro test methods. The study aimed to test the change of expression patterns of surface markers on THP-1 cells by chemicals as a predictive in vitro method for contact sensitization. We investigated the expression of CD54, CD86, CD83, CD80, and CD40 after a 1-day exposure to sensitizers (1-chloro-2,4-dinitrobenzene; 2,4-dinitrofluorobenzene; benzocaine; 5-chloro-2-methyl-4-isothiazolin-3-one; hexyl cinnamic aldehyde; eugenol; nickel sulfate hexahydrate; potassium dichromate; cobalt sulfate; 2-mercaptobenzothiazole; and ammonium tetrachloroplatinate) and non-sensitizers (sodium lauryl sulfate, benzalkonium chloride, lactic acid, salicylic acid, isopropanol, and dimethyl sulphoxide). The test concentrations were 0.1x, 0.5x, and 1x of the 50% inhibitory concentration, and the relative fluorescence intensity was used as an expression indicator. By evaluating the expression patterns of CD54, CD86, and CD40, we could classify the chemicals as sensitizers or non-sensitizers, but CD80 and CD83 showed non-specific patterns of expression. These data suggest that the THP-1 cells are good model for screening contact sensitizers and CD40 could be a useful marker complementary to CD54 and CD86.

  13. Enhanced expression of IL-8 in normal human keratinocytes and human keratinocyte cell line HaCaT in vitro after stimulation with contact sensitizers, tolerogens and irritants.

    Science.gov (United States)

    Mohamadzadeh, M; Müller, M; Hultsch, T; Enk, A; Saloga, J; Knop, J

    1994-12-01

    To investigate the interleukin-8 production of keratinocytes after stimulation in vitro we have used various agents: (i) contact sensitizer (2,4-dinitrofluorobenzene, 3-n-pentadecylcatechol); (ii) tolerogen (5-methyl-3-n-pentadecylcatechol); (iii) irritant (sodium lauryl sulfate). Interleukin-8 gene expression was assessed by northern blot hybridization of the total cytoplasmic RNA extracted from subconfluent normal human keratinocyte cultures and the keratinocyte cell line HaCaT using a radiolabeled DNA probe specific for human interleukin-8. Interleukin-8 gene expression was markedly increased upon in vitro stimulation after 1-6 h with contact sensitizers, tolerogen and the irritant. In contrast, interleukin-8 production was not detectable in unstimulated normal human keratinocytes or the HaCaT keratinocyte cell line. These results suggest that the induction and production of interleukin-8 is a response to nonspecific stimuli and may play a critical role in the early response to immunogenic or inflammatory signals in man.

  14. Development of an in vitro skin sensitization test using human cell lines; human Cell Line Activation Test (h-CLAT). II. An inter-laboratory study of the h-CLAT.

    Science.gov (United States)

    Sakaguchi, H; Ashikaga, T; Miyazawa, M; Yoshida, Y; Ito, Y; Yoneyama, K; Hirota, M; Itagaki, H; Toyoda, H; Suzuki, H

    2006-08-01

    Recent regulatory changes have placed a major emphasis on in vitro safety testing and alternative models. In regard to skin sensitization tests, dendritic cells (DCs) derived from human peripheral blood have been considered in the development of new in vitro alternatives. Human cell lines have been also reported recently. In our previous study, we suggested that measuring CD86 and/or CD54 expression on THP-1 cells (human monocytic leukemia cell line) could be used as an in vitro skin sensitization method. An inter-laboratory study among two laboratories was undertaken in Japan in order to further develop an in vitro skin sensitization model. In the present study, we used two human cell lines: THP-1 and U-937 (human histiocytic lymphoma cell line). First we optimized our test protocol (refer to the related paper entitled "optimization of the h-CLAT protocol" within this journal) and then we did an inter-laboratory validation with nine chemicals using the optimized protocol. We measured the expression of CD86 and CD54 on the above cells using flow cytometry after a 24h and 48h exposure to six known allergens (e.g., DNCB, pPD, NiSO(4)) and three non-allergens (e.g., SLS, tween 80). For the sample test concentration, four doses (0.1x, 0.5x, 1x, and 2x of the 50% inhibitory concentration (IC(50))) were evaluated. IC(50) was calculated using MTT assay. We found that allergens/non-allergens were better predicted using THP-1 cells compared to U-937 cells following a 24 h and a 48 h exposure. We also found that the 24h treatment time tended to have a better accuracy than the 48 h treatment time for THP-1 cells. Expression of CD86 and CD54 were good predictive markers for THP-1 cells, but for U-937 cells, expression of CD86 was a better predictor than CD54, at the 24h and the 48 h treatment time. The accuracy also improved when both markers (CD86 and CD54) were used as compared with a single marker for THP-1 cells. Both laboratories gave a good prediction of allergen

  15. Hormone resistance in two MCF-7 breast cancer cell lines is associated with reduced mTOR signaling, decreased glycolysis and increased sensitivity to cytotoxic drugs

    Directory of Open Access Journals (Sweden)

    Euphemia Yee Leung

    2014-09-01

    Full Text Available The mTOR pathway is a key regulator of multiple cellular signaling pathways and is a potential target for therapy. We have previously developed two hormone-resistant sub-lines of the MCF-7 human breast cancer line, designated TamC3 and TamR3, which were characterized by reduced mTOR signaling, reduced cell volume and resistance to mTOR inhibition. Here we show that these lines exhibit increased sensitivity to carboplatin, oxaliplatin, 5-fluorouracil, camptothecin, doxorubicin, paclitaxel, docetaxel and hydrogen peroxide. The mechanisms underlying these changes have not yet been characterized but may include a shift from glycolysis to mitochondrial respiration. If this phenotype is found in clinical hormone-resistant breast cancers, conventional cytotoxic therapy may be a preferred option for treatment.

  16. Combined use of anti-ErbB monoclonal antibodies and erlotinib enhances antibody-dependent cellular cytotoxicity of wild-type erlotinib-sensitive NSCLC cell lines

    Directory of Open Access Journals (Sweden)

    Cavazzoni Andrea

    2012-12-01

    Full Text Available Abstract Background The epidermal growth factor receptor (EGFR is an established target for anti-cancer treatment in different tumour types. Two different strategies have been explored to inhibit this pivotal molecule in epithelial cancer development: small molecules TKIs and monoclonal antibodies. ErbB/HER-targeting by monoclonal antibodies such as cetuximab and trastuzumab or tyrosine-kinase inhibitors as gefitinib or erlotinib has been proven effective in the treatment of advanced NSCLC. Results In this study we explored the potential of combining either erlotinib with cetuximab or trastuzumab to improve the efficacy of EGFR targeted therapy in EGFR wild-type NSCLC cell lines. Erlotinib treatment was observed to increase EGFR and/or HER2 expression at the plasma membrane level only in NSCLC cell lines sensitive to the drug inducing protein stabilization. The combined treatment had marginal effect on cell proliferation but markedly increased antibody-dependent, NK mediated, cytotoxicity in vitro. Moreover, in the Calu-3 xenograft model, the combination significantly inhibited tumour growth when compared with erlotinib and cetuximab alone. Conclusion Our results indicate that erlotinib increases surface expression of EGFR and/or HER2 only in EGFR-TKI sensitive NSCLC cell lines and, in turns, leads to increased susceptibility to ADCC both in vitro and in a xenograft models. The combination of erlotinib with monoclonal antibodies represents a potential strategy to improve the treatment of wild-type EGFR NSCLC patients sensitive to erlotinib.

  17. In vitro radiation and chemotherapy sensitivity of established cell lines of human small cell lung cancer and its large cell morphological variants

    International Nuclear Information System (INIS)

    Carney, D.N.; Mitchell, J.B.; Kinsella, T.J.

    1983-01-01

    The in vitro response to radiation and chemotherapeutic drugs of cell lines established from 7 patients with small cell (SC) lung cancer were tested using a soft agarose clonogenic assay. Five cell lines retained the typical morphological and biochemical amine precursor uptake decarboxylation characteristics of SC, while two cell lines had undergone ''transformation'' to large cell (LC) morphological variants with loss of amine precursor uptake decarboxylation cell characteristics of SC. The radiation survival curves for the SC lines were characterized by D0 values ranging from 51 to 140 rads and extrapolation values (n) ranging from 1.0 to 3.3. While the D0 values of the radiation survival curves of the LC variants were similar (91 and 80 rads), the extrapolation values were 5.6 and 11.1 In vitro chemosensitivity testing of the cell lines revealed an excellent correlation between prior treatment status of the patient and in vitro sensitivity or resistance. No correlation was observed between in vitro chemosensitivity and radiation response. These data suggest that transformation of SC to LC with loss of amine precursor uptake and decarboxylation characteristics is associated with a marked increase in radiation resistance (n) in vitro. The observation of a 2- to 5-fold increase in survival of the LC compared to the SC lines following 200 rads suggests that the use of larger daily radiation fractions and/or radiation-sensitizing drugs might lead to a significantly greater clinical response in patients with LC morphology. This clinical approach may have a major impact on patient response and survival

  18. Integrated cantilever-based flow sensors with tunable sensitivity for in-line monitoring of flow fluctuations in microfluidic systems

    DEFF Research Database (Denmark)

    Noeth, Nadine-Nicole; Keller, Stephan Sylvest; Boisen, Anja

    2014-01-01

    For devices such as bio-/chemical sensors in microfluidic systems, flow fluctuations result in noise in the sensor output. Here, we demonstrate in-line monitoring of flow fluctuations with a cantilever-like sensor integrated in a microfluidic channel. The cantilevers are fabricated in different...... is directly proportional to the flow rate fluctuations in the microfluidic channel. The SiN cantilevers show a detection limit below 1 nL/min and the thinnest SU-8 cantilevers a detection limit below 5 nL/min. Finally, the sensor is applied for in-line monitoring of flow fluctuations generated by external...

  19. The dominant erosion processes supplying fine sediment to three major rivers in tropical Australia, the Daly (NT), Mitchell (Qld) and Flinders (Qld) Rivers

    Science.gov (United States)

    Caitcheon, Gary G.; Olley, Jon M.; Pantus, Francis; Hancock, Gary; Leslie, Christopher

    2012-05-01

    The tropics of northern Australia have received relatively little attention with regard to the impact of soil erosion on the many large river systems that are an important part of Australia's water resource, especially given the high potential for erosion when long dry seasons are followed by intense wet season rain. Here we use 137Cs concentrations to determine the erosion processes supplying sediment to two major northern Australian Rivers; the Daly River (Northern Territory), and the Mitchell River (Queensland). We also present data from five sediment samples collected from a 100 km reach of the Cloncurry River, a major tributary of the Flinders River (Queensland). Concentrations of 137Cs in the surface soil and subsurface (channel banks and gully) samples were used to derive 'best fit' probability density functions describing their distributions. These modelled distributions are then used to estimate the relative contribution of these two components to the river sediments. Our results are consistent with channel and gully erosion being the dominant source of sediment, with more than 90% of sediment transported along the main stem of these rivers originating from subsoil. We summarize the findings of similar studies on tropical Australian rivers and conclude that the primary source of sediment delivered to these systems is gully and channel bank erosion. Previously, as a result of catchment scale modelling, sheet-wash and rill erosion was considered to be the major sediment source in these rivers. Identifying the relative importance of sediment sources, as shown in this paper, will provide valuable information for land management planning in the region. This study also reinforces the importance of testing model predictions before they are used to target investment in remedial action.

  20. Evaluation of the Flinders Technology Associates Cards for Storage and Temperature Challenges in Field Conditions for Foot-and-Mouth Disease Virus Surveillance.

    Science.gov (United States)

    Madhanmohan, M; Yuvaraj, S; Manikumar, K; Kumar, R; Nagendrakumar, S B; Rana, S K; Srinivasan, V A

    2016-12-01

    Foot-and-mouth disease virus (FMDV) samples transported to the laboratory from far and inaccessible areas for diagnosis and identification of FMDV pose a major problem in a tropical country like India, where wide fluctuation of temperature over a large geographical area is common. Inadequate storage methods lead to spoilage of FMDV samples collected from clinically positive animals in the field. Such samples are declared as non-typeable by the typing laboratories with the consequent loss of valuable epidemiological data. In this study, an attempt was made to evaluate the robustness of Flinders Technology Associates (FTA) cards for storage and transportation of FMDV samples in different climatic conditions which will be useful for FMDV surveillance. Simulation transport studies were conducted using FTA impregnated FMDV samples during post-monsoon (September-October 2010) and summer season (May-June 2012). FMDV genome or serotype could be identified from the FTA cards after the simulation transport studies with varying temperature (22-45°C) and relative humidity (20-100%). The stability of the viral RNA, the absence of infectivity and ease of processing the sample for molecular methods make the FTA cards an useful option for transport of FMDV genome for identification and type determination. The method can be used routinely for FMDV research as it is economical and the cards can be transported easily in envelopes by regular courier/postal systems. The absence of live virus in FTA card can be viewed as an advantage as it restricts the risk of transmission of live virus. © 2015 Blackwell Verlag GmbH.

  1. Variation in cisplatinum sensitivity is not associated with Fanconi Anemia/BRCA pathway inactivation in head and neck squamous cell carcinoma cell lines.

    Science.gov (United States)

    Snyder, Eric R; Ricker, Justin L; Chen, Zhong; Waes, Carter Van

    2007-01-08

    Fanconi Anemia has recently been associated with a high risk of head and neck squamous cell carcinoma (HNSCC). Inactivation of the Fanconi Anemia (FANC-BRCA) pathway via promoter methylation of the FANCF gene has been proposed to be responsible for variation in cisplatinum (CDDP) sensitivity seen in ovarian and HNSCCs. Promoter methylation of the FANCF gene has been observed in 15% of HNSCC specimens, but the relationship to FANC pathway activation and CDDP sensitivity has not been reported. In the present study, 10 HNSCC cell lines were examined for expression of nine genes involved in the FANC-BRCA pathway by RT-PCR: FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCL, BRCA1 and BRCA2. FANC pathway function was evaluated by western blotting for FANCD2 mono-ubiquitination. All of the cell lines were also analyzed for variation in CDDP cytotoxicity. While significant differences were found in CDDP cytotoxicity, Fanconi pathway defects are an infrequent cause, as no evidence of transcriptional down-regulation of FANCF or other FANC mRNAs, or functional FANC-BRCA pathway defects were observed. These findings suggest that the variation in CDDP sensitivity of many HNSCCs is most frequently due to factors other than FANC-BRCA pathway inactivation.

  2. An in vitro test to screen skin sensitizers using a stable THP-1-derived IL-8 reporter cell line, THP-G8.

    Science.gov (United States)

    Takahashi, Toshiya; Kimura, Yutaka; Saito, Rumiko; Nakajima, Yoshihiro; Ohmiya, Yoshihiro; Yamasaki, Kenshi; Aiba, Setsuya

    2011-12-01

    Several studies have suggested that interleukin (IL)-8 can serve as a biomarker for discrimination of skin sensitizers from nonsensitizers. We established a stable THP-1-derived IL-8 reporter cell line, THP-G8, which harbors SLO and SLR luciferase genes under the control of IL-8 and glyceraldehyde 3-phosphate dehydrogenase promoters, respectively. After 6 h treatment with chemicals, normalized SLO luciferase activity (nSLO-LA) was calculated by dividing SLO-LA by SLR-LA, and the fold induction of nSLO-LA (FInSLO-LA) was calculated by dividing nSLO-LA of chemically treated cells by that of nontreated cells. The nSLO-LA of THP-G8 cells increased in response to lipopolysaccharide (LPS) and several sensitizers. The FInSLO-LA in THP-G8 cells induced by LPS or sensitizers positively correlated with their induction of IL-8 messenger RNA in THP-1 cells. The nSLO-LA value of THP-G8 cells was significantly increased (FInSLO-LA ≥ 1.4) by 13 of the 15 sensitizers as well as by 5 of the 7 nonsensitizers. Interestingly, pretreatment with N-acetylcysteine suppressed the increase in FInSLO-LA induced by all sensitizers (inhibition index (II) ≤ 0.8) but did not suppress that induced by most of the nonsensitizers. We then evaluated the performance of this assay using values of FInSLO-LA ≥ 1.4 and II ≤ 0.8 in at least two of three independent experiments as the criteria of a sensitizer, which resulted in test accuracies of 82% for the 22 chemicals used and of 88% for the chemicals proposed by European Center for the Validation of Alternative Methods. This newly developed assay is a candidate replacement for animal tests of skin sensitization because of its accuracy, convenience, and high throughput performance.

  3. Behavioural thermoregulation in a temperature-sensitive coral reef fish, the five-lined cardinalfish (Cheilodipterus quinquelineatus)

    DEFF Research Database (Denmark)

    Nay, Tiffany J.; Johansen, Jacob L.; Habary, Adam

    2015-01-01

    provide a strategy to cope with changing conditions. A temperature-sensitive coral reef cardinalfish (Cheilodipterusquinquelineatus) was exposed to 28 °C (average at collection site) or 32 °C (predicted end-of-century) for 6 weeks. Tpref was determined using a shuttlebox system, which allowed fish...... than night-time movements. Understanding temperature-mediated movements is imperative for predicting how ocean warming will influence coral reef species and distribution patterns....

  4. Reconfigurable and ultra-sensitive in-line Mach-Zehnder interferometer based on the fusion of microfiber and microfluid

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Shecheng [Key Laboratory of Optical Information Science and Technology, Ministry of Education, Institute of Modern Optics, Nankai University, Tianjin 300071 (China); Institute of Micro and Nano Optics, Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen 518060 (China); Zhang, Weigang, E-mail: zhangwg@nankai.edu.cn, E-mail: haozhang@nankai.edu.cn; Zhang, Hao, E-mail: zhangwg@nankai.edu.cn, E-mail: haozhang@nankai.edu.cn [Key Laboratory of Optical Information Science and Technology, Ministry of Education, Institute of Modern Optics, Nankai University, Tianjin 300071 (China); Zhang, Chonglei [Institute of Micro and Nano Optics, Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen 518060 (China)

    2015-02-23

    A reconfigurable Mach-Zenhnder interferometer (MZI) based on a microfluidic cavity (MFC) constructed by embedding a microfiber between two segments of single-mode fibers with pre-designed lateral offset has been proposed and experimentally demonstrated. The MFC serves as an interference arm with an eccentric annular cross section and allows convenient sample (gas or liquids) replacement procedure. The microfiber works as the other interference arm that provides the proposed device with ease of reconstruction and also enhances the force sensitivity. The re-configurability and the ultra-wide tuning sensitivity range are demonstrated by immersing the MZI constructed with a 484 μm-long-MFC and a microfiber 44 μm in diameter in different droplets. Ultrahigh sensitivities of 34.65 nm/°C (∼88 380 nm/RIU) and −493.7 nm/N (∼−590 pm/με) are experimentally achieved using a droplet with a refractive index of ∼1.44.

  5. Reconfigurable and ultra-sensitive in-line Mach-Zehnder interferometer based on the fusion of microfiber and microfluid

    International Nuclear Information System (INIS)

    Gao, Shecheng; Zhang, Weigang; Zhang, Hao; Zhang, Chonglei

    2015-01-01

    A reconfigurable Mach-Zenhnder interferometer (MZI) based on a microfluidic cavity (MFC) constructed by embedding a microfiber between two segments of single-mode fibers with pre-designed lateral offset has been proposed and experimentally demonstrated. The MFC serves as an interference arm with an eccentric annular cross section and allows convenient sample (gas or liquids) replacement procedure. The microfiber works as the other interference arm that provides the proposed device with ease of reconstruction and also enhances the force sensitivity. The re-configurability and the ultra-wide tuning sensitivity range are demonstrated by immersing the MZI constructed with a 484 μm-long-MFC and a microfiber 44 μm in diameter in different droplets. Ultrahigh sensitivities of 34.65 nm/°C (∼88 380 nm/RIU) and −493.7 nm/N (∼−590 pm/με) are experimentally achieved using a droplet with a refractive index of ∼1.44

  6. Effect of recombinant adenovirus encoding human p53 tumor suppressor gene (rAd-p53) on the growth and radiotherapeutic sensitivity of human lymphoma cell lines

    International Nuclear Information System (INIS)

    Yu Zeyang; Fan Wo; Li Dongqing; Zhu Ran; Wang Yongqing; Wu Jinchang

    2008-01-01

    Objective: To explore the inhibitory effect and radiation sensitization of recombinant adenovirus encoding human p53 tumor suppressor gene (rAd-p53) on human lymphoma cell lines. Methods: Human lymphoma cell lines Raji and Daudi were treated with rAd-p53, radiation therapy and combined treatment, respectively. The cell growth inhibition was assessed by MTT. The p53 protein expression was detected by Western blotting, and p53 mRNA was detected by BT-PCB. Results: The MTT results showed that the inhibitory effect and radiosensitivity enhancement of rAd-p53 on human lymphoma cell lines were not obvious [Raji: (27.5±4.1)%; Daudi: (28.1±1.6)%]. The results of Western blotting and BT-PCB showed that extrinsic p53 protein and p53 mRNA were expressed to some degree, but not at high-level. In addition, the results didn't demonstrate obvious radiosensitivity enhancement. Conclusions: The role of inhibition and radiosensitivity enhancement of rAd-p53 was not significant on human lymphoma cell lines. (authors)

  7. Evaluation of the Trajectory Sensitivity Analysis of the DFIG Control Parameters in Response to Changes in Wind Speed and the Line Impedance Connection to the Grid DFIG

    Directory of Open Access Journals (Sweden)

    Mehdi Fooladgar

    2015-01-01

    Full Text Available Economic and environmental conditions often make large stations and transmission lines, restrictions are placed. Small and medium-sized production units connected to existing systems as a strategy is in progress. These units are usually near the center of the load placed and distributed generators (DG famous are the DG are allowed types vary, such as induction generators rack squirrel-connected wind turbines, generators fed induction double mounted wind turbines, fuel cells connected to the system by power electronic converters or synchronous generator connected to the turbine combustion [10]. This way sensitivity analysis in systems of distributed generation (DG is assessed. It is shown that the method can detect the effect of control parameters listed wind turbine connected to a double-fed induction generator (DFIG Badoou the impedance of the changing the speed of on the stability of the transmission line useful system invested. The control parameters of the importance of influencing the behavior of DFIG are divided.

  8. Systematic assessment of multi-gene predictors of pan-cancer cell line sensitivity to drugs exploiting gene expression data [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Linh Nguyen

    2016-12-01

    Full Text Available Background: Selected gene mutations are routinely used to guide the selection of cancer drugs for a given patient tumour. Large pharmacogenomic data sets were introduced to discover more of these single-gene markers of drug sensitivity. Very recently, machine learning regression has been used to investigate how well cancer cell line sensitivity to drugs is predicted depending on the type of molecular profile. The latter has revealed that gene expression data is the most predictive profile in the pan-cancer setting. However, no study to date has exploited GDSC data to systematically compare the performance of machine learning models based on multi-gene expression data against that of widely-used single-gene markers based on genomics data. Methods: Here we present this systematic comparison using Random Forest (RF classifiers exploiting the expression levels of 13,321 genes and an average of 501 tested cell lines per drug. To account for time-dependent batch effects in IC50 measurements, we employ independent test sets generated with more recent GDSC data than that used to train the predictors and show that this is a more realistic validation than K-fold cross-validation. Results and Discussion: Across 127 GDSC drugs, our results show that the single-gene markers unveiled by the MANOVA analysis tend to achieve higher precision than these RF-based multi-gene models, at the cost of generally having a poor recall (i.e. correctly detecting only a small part of the cell lines sensitive to the drug. Regarding overall classification performance, about two thirds of the drugs are better predicted by multi-gene RF classifiers. Among the drugs with the most predictive of these models, we found pyrimethamine, sunitinib and 17-AAG. Conclusions: We now know that this type of models can predict in vitro tumour response to these drugs. These models can thus be further investigated on in vivo tumour models.

  9. Fibulin-3 negatively regulates ALDH1 via c-MET suppression and increases γ-radiation-induced sensitivity in some pancreatic cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In-Gyu, E-mail: igkim@kaeri.re.kr [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Department of Radiation Biotechnology and Applied Radioisotope, Korea University of Science and Technology (UST), 989-111 Daedeok-daero, Yusong-gu, Daejeon 305-353 (Korea, Republic of); Lee, Jae-Ha [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Department of Radiation Biotechnology and Applied Radioisotope, Korea University of Science and Technology (UST), 989-111 Daedeok-daero, Yusong-gu, Daejeon 305-353 (Korea, Republic of); Kim, Seo-Yoen; Kim, Jeong-Yul [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Cho, Eun-Wie [Epigenomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea, Republic of)

    2014-11-21

    Highlights: • FBLN-3 gene was poorly expressed in some pancreatic cancer lines. • FBLN-3 promoter region was highly methylated in some pancreatic cancer cell lines. • FBLN-3 inhibited c-MET activation and expression and reduced cellular level of ALDH1. • FBLN-3/c-Met/ALDH1 axis modulates stemness and EMT in pancreatic cancer cells. - Abstract: Fibulin-3 (FBLN-3) has been postulated to be either a tumor suppressor or promoter depending on the cell type, and hypermethylation of the FBLN-3 promoter is often associated with human disease, especially cancer. We report that the promoter region of the FBLN-3 was significantly methylated (>95%) in some pancreatic cancer cell lines and thus FBLN-3 was poorly expressed in pancreatic cancer cell lines such as AsPC-1 and MiaPaCa-2. FBLN-3 overexpression significantly down-regulated the cellular level of c-MET and inhibited hepatocyte growth factor-induced c-MET activation, which were closely associated with γ-radiation resistance of cancer cells. Moreover, we also showed that c-MET suppression or inactivation decreased the cellular level of ALDH1 isozymes (ALDH1A1 or ALDH1A3), which serve as cancer stem cell markers, and subsequently induced inhibition of cell growth in pancreatic cancer cells. Therefore, forced overexpression of FBLN-3 sensitized cells to cytotoxic agents such as γ-radiation and strongly inhibited the stemness and epithelial to mesenchymal transition (EMT) property of pancreatic cancer cells. On the other hand, if FBLN3 was suppressed in FBLN-3-expressing BxPC3 cells, the results were opposite. This study provides the first demonstration that the FBLN-3/c-MET/ALDH1 axis in pancreatic cancer cells partially modulates stemness and EMT as well as sensitization of cells to the detrimental effects of γ-radiation.

  10. Predicting skin sensitization potential and inter-laboratory reproducibility of a human Cell Line Activation Test (h-CLAT) in the European Cosmetics Association (COLIPA) ring trials.

    Science.gov (United States)

    Sakaguchi, Hitoshi; Ryan, Cindy; Ovigne, Jean-Marc; Schroeder, Klaus R; Ashikaga, Takao

    2010-09-01

    Regulatory policies in Europe prohibited the testing of cosmetic ingredients in animals for a number of toxicological endpoints. Currently no validated non-animal test methods exist for skin sensitization. Evaluation of changes in cell surface marker expression in dendritic cell (DC)-surrogate cell lines represents one non-animal approach. The human Cell Line Activation Test (h-CLAT) examines the level of CD86 and CD54 expression on the surface of THP-1 cells, a human monocytic leukemia cell line, following 24h of chemical exposure. To examine protocol transferability, between-lab reproducibility, and predictive capacity, the h-CLAT has been evaluated by five independent laboratories in several ring trials (RTs) coordinated by the European Cosmetics Association (COLIPA). The results of the first and second RTs demonstrated that the protocol was transferable and basically had good between-lab reproducibility and predictivity, but there were some false negative data. To improve performance, protocol and prediction model were modified. Using the modified prediction model in the first and second RT, accuracy was improved. However, about 15% of the outcomes were not correctly identified, which exposes some of the limitations of the assay. For the chemicals evaluated, the limitation may due to chemical being a weak allergen or having low solubility (ex. alpha-hexylcinnamaldehyde). The third RT evaluated the modified prediction model and satisfactory results were obtained. From the RT data, the feasibility of utilizing cell lines as surrogate DC in development of in vitro skin sensitization methods shows promise. The data also support initiating formal pre-validation of the h-CLAT in order to fully understand the capabilities and limitations of the assay. Copyright 2010 Elsevier Ltd. All rights reserved.

  11. Fibulin-3 negatively regulates ALDH1 via c-MET suppression and increases γ-radiation-induced sensitivity in some pancreatic cancer cell lines

    International Nuclear Information System (INIS)

    Kim, In-Gyu; Lee, Jae-Ha; Kim, Seo-Yoen; Kim, Jeong-Yul; Cho, Eun-Wie

    2014-01-01

    Highlights: • FBLN-3 gene was poorly expressed in some pancreatic cancer lines. • FBLN-3 promoter region was highly methylated in some pancreatic cancer cell lines. • FBLN-3 inhibited c-MET activation and expression and reduced cellular level of ALDH1. • FBLN-3/c-Met/ALDH1 axis modulates stemness and EMT in pancreatic cancer cells. - Abstract: Fibulin-3 (FBLN-3) has been postulated to be either a tumor suppressor or promoter depending on the cell type, and hypermethylation of the FBLN-3 promoter is often associated with human disease, especially cancer. We report that the promoter region of the FBLN-3 was significantly methylated (>95%) in some pancreatic cancer cell lines and thus FBLN-3 was poorly expressed in pancreatic cancer cell lines such as AsPC-1 and MiaPaCa-2. FBLN-3 overexpression significantly down-regulated the cellular level of c-MET and inhibited hepatocyte growth factor-induced c-MET activation, which were closely associated with γ-radiation resistance of cancer cells. Moreover, we also showed that c-MET suppression or inactivation decreased the cellular level of ALDH1 isozymes (ALDH1A1 or ALDH1A3), which serve as cancer stem cell markers, and subsequently induced inhibition of cell growth in pancreatic cancer cells. Therefore, forced overexpression of FBLN-3 sensitized cells to cytotoxic agents such as γ-radiation and strongly inhibited the stemness and epithelial to mesenchymal transition (EMT) property of pancreatic cancer cells. On the other hand, if FBLN3 was suppressed in FBLN-3-expressing BxPC3 cells, the results were opposite. This study provides the first demonstration that the FBLN-3/c-MET/ALDH1 axis in pancreatic cancer cells partially modulates stemness and EMT as well as sensitization of cells to the detrimental effects of γ-radiation

  12. The effects of 6-mercaptopurine nucleotide derivatives on the growth and survival of 6-mercaptopurine-sensitive and -resistant cell culture lines.

    OpenAIRE

    Johnston, H. P.; Hawley, P.; White, S. E.; Gibson, I.; Tidd, D. M.

    1985-01-01

    6-Mercaptopurine (MP)-sensitive and -resistant cell culture lines were used to further characterize the apparent ability of MP nucleotide derivatives to overcome resistance to the parent drug. 6-Mercaptopurine-9-beta-D-ribofuranoside 5'-monophosphate [MPRP], bis(6-mercaptopurine-9-beta-D-ribofuranoside)-5', 5"'-monophosphate [bis(MPR)P], bis(O2',O3'-dibutyryl-6-mercaptopurine-9-beta-D-ribofuranoside)-5', 5"'-monophosphate [bis(dibut.MPR)P], and O2',O3'-dibutyryl-6-mercaptopurine-9-beta-D-ribo...

  13. Effect of producer cell line on functional activity of anti-D monoclonal antibodies destined for prevention of rhesus sensitization.

    Science.gov (United States)

    Olovnikova, N I; Ershler, M A; Belkina, E V; Nikolaeva, T L; Miterev, G Yu

    2009-04-01

    The ability of anti-D antibodies to cause antigen-specific immunosuppression depends on their interaction with low-affinity Fcgamma-receptors. Human monoclonal antibodies to D antigen of the rhesus system were investigated by antibody-dependent cytotoxicity assay in order to estimate their ability to induce hemolysis mediated by low-affinity Fcgamma receptors. We demonstrate that affinity of monoclonal antibodies to receptors of this type does not depend on primary structure of Fc-fragment, but depends on the producer cell line which expresses the antibodies. Monoclonal IgG1 antibodies interacting with FcgammaRIIa and FcgammaRIII lost this property, if they were secreted by human-mouse heterohybridoma, but not by human B-cell line. On the opposite, monoclonal antibodies that could not activate low-affinity Fcgamma receptors were highly active after human cells fusion with rat myeloma YB2/0. Hemolytic activity of IgG3 remained unchanged after fusion of human cells with rodent cells.

  14. Absolute on-line in-pile measurement of neutron fluxes using self-powered neutron detectors: Monte Carlo sensitivity calculations

    Energy Technology Data Exchange (ETDEWEB)

    Vermeeren, L. [SCK/CEN, B-2400 Mol (Belgium)

    2001-07-01

    Self-powered neutron detectors (SPND) are well suited to monitor continuously the neutronic operating conditions of driver fuel of research reactors and to follow its burnup evolution. This is of particular importance when advanced or new MTR fuel designs need to be qualified. We have developed a detailed MCNP-4B based Monte Carlo approach for the calculation of neutron sensitivities of SPNDs. Results for the neutron sensitivity of a Rh SPND are in excellent agreement with experimental data recently obtained at the BR2 research reactor. A critical comparison of the Monte Carlo results with results from standard analytical methods reveals an important deficiency of the analytical methods in the description of the electron transport efficiency. Our calculation method allows a reliable on-line determination of the absolute in-pile neutron flux. (author)

  15. Absolute on-line in-pile measurement of neutron fluxes using self-powered neutron detectors: Monte Carlo sensitivity calculations

    International Nuclear Information System (INIS)

    Vermeeren, L.

    2001-01-01

    Self-powered neutron detectors (SPND) are well suited to monitor continuously the neutronic operating conditions of driver fuel of research reactors and to follow its burnup evolution. This is of particular importance when advanced or new MTR fuel designs need to be qualified. We have developed a detailed MCNP-4B based Monte Carlo approach for the calculation of neutron sensitivities of SPNDs. Results for the neutron sensitivity of a Rh SPND are in excellent agreement with experimental data recently obtained at the BR2 research reactor. A critical comparison of the Monte Carlo results with results from standard analytical methods reveals an important deficiency of the analytical methods in the description of the electron transport efficiency. Our calculation method allows a reliable on-line determination of the absolute in-pile neutron flux. (author)

  16. Cell Line Derived 5-FU and Irinotecan Drug-Sensitivity Profiles Evaluated in Adjuvant Colon Cancer Trial Data

    DEFF Research Database (Denmark)

    Buhl, Ida Kappel; Gerster, Sarah; Delorenzi, Mauro

    2016-01-01

    patients who benefitted from the addition of irinotecan to 5-FU, we used gene expression profiles based on cell lines and clinical tumor material. These profiles were applied to expression data obtained from pretreatment formalin fixed paraffin embedded (FFPE) tumor tissue from 636 stage III colon cancer...... patients enrolled in the PETACC-3 prospective randomized clinical trial. A 5-FU profile developed similarly was assessed by comparing the PETACC-3 cohort with a cohort of 359 stage II colon cancer patients who underwent surgery but received no adjuvant therapy. RESULTS: There was no statistically...... to identify colon cancer patients who may benefit from 5-FU, however, any biomarker predicting benefit for adjuvant 5-FU must be rigorously evaluated in independent cohorts. Given differences between the two study cohorts, the present results should be further validated....

  17. Effects of ultraviolet irradiation on the cell cycle in normal and UV-sensitive cell lines with reference to the nature of the defect in xeroderma pigmentosum variant

    International Nuclear Information System (INIS)

    Imray, P.; Mangan, T.; Saul, A.; Kidson, C.

    1983-01-01

    Analysis of the distribution of cells through the phases of the cell cycle by DNA flow cytofluorimetry has been utilized to investigate the effects of ultraviolet (UV) irradiation on cell-cycle progression in normal and UV-sensitive lymphoblastoid cell lines. In time-course studies only slight perturbation of DNA distribution was seen in normal cells, or UV-sensitive familial melanoma (FM) lines in the 48 h following irradiation. Xeroderma pigmentosum (XPA) excision-deficient cells showed a large increase in the proportion of cells in S phase 16-40 h post-irradiation. XP variant (XPV) cells were blocked in G 1 and S phases with the complete absence of cells with G 2 DNA content 16-28 h after irradiation. By 48 h post-irradiation the DNA distribution of XPA and XPV cells had returned to that of an unirradiated control. When colcemid was added to the cultures immediately after irradiation to prevent mitotic cells dividing and re-entering the cell cycle, progression through the first cycle after irradiation was followed. UV irradiation did not affect the rate of movement of cells out of G 1 into S phase in normal, FM or XPA cells. The proportion of cells in S phase was increased in UV-irradiated cultures in these cell types and the number of cells entering the G 2 +M compartment was reduced. (orig./AJ)

  18. Evaluation of the sensitizing potential of antibiotics in vitro using the human cell lines THP-1 and MUTZ-LC and primary monocyte‐derived dendritic cells

    International Nuclear Information System (INIS)

    Sebastian, Katrin; Ott, Hagen; Zwadlo-Klarwasser, Gabriele; Skazik-Voogt, Claudia; Marquardt, Yvonne; Czaja, Katharina; Merk, Hans F.; Baron, Jens Malte

    2012-01-01

    Since the 7th amendment to the EU cosmetics directive foresees a complete ban on animal testing, alternative in vitro methods have been established to evaluate the sensitizing potential of small molecular weight compounds. To find out whether these novel in vitro assays are also capable to predict the sensitizing potential of small molecular weight drugs, model compounds such as beta-lactams and sulfonamides – which are the most frequent cause of adverse drug reactions – were co-incubated with THP-1, MUTZ-LC, or primary monocyte‐derived dendritic cells for 48 h and subsequent expression of selected marker genes (IL-8, IL-1β, CES1, NQO1, GCLM, PIR and TRIM16) was studied by real time PCR. Benzylpenicillin and phenoxymethylpenicillin were recognized as sensitizing compounds because they are capable to induce the mRNA expression of these genes in moDCs and, except for IL-8, in THP-1 cells but not in MUTZ-LC. Ampicillin stimulated the expression of some marker genes in moDCs and THP-1 cells. SMX did not affect the expression of these genes in THP-1, however, in moDCs, at least PIR was enhanced and there was an increase of the release of IL-8. These data reveal that novel in vitro DC based assays might play a role in the evaluation of the allergenic potential of novel drug compounds, but these systems seem to lack the ability to detect the sensitizing potential of prohaptens that require metabolic activation prior to sensitization and moDCs seem to be superior with regard to the sensitivity compared with THP-1 and MUTZ-3 cell lines. -- Highlights: ► We tested the sensitizing potential of small molecular weight drugs in vitro. ► In vitro assays were performed with moDCs and THP-1 cells. ► Beta-lactam antibiotics can be recognized as sensitizing compounds. ► They affect the expression of metabolic enzymes, cytokines and transcription factors. ► Sulfamethoxazole has no measurable effect on THP-1 cells and moDCs.

  19. Evaluation of the sensitizing potential of antibiotics in vitro using the human cell lines THP-1 and MUTZ-LC and primary monocyte‐derived dendritic cells

    Energy Technology Data Exchange (ETDEWEB)

    Sebastian, Katrin, E-mail: ksebastian@ukaachen.de [Department of Dermatology and Allergology, RWTH Aachen University Hospital, D-52074 Aachen (Germany); Ott, Hagen [Department of Dermatology and Allergology, RWTH Aachen University Hospital, D-52074 Aachen (Germany); Zwadlo-Klarwasser, Gabriele [IZKF (BIOMAT), RWTH Aachen University Hospital, D-52074 Aachen (Germany); Skazik-Voogt, Claudia; Marquardt, Yvonne; Czaja, Katharina; Merk, Hans F.; Baron, Jens Malte [Department of Dermatology and Allergology, RWTH Aachen University Hospital, D-52074 Aachen (Germany)

    2012-08-01

    Since the 7th amendment to the EU cosmetics directive foresees a complete ban on animal testing, alternative in vitro methods have been established to evaluate the sensitizing potential of small molecular weight compounds. To find out whether these novel in vitro assays are also capable to predict the sensitizing potential of small molecular weight drugs, model compounds such as beta-lactams and sulfonamides – which are the most frequent cause of adverse drug reactions – were co-incubated with THP-1, MUTZ-LC, or primary monocyte‐derived dendritic cells for 48 h and subsequent expression of selected marker genes (IL-8, IL-1β, CES1, NQO1, GCLM, PIR and TRIM16) was studied by real time PCR. Benzylpenicillin and phenoxymethylpenicillin were recognized as sensitizing compounds because they are capable to induce the mRNA expression of these genes in moDCs and, except for IL-8, in THP-1 cells but not in MUTZ-LC. Ampicillin stimulated the expression of some marker genes in moDCs and THP-1 cells. SMX did not affect the expression of these genes in THP-1, however, in moDCs, at least PIR was enhanced and there was an increase of the release of IL-8. These data reveal that novel in vitro DC based assays might play a role in the evaluation of the allergenic potential of novel drug compounds, but these systems seem to lack the ability to detect the sensitizing potential of prohaptens that require metabolic activation prior to sensitization and moDCs seem to be superior with regard to the sensitivity compared with THP-1 and MUTZ-3 cell lines. -- Highlights: ► We tested the sensitizing potential of small molecular weight drugs in vitro. ► In vitro assays were performed with moDCs and THP-1 cells. ► Beta-lactam antibiotics can be recognized as sensitizing compounds. ► They affect the expression of metabolic enzymes, cytokines and transcription factors. ► Sulfamethoxazole has no measurable effect on THP-1 cells and moDCs.

  20. Systematic assessment of multi-gene predictors of pan-cancer cell line sensitivity to drugs exploiting gene expression data [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Linh Nguyen

    2017-03-01

    Full Text Available Background: Selected gene mutations are routinely used to guide the selection of cancer drugs for a given patient tumour. Large pharmacogenomic data sets, such as those by Genomics of Drug Sensitivity in Cancer (GDSC consortium, were introduced to discover more of these single-gene markers of drug sensitivity. Very recently, machine learning regression has been used to investigate how well cancer cell line sensitivity to drugs is predicted depending on the type of molecular profile. The latter has revealed that gene expression data is the most predictive profile in the pan-cancer setting. However, no study to date has exploited GDSC data to systematically compare the performance of machine learning models based on multi-gene expression data against that of widely-used single-gene markers based on genomics data. Methods: Here we present this systematic comparison using Random Forest (RF classifiers exploiting the expression levels of 13,321 genes and an average of 501 tested cell lines per drug. To account for time-dependent batch effects in IC50 measurements, we employ independent test sets generated with more recent GDSC data than that used to train the predictors and show that this is a more realistic validation than standard k-fold cross-validation. Results and Discussion: Across 127 GDSC drugs, our results show that the single-gene markers unveiled by the MANOVA analysis tend to achieve higher precision than these RF-based multi-gene models, at the cost of generally having a poor recall (i.e. correctly detecting only a small part of the cell lines sensitive to the drug. Regarding overall classification performance, about two thirds of the drugs are better predicted by the multi-gene RF classifiers. Among the drugs with the most predictive of these models, we found pyrimethamine, sunitinib and 17-AAG. Conclusions: Thanks to this unbiased validation, we now know that this type of models can predict in vitro tumour response to some of these

  1. Epigenetics-related genes in prostate cancer: expression profile in prostate cancer tissues, androgen-sensitive and -insensitive cell lines.

    Science.gov (United States)

    Shaikhibrahim, Zaki; Lindstrot, Andreas; Ochsenfahrt, Jacqueline; Fuchs, Kerstin; Wernert, Nicolas

    2013-01-01

    Epigenetic changes have been suggested to drive prostate cancer (PCa) development and progression. Therefore, in this study, we aimed to identify novel epigenetics-related genes in PCa tissues, and to examine their expression in metastatic PCa cell lines. We analyzed the expression of epigenetics-related genes via a clustering analysis based on gene function in moderately and poorly differentiated PCa glands compared to normal glands of the peripheral zone (prostate proper) from PCa patients using Whole Human Genome Oligo Microarrays. Our analysis identified 12 epigenetics-related genes with a more than 2-fold increase or decrease in expression and a p-value epigenetics-related genes that we identified in primary PCa tissues may provide further insight into the role that epigenetic changes play in PCa. Moreover, some of the genes that we identified may play important roles in primary PCa and metastasis, in primary PCa only, or in metastasis only. Follow-up studies are required to investigate the functional role and the role that the expression of these genes play in the outcome and progression of PCa using tissue microarrays.

  2. Fast and sensitive medical diagnostic protocol based on integrating circular current lines for magnetic washing and optical detection of fluorescent magnetic nanobeads

    Directory of Open Access Journals (Sweden)

    Jaiyam Sharma

    2016-07-01

    Full Text Available Magnetic nanoparticles (MNPs are increasingly being used as ‘magnetic labels’ in medical diagnostics. Practical applications of MNPs necessitate reducing their non-specific interactions with sensor surfaces that result in noise in measurements. Here we describe the design and implementation of a sensing platform that incorporates circular shaped current lines that reduce non-specific binding by enabling the “magnetic washing” of loosely attached MNPs attached to the senor surface. Generating magnetic fields by passing electrical currents through the circular shaped current lines enabled the capture and collection of fluorescent MNPs that was more efficient and effective than straight current lines reported to-date. The use of fluorescent MNPs allows their optical detection rather than with widely used magnetoresistive sensors. As a result our approach is not affected by magnetic noise due to the flow of currents. Our design is expected to improve the speed, accuracy, and sensitivity of MNPs based medical diagnostics. Keywords: Biosensors, Magnetic beads, Fluorescent magnetic nanoparticles, Lab on chip, Point of care testing

  3. Systemic analysis of different colorectal cancer cell lines and TCGA datasets identified IGF-1R/EGFR-PPAR-CASPASE axis as important indicator for radiotherapy sensitivity.

    Science.gov (United States)

    Chen, Lin; Zhu, Zhe; Gao, Wei; Jiang, Qixin; Yu, Jiangming; Fu, Chuangang

    2017-09-05

    Insulin-like growth factor 1 receptor (IGF-1R) is proved to contribute the development of many types of cancers. But, little is known about its roles in radio-resistance of colorectal cancer (CRC). Here, we demonstrated that low IGF-1R expression value was associated with the better radiotherapy sensitivity of CRC. Besides, through Quantitative Real-time PCR (qRT-PCR), the elevated expression value of epidermal growth factor receptor (EGFR) was observed in CRC cell lines (HT29, RKO) with high radio-sensitivity compared with those with low sensitivity (SW480, LOVO). The irradiation induced apoptosis rates of wild type and EGFR agonist (EGF) or IGF-1R inhibitor (NVP-ADW742) treated HT29 and SW480 cells were quantified by flow cytometry. As a result, the apoptosis rate of EGF and NVP-ADW742 treated HT29 cells was significantly higher than that of those wild type ones, which indicated that high EGFR and low IGF-1R expression level in CRC was associated with the high sensitivity to radiotherapy. We next conducted systemic bioinformatics analysis of genome-wide expression profiles of CRC samples from the Cancer Genome Atlas (TCGA). Differential expression analysis between IGF-1R and EGFR abnormal CRC samples, i.e. CRC samples with higher IGF-1R and lower EGFR expression levels based on their median expression values, and the rest of CRC samples identified potential genes contribute to radiotherapy sensitivity. Functional enrichment of analysis of those differential expression genes (DEGs) in the Database for Annotation, Visualization and Integrated Discovery (DAVID) indicated PPAR signaling pathway as an important pathway for the radio-resistance of CRC. Our study identified the potential biomarkers for the rational selection of radiotherapy for CRC patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. A combination of positive dielectrophoresis driven on-line enrichment and aptamer-fluorescent silica nanoparticle label for rapid and sensitive detection of Staphylococcus aureus.

    Science.gov (United States)

    Shangguan, Jingfang; Li, Yuhong; He, Dinggeng; He, Xiaoxiao; Wang, Kemin; Zou, Zhen; Shi, Hui

    2015-07-07

    Staphylococcus aureus (S. aureus) is an important human pathogen that causes several diseases ranging from superficial skin infections to life-threatening diseases. Here, a method combining positive dielectrophoresis (pDEP) driven on-line enrichment and aptamer-fluorescent silica nanoparticle label has been developed for the rapid and sensitive detection of S. aureus in microfluidic channels. An aptamer, having high affinity to S. aureus, is used as the molecular recognition tool and immobilized onto chloropropyl functionalized fluorescent silica nanoparticles through a click chemistry approach to obtain S. aureus aptamer-nanoparticle bioconjugates (Apt(S.aureus)/FNPs). The pDEP driven on-line enrichment technology was used for accumulating the Apt(S.aureus)/FNP labeled S. aureus. After incubating with S. aureus, the mixture of Apt(S.aureus)/FNP labeled S. aureus and Apt(S.aureus)/FNPs was directly introduced into the pDEP-based microfluidic system. By applying an AC voltage in a pDEP frequency region, the Apt(S.aureus)/FNP labelled S. aureus moved to the electrodes and accumulated in the electrode gap, while the free Apt(S.aureus)/FNPs flowed away. The signal that came from the Apt(S.aureus)/FNP labelled S. aureus in the focused detection areas was then detected. Profiting from the specificity of aptamer, signal amplification of FNP label and pDEP on-line enrichment, this assay can detect as low as 93 and 270 cfu mL(-1)S. aureus in deionized water and spiked water samples, respectively, with higher sensitivities than our previously reported Apt(S.aureus)/FNP based flow cytometry. Moreover, without the need for separation and washing steps usually required for FNP label involved bioassays, the total assay time including sample pretreatment was within 2 h.

  5. The hypoxic tumor microenvironment and drug resistance against EGFR inhibitors: preclinical study in cetuximab-sensitive head and neck squamous cell carcinoma cell lines.

    Science.gov (United States)

    Boeckx, Carolien; Van den Bossche, Jolien; De Pauw, Ines; Peeters, Marc; Lardon, Filip; Baay, Marc; Wouters, An

    2015-06-02

    Increased expression of the epidermal growth factor receptor (EGFR) is observed in more than 90% of all head and neck squamous cell carcinomas (HNSCC). Therefore, EGFR has emerged as a promising therapeutic target. Nevertheless, drug resistance remains a major challenge and an important potential mechanism of drug resistance involves the hypoxic tumor microenvironment. Therefore, we investigated the cytotoxic effect of the EGFR-targeting agents cetuximab and erlotinib under normoxia versus hypoxia. Three cetuximab-sensitive HNSCC cell lines (SC263, LICR-HN2 and LICR-HN5) were treated with either cetuximab or erlotinib. Cells were incubated under normal or reduced oxygen conditions (<0.1% O2) for 24 or 72 h immediately after drug addition. Cell survival was assessed with the sulforhodamine B assay. Cetuximab and erlotinib established a dose-dependent growth inhibition under both normal and prolonged reduced oxygen conditions in all three HNSCC cell lines. However, a significantly increased sensitivity to cetuximab was observed in SC263 cells exposed to hypoxia for 72 h (p = 0.05), with IC50 values of 2.38 ± 0.59 nM, 0.64 ± 0.38 nM, and 0.10 ± 0.05 nM under normoxia, hypoxia for 24 h and hypoxia for 72 h, respectively. LICR-HN5 cells showed an increased sensitivity towards erlotinib when cells were incubated under hypoxia for 24 h (p = 0.05). Our results suggest that both EGFR-inhibitors cetuximab and erlotinib maintain their growth inhibitory effect under hypoxia. These results suggest that resistance to anti-EGFR therapy in HNSCC is probably not the result of hypoxic regions within the tumor and other mechanisms are involved.

  6. Determination of phenols by flow injection and liquid chromatography with on-line quinine-sensitized photo-oxidation and quenched luminol chemiluminescence detection

    International Nuclear Information System (INIS)

    Zhang Wei; Danielson, Neil D.

    2003-01-01

    An on-line quinine-sensitized photo-oxidation with quenched chemiluminescence (CL) detection method is developed for phenols using flow injection (FI) and liquid chromatography (LC). This detection method is based on the decrease of light emission from the luminol CL reaction due to the photo-oxidation of phenols that scavenge the photogenerated reactive oxygen species (e.g. singlet oxygen ( 1 O 2 ) and superoxide (O 2 · - )). On-line photo-oxidation is achieved using a coil photo-reactor made from fluoroethylene-propylene copolymer tubing (3048 mmx0.25 mm i.d.) coiled around a mercury UV lamp. A buffer of pH 7 and a concentration of 350 μM for quinine sulfate are determined optimum for the sensitized photo-oxidation. Using a carrier system flow rate of 60 μl/min, calibration curves taken by FI for 10 phenolic compounds in aqueous solutions showed this decreasing sensitivity order: 4-chlorophenol, phenol, 4-nitrophenol, 3-hydroxy-L-kynurenine, 2-nitrophenol, salicylate, 3-nitrophenol, catechol, 2,4-dinitrophenol, and 2,4-dichlorophenol. This detection method using two tandem coil photo-reactors is also applied for the LC separation of phenol, 4-nitrophenol and 4-chlorophenol on an octadecyl (C18) silica LC column using acetonitrile-H 2 O (40:60, v/v) as a mobile phase. The quenched CL detection limits (about 1 μM or 20 pmol) for phenol and 4-chlorophenol are comparable to those for UV detection at 254 nm. Some selectivity in the quenched CL detection is evident by no interference in the FI phenol response even when benzaldehyde and phenethanol concentrations are 8 and 15 times that of phenol

  7. Behavioural thermoregulation in a temperature-sensitive coral reef fish, the five-lined cardinalfish ( Cheilodipterus quinquelineatus)

    Science.gov (United States)

    Nay, Tiffany J.; Johansen, Jacob L.; Habary, Adam; Steffensen, John F.; Rummer, Jodie L.

    2015-12-01

    As global temperatures increase, fish populations at low latitudes are thought to be at risk as they are adapted to narrow temperature ranges and live at temperatures close to their thermal tolerance limits. Behavioural movements, based on a preference for a specific temperature ( T pref), may provide a strategy to cope with changing conditions. A temperature-sensitive coral reef cardinalfish ( Cheilodipterus quinquelineatus) was exposed to 28 °C (average at collection site) or 32 °C (predicted end-of-century) for 6 weeks. T pref was determined using a shuttlebox system, which allowed fish to behaviourally manipulate their thermal environment. Regardless of treatment temperature, fish preferred 29.5 ± 0.25 °C, approximating summer average temperatures in the wild. However, 32 °C fish moved more frequently to correct their thermal environment than 28 °C fish, and daytime movements were more frequent than night-time movements. Understanding temperature-mediated movements is imperative for predicting how ocean warming will influence coral reef species and distribution patterns.

  8. Comparison of heat and/or radiation sensitivity and membrane composition of seven X-ray-transformed C3H 10T1/2 cell lines and normal C3H 10T1/2 cells

    International Nuclear Information System (INIS)

    Raaphorst, G.P.; Vadasz, J.A.; Azzam, E.I.; Sargent, M.D.; Borsa, J.; Einspenner, M.

    1985-01-01

    C3H 10T1/2 mouse embryo cells were transformed by X-irradiation, and seven transformed clones were isolated and propagated as cell lines. Some of these cell lines produced tumors in syngeneic mice and grew in agarose while the normal C3H 10T1/2 cell line did not possess these characteristics. Exponentially growing cell cultures with comparable cell-cycle distributions as measured by flow cytometry were tested for heat and X-ray sensitivity. The heat and X-ray sensitivity varied randomly compared to the normal cell line. One cell line was more heat resistant and one more heat sensitive than the normal cell line, and the others had sensitivities comparable to the normal cell line. Measurements on some of the biochemical parameters of the particulate fraction of cells after sonication and 24,000 X g centrifugation showed that altered thermal sensitivity was not correlated with protein, cholesterol, or phospholipid content of this fraction

  9. Resolving three-dimensional shape of sub-50 nm wide lines with nanometer-scale sensitivity using conventional optical microscopes

    International Nuclear Information System (INIS)

    Attota, Ravikiran; Dixson, Ronald G.

    2014-01-01

    We experimentally demonstrate that the three-dimensional (3-D) shape variations of nanometer-scale objects can be resolved and measured with sub-nanometer scale sensitivity using conventional optical microscopes by analyzing 4-D optical data using the through-focus scanning optical microscopy (TSOM) method. These initial results show that TSOM-determined cross-sectional (3-D) shape differences of 30 nm–40 nm wide lines agree well with critical-dimension atomic force microscope measurements. The TSOM method showed a linewidth uncertainty of 1.22 nm (k = 2). Complex optical simulations are not needed for analysis using the TSOM method, making the process simple, economical, fast, and ideally suited for high volume nanomanufacturing process monitoring.

  10. Complementation of the UV-sensitive phenotype of a xeroderma pigmentosum human cell line by transfection with a cDNA clone library

    International Nuclear Information System (INIS)

    Teitz, T.; Naiman, T.; Avissar, S.S.; Bar, S.; Okayama, H.; Canaani, D.

    1987-01-01

    In previous work, a xeroderma pigmentosum cell line belonging to complementation group C was established by transformation with origin-defective simian virus 40. We now report the complementation of the UV sensitivity of this cell line by gene transfer. A human cDNA clone library constructed in a mammalian expression vector, and itself incorporated in a lambda phage vector, was introduced into the cells as a calcium phosphate precipitate. Following selection to G418 resistance, provided by the neo gene of the vector, transformants were selected for UV resistance. Twenty-one cell clones were obtained with UV-resistance levels typical of normal human fibroblasts. All transformants contained vector DNA sequences in their nuclei. Upon further propagation in the absence of selection for G418 resistance, about half of the primary transformants remained UV-resistant. Secondary transformants were generated by transfection with a partial digest of total chromosomal DNA from one of these stable transformants. This resulted in 15 G418-resistant clones, 2 of which exhibited a UV-resistant phenotype. The other primary clones lost UV resistance rapidly when subcultured in the absence of G418. Importantly, several retained UV resistance under G418 selection pressure. The acquisition of UV resistance by secondary transformants derived by transfection of DNA from a stable primary transformant, and the linkage between G418 and UV resistances in the unstable primary transformants, strongly suggests that the transformants acquired UV resistance through DNA-mediated gene transfer and not by reversion

  11. A UV-resistant mutant without an increased repair synthesis activity, established from a UV-sensitive human clonal cell line

    International Nuclear Information System (INIS)

    Suzuki, N.

    1984-01-01

    When cells of a human clonal cell line, RSa, with high sensitivity to UV lethality, were treated with the mutagen, ethyl methanesulfonate, a variant cell strain, UVr-1, was established as a mutant resistant to 254-nm far-ultraviolet radiation (UV). Cell proliferation studies showed that UVr-1 cells survived and actively proliferated at doses of UV-irradiation that greatly suppressed the proliferation of RSa cells. Colony-formation assays also confirmed the increased resistance of UVr-1 cells to UV. The recovery from a UV-induced inhibition in DNA synthesis, as [methyl- 3 H]thymidine uptake into cellular DNA, was more pronounced in UVr-1 cells than in RSa cells. Nevertheless, there was no significant difference in the activity of UV-induced DNA repair synthesis in either cell line, as estimated by the extent of unscheduled DNA synthesis and DNA repair replication. These characteristics of UVr-1 cells are discussed in the light of a previously reported UV-resistant variant, UVr-10, which had an increased DNA repair synthesis activity. (Auth.)

  12. Transition between bulk and surface refractive index sensitivity of micro-cavity in-line Mach-Zehnder interferometer induced by thin film deposition.

    Science.gov (United States)

    Śmietana, Mateusz; Janik, Monika; Koba, Marcin; Bock, Wojtek J

    2017-10-16

    In this work we discuss the refractive index (RI) sensitivity of a micro-cavity in-line Mach-Zehnder interferometer in the form of a cylindrical hole (40-50 μm in diameter) fabricated in a standard single-mode optical fiber using a femtosecond laser. The surface of the micro-cavity was coated with up to 400 nm aluminum oxide thin film using the atomic layer deposition method. Next, the film was progressively chemically etched and the influence on changes in the RI of liquid in the micro-cavity was determined at different stages of the experiment, i.e., at different thicknesses of the film. An effect of transition between sensitivity to the film thickness (surface) and the RI of liquid in the cavity (bulk) is demonstrated for the first time. We have found that depending on the interferometer working conditions determined by thin film properties, the device can be used for investigation of phenomena taking place at the surface, such as in case of specific label-free biosensing applications, or for small-volume RI analysis as required in analytical chemistry.

  13. Comparison of multi-pole shaping and delay line clipping pre-amplifiers for position sensitive NaI(Tl) detectors

    International Nuclear Information System (INIS)

    Freifelder, R.; Karp, J.S.; Wear, J.A.; Lockyer, N.S.; Newcomer, F.M.; Surti, S.; Berg, R. van

    1998-01-01

    NaI(Tl) position sensitive detectors have been used in medical imaging for many years. For PET applications without collimators, the high counting rates place severe demands on such large area detectors. The NaI(Tl) detectors in the PENN-PET scanners are read-out via photomultiplier tubes and preamplifiers. Those preamplifiers use a delay-line clipping technique to shorten the characteristic 240 ns fall time of the NaI(Tl) signal. As an alternative, the authors have investigated a pole-zero network to shorten the signal followed by a multi-pole shaper to produce a symmetric signal suitable for high counting rates. This has been compared to the current design by measuring the energy and spatial resolution of a single detector as a function of different preamplifier designs. Data were taken over a range of ADC integration times and countrates. The new design shows improved energy resolution with short integration times. Effects on spatial resolution and deadtime are reported for large position sensitive detectors at different countrates

  14. Prediction of preservative sensitization potential using surface marker CD86 and/or CD54 expression on human cell line, THP-1.

    Science.gov (United States)

    Sakaguchi, Hitoshi; Miyazawa, Masaaki; Yoshida, Yukiko; Ito, Yuichi; Suzuki, Hiroyuki

    2007-02-01

    Preservatives are important components in many products, but have a history of purported allergy. Several assays [e.g., guinea pig maximization test (GPMT), local lymph node assay (LLNA)] are used to evaluate allergy potential of preservatives. We recently developed the human Cell Line Activation Test (h-CLAT), an in vitro skin sensitization test using human THP-1 cells. This test evaluates the augmentation of CD86 and CD54 expression, which are key events in the sensitization process, as an indicator of allergy following treatment with test chemical. Earlier, we found that a sub-toxic concentration was needed for the up-regulation of surface marker expression. In this study, we further evaluate the capability of h-CLAT to predict allergy potential using eight preservatives. Cytotoxicity was determined using propidium iodide with flow cytometry analysis and five doses that produce a 95, 85, 75, 65, and 50% cell viability were selected. If a material did not have any cytotoxicity at the highest technical dose (HTD), five doses are set using serial 1.3 dilutions of the HTD. The test materials used were six known allergic preservatives (e.g., methylchloroisothiazolinone/methylisothiazolinone, formaldehyde), and two non-allergic preservatives (methylparaben and 4-hydroxybenzoic acid). All allergic preservatives augmented CD86 and/or CD54 expression, indicating h-CLAT correctly identified the allergens. No augmentation was observed with the non-allergic preservatives; also correctly identified by h-CLAT. In addition, we report two threshold concentrations that may be used to categorize skin sensitization potency like the LLNA estimated concentration that yield a three-fold stimulation (EC3) value. These corresponding values are the estimated concentration which gives a relative fluorescence intensity (RFI) = 150 for CD86 and an RFI = 200 for CD54. These data suggest that h-CLAT, using THP-1 cells, may be able to predict the allergy potential of preservatives and

  15. Bioluminescent human breast cancer cell lines that permit rapid and sensitive in vivo detection of mammary tumors and multiple metastases in immune deficient mice

    International Nuclear Information System (INIS)

    Jenkins, Darlene E; Hornig, Yvette S; Oei, Yoko; Dusich, Joan; Purchio, Tony

    2005-01-01

    Our goal was to generate xenograft mouse models of human breast cancer based on luciferase-expressing MDA-MB-231 tumor cells that would provide rapid mammary tumor growth; produce metastasis to clinically relevant tissues such as lymph nodes, lung, and bone; and permit sensitive in vivo detection of both primary and secondary tumor sites by bioluminescent imaging. Two clonal cell sublines of human MDA-MB-231 cells that stably expressed firefly luciferase were isolated following transfection of the parental cells with luciferase cDNA. Each subline was passaged once or twice in vivo to enhance primary tumor growth and to increase metastasis. The resulting luciferase-expressing D3H1 and D3H2LN cells were analyzed for long-term bioluminescent stability, primary tumor growth, and distal metastasis to lymph nodes, lungs, bone and soft tissues by bioluminescent imaging. Cells were injected into the mammary fat pad of nude and nude-beige mice or were delivered systemically via intracardiac injection. Metastasis was also evaluated by ex vivo imaging and histologic analysis postmortem. The D3H1 and D3H2LN cell lines exhibited long-term stable luciferase expression for up to 4–6 months of accumulative tumor growth time in vivo. Bioluminescent imaging quantified primary mammary fat pad tumor development and detected early spontaneous lymph node metastasis in vivo. Increased frequency of spontaneous lymph node metastasis was observed with D3H2LN tumors as compared with D3H1 tumors. With postmortem ex vivo imaging, we detected additional lung micrometastasis in mice with D3H2LN mammary tumors. Subsequent histologic evaluation of tissue sections from lymph nodes and lung lobes confirmed spontaneous tumor metastasis at these sites. Following intracardiac injection of the MDA-MB-231-luc tumor cells, early metastasis to skeletal tissues, lymph nodes, brain and various visceral organs was detected. Weekly in vivo imaging data permitted longitudinal analysis of metastasis at

  16. Patterns of cytosine methylation in an elite rice hybrid and its parental lines, detected by a methylation-sensitive amplification polymorphism technique.

    Science.gov (United States)

    Xiong, L Z; Xu, C G; Saghai Maroof, M A; Zhang, Q

    1999-04-01

    DNA methylation is known to play an important role in the regulation of gene expression in eukaryotes. In this study, we assessed the extent and pattern of cytosine methylation in the rice genome, using the technique of methylation-sensitive amplified polymorphism (MSAP), which is a modification of the amplified fragment length polymorphism (AFLP) method that makes use of the differential sensitivity of a pair of isoschizomers to cytosine methylation. The tissues assayed included seedlings and flag leaves of an elite rice hybrid, Shanyou 63, and the parental lines Zhenshan 97 and Minghui 63. In all, 1076 fragments, each representing a recognition site cleaved by either or both of the isoschizomers, were amplified using 16 pairs of selective primers. A total of 195 sites were found to be methylated at cytosines in one or both parents, and the two parents showed approximately the same overall degree of methylation (16.3%), as revealed by the incidence of differential digestion by the isoschizomers. Four classes of patterns were identified in a comparative assay of cytosine methylation in the parents and hybrid; increased methylation was detected in the hybrid compared to the parents at some of the recognition sites, while decreased methylation in the hybrid was detected at other sites. A small proportion of the sites was found to be differentially methylated in seedlings and flag leaves; DNA from young seedlings was methylated to a greater extent than that from flag leaves. Almost all of the methylation patterns detected by MSAP could be confirmed by Southern analysis using the isolated amplified fragments as probes. The results clearly demonstrate that the MSAP technique is highly efficient for large-scale detection of cytosine methylation in the rice genome. We believe that the technique can be adapted for use in other plant species.

  17. The relationship between powdery mildew (Sphaerotheca fuliginea) resistance and leaf chlorosis sensitivity in cucumber (Cucumis sativus) studied in single seed descent lines

    NARCIS (Netherlands)

    Zijlstra, S.; Jansen, R.C.; Groot, S.P.C.

    1995-01-01

    The genetic relation between powdery mildew resistance and sensitivity for leaf chlorosis of glasshouse cucumber was investigated. The powdery mildew resistant, leaf chlorosis sensitive hybrid variety 'Profito' was crossed with the powdery mildew susceptible, non chlorosis sensitive hybrid variety

  18. De-optical-line-terminal hybrid access-aggregation optical network for time-sensitive services based on software-defined networking orchestration

    Science.gov (United States)

    Bai, Wei; Yang, Hui; Xiao, Hongyun; Yu, Ao; He, Linkuan; Zhang, Jie; Li, Zhen; Du, Yi

    2017-11-01

    With the increase in varieties of services in network, time-sensitive services (TSSs) appear and bring forward an impending need for delay performance. Ultralow-latency communication has become one of the important development goals for many scenarios in the coming 5G era (e.g., robotics and driverless cars). However, the conventional methods, which decrease delay by promoting the available resources and the network transmission speed, have limited effect; a new breakthrough for ultralow-latency communication is necessary. We propose a de-optical-line-terminal (De-OLT) hybrid access-aggregation optical network (DAON) for TSS based on software-defined networking (SDN) orchestration. In this network, low-latency all-optical communication based on optical burst switching can be achieved by removing OLT. For supporting this network and guaranteeing the quality of service for TSSs, we design SDN-driven control method and service provision method. Numerical results demonstrate the proposed DAON promotes network service efficiency and avoids traffic congestion.

  19. Pressure-assisted electrokinetic injection for on-line enrichment in capillary electrophoresis-mass spectrometry: a sensitive method for measurement of ten haloacetic acids in drinking water.

    Science.gov (United States)

    Zhang, Huijuan; Zhu, Jiping; Aranda-Rodriguez, Rocio; Feng, Yong-Lai

    2011-11-07

    Haloacetic acids (HAAs) are by-products of the chlorination of drinking water containing natural organic matter and bromide. A simple and sensitive method has been developed for determination of ten HAAs in drinking water. The pressure-assisted electrokinetic injection (PAEKI), an on-line enrichment technique, was employed to introduce the sample into a capillary electrophoresis (CE)-electrospray ionization-tandem mass spectrometry system (ESI-MS/MS). HAAs were monitored in selected reaction monitoring mode. With 3 min of PAEKI time, the ten major HAAs (HAA10) in drinking water were enriched up to 20,000-fold into the capillary without compromising resolution. A simple solid phase clean-up method has been developed to eliminate the influence of ionic matrices from drinking water on PAEKI. Under conditions optimized for mass spectrometry, PAEKI and capillary electrophoresis, detection limits defined as three times ratio of signal to noise have been achieved in a range of 0.013-0.12 μg L(-1) for ten HAAs in water sample. The overall recoveries for all ten HAAs in drinking water samples were between 76 and 125%. Six HAAs including monochloro- (MCAA), dichloro- (DCAA), trichloro- (TCAA), monobromo- (MBAA), bromochloro- (BCAA), and bromodichloroacetic acids (BDCAA) were found in tap water samples collected. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  20. Cellular determinants of the inverse cross sensitivity of mouse lymphoma L5178Y cell lines to ionizing radiation and hydrogen peroxide

    International Nuclear Information System (INIS)

    Kruszewski, M.

    1999-01-01

    The pair of L5178Y sublines (LY-R and LY-S) is exceptional among mammalian cell lines because of their unique inverse cross-sensitivity to ionizing radiation and hydrogen peroxide. The high sensitivity of LY-S cells to ionizing radiation is reasonably explained by the impairment of DNA double strand breaks rejoining. Although the enzymatic defect of LY-S cells is not yet identified, the more pronounced effect of DNA-dependent protein kinase (DNA-PK) inhibitor (OK-1035) on DNA damage repair after 8 Gy x-irradiation in LY-R cells than in LY-S cells, suggests that LY-S cells may be defective in DNA-PK activity or in the other enzymatic activities downstream from DNA-PK. An additional feature is a higher protection of DNA against ionizing radiation by nuclear proteins in LY-R cells. These data support the concept that nuclear matrix organization may contribute to the cellular susceptibility to DNA damaging agents. Ionizing radiation-sensitive LY-S cells suffer also more DNA base damage than ionizing radiation-resistant LY-R cells. However, the repair rates of the γ-ray-induced DNA base damage in LY sublines are related neither to the initial amounts of the damaged bases nor to the lethal or mutagenic effects of ionizing radiation. In contrast, hydrogen peroxide (H 2 O 2 ) sensitive LY-R cells suffer more DNA base damage after H 2 O 2 treatment. This may be due to the lower activity of catalase and/or the lower level of glutathione and other monobromobimane-reactive thiols in LY-R cells than in LY-S cells. However, the main cause of LY-R cells' sensitivity to H 2 O 2 seems to be a higher iron ion content in these cells as compared to LY-S cells. A higher content of iron ions and a higher iron:copper ratio is found in isolated nuclei of LY-R cells than in those of LY-S cells. This is further confirmed by a higher ''labile iron'' pool in LY-R cells than in LY-S cells. Further evidence of different ions content in LY cells and its influence on nuclear matrix organization

  1. The effects of 6-mercaptopurine nucleotide derivatives on the growth and survival of 6-mercaptopurine-sensitive and -resistant cell culture lines.

    Science.gov (United States)

    Johnston, H P; Hawley, P; White, S E; Gibson, I; Tidd, D M

    1985-04-01

    6-Mercaptopurine (MP)-sensitive and -resistant cell culture lines were used to further characterize the apparent ability of MP nucleotide derivatives to overcome resistance to the parent drug. 6-Mercaptopurine-9-beta-D-ribofuranoside 5'-monophosphate [MPRP], bis(6-mercaptopurine-9-beta-D-ribofuranoside)-5', 5"'-monophosphate [bis(MPR)P], bis(O2',O3'-dibutyryl-6-mercaptopurine-9-beta-D-ribofuranoside)-5', 5"'-monophosphate [bis(dibut.MPR)P], and O2',O3'-dibutyryl-6-mercaptopurine-9-beta-D-ribofuranoside 5'-monophosphate [dibut.MPRP] were tested for cytotoxic and/or growth inhibitory effects against MP-resistant sublines of V79 Chinese hamster lung fibroblasts (CH/TG) and L1210 mouse leukaemia cells (L1210/MPR) in which deficiencies of hypoxanthine-guanine phosphoribosyltransferase, and hence drug nucleotide forming capacity were the basis of resistance. L1210/MPR cells were totally resistant to 1 mM 6-mercaptopurine-9-beta-D-ribofuranoside [MPR] and 2 mM MPRP, but were inhibited by high concentrations (greater than 0.25 mM) of bis(MPR)P. These results suggested that bis(MPR)P was taken up by cells as the intact molecule since MPR and MPRP were its extracellular breakdown products. L1210/MPR cells were much more sensitive to the lipophilic bis(dibut.MPR)P derivative which had a predominantly cytotoxic action as judged by trypan blue staining and the ability of treated cells to produce macroscopic colonies in soft agar medium. However, cells killed by bis(dibut.MPR)P did not disintegrate appreciably over periods of up to 10 days. The effects of bis(dibut.MPR)P were probably the result of cellular uptake of the intact molecule. Dibut.MPRP showed minimal ability to inhibit L1210/MPR cells although this compound was a possible breakdown product of bis(dibut.MPR)P and a source of the same extracellular degradation products. The median cell size decreased in L1210/MPR cultures during exposure to both bis(MPR)P and bis(dibut.MPR)P. This effect was elicited more rapidly and

  2. The effects of 6-mercaptopurine nucleotide derivatives on the growth and survival of 6-mercaptopurine-sensitive and -resistant cell culture lines.

    Science.gov (United States)

    Johnston, H. P.; Hawley, P.; White, S. E.; Gibson, I.; Tidd, D. M.

    1985-01-01

    6-Mercaptopurine (MP)-sensitive and -resistant cell culture lines were used to further characterize the apparent ability of MP nucleotide derivatives to overcome resistance to the parent drug. 6-Mercaptopurine-9-beta-D-ribofuranoside 5'-monophosphate [MPRP], bis(6-mercaptopurine-9-beta-D-ribofuranoside)-5', 5"'-monophosphate [bis(MPR)P], bis(O2',O3'-dibutyryl-6-mercaptopurine-9-beta-D-ribofuranoside)-5', 5"'-monophosphate [bis(dibut.MPR)P], and O2',O3'-dibutyryl-6-mercaptopurine-9-beta-D-ribofuranoside 5'-monophosphate [dibut.MPRP] were tested for cytotoxic and/or growth inhibitory effects against MP-resistant sublines of V79 Chinese hamster lung fibroblasts (CH/TG) and L1210 mouse leukaemia cells (L1210/MPR) in which deficiencies of hypoxanthine-guanine phosphoribosyltransferase, and hence drug nucleotide forming capacity were the basis of resistance. L1210/MPR cells were totally resistant to 1 mM 6-mercaptopurine-9-beta-D-ribofuranoside [MPR] and 2 mM MPRP, but were inhibited by high concentrations (greater than 0.25 mM) of bis(MPR)P. These results suggested that bis(MPR)P was taken up by cells as the intact molecule since MPR and MPRP were its extracellular breakdown products. L1210/MPR cells were much more sensitive to the lipophilic bis(dibut.MPR)P derivative which had a predominantly cytotoxic action as judged by trypan blue staining and the ability of treated cells to produce macroscopic colonies in soft agar medium. However, cells killed by bis(dibut.MPR)P did not disintegrate appreciably over periods of up to 10 days. The effects of bis(dibut.MPR)P were probably the result of cellular uptake of the intact molecule. Dibut.MPRP showed minimal ability to inhibit L1210/MPR cells although this compound was a possible breakdown product of bis(dibut.MPR)P and a source of the same extracellular degradation products. The median cell size decreased in L1210/MPR cultures during exposure to both bis(MPR)P and bis(dibut.MPR)P. This effect was elicited more rapidly and

  3. TIMP-1 overexpression does not affect sensitivity to HER2-targeting drugs in the HER2-gene-amplified SK-BR-3 human breast cancer cell line

    DEFF Research Database (Denmark)

    Deng, Xiaohong; Fogh, Louise; Lademann, Ulrik Axel

    2013-01-01

    affect sensitivity to the HER2-targeting drugs trastuzumab and lapatinib. SK-BR-3 human breast cancer cells were stably transfected with TIMP-1, characterized with regard to TIMP-1 protein expression, proliferation, and functionality of the secreted TIMP-1, and the sensitivity to trastuzumab...... and lapatinib was studied in five selected single-cell subclones expressing TIMP-1 protein at various levels plus the parental SK-BR-3 cell line. Both trastuzumab and lapatinib reduced cell viability, as determined by MTT assay, but the sensitivity to the drugs was not associated with the expression level...... to trastuzumab and lapatinib....

  4. N-acetylaspartate (NAA) induces neuronal differentiation of SH-SY5Y neuroblastoma cell line and sensitizes it to chemotherapeutic agents.

    Science.gov (United States)

    Mazzoccoli, Carmela; Ruggieri, Vitalba; Tataranni, Tiziana; Agriesti, Francesca; Laurenzana, Ilaria; Fratello, Angelo; Capitanio, Nazzareno; Piccoli, Claudia

    2016-05-03

    Neuroblastoma is the most commonly extra-cranial solid tumor of childhood frequently diagnosed. The nervous system-specific metabolite N-acetylaspartate (NAA) is synthesized from aspartate and acetyl-CoA in neurons, it is among the most abundant metabolites present in the central nervous system (CNS) and appears to be involved in many CNS disorders. The functional significance of the high NAA concentration in the brain remains uncertain, but it confers to NAA a unique clinical significance exploited in magnetic resonance spectroscopy. In the current study, we show that treatment of SH-SY5Y neuroblastoma-derived cell line with sub-cytotoxic physiological concentrations of NAA inhibits cell growth. This effect is partly due to enhanced apoptosis, shown by decrease of the anti-apoptotic factors survivin and Bcl-xL, and partly to arrest of the cell-cycle progression, linked to enhanced expression of the cyclin-inhibitors p53, p21Cip1/Waf1 and p27Kip1. Moreover, NAA-treated SH-SY5Y cells exhibited morphological changes accompanied with increase of the neurogenic markers TH and MAP2 and down-regulation of the pluripotency markers OCT4 and CXCR4/CD184. Finally, NAA-pre-treated SH-SY5Y cells resulted more sensitive to the cytotoxic effect of the chemotherapeutic drugs Cisplatin and 5-fluorouracil.To our knowledge, this is the first study demonstrating the neuronal differentiating effects of NAA in neuroblastoma cells. NAA may be a potential preconditioning or adjuvant compound in chemotherapeutic treatment.

  5. Tricyclic Antidepressant Amitriptyline-induced Glial Cell Line-derived Neurotrophic Factor Production Involves Pertussis Toxin-sensitive Gαi/o Activation in Astroglial Cells.

    Science.gov (United States)

    Hisaoka-Nakashima, Kazue; Miyano, Kanako; Matsumoto, Chie; Kajitani, Naoto; Abe, Hiromi; Okada-Tsuchioka, Mami; Yokoyama, Akinobu; Uezono, Yasuhito; Morioka, Norimitsu; Nakata, Yoshihiro; Takebayashi, Minoru

    2015-05-29

    Further elaborating the mechanism of antidepressants, beyond modulation of monoaminergic neurotransmission, this study sought to elucidate the mechanism of amitriptyline-induced production of glial cell line-derived neurotrophic factor (GDNF) in astroglial cells. Previous studies demonstrated that an amitriptyline-evoked matrix metalloproteinase (MMP)/FGF receptor (FGFR)/FGFR substrate 2α (FRS2α)/ERK cascade is crucial for GDNF production, but how amitriptyline triggers this cascade remains unknown. MMP is activated by intracellular mediators such as G proteins, and this study sought to clarify the involvement of G protein signaling in amitriptyline-evoked GDNF production in rat C6 astroglial cells (C6 cells), primary cultured rat astrocytes, and normal human astrocytes. Amitriptyline-evoked GDNF mRNA expression and release were inhibited by pertussis toxin (PTX), a Gα(i/o) inhibitor, but not by NF449, a Gα(s) inhibitor, or YM-254890, a Gαq inhibitor. The activation of the GDNF production cascade (FGFR/FRS2α/ERK) was also inhibited by PTX. Deletion of Gα(ο1) and Gα(i3) by RNAi demonstrated that these G proteins play important roles in amitriptyline signaling. G protein activation was directly analyzed by electrical impedance-based biosensors (CellKey(TM) assay), using a label-free (without use of fluorescent proteins/probes or radioisotopes) and real time approach. Amitriptyline increased impedance, indicating Gα(i/o) activation that was suppressed by PTX treatment. The impedance evoked by amitriptyline was not affected by inhibitors of the GDNF production cascade. Furthermore, FGF2 treatment did not elicit any effect on impedance, indicating that amitriptyline targets PTX-sensitive Gα(i/o) upstream of the MMP/FGFR/FRS2α/ERK cascade. These results suggest novel targeting for the development of antidepressants. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Development of Nano-Liposomal Formulations of Epidermal Growth Factor Receptor Inhibitors and their Pharmacological Interactions on Drug-Sensitive and Drug-Resistant Cancer Cell Lines

    Science.gov (United States)

    Trummer, Brian J.

    , due to leaky tumor vasculature and the resulting Enhanced Permeability and Retention (EPR) phenomenon. In Chapter 2 we report that both gefitinib and the structurally similar EGFR inhibitor erlotinib display environment-dependent fluorescence properties. Peak excitation was 345 nm, and the emission peak ranged from 365 to 476 nm, depending upon the polarity of the environment and physical state of the drug. The fluorescence was negligible in aqueous solution, but intense in organic solvents or membrane bilayers. The environment-sensitive fluorescence properties of these drugs enabled rapid evaluation of numerous parameters affecting liposomal drug incorporation and performance. Up to 4-6 mol% of gefitinib could be incorporated in the liposome bilayer, based upon hydrophobic interactions with membrane bilayers. In contrast, 40-60 mol% could be loaded into the aqueous core of pre-formed liposomes at high efficiency, using a remote loading procedure. A stable formulation consisting of distearoylphosphatidylcholine: polyethylene glycol-distereoylphosphatidylethanolamine: cholesterol (DSPC:PEGDSPE:Chol, 9:1:5 mol:mol:mol) and containing drug at 50-60 mol% gefitinib (L-GEF) showed minimal leakage in serum-containing medium over 24 h at 37°C, which should be sufficient to improve biodistribution in vivo. Chapter 3 investigated the pharmacological activity of liposome-encapsulated gefitinib, alone and in combination with several prevalent anticancer agents. Experiments with MCF7 breast cancer cell lines demonstrated that liposome encapsulated gefitinib formulation (L-GEF) had a 2-fold higher IC50 (concentration of drug resulting in half-maximal growth inhibition) than free gefitinib. Lower in vitro potency would be consistent with delayed drug release from the carrier. Therapeutic effects were investigated in combination with the cytotoxic agents paclitaxel and doxorubicin. The drug-resistant MCF7R cell line was 23-fold more resistant to paclitaxel than the parental, drug-sensitive

  7. Comparision of the Cytotoxic Effects of Birch Bark Extract, Betulin and Betulinic Acid Towards Human Gastric Carcinoma and Pancreatic Carcinoma Drug-sensitive and Drug-Resistant Cell Lines

    Directory of Open Access Journals (Sweden)

    Hermann Lage

    2009-04-01

    Full Text Available Betulin and betulinic acid are naturally occurring pentacyclic triterpenes showing cytotoxicity towards a number of cancer cell lines. These compounds can be found in the bark of the many plants. In this report we have compared the cytotoxic activity of crude birch bark extract and purified betulin and betulinic acid towards human gastric carcinoma (EPG85-257 and human pancreatic carcinoma (EPP85-181 drug-sensitive and drug-resistant (daunorubicin and mitoxantrone cell lines. Our results show significant differences in sensitivity between cell lines depending on the compound used, and suggest that both betulin and betulinic acid can be considered as a promising leads in the treatment of cancer.

  8. High sensitivity but normal DNA-repair activity after UV irradiation in Epstein-Barr virus-transformed lymphoblastoid cell lines from Chediak-Higashi syndrome

    International Nuclear Information System (INIS)

    Tanaka, H.; Orii, T.

    1980-01-01

    We established lymphoblastoid cell lines from 2 children with Chediak-Higashi syndrome (CHS), 2 xeroderma pigmentosum (XP) patients and control donors after transformation of peripheral lymphocytes by Epstein-Barr virus (EBV). We used these lymphoblastoid cell lines to investigate repair activity after ultraviolet irradiation. Cell survival of both CHS lymphoblastoid cell lines after irradiation by UV and treatment by 4-nitroquinoline 1-oxide (4NQO) fell between those of the XP and control cells lines. Unscheduled DNA synthesis of CHS cells after UV irradiation occured at rates similar to those of control cells. (orig.)

  9. N. plumbaginifolia zeaxanthin epoxidase transgenic lines have unaltered baseline ABA accumulations in roots and xylem sap, but contrasting sensitivities of ABA accumulation to water deficit.

    Science.gov (United States)

    Borel, C; Audran, C; Frey, A; Marion-Poll, A; Tardieu, F; Simonneau, T

    2001-03-01

    A series of transgenic lines of Nicotiana plumbaginifolia with modified expression of zeaxanthin epoxidase gene (ZEP) provided contrasting ABA accumulation in roots and xylem sap. For mild water stress, concentration of ABA in the xylem sap ([ABA](xylem)) was clearly lower in plants underexpressing ZEP mRNA (complemented mutants and antisense transgenic lines) than in wild-type. In well-watered conditions, all lines presented similar [ABA](xylem) and similar ABA accumulation rates in detached roots. Plants could, therefore, be grown under normal light intensities and evaporative demand. Both ZEP mRNA abundance and ABA accumulation rate in roots increased with water deficit in all transgenic lines, except in complemented aba2-s1 mutants in which the ZEP gene was controlled by a constitutive promoter which does not respond to water deficit. These lines presented no change in root ABA content either with time or dehydration. The increase in ZEP mRNA abundance in roots with decreasing RWC was more pronounced in detached roots than in whole plants, suggesting a difference in mechanism. In all transgenic lines, a linear relationship was observed between predawn leaf water potential and [ABA](xylem), which could be reproduced in several experiments in the greenhouse and in the growth chamber. It is therefore possible to represent the effect of the transformation by a single parameter, thereby allowing the use of a quantitative approach to assist understanding of the behaviour of transgenic lines.

  10. Acquired TGF beta 1 sensitivity and TGF beta 1 expression in cell lines established from a single small cell lung cancer patient during clinical progression

    DEFF Research Database (Denmark)

    Nørgaard, P; Damstrup, L; Rygaard, K

    1996-01-01

    Three small cell lung cancer cell lines established from a single patient during longitudinal follow-up were examined for in vitro expression of TGF beta and TGF beta receptors, i.e. the components of an autocrine loop. GLC 14 was established prior to treatment, GLC 16 on relapse after chemotherapy...... was found in GLC 16 and GLC 19. These cell lines were also growth inhibited by exogenously administrated TGF beta 1. TGF beta 1 mRNA and protein in its latent form was only expressed in the radiotherapy-resistant cell line, GLC 19. The results indicate that disease progression in this patient was paralleled...... II receptor gene, as examined by Southern blotting. Also, the type I receptor could not be detected by ligand binding assay in this cell line, despite expression of mRNA for this receptor. This agrees with previous findings that type I receptor cannot bind TGF beta 1 without co-expression of the type...

  11. Analysis of proviral integration in human mammary epithelial cell lines immortalized by retroviral infection with a temperature-sensitive SV40 T-antigen construct.

    Science.gov (United States)

    Stamps, A C; Davies, S C; Burman, J; O'Hare, M J

    1994-06-15

    A panel of eight conditionally immortal lines derived by infection of human breast epithelial cells with an amphotropic retrovirus transducing a ts mutant of SV40 large T-antigen was analyzed with respect to individual retroviral integration patterns. Each line contained multiple integration sites which were clonal and stable over extended passage. Similar integration patterns were observed between individual lines arising separately from the same stock of pre-immortal cells, suggesting a common progenitor. Retroviral integration analysis of pre-immortal cells at different stages of pre-crisis growth showed changes indicative of a progressive transition from polyclonality to clonality as the cells approached crisis. Each of the immortal lines contained a sub-set of the integration sites of their pre-immortal progenitors, with individual combinations and copy numbers of sites. Since all the cell lines appeared to originate from single foci in separate flasks, it is likely that each set arose from a common clone of pre-immortal cells as the result of separate genetic events. There was no evidence from this analysis to suggest that specific integration sites played any part either in the selection of pre-crisis clones or in the subsequent establishment of immortal lines.

  12. Development of a high resolution, high sensitivity cylindrical crystal spectrometer for line shape diagnostics of x-rays emitted from hot plasmas. Progress report, August 1, 1977--July 31, 1978

    International Nuclear Information System (INIS)

    Taylor, P.O.; Schnopper, H.

    1978-05-01

    This report oulines progress towards development of a high resolution, high throughput, curved crystal spectrometer suitable for line shape diagnostics of x-rays emitted from hot plasmas. The instrument is designed to interface with the MIT Tokamak (Alcator) with the initial aim of studying the prominent MoL lines which occur in the x-ray spectrum. However, it will have the versatility to function over an energy range of at least 1.5 keV to 7 keV allowing determination of temperature, charge state and density distributions for important impurity ions. The spectrometer employs a large, cylindrically bent crystal which focuses the dispersed x-rays along the cylinder axis where they are recorded by a position sensitive proportional counter. Thus, a wide energy range of the spectrum can be recorded simultaneously and sensitively from a short duration plasma. Computer control of data acquisition and analysis will allow real-time diagnostics

  13. The relationship between CD86/CD54 expression and THP-1 cell viability in an in vitro skin sensitization test--human cell line activation test (h-CLAT).

    Science.gov (United States)

    Sakaguchi, Hitoshi; Ashikaga, Takao; Miyazawa, Masaaki; Kosaka, Nanae; Ito, Yuichi; Yoneyama, Katsurako; Sono, Sakiko; Itagaki, Hiroshi; Toyoda, Hidekazu; Suzuki, Hiroyuki

    2009-04-01

    Recent regulations for cosmetics in Europe prohibit animal testing for evaluating the sensitization potential of chemicals to improve animal welfare. Yet, there is not an acceptable Organization for Economic Co-operation and Development non-animal skin sensitization test method. Several in vitro skin sensitization methods that focus on the activation of Langerhans cells, including human cell lines, are being evaluated as possible alternatives. In our previous study, we optimized our human cell line activation test (h-CLAT) using THP-1 cells (monocytic leukemia cell line) and conducted an inter-laboratory study. We found that measuring CD86/CD54 expression may be useful for predicting skin sensitization. The aim of this study was to confirm the relationship between CD86/CD54 expression and THP-1 cell viability in the h-CLAT. In this study, 21 allergens (e.g., dinitrochlorobenzene, p-phenylenediamine, Ni) and 8 non-allergens (e.g., SLS, lactic acid) were evaluated. For each chemical, more than 10 concentrations that gave a predicted cell viability range of 20-95% were used. The data showed that expression patterns of CD86/CD54 differed depending on chemical. For most allergens, cytotoxicity (65-90% cell viability) was needed for enhancement of CD86/CD54 expression. The criteria of "CD86 > or = 150 or CD54 > or = 200" resulted in an accuracy of 93%, which confirms appropriate cut-off criteria for h-CLAT. Furthermore, a good correlation was observed between EC3 of local lymph node assay and EC150(CD86) or EC200(CD54) of h-CLAT (12 or 16 chemicals, respectively), which would provide a useful estimate of allergic potency. These findings suggest that h-CLAT would be a good robust in vitro skin sensitization test.

  14. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: Puget Sound and Strait of Juan de Fuca, Washington: SOCECON (Socioeconomic Resource Points and Lines)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains points that represent the following sensitive human-use socioeconomic sites in Puget Sound and the Strait of Juan de Fuca, Washington: access...

  15. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: Puget Sound and Strait of Juan de Fuca, Washington: FISHL (Fish Lines)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains sensitive biological resource data for marine, estuarine, and anadromous fish in Puget Sound and Strait of Juan de Fuca, Washington. Vector...

  16. Relationships between the H and A-O blood types, phosphohexose isomerase and 6-phosphogluconate dehydrogenase red cell enzyme systems and halothane sensitivity, and economic traits in a superior and an inferior selection line of swiss landrace pigs.

    Science.gov (United States)

    Vögeli, P; Stranzinger, G; Schneebeli, H; Hagger, C; Künzi, N; Gerwig, C

    1984-12-01

    Associations between production traits and the genes for halothane sensitivity (HAL), S, A and H blood group systems and phosphohexose isomerase (PHI) and 6-phosphogluconate dehydrogenase (6-PGD) enzyme systems were investigated in two lines of pigs selected for an index. The phenotypic variance-covariance matrix of the index included backfat thickness and daily gain, whereas the genetic variance-covariance matrix included daily gain, feed conversion and percentage of lean meat. The experiment was conducted at the experimental station of the Institute of Animal Production and has been underway since 1973. The same index was applied but in two opposite directions to give a superior and inferior line in relation to the production traits. One hundred twenty-nine animals of the superior line in the seventh generation and 88 animals of the inferior line in the sixth generation were studied. Forty-two percent (54/129) of the animals of the superior line were halothane-positive. No animals in the inferior line were halothane reactors. Of the halothane-positive pigs, 70.4% (38/54) in the superior line had the HaHa and 94.4% (51/54) had the SsSs genotype, whereas only 4% (3/75) of the HaHa and 12% (9/75) of the SsSs pigs were halothane-negative. By practicing selection at the H and S loci, it seems possible to efficiently reduce halothane sensitivity in Swiss Landrace pigs. In pigs of the superior line, there were significant differences in percentage of lean meat, carcass length, pH1 (pH value at 45 min to 1 h postmortem, M. longissimus) and reflectance values among genotypes of the HAL, S and H systems and among some genotypes of the 6-PGD system. Poorest meat quality, highest percentage of lean meat and shortest carcass length were observed in pigs homozygous for the alleles HALn, Ss, Ha, PHIB and 6-PGDA. In the inferior line, these associations were absent. As the HAL locus is associated with the above mentioned production traits, linkage disequilibria may explain the

  17. Newly established tumourigenic primary human colon cancer cell lines are sensitive to TRAIL-induced apoptosis in vitro and in vivo

    Czech Academy of Sciences Publication Activity Database

    Oikonomou, E.; Kothonidis, K.; Zografos, G.; Nasioulas, G.; Anděra, Ladislav; Pintzas, A.

    2007-01-01

    Roč. 97, č. 12 (2007), s. 73-84 ISSN 0007-0920 Grant - others:EU(XE) LSHC-CT-2006-037278 Institutional research plan: CEZ:AV0Z50520514 Keywords : TRAIL * apoptosis * colon cancer cell lines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.635, year: 2007

  18. Changes in sensitivity to radiation and to bleomycin occurring during the life history of monolayer cultures of a mouse tumour cell line

    International Nuclear Information System (INIS)

    Twentyman, P.R.; Bleehen, N.M.

    1975-01-01

    The response to X-radiation and to bleomycin has been measured at a number of times during the life of monolayer cultures of EMT6 mouse tumour cells. Little change in radiation sensitivity was seen at any time and no loss of the shoulder to the survival curve occurred. Cultures in early plateau phase (where a considerable amount of cell proliferation is balanced by cell loss) showed a reduced sensitivity to bleomycin when compared with cells in exponential growth. However, after a longer period in plateau phase, when proliferation had virtually ceased, the sensitivity became greater than that of exponential phase cells. These findings are discussed with reference to the conflicting results of other workers. (author)

  19. The effect of caffeine on post-replication repair and survival in two L5178Y cell lines with different sensitivities to UV irradiation

    International Nuclear Information System (INIS)

    Walicka, M.; Beer, J.Z.; Koerner, I.; Malz, W.

    1978-01-01

    2 Strains of murine lymphoma L5178Y cells that varied from the point of view of sensitivity to UV irradiation (mean lethal doses: 3.6 and 8.5 J/m 2 for L5178Y-R and L5178Y-S cells, respectively) also differed with respect to sensitization by caffeine. L5178Y-S cells were sensitized to UV irradiation by 0.75 mM caffeine, whereas in the same conditions L5178Y-R cells were not sensitized. Sedimentation analysis of the newly synthesized DNA indicated UV-induced gap formation in L5178Y-S cells only. The subsequent gap filling was inhibited by caffeine. Exposure to UV irradiation induced no gaps in L5178Y-R cells. However, when caffeine was added immediately after irradiation, DNA with reduced molecular weight was found in irradiated cells of both strains after a 2-h chase. On the other hand, caffeine inhibited elongation of undamaged DNA strands in neither of the 2 cell strains. (Auth.)

  20. Efficacy and safety of endocrine monotherapy as first-line treatment for hormone-sensitive advanced breast cancer: A network meta-analysis.

    Science.gov (United States)

    Zhang, Jingwen; Huang, Yanhong; Wang, Changyi; He, Yuanfang; Zheng, Shukai; Wu, Kusheng

    2017-08-01

    Endocrine therapy was recommended as the preferred first-line treatment for hormone receptor-positive (HR+, i.e., ER+ and/or PgR+), human epidermal growth factor receptor-2-negative (HER2-) postmenopausal advanced breast cancer (ABC), but which endocrine monotherapy is optimal lacks consensus. We aimed to identify the optimal endocrine monotherapy with a network meta-analysis. We performed a network meta-analysis for a comprehensive analysis of 6 first-line endocrine monotherapies (letrozole, anastrozole, exemestane, tamoxifen, fulvestrant 250 mg and 500 mg) for HR+ HER2- metastatic or locally advanced breast cancer in postmenopausal patients. The main outcomes were objective response rate (ORR), time to progression (TTP), and progression-free survival (PFS). Secondary outcomes were adverse events. We identified 27 articles of 8 randomized controlled trials including 3492 patients in the network meta-analysis. For ORR, the treatments ranked in descending order of effectiveness were letrozole > exemestane > anastrozole > fulvestrant 500 mg > tamoxifen > fulvestrant 250 mg. For TTP/PFS, the order was fulvestrant 500 mg > letrozole > anastrozole > exemestane > tamoxifen > fulvestrant 250 mg. We directly compared adverse events and found that tamoxifen produced more hot flash events than fulvestrant 250 mg. Fulvestrant 500 mg and letrozole might be optimal first-line endocrine monotherapy choices for HR+ HER2- ABC because of efficacious ORR and TTP/PFS, with a favorable tolerability profile. However, direct comparisons among endocrine monotherapies in the first-line therapy setting are still required to robustly demonstrate any differences among these endocrine agents. Clinical choices should also depend on the specific disease situation and duration of endocrine therapy.

  1. A novel rapid genotyping technique for Collie eye anomaly: SYBR Green-based real-time polymerase chain reaction method applicable to blood and saliva specimens on Flinders Technology Associates filter paper.

    Science.gov (United States)

    Chang, Hye-Sook; Mizukami, Keijiro; Yabuki, Akira; Hossain, Mohammad A; Rahman, Mohammad M; Uddin, Mohammad M; Arai, Toshiro; Yamato, Osamu

    2010-09-01

    Collie eye anomaly (CEA) is a canine inherited ocular disease that shows a wide variety of manifestations and severity of clinical lesions. Recently, a CEA-associated mutation was reported, and a DNA test that uses conventional polymerase chain reaction (PCR) has now become available. The objective of the current study was to develop a novel rapid genotyping technique by using SYBR Green-based real-time PCR for future large-scale surveys as a key part in the strategy to eradicate CEA by selective breeding. First, a SYBR Green-based real-time PCR assay for genotyping of CEA was developed and evaluated by using purified DNA samples from normal, carrier, and affected Border Collies in which genotypes had previously been determined by conventional PCR. This real-time PCR assay demonstrated appropriate amplifications in all genotypes, and the results were consistent with those of conventional PCR. Second, the availability of Flinders Technology Associates filter paper (FTA card) as DNA templates for the real-time PCR assay was evaluated by using blood and saliva specimens to determine suitability for CEA screening. DNA-containing solution prepared from a disc of blood- or saliva-spotted FTA cards was available directly as templates for the real-time PCR assay when the volume of solution was 2.5% of the PCR mixture. In conclusion, SYBR Green-based real-time PCR combined with FTA cards is a rapid genotyping technique for CEA that can markedly shorten the overall time required for genotyping as well as simplify the sample preparation. Therefore, this newly developed technique suits large-scale screening in breeding populations of Collie-related breeds.

  2. Efficacy of icotinib versus traditional chemotherapy as first-line treatment for preventing brain metastasis from advanced lung adenocarcinoma in patients with epidermal growth factor receptor-sensitive mutation.

    Science.gov (United States)

    Zhao, Xiao; Zhu, Guangqin; Chen, Huoming; Yang, Ping; Li, Fang; Du, Nan

    2016-01-01

    This study aimed to investigate the potential use of icotinib as first-line treatment to prevent brain metastasis from advanced lung adenocarcinoma. This investigation was designed as a retrospective nonrandomized controlled study. Enrolled patients received either icotinib or traditional chemotherapy as their first-line treatment. The therapeutic efficacy was compared among patients with advanced. (stages IIIB and IV) lung adenocarcinoma with epidermal growth factor receptor (EGFR)-sensitive mutation. The primary endpoint was the cumulative incidence of brain metastasis, whereas, the secondary endpoint was overall survival(OS). Death without brain metastasis was considered a competitive risk to calculate the cumulative risk of brain metastasis. Survival analysis was conducted using the Kaplan-Meier method and statistical significance was determined using the log-rank test. The present study included 396 patients with 131 in the icotinib group and 265 in the chemotherapy group. Among those with EGFR-sensitive mutation, the cumulative risk of brain metastasis was lower in the icotinib group than in the chemotherapy group. However, no significant difference in OS was observed between the two groups. Icotinib can effectively reduce the incidence of brain metastasis and therefore improve prognosis in advanced lung adenocarcinoma patients with EGFR.sensitive mutation.

  3. Efficacy of icotinib versus traditional chemotherapy as first-line treatment for preventing brain metastasis from advanced lung adenocarcinoma in patients with epidermal growth factor receptor-sensitive mutation

    Directory of Open Access Journals (Sweden)

    Xiao Zhao

    2014-01-01

    Full Text Available Objective: This study aimed to investigate the potential use of icotinib as first-line treatment to prevent brain metastasis from advanced lung adenocarcinoma. Patients and Methods: This investigation was designed as a retrospective nonrandomized controlled study. Enrolled patients received either icotinib or traditional chemotherapy as their first-line treatment. The therapeutic efficacy was compared among patients with advanced (stages IIIB and IV lung adenocarcinoma with epidermal growth factor receptor (EGFR-sensitive mutation. The primary endpoint was the cumulative incidence of brain metastasis, whereas the secondary endpoint was overall survival (OS. Death without brain metastasis was considered a competitive risk to calculate the cumulative risk of brain metastasis. Survival analysis was conducted using the Kaplan-Meier method and statistical significance were determined using the log-rank test. Results: The present study included 396 patients with 131 in the icotinib group and 265 in the chemotherapy group. Among those with EGFR-sensitive mutation, the cumulative risk of brain metastasis was lower in the icotinib group than in the chemotherapy group. However, no significant difference in OS was observed between the two groups. Conclusion: Icotinib can effectively reduce the incidence of brain metastasis and therefore improve prognosis in advanced lung adenocarcinoma patients with EGFR-sensitive mutation.

  4. Design and development of a highly sensitive, field portable plasma source instrument for on-line liquid stream monitoring and real-time sample analysis

    International Nuclear Information System (INIS)

    Duan, Yixiang; Su, Yongxuan; Jin, Zhe; Abeln, Stephen P.

    2000-01-01

    The development of a highly sensitive, field portable, low-powered instrument for on-site, real-time liquid waste stream monitoring is described in this article. A series of factors such as system sensitivity and portability, plasma source, sample introduction, desolvation system, power supply, and the instrument configuration, were carefully considered in the design of the portable instrument. A newly designed, miniature, modified microwave plasma source was selected as the emission source for spectroscopy measurement, and an integrated small spectrometer with a charge-coupled device detector was installed for signal processing and detection. An innovative beam collection system with optical fibers was designed and used for emission signal collection. Microwave plasma can be sustained with various gases at relatively low power, and it possesses high detection capabilities for both metal and nonmetal pollutants, making it desirable to use for on-site, real-time, liquid waste stream monitoring. An effective in situ sampling system was coupled with a high efficiency desolvation device for direct-sampling liquid samples into the plasma. A portable computer control system is used for data processing. The new, integrated instrument can be easily used for on-site, real-time monitoring in the field. The system possesses a series of advantages, including high sensitivity for metal and nonmetal elements; in situ sampling; compact structure; low cost; and ease of operation and handling. These advantages will significantly overcome the limitations of previous monitoring techniques and make great contributions to environmental restoration and monitoring. (c)

  5. Genetic inactivation of the Fanconi anemia gene FANCC identified in the hepatocellular carcinoma cell line HuH-7 confers sensitivity towards DNA-interstrand crosslinking agents

    Directory of Open Access Journals (Sweden)

    Bassermann Florian

    2010-05-01

    Full Text Available Abstract Background Inactivation of the Fanconi anemia (FA pathway through defects in one of 13 FA genes occurs at low frequency in various solid cancer entities among the general population. As FA pathway inactivation confers a distinct hypersensitivity towards DNA interstrand-crosslinking (ICL-agents, FA defects represent rational targets for individualized therapeutic strategies. Except for pancreatic cancer, however, the prevalence of FA defects in gastrointestinal (GI tumors has not yet been systematically explored. Results A panel of GI cancer cell lines was screened for FA pathway inactivation applying FANCD2 monoubiquitination and FANCD2/RAD51 nuclear focus formation and a newly identified FA pathway-deficient cell line was functionally characterized. The hepatocellular carcinoma (HCC line HuH-7 was defective in FANCD2 monoubiquitination and FANCD2 nuclear focus formation but proficient in RAD51 focus formation. Gene complementation studies revealed that this proximal FA pathway inactivation was attributable to defective FANCC function in HuH-7 cells. Accordingly, a homozygous inactivating FANCC nonsense mutation (c.553C > T, p.R185X was identified in HuH-7, resulting in partial transcriptional skipping of exon 6 and leading to the classic cellular FA hypersensitivity phenotype; HuH-7 cells exhibited a strongly reduced proliferation rate and a pronounced G2 cell cycle arrest at distinctly lower concentrations of ICL-agents than a panel of non-isogenic, FA pathway-proficient HCC cell lines. Upon retroviral transduction of HuH-7 cells with FANCC cDNA, FA pathway functions were restored and ICL-hypersensitivity abrogated. Analyses of 18 surgical HCC specimens yielded no further examples for genetic or epigenetic inactivation of FANCC, FANCF, or FANCG in HCC, suggesting a low prevalence of proximal FA pathway inactivation in this tumor type. Conclusions As the majority of HCC are chemoresistant, assessment of FA pathway function in HCC could

  6. Modulation of P-glycoprotein activity by novel synthetic curcumin derivatives in sensitive and multidrug-resistant T-cell acute lymphoblastic leukemia cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Ooko, Edna [Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz (Germany); Alsalim, Tahseen; Saeed, Bahjat [Department of Chemistry, College of Education for Pure Sciences, University of Basrah, P.O. Box 49 Basrah, Al Basrah (Iraq); Saeed, Mohamed E.M.; Kadioglu, Onat [Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz (Germany); Abbo, Hanna S. [Department of Chemistry, University of the Western Cape, P/B X17, Bellville, 7535 Cape Town (South Africa); Titinchi, Salam J.J., E-mail: stitinchi@uwc.ac.za [Department of Chemistry, University of the Western Cape, P/B X17, Bellville, 7535 Cape Town (South Africa); Efferth, Thomas, E-mail: efferth@uni-mainz.de [Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz (Germany)

    2016-08-15

    Background: Multidrug resistance (MDR) and drug transporter P-glycoprotein (P-gp) represent major obstacles in cancer chemotherapy. We investigated 19 synthetic curcumin derivatives in drug-sensitive acute lymphoblastic CCRF–CEM leukemia cells and their multidrug-resistant P-gp-overexpressing subline, CEM/ADR5000. Material and methods: Cytotoxicity was tested by resazurin assays. Doxorubicin uptake was assessed by flow cytometry. Binding modes of compounds to P-gp were analyzed by molecular docking. Chemical features responsible for bioactivity were studied by quantitative structure activity relationship (QSAR) analyses. A 7-descriptor QSAR model was correlated with doxorubicin uptake values, IC{sub 50} values and binding energies. Results: The compounds displayed IC{sub 50} values between 0.7 ± 0.03 and 20.2 ± 0.25 μM. CEM/ADR5000 cells exhibited cross-resistance to 10 compounds, collateral sensitivity to three compounds and regular sensitivity to the remaining six curcumins. Molecular docking studies at the intra-channel transmembrane domain of human P-gp resulted in lowest binding energies ranging from − 9.00 ± 0.10 to − 6.20 ± 0.02 kcal/mol and pKi values from 0.24 ± 0.04 to 29.17 ± 0.88 μM. At the ATP-binding site of P-gp, lowest binding energies ranged from − 9.78 ± 0.17 to − 6.79 ± 0.01 kcal/mol and pKi values from 0.07 ± 0.02 to 0.03 ± 0.03 μM. CEM/ADR5000 cells accumulated approximately 4-fold less doxorubicin than CCRF–CEM cells. The control P-gp inhibitor, verapamil, partially increased doxorubicin uptake in CEM/ADR5000 cells. Six curcumins increased doxorubicin uptake in resistant cells or even exceeded uptake levels compared to sensitive one. QSAR yielded good activity prediction (R = 0.797 and R = 0.794 for training and test sets). Conclusion: Selected derivatives may serve to guide future design of novel P-gp inhibitors and collateral sensitive drugs to combat MDR. - Highlights: • Novel derivatives of curcumin in reversing

  7. Modulation of P-glycoprotein activity by novel synthetic curcumin derivatives in sensitive and multidrug-resistant T-cell acute lymphoblastic leukemia cell lines

    International Nuclear Information System (INIS)

    Ooko, Edna; Alsalim, Tahseen; Saeed, Bahjat; Saeed, Mohamed E.M.; Kadioglu, Onat; Abbo, Hanna S.; Titinchi, Salam J.J.; Efferth, Thomas

    2016-01-01

    Background: Multidrug resistance (MDR) and drug transporter P-glycoprotein (P-gp) represent major obstacles in cancer chemotherapy. We investigated 19 synthetic curcumin derivatives in drug-sensitive acute lymphoblastic CCRF–CEM leukemia cells and their multidrug-resistant P-gp-overexpressing subline, CEM/ADR5000. Material and methods: Cytotoxicity was tested by resazurin assays. Doxorubicin uptake was assessed by flow cytometry. Binding modes of compounds to P-gp were analyzed by molecular docking. Chemical features responsible for bioactivity were studied by quantitative structure activity relationship (QSAR) analyses. A 7-descriptor QSAR model was correlated with doxorubicin uptake values, IC 50 values and binding energies. Results: The compounds displayed IC 50 values between 0.7 ± 0.03 and 20.2 ± 0.25 μM. CEM/ADR5000 cells exhibited cross-resistance to 10 compounds, collateral sensitivity to three compounds and regular sensitivity to the remaining six curcumins. Molecular docking studies at the intra-channel transmembrane domain of human P-gp resulted in lowest binding energies ranging from − 9.00 ± 0.10 to − 6.20 ± 0.02 kcal/mol and pKi values from 0.24 ± 0.04 to 29.17 ± 0.88 μM. At the ATP-binding site of P-gp, lowest binding energies ranged from − 9.78 ± 0.17 to − 6.79 ± 0.01 kcal/mol and pKi values from 0.07 ± 0.02 to 0.03 ± 0.03 μM. CEM/ADR5000 cells accumulated approximately 4-fold less doxorubicin than CCRF–CEM cells. The control P-gp inhibitor, verapamil, partially increased doxorubicin uptake in CEM/ADR5000 cells. Six curcumins increased doxorubicin uptake in resistant cells or even exceeded uptake levels compared to sensitive one. QSAR yielded good activity prediction (R = 0.797 and R = 0.794 for training and test sets). Conclusion: Selected derivatives may serve to guide future design of novel P-gp inhibitors and collateral sensitive drugs to combat MDR. - Highlights: • Novel derivatives of curcumin in reversing multidrug

  8. Sensitivity, applicability and validation of bi-gaussian off- and on-line models for the evaluation of the consequences of accidental releases in nuclear facilities

    International Nuclear Information System (INIS)

    Kretzschmar, J.G.; Mertens, I.; Vanderborght, B.

    1984-01-01

    A computer code CAERS (Computer Aided Emergency Response System) has been developed for the simulation of the short-term concentrations caused by an atmospheric emission. The concentration calculations are based on the bi-gaussian theorem with the possibility of using twelve different sets of turbulence typing schemes and dispersion parameters or the plume can be simulated with a bi-dimensional puff trajectory model with tri-gaussian diffusion of the puffs. With the puff trajectory model the emission and the wind conditions can be variable in time. Sixteen SF 6 tracer dispersion experiments, with mobile as well as stationary time averaging sampling, have been carried out for the validation of the on-line and off-line models of CAERS. The tracer experiments of this study have shown that the CAERS system, using the bi-gaussian model and the SCK/CEN turbulence typing scheme, can simulate short time concentration levels very well. The variations of the plume under non-steady emission and meteo conditions are well simulated by the puff trajectory model. This leads to the general conclusion that the atmospheric dispersion models of the CAERS system can give a significant contribution to the management and the interpretation of air pollution concentration measurements in emergency situations

  9. Influence of vitamin D on cisplatin sensitivity in testicular germ cell cancer-derived cell lines and in a NTera2 xenograft model

    DEFF Research Database (Denmark)

    Jørgensen, Anne; Blomberg Jensen, Martin; Nielsen, John Erik

    2013-01-01

    The active form of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) has anti-proliferative, pro-apoptotic, and pro-differentiating effects in somatic cancer cells in vitro and in vivo. 1,25(OH)(2)D(3) also augments the anti-tumor effects of several chemotherapeutic agents, including...... cisplatin, which may have clinical relevance. Given the pro-differentiation effect of vitamin D recently demonstrated in testicular germ cell tumors (TGCTs), we hypothesized that 1,25(OH)(2)D(3) could be a beneficial adjunctive to existing chemotherapy regime used to treat these tumors. In this study, cell...... survival effects of 1,25(OH)(2)D(3), another pro-differentiation compound, retinoic acid and cisplatin were investigated in TGCT-derived cell lines in vitro. 1,25(OH)(2)D(3) augmented the effect of cisplatin in an embryonal carcinoma-derived cell line (NTera2), possibly through downregulation...

  10. HMOX1 and NQO1 genes are upregulated in response to contact sensitizers in dendritic cells and THP-1 cell line: role of the Keap1/Nrf2 pathway.

    Science.gov (United States)

    Ade, Nadège; Leon, Fanny; Pallardy, Marc; Peiffer, Jean-Luc; Kerdine-Romer, Saadia; Tissier, Marie-Hélène; Bonnet, Pierre-Antoine; Fabre, Isabelle; Ourlin, Jean-Claude

    2009-02-01

    Electrophilicity is one of the most common features of skin contact sensitizers and is necessary for protein haptenation. The Keap1 (Kelch-like ECH-associated protein 1)/Nrf2 -signaling pathway is dedicated to the detection of electrophilic stress in cells leading to the upregulation of genes involved in protection or neutralization of chemical reactive species. Signals provided by chemical stress could play an important role in dendritic cell activation and the aim of this work was to test whether contact sensitizers were specific activators of the Keap1/Nrf2 pathway. CD34-derived dendritic cells (CD34-DC) and the THP-1 myeloid cell line were treated by a panel of sensitizers (Ni, 1-chloro 2,4-dinitrobenzene, cinnamaldehyde, 7-hydroxycitronellal, 1,4-dihydroquinone, alpha-methyl-trans-cinnamaldehyde, 2-4-tert-(butylbenzyl)propionaldehyde or Lilial, and 1,4-phenylenediamine), irritants (sodium dodecyl sulfate, benzalkonium chloride), and a nonsensitizer molecule (chlorobenzene). Three well-known Nrf2 activators (tert-butylhydroquinone, lipoic acid, sulforaphane) were also tested. Expression of hmox1 and nqo1 was measured using real-time PCR and cellular accumulation of Nrf2 was assessed by Western blot. Our results showed an increased expression at early time points of hmox1 and nqo1 mRNAs in response to sensitizers but not to irritants. Accumulation of the Nrf2 protein was also observed only with chemical sensitizers. A significant inhibition of the expression of hmox1 and nqo1 mRNAs and CD86 expression was found in 1-chloro 2,4-dinitrobenzene-treated THP-1 cells preincubated with N-acetyl cysteine, a glutathione precursor. Altogether, these data suggested that the Keap1/Nrf2-signaling pathway was activated by electrophilic molecules including sensitizers in dendritic cells and in the THP-1 cell line. Monitoring of this pathway may provide new biomarkers (e.g., Nrf2, hmox1) for the detection of the sensitization potential of chemicals.

  11. Insulin sensitivity and β-cell function in normoglycemic offspring of individuals with type 2 diabetes mellitus: Impact of line of inheritance

    Directory of Open Access Journals (Sweden)

    Edavan P Praveen

    2012-01-01

    Full Text Available Aims: The aim was to study the effect of family history of type 2 diabetes mellitus (T2DM on insulin sensitivity and b-cell function in normoglycemic offspring. Material and Methods: Offspring of T2DM patients (cases and individuals without family history of T2DM (controls were the subjects for this cross-sectional study. All participants underwent 75 g OGTT and samples were collected for plasma insulin, C-peptide, and proinsulin at 0, 30, 60, and 120 minutes. Results: A total of 271 cases (age 22 ± 10 years; 53% males and 259 controls (28 ± 10 years, 66% males were enrolled for the study. BMI, plasma insulin, C-peptide, proinsulin, HOMA-IR, and insulinogenic index (0-120 were significantly higher and whole-body insulin sensitivity (WBISI and disposition index (0-120 [DI 120] were lower in cases compared to controls. After adjusting for BMI, proinsulin at 120 minutes, area under the curve (AUC of proinsulin (during OGTT and AUC proinsulin/AUC C-peptide were significantly higher in cases. Cases were subdivided into four groups according to inheritance pattern; paternal DM (PDM, maternal DM (MDM, grandparental DM (GPDM, and both parents DM (BPDM. The magnitude of differences varied with relationship (greater when both parents and grandparents were affected. Mean HOMA-IR was higher by 127% and 50% and DI 120 was lower by 33% and 18% (adjusted for age and gender in the BPDM and GPDM groups respectively compared to controls. Conclusions: We observed higher BMI, plasma insulin, C-peptide, and proinsulin and lower insulin sensitivity and b-cell compensation in normoglycemic offspring of T2DM subjects compared to controls. Differences were greater when both parents and grandparents had T2DM.

  12. Development of an artificial neural network model for risk assessment of skin sensitization using human cell line activation test, direct peptide reactivity assay, KeratinoSens™ and in silico structure alert parameter.

    Science.gov (United States)

    Hirota, Morihiko; Ashikaga, Takao; Kouzuki, Hirokazu

    2018-04-01

    It is important to predict the potential of cosmetic ingredients to cause skin sensitization, and in accordance with the European Union cosmetic directive for the replacement of animal tests, several in vitro tests based on the adverse outcome pathway have been developed for hazard identification, such as the direct peptide reactivity assay, KeratinoSens™ and the human cell line activation test. Here, we describe the development of an artificial neural network (ANN) prediction model for skin sensitization risk assessment based on the integrated testing strategy concept, using direct peptide reactivity assay, KeratinoSens™, human cell line activation test and an in silico or structure alert parameter. We first investigated the relationship between published murine local lymph node assay EC3 values, which represent skin sensitization potency, and in vitro test results using a panel of about 134 chemicals for which all the required data were available. Predictions based on ANN analysis using combinations of parameters from all three in vitro tests showed a good correlation with local lymph node assay EC3 values. However, when the ANN model was applied to a testing set of 28 chemicals that had not been included in the training set, predicted EC3s were overestimated for some chemicals. Incorporation of an additional in silico or structure alert descriptor (obtained with TIMES-M or Toxtree software) in the ANN model improved the results. Our findings suggest that the ANN model based on the integrated testing strategy concept could be useful for evaluating the skin sensitization potential. Copyright © 2017 John Wiley & Sons, Ltd.

  13. On-line complexation/cloud point preconcentration for the sensitive determination of dysprosium in urine by flow injection inductively coupled plasma-optical emission spectrometry

    International Nuclear Information System (INIS)

    Ortega, Claudia; Cerutti, Soledad; Silva, Maria F.; Olsina, Roberto A.; Martinez, Luis D.

    2003-01-01

    An on-line dysprosium preconcentration and determination system based on the hyphenation of cloud point extraction (CPE) to flow injection analysis (FIA) associated with ICP-OES was studied. For the preconcentration of dysprosium, a Dy(III)-2-(5-bromo-2-pyridylazo)-5-diethylaminophenol complex was formed on-line at pH 9.22 in the presence of nonionic micelles of PONPE-7.5. The micellar system containing the complex was thermostated at 30 C in order to promote phase separation, and the surfactant-rich phase was retained in a microcolumn packed with cotton at pH 9.2. The surfactant-rich phase was eluted with 4 mol L -1 nitric acid at a flow rate of 1.5 mL min -1 , directly in the nebulizer of the plasma. An enhancement factor of 50 was obtained for the preconcentration of 50 mL of sample solution. The detection limit value for the preconcentration of 50 mL of aqueous solution of Dy was 0.03 μg L -1 . The precision for 10 replicate determinations at the 2.0 μg L -1 Dy level was 2.2% relative standard deviation (RSD), calculated from the peak heights obtained. The calibration graph using the preconcentration system for dysprosium was linear with a correlation coefficient of 0.9994 at levels near the detection limits up to at least 100 μg L -1 . The method was successfully applied to the determination of dysprosium in urine. (orig.)

  14. Heat shock protein 90 chaperone complex inhibitor enhanced radiosensitivity through modification of response to hormone and degradation of androgen receptor in hormone sensitive prostate cancer cell line

    International Nuclear Information System (INIS)

    Mitsuhashi, N.; Harashima, K.; Akimoto, T.

    2003-01-01

    It is easily speculated that androgen or androgen deprivation affects proliferative activity or radiosensitivity, but there has been enough information how androgen or androgen deprivation influences the response to radiation. In this setting, the effect of dihydrotestosterone (DHT) on cellular growth and radiosensitivity was examined in hormone-responsive human prostate cancer cell line (LnCap). The binding of androgen receptor (AR) with heat shock protein 90 (Hsp90) plays an important role in stability of the function of receptor. It was, therefore, examined how Hsp90 chaperone complex inhibitor modified the effect of DHT on radiosensitivity in addition to the effect of DHT, especially focusing on AR and its downstream signal transduction pathways. Hydroxy-flutamide (OH-flutamide) was also used to confirm the effect of activation of AR on radiosensitivity because AR of LnCap has a point mutation, leading to activation of AR caused by the binding of OH-flutamide. Radicicol was used as a Hsp90 chaperone complex inhibitor, and incubated with cells at a concentration of 500 nM. Radicicol was incubated with cells for 9 h, and cells were irradiated 1 h after the start of incubation. DHT and OH-flutamide were incubated with cells until staining. DHT or OH-flutamide resulted in stimulation of cellular growth in contrast to inhibition of cellular growth caused by higher concentrations, so that we adopted 1 nM as a concentration of DHT and 1μM as a concentration of OH-flutamide. DHT or OH-flutamide in combination with radiation resulted in slight decrease in radiosensitivity compared with radiation alone. Radicicol at a concentration of 500 nM in combination with DHT or OH-flutamide abolished decrease in radiosensitivity caused by DHT or OH-flutamide. In terms of the expression of AR, radicicol in combination with radiation and/or DHT, OH-flutamide induced degradation of AR. In consistent with degradation of AR, the expression of prostate specific antigen (PSA) decreased

  15. Inhibition and recovery of semiconservative DNA synthesis in normal and solar UV sensitive ICR 2A frog cell lines following the induction of non-dimer DNA damage by sunlamp UV > 315 nm

    Energy Technology Data Exchange (ETDEWEB)

    Rosenstein, B.S. (Brown Univ., Providence, RI (USA). Dept. of Radiation Medicine)

    1989-08-01

    Cultures of solar UV-sensitive cell lines DRP 36 and DRP 153, and of the parental ICR 2A cell line, were exposed to 150 kJ/m{sup 2} of sunlamp UV>315nm plus photoreactivating light, resulting in the induction primarily of non-dimer DNA damage. Following either 0, 3, 6, 12 or 24 h incubation, cultures were pulse-labelled with ({sup 3}H) thymidine, and the synthesis of different size classes of replicon intermediates measured using alkaline step elution assay. For all three cell lines tested, an immediate depression of low molecular weight DNA synthesis was observed, followed by inhibition of all size classes of replicon intermediates. Within 12 h following irradiation, recovery of DNA synthesis was observed, generally most apparent for low molecular weight DNA. The ICR 2A cells exhibited a nearly full recovery in all size classes of DNA synthesized by 24 h. A much smaller recovery of continued inhibition was primarily in the synthesis of full replicon size DNA, and most pronounced for DRP 36 cells. (author).

  16. Facile green synthesis of graphene-Au nanorod nanoassembly for on-line extraction and sensitive stripping analysis of methyl parathion

    International Nuclear Information System (INIS)

    Zhu, Wenxin; Liu, Wei; Li, Tianbao; Yue, Xiaoyue; Liu, Tao; Zhang, Wentao; Yu, Shaoxuan; Zhang, Daohong; Wang, Jianlong

    2014-01-01

    Graphical abstract: Schematic illustration for the facile green fabrication of GN-AuNRs/GCE and its application for the extraction and electroanalysis of MP. - Highlights: • This paper described a facile green electrochemical approach to synthesize graphene-AuNRs nanocomposite. • The as-synthesized sensor shows low LOD and wide linear concentration range towards MP. • The sensor can be well used for the determination of MP in water and kiwi fruits samples. • This paper further enlarges the scope of facile green synthetic methods of GN-based hybrids. - Abstract: This paper described a facile green electrochemical approach to synthesize graphene-AuNRs nanocomposite (GN-AuNRs) onto glassy carbon electrode (GCE) for electrocatalytic analysis of methyl parathion (MP). This electrochemical synthesis of GN-AuNRs hybrid is environmentally friendly for not involving the chemical reduction of graphene oxide (GO) and facile for just on the basis of electrostatic interaction between GO and AuNRs, as well as electrochemical reduction of GO-AuNRs to GN-AuNRs. Combined the high conductivity, large surface area, good adsorption capacity towards aromatic rings and high catalytic ability of graphene with the excellent electronic properties and adsorption capacity of AuNRs, the high sensitive methyl parathion sensor was fabricated with the GN-AuNRs nanocomposite. The limit of detection (LOD) of the proposed sensor was calculated to be 0.82 ng/mL, which was lower than many previously reported enzyme or nonenzyme-based sensors. In the meantime, the linear detection range of this sensor was from 10 to 500 ng/mL and 750 to 4000 ng/mL, which was also wider than many other enzyme or enzymeless sensors. Furthermore, the facile and green electrochemical reduction strategy provided here could also be used to construct more GN-based hybrids. And the GN-based hybrid might be a new and highly efficient SPE factor, which opens new opportunities for green, facile and sensitive analysis of

  17. A simple and highly sensitive on-line column extraction liquid chromatography-tandem mass spectrometry method for the determination of protein-unbound tacrolimus in human plasma samples.

    Science.gov (United States)

    Bittersohl, Heike; Schniedewind, Björn; Christians, Uwe; Luppa, Peter B

    2018-04-27

    Therapeutic drug monitoring (TDM) of the immunosuppressive drug tacrolimus is essential to avoid side effects and rejection of the allograft after transplantation. In the blood circulation, tacrolimus is largely located inside erythrocytes or bound to plasma proteins and less than 0.1% is protein-unbound (free). One basic principle of clinical pharmacology is that only free drug is pharmacologically active and monitoring this portion has the potential to better reflect the drug effect than conventional measurements of total tacrolimus in whole blood. To address this, a highly sensitive and straightforward on-line liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed, validated and applied to patient plasma samples. The sample preparation included ultracentrifugation and addition of the stable isotope labeled drug analogue D2,13C-tacrolimus, followed by on-line sample extraction and measurement using a Sciex QTRAP ® 6500 in the multiple reaction monitoring mode. Due to very low concentrations of protein-unbound tacrolimus, it was important to develop a highly sensitive, precise and accurate assay. Here, we first report the efficient formation of tacrolimus lithium adduct ions, which greatly increased assay sensitivity. A lower limit of quantification (LLOQ) of 1 pg/mL (10 fg on column) was achieved and the assay was linear between 1 and 200 pg/mL. There was no carry-over detected. The inaccuracy ranged from -9.8 to 7.4% and the greatest imprecision was 7.5%. The matrix factor was found to be smaller than 1.1%. In summary, this method represents a suitable tool to investigate the potential clinical value of free tacrolimus monitoring in organ transplant recipients. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. The translational blocking of α5 and α6 integrin subunits affects migration and invasion, and increases sensitivity to carboplatin of SKOV-3 ovarian cancer cell line

    Energy Technology Data Exchange (ETDEWEB)

    Villegas-Pineda, Julio César, E-mail: jcvillegas@cinvestav.mx; Toledo-Leyva, Alfredo, E-mail: toledo_leyva@hotmail.com; Osorio-Trujillo, Juan Carlos, E-mail: clostrujillo2@yahoo.com.mx; Hernández-Ramírez, Verónica Ivonne, E-mail: arturomvi@hotmail.com; Talamás-Rohana, Patricia, E-mail: ptr@cinvestav.mx

    2017-02-15

    Epithelial ovarian cancer is the most lethal gynecologic malignancy. Integrins, overexpressed in cancer, are involved in various processes that favor the development of the disease. This study focused on determining the degree of involvement of α5, α6 and β3 integrin subunits in the establishment/development of epithelial ovarian cancer (EOC), such as proliferation, migration, invasion, and response to carboplatin. The translation of the α5, α6 and β3 integrins was blocked using morpholines, generating morphant cells for these proteins, which were corroborated by immunofluorescence assays. WST-1 proliferation assay showed that silencing of α5, α6, and β3 integrins does not affect the survival of morphants. Wound healing and transwell chamber assays showed that blocking α5 and α6 integrins decrease, in lesser and greater level respectively, the migratory and the invasive capacity of SKOV-3 cells. Finally, blocking α5 and α6 integrins partially sensitized the cells response to carboplatin, while blocking integrin β3 generated resistance to this drug. Statistical analyses were performed with the GraphPad Prism 5.0 software employing one way and two-way ANOVA tests; data are shown as average±SD. Results suggest that α5 and α6 integrins could become good candidates for chemotherapy targets in EOC.

  19. Design and synthesis of pH-sensitive polyamino-ester magneto-dendrimers: Surface functional groups effect on viability of human prostate carcinoma cell lines DU145.

    Science.gov (United States)

    Dayyani, Nahid; Khoee, Sepideh; Ramazani, Ali

    2015-06-15

    Novel pH-sensitive, biocompatible and biodegradable magneto-dendrimers with OH and/or NH2 functional groups based on poly amino-ester were synthesized for delivery of anti-cancer drugs. Magnetite nanoparticles (MNPs) were synthesized by the co-precipitation method and their surfaces were modified by 3-aminopropyl triethoxysilane. The first and second generations of the magneto-dendrimer with hydroxyl end groups were produced by sequential acrylation and Michael addition reactions using the required amounts of acryloyl chloride and diethanolamine, respectively. The dendrimer containing amino functional surface groups up to second generation was synthesized by the same method using the necessary amounts of acryloyl chloride and ethylenediamine. These dendrimers were fully characterized by the Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), dynamic light scattering (DLS) and zeta potential analysis, vibrating-sample magnetometer (VSM), scanning electron microscope (SEM), transmission electron microscopy (TEM) and selected area electron diffraction (SAED). In-vitro release profiles of the drug-loaded magnetic nanoparticles and their cytotoxicity assay were investigated at two pHs (7.4 and 5.8). The hydrolytic degradation behavior of magneto-dendrimers was evaluated in PBS buffer. Our research suggests that magneto-dendrimers having amine or hydroxyl functional groups could be considered as the suitable nanocarriers for therapy applications. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  20. Development of a rapid and sensitive LC-ESI/MS/MS assay for the quantification of propofol using a simple off-line dansyl chloride derivatization reaction to enhance signal intensity.

    Science.gov (United States)

    Beaudry, Francis; Guénette, Sarah Annie; Winterborn, Andrew; Marier, Jean-Francois; Vachon, Pascal

    2005-09-15

    A rapid, selective and sensitive method was developed for the determination of propofol concentration using an off-line dansyl chloride derivatization step to enhance signal intensity. The method consisted of a protein precipitation extraction followed by derivatization with dansyl chloride and analysis by liquid chromatography ionspray tandem mass spectrometry (LC-ESI/MS/MS). The separation was achieved using a 100 mm x 2 mm C8 analytical column combined with an isocratic mobile phase composed of 80:20 acetonitrile: 0.5% formic acid in water. Signal intensity of the propofol-dansyl chloride derivative was increased up to 200-fold as compared to the underivatized propofol in positive electrospray mode. An analytical range of 20-20,000 ng/mL was used in the calibration curve of plasma and blood samples. The novel method met all requirements of specificity, sensitivity, linearity, precision, accuracy and stability. A pharmacokinetic study was performed in rats and the novel analytical method was used as a routine analysis to provide enhanced measurements of plasma and blood concentrations of propofol. Blood and plasma pharmacokinetic results show that a very important fraction of propofol distributes into red blood cells. In conclusion, a rapid and sensitive LC-ESI/MS/MS method using a derivatization agent was developed to enhance signal intensity of propofol. Routine analysis with the novel method provided accurate results and enhanced the detection levels of plasma and blood concentrations of propofol to better characterize the in vivo biodisposition of propofol.

  1. Sensitive innovation

    DEFF Research Database (Denmark)

    Søndergaard, Katia Dupret

    Present paper discusses sources of innovation as heterogenic and at times intangible processes. Arguing for heterogeneity and intangibility as sources of innovation originates from a theoretical reading in STS and ANT studies (e.g. Callon 1986, Latour 1996, Mol 2002, Pols 2005) and from field work...... in the area of mental health (Dupret Søndergaard 2009, 2010). The concept of sensitive innovation is developed to capture and conceptualise exactly those heterogenic and intangible processes. Sensitive innovation is therefore primarily a way to understand innovative sources that can be......, but are not necessarily, recognized and acknowledged as such in the outer organisational culture or by management. The added value that qualifies these processes to be defined as “innovative” are thus argued for along different lines than in more traditional innovation studies (e.g. studies that build on the classic...

  2. A multicenter, non-randomized, phase II study of docetaxel and carboplatin administered every 3 weeks as second line chemotherapy in patients with first relapse of platinum sensitive epithelial ovarian, peritoneal or fallopian tube cancer

    DEFF Research Database (Denmark)

    Wang, Yun; Herrstedt, Jørn; Havsteen, Hanne

    2014-01-01

    of 398 cycles were given. Grade 3/4 neutropenia was seen in 80% (59 of 74) patients with an incidence of febrile neutropenia of 16%. Grade 2/3 sensory peripheral neuropathy occurred in 7% of patients, but no grade 4 sensory peripheral neuropathy was observed. Sixty patients were evaluable for response...... of platinum-sensitive ovarian, peritoneal and Fallopian tube cancer. The major toxicity was neutropenia, while the frequency of peripheral neuropathy was low.......BACKGROUND: In patients with ovarian cancer relapsing at least 6 months after end of primary treatment, the addition of paclitaxel to platinum treatment has been shown to improve survival but at the cost of significant neuropathy. In the first line setting, the carboplatin-docetaxel combination...

  3. A fast and sensitive method for the simultaneous analysis of a wide range of per- and polyfluoroalkyl substances in indoor dust using on-line solid phase extraction-ultrahigh performance liquid chromatography-time-of-flight-mass spectrometry.

    Science.gov (United States)

    Padilla-Sánchez, Juan Antonio; Haug, Line Småstuen

    2016-05-06

    A fast and sensitive method for simultaneous determination of 18 traditional and 6 alternative per- and polyfluoroalkyl substances (PFASs) using solid-liquid extraction (SLE), off-line clean-up using activated carbon and on-line solid phase extraction-ultrahigh performance liquid chromatography-time-of-flight-mass spectrometry (on-line SPE-UHPLC-TOF-MS) was developed. The extraction efficiency was studied and recoveries in range the 58-114% were obtained. Extraction and injection volumes were also optimized to 2mL and 400μL, respectively. The method was validated by spiking dust from a vacuum cleaner bag that had been found to contain low levels of the PFASs in focus. Low method detection limits (MDLs) and method quantification limits (MQLs) in the range 0.008-0.846ngg(-1) and 0.027-2.820ngg(-1) were obtained, respectively. For most of the PFASs, the accuracies were between 70 and 125% in the range from 2 to100ngg(-1) dust. Intra-day and inter-day precisions were in general well below 30%. Analysis of a Standard Reference Material (SRM 2585) showed high accordance with results obtained by other laboratories. Finally, the method was applied to seven indoor dust samples, and PFAS concentrations in the range 0.02-132ngg(-1) were found. The highest median concentrations were observed for some of the alternative PFASs, such as 6:2-diPAP (25ngg(-1)), 8:2-diPAP (49ngg(-1)), and PFOPA (23ngg(-1)), illustrating the importance of inclusion of new PFASs in the analytical methods. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Microwave assisted saponification (MAS) followed by on-line liquid chromatography (LC)-gas chromatography (GC) for high-throughput and high-sensitivity determination of mineral oil in different cereal-based foodstuffs.

    Science.gov (United States)

    Moret, Sabrina; Scolaro, Marianna; Barp, Laura; Purcaro, Giorgia; Conte, Lanfranco S

    2016-04-01

    A high throughput, high-sensitivity procedure, involving simultaneous microwave-assisted extraction (MAS) and unsaponifiable extraction, followed by on-line liquid chromatography (LC)-gas chromatography (GC), has been optimised for rapid and efficient extraction and analytical determination of mineral oil saturated hydrocarbons (MOSH) and mineral oil aromatic hydrocarbons (MOAH) in cereal-based products of different composition. MAS has the advantage of eliminating fat before LC-GC analysis, allowing an increase in the amount of sample extract injected, and hence in sensitivity. The proposed method gave practically quantitative recoveries and good repeatability. Among the different cereal-based products analysed (dry semolina and egg pasta, bread, biscuits, and cakes), egg pasta packed in direct contact with recycled paperboard had on average the highest total MOSH level (15.9 mg kg(-1)), followed by cakes (10.4 mg kg(-1)) and bread (7.5 mg kg(-1)). About 50% of the pasta and bread samples and 20% of the biscuits and cake samples had detectable MOAH amounts. The highest concentrations were found in an egg pasta in direct contact with recycled paperboard (3.6 mg kg(-1)) and in a milk bread (3.6 mg kg(-1)). Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Conjugated and Entrapped HPMA-PLA Nano-Polymeric Micelles Based Dual Delivery of First Line Anti TB Drugs: Improved and Safe Drug Delivery against Sensitive and Resistant Mycobacterium Tuberculosis.

    Science.gov (United States)

    Upadhyay, Seema; Khan, Iliyas; Gothwal, Avinash; Pachouri, Praveen K; Bhaskar, N; Gupta, Umesh D; Chauhan, Devendra S; Gupta, Umesh

    2017-09-01

    First line antiTB drugs have several physical and toxic manifestations which limit their applications. RIF is a hydrophobic drug and has low water solubility and INH is hepatotoxic. The main objective of the study was to synthesize, characterize HPMA-PLA co-polymeric micelles for the effective dual delivery of INH and RIF. HPMA-PLA co-polymer and HPMA-PLA-INH (HPI) conjugates were synthesized and characterized by FT-IR and 1 H-NMR spectroscopy. Later on RIF loaded HPMA-PLA-INH co-polymeric micelles (PMRI) were formulated and characterized for size, zeta potential and surface morphology (SEM, TEM) as well as critical micellar concentration. The safety was assessed through RBC's interaction study. The prepared PMRI were evaluated through MABA assay against sensitive and resistant strains of M. Tuberculosis. Size, zeta and entrapment efficiency for RIF loaded HPMA-PLA-INH polymeric micelles (PMRI) was 87.64 ± 1.98 nm, -19 ± 1.93 mV and 97.2 ± 1.56%, respectively. In vitro release followed controlled and sustained delivery pattern. Sustained release was also supported by release kinetics. Haemolytic toxicity of HPI and PMRI was 8.57 and 7.05% (p PLA polymeric micelles (PMRI) were more effective against sensitive and resistant M tuberculosis. The developed approach can lead to improved patient compliance and reduced dosing in future, offering improved treatment of tuberculosis.

  6. Expression profiling of a genetic animal model of depression reveals novel molecular pathways underlying depressive-like behaviours.

    Directory of Open Access Journals (Sweden)

    Ekaterini Blaveri

    2010-09-01

    Full Text Available The Flinders model is a validated genetic rat model of depression that exhibits a number of behavioural, neurochemical and pharmacological features consistent with those observed in human depression.In this study we have used genome-wide microarray expression profiling of the hippocampus and prefrontal/frontal cortex of Flinders Depression Sensitive (FSL and control Flinders Depression Resistant (FRL lines to understand molecular basis for the differences between the two lines. We profiled two independent cohorts of Flinders animals derived from the same colony six months apart, each cohort statistically powered to allow independent as well as combined analysis. Using this approach, we were able to validate using real-time-PCR a core set of gene expression differences that showed statistical significance in each of the temporally distinct cohorts, representing consistently maintained features of the model. Small but statistically significant increases were confirmed for cholinergic (chrm2, chrna7 and serotonergic receptors (Htr1a, Htr2a in FSL rats consistent with known neurochemical changes in the model. Much larger gene changes were validated in a number of novel genes as exemplified by TMEM176A, which showed 35-fold enrichment in the cortex and 30-fold enrichment in hippocampus of FRL animals relative to FSL.These data provide significant insights into the molecular differences underlying the Flinders model, and have potential relevance to broader depression research.

  7. High sensitivity cavity ring down spectroscopy of N_2O near 1.22 µm: (II) "1"4N_2"1"6O line intensity modeling and global fit of "1"4N_2"1"8O line positions

    International Nuclear Information System (INIS)

    Tashkun, S.A.; Perevalov, V.I.; Karlovets, E.V.; Kassi, S.; Campargue, A.

    2016-01-01

    In a recent work (Karlovets et al., 2016 [1]), we reported the measurement and rovibrational assignments of more than 3300 transitions belonging to 64 bands of five nitrous oxide isotopologues ("1"4N_2"1"6O, "1"4N"1"5N"1"6O, "1"5N"1"4N"1"6O, "1"4N_2"1"8O and "1"4N_2"1"7O) in the high sensitivity CRDS spectrum recorded in the 7915–8334 cm"−"1 spectral range. The assignments were performed by comparison with predictions of the effective Hamiltonian models developed for each isotopologue. In the present paper, the large amount of measurements from our previous work mentioned above and literature are gathered to refine the modeling of the nitrous oxide spectrum in two ways: (i) improvement of the intensity modeling for the principal isotopologue, "1"4N_2"1"6O, near 8000 cm"−"1 from a new fit of the relevant effective dipole moment parameters, (ii) global modeling of "1"4N_2"1"8O line positions from a new fit of the parameters of the global effective Hamiltonian using an exhaustive input dataset collected in the literature in the 12–8231 cm"−"1 region. The fitted set of 81 parameters allowed reproducing near 5800 measured line positions with an RMS deviation of 0.0016 cm"−"1. The dimensionless weighted standard deviation of the fit is 1.22. As an illustration of the improvement of the predictive capabilities of the obtained effective Hamiltonian, two new "1"4N_2"1"8O bands could be assigned in the CRDS spectrum in the 7915–8334 cm"−"1 spectral range. A line list at 296 K has been generated in the 0–10,700 cm"−"1 range for "1"4N_2"1"8O in natural abundance with a 10"−"3"0 cm/molecule intensity cutoff. - Highlights: • Line parameters of two new "1"4N_2"1"8O bands centered at 7966 cm"−"1 and at 8214 cm"−"1. • Refined sets of the "1"4N_2"1"6O effective dipole moment parameters for ΔP=13,14 series. • Global modeling of "1"4N_2"1"8O line positions and intensities in the 12–8231 cm"−"1 range. • 5800 observed of "1"4N_2"1"8O line positions

  8. Cellular determinants of the inverse cross sensitivity of mouse lymphoma L5178Y cell lines to ionizing radiation and hydrogen peroxide; Podloze odwrotnej krzyzowej opornosci komorek L5178Y na promieniowanie jonizujace i nadtlenek wodoru

    Energy Technology Data Exchange (ETDEWEB)

    Kruszewski, M [Dept. of Radiobiology and Health Protection, Inst. of Nuclear Chemistry and Technology, Warsaw (Poland)

    1999-07-01

    The pair of L5178Y sublines (LY-R and LY-S) is exceptional among mammalian cell lines because of their unique inverse cross-sensitivity to ionizing radiation and hydrogen peroxide. The high sensitivity of LY-S cells to ionizing radiation is reasonably explained by the impairment of DNA double strand breaks rejoining. Although the enzymatic defect of LY-S cells is not yet identified, the more pronounced effect of DNA-dependent protein kinase (DNA-PK) inhibitor (OK-1035) on DNA damage repair after 8 Gy x-irradiation in LY-R cells than in LY-S cells, suggests that LY-S cells may be defective in DNA-PK activity or in the other enzymatic activities downstream from DNA-PK. An additional feature is a higher protection of DNA against ionizing radiation by nuclear proteins in LY-R cells. These data support the concept that nuclear matrix organization may contribute to the cellular susceptibility to DNA damaging agents. Ionizing radiation-sensitive LY-S cells suffer also more DNA base damage than ionizing radiation-resistant LY-R cells. However, the repair rates of the {gamma}-ray-induced DNA base damage in LY sublines are related neither to the initial amounts of the damaged bases nor to the lethal or mutagenic effects of ionizing radiation. In contrast, hydrogen peroxide (H{sub 2}O{sub 2}) sensitive LY-R cells suffer more DNA base damage after H{sub 2}O{sub 2} treatment. This may be due to the lower activity of catalase and/or the lower level of glutathione and other monobromobimane-reactive thiols in LY-R cells than in LY-S cells. However, the main cause of LY-R cells' sensitivity to H{sub 2}O{sub 2} seems to be a higher iron ion content in these cells as compared to LY-S cells. A higher content of iron ions and a higher iron:copper ratio is found in isolated nuclei of LY-R cells than in those of LY-S cells. This is further confirmed by a higher ''labile iron'' pool in LY-R cells than in LY-S cells. Further evidence of different ions content in LY cells and its influence

  9. Radiosensitivity of mesothelioma cell lines

    International Nuclear Information System (INIS)

    Haekkinen, A.M.; Laasonen, A.; Linnainmaa, K.; Mattson, K.; Pyrhoenen, S.

    1996-01-01

    The present study was carried out in order to examine the radiosensitivity of malignant pleural mesothelioma cell lines. Cell kinetics, radiation-induced delay of the cell cycle and DNA ploidy of the cell lines were also determined. For comparison an HeLa and a human foetal fibroblast cell line were simultaneously explored. Six previously cytogenetically and histologically characterized mesothelioma tumor cell lines were applied. A rapid tiazolyl blue microtiter (MTT) assay was used to analyze radiosensitivity and cell kinetics and DNA ploidy of the cultured cells were determined by flow cytometry. The survival fraction after a dose of 2 Gy (SF2), parameters α and β of the linear quadratic model (LQ-model) and mean inactivation dose (D MID ) were also estimated. The DNA index of four cell lines equaled 1.0 and two cell lines equaled 1.5 and 1.6. Different mesothelioma cell lines showed a great variation in radiosensitivity. Mean survival fraction after a radiation dose of 2 Gy (SF2) was 0.60 and ranged from 0.36 to 0.81 and mean α value was 0.26 (range 0.48-0.083). The SF2 of the most sensitive diploid mesothelioma cell line was 0.36: Less than that of the foetal fibroblast cell line (0.49). The survival fractions (0.81 and 0.74) of the two most resistant cell lines, which also were aneuploid, were equal to that of the HeLa cell line (0.78). The α/β ratios of the most sensitive cell lines were almost an order of magnitude greater than those of the two most resistant cell lines. Radiation-induced delay of the most resistant aneuploid cell line was similar to that of HeLa cells but in the most sensitive (diploid cells) there was practically no entry into the G1 phase following the 2 Gy radiation dose during 36 h. (orig.)

  10. High Line

    DEFF Research Database (Denmark)

    Kiib, Hans

    2015-01-01

    At just over 10 meters above street level, the High Line extends three kilometers through three districts of Southwestern Manhattan in New York. It consists of simple steel construction, and previously served as an elevated rail line connection between Penn Station on 34th Street and the many....... The High Line project has been carried out as part of an open conversion strategy. The result is a remarkable urban architectural project, which works as a catalyst for the urban development of Western Manhattan. The greater project includes the restoration and reuse of many old industrial buildings...

  11. World lines.

    OpenAIRE

    Waser Jürgen; Fuchs Raphael; Ribicic Hrvoje; Schindler Benjamin; Blöschl Günther; Gröller Eduard

    2010-01-01

    In this paper we present World Lines as a novel interactive visualization that provides complete control over multiple heterogeneous simulation runs. In many application areas decisions can only be made by exploring alternative scenarios. The goal of the suggested approach is to support users in this decision making process. In this setting the data domain is extended to a set of alternative worlds where only one outcome will actually happen. World Lines integrate simulation visualization and...

  12. Silver linings.

    Science.gov (United States)

    Bultas, Margaret W; Pohlman, Shawn

    2014-01-01

    The purpose of this interpretive phenomenological study was to gain a better understanding of the experiences of 11 mothers of preschool children with autism spectrum disorder (ASD). Mothers were interviewed three times over a 6 week period. Interviews were analyzed using interpretive methods. This manuscript highlights one particular theme-a positive perspective mothers described as the "silver lining." This "silver lining" represents optimism despite the adversities associated with parenting a child with ASD. A deeper understanding of this side of mothering children with ASD may help health care providers improve rapport, communication, and result in more authentic family centered care. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Rapid line scan MR angiography

    International Nuclear Information System (INIS)

    Frahm, J.; Merboldt, K.D.; Hanicke, W.; Bruhn, H.

    1987-01-01

    Direct MR angiography may be performed using line scan imaging techniques combined with presaturation of stationary spins. Thus, a single line scan echo yields a projection of vessels due to the signal from reflowing unsaturated spins. Reconstruction of an angiographic image is performed line by line at slightly incremented positions. In particular, line scan angiography is direct and fast without a sensitivity to artifacts even for high flow rates. Image resolution and field of view may be chosen without restrictions, and zoom images using enhanced gradients may be recorded without aliasing artifacts. The method is robust with respect to eddy currents and pulsatile flow. Line scan MR angiograms of phantoms, animals, and human volunteers have been recorded using 90 0 radio frequency pulses and gradient-recalled echoes

  14. Sensitivity analysis

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003741.htm Sensitivity analysis To use the sharing features on this page, please enable JavaScript. Sensitivity analysis determines the effectiveness of antibiotics against microorganisms (germs) ...

  15. Digital Model of Railway Electric Traction Lines

    Science.gov (United States)

    Garg, Rachana; Mahajan, Priya; Kumar, Parmod

    2017-08-01

    The characteristic impedance and propagation constant define the behavior of signal propagation over the transmission lines. The digital model for railway traction lines which includes railway tracks is developed, using curve fitting technique in MATLAB. The sensitivity of this model has been computed with respect to frequency. The digital sensitivity values are compared with the values of analog sensitivity. The developed model is useful for digital protection, integrated operation, control and planning of the system.

  16. production lines

    Directory of Open Access Journals (Sweden)

    Jingshan Li

    2000-01-01

    Full Text Available In this work, serial production lines with finished goods buffers operating in the pull regime are considered. The machines are assumed to obey Bernoulli reliability model. The problem of satisfying customers demand is addressed. The level of demand satisfaction is quantified by the due-time performance (DTP, which is defined as the probability to ship to the customer a required number of parts during a fixed time interval. Within this scenario, the definitions of DTP bottlenecks are introduced and a method for their identification is developed.

  17. Line facilities outline

    International Nuclear Information System (INIS)

    1998-08-01

    This book deals with line facilities. The contents of this book are outline line of wire telecommunication ; development of line, classification of section of line and theory of transmission of line, cable line ; structure of line, line of cable in town, line out of town, domestic cable and other lines, Optical communication ; line of optical cable, transmission method, measurement of optical communication and cable of the sea bottom, Equipment of telecommunication line ; telecommunication line facilities and telecommunication of public works, construction of cable line and maintenance and Regulation of line equipment ; regulation on technique, construction and maintenance.

  18. Radiosensitivity of mesothelioma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Haekkinen, A.M. [Dept. of Oncology, Univ. Central Hospital, Helsinki (Finland); Laasonen, A. [Dept. of Pathology, Central Hospital of Etelae-Pohjanmaa, Seinaejoki (Finland); Linnainmaa, K. [Dept. of Industrial Hygiene and Toxicology, Inst. of Occupational Health, Helsinki (Finland); Mattson, K. [Dept. Pulmonary Medicine, Univ. Central Hospital, Helsinki (Finland); Pyrhoenen, S. [Dept. of Oncology, Univ. Central Hospital, Helsinki (Finland)

    1996-10-01

    The present study was carried out in order to examine the radiosensitivity of malignant pleural mesothelioma cell lines. Cell kinetics, radiation-induced delay of the cell cycle and DNA ploidy of the cell lines were also determined. For comparison an HeLa and a human foetal fibroblast cell line were simultaneously explored. Six previously cytogenetically and histologically characterized mesothelioma tumor cell lines were applied. A rapid tiazolyl blue microtiter (MTT) assay was used to analyze radiosensitivity and cell kinetics and DNA ploidy of the cultured cells were determined by flow cytometry. The survival fraction after a dose of 2 Gy (SF2), parameters {alpha} and {beta} of the linear quadratic model (LQ-model) and mean inactivation dose (D{sub MID}) were also estimated. The DNA index of four cell lines equaled 1.0 and two cell lines equaled 1.5 and 1.6. Different mesothelioma cell lines showed a great variation in radiosensitivity. Mean survival fraction after a radiation dose of 2 Gy (SF2) was 0.60 and ranged from 0.36 to 0.81 and mean {alpha} value was 0.26 (range 0.48-0.083). The SF2 of the most sensitive diploid mesothelioma cell line was 0.36: Less than that of the foetal fibroblast cell line (0.49). The survival fractions (0.81 and 0.74) of the two most resistant cell lines, which also were aneuploid, were equal to that of the HeLa cell line (0.78). The {alpha}/{beta} ratios of the most sensitive cell lines were almost an order of magnitude greater than those of the two most resistant cell lines. Radiation-induced delay of the most resistant aneuploid cell line was similar to that of HeLa cells but in the most sensitive (diploid cells) there was practically no entry into the G1 phase following the 2 Gy radiation dose during 36 h. (orig.).

  19. Ultrastructural morphology and localisation of cisplatin-induced platinum-DNA adducts in a cisplatin-sensitive and -resistant human small cell lung cancer cell line using electron microscopy

    NARCIS (Netherlands)

    Meijer, C; van Luyn, MJA; Nienhuis, EF; Blom, N; Mulder, NH; de Vries, EGE

    2001-01-01

    Ultrastructural morphology (transmission electron microscopy) and localisation of cisplatin-induced platinum (Pt)-DNA adducts (immunoelectron microscopy) were analysed in the human small cell lung cancer cell line GLC(4) and its 40-fold in vitro acquired cisplatin-resistant subline GLC(4)-CDDP,

  20. Parallel Lines

    Directory of Open Access Journals (Sweden)

    James G. Worner

    2017-05-01

    Full Text Available James Worner is an Australian-based writer and scholar currently pursuing a PhD at the University of Technology Sydney. His research seeks to expose masculinities lost in the shadow of Australia’s Anzac hegemony while exploring new opportunities for contemporary historiography. He is the recipient of the Doctoral Scholarship in Historical Consciousness at the university’s Australian Centre of Public History and will be hosted by the University of Bologna during 2017 on a doctoral research writing scholarship.   ‘Parallel Lines’ is one of a collection of stories, The Shapes of Us, exploring liminal spaces of modern life: class, gender, sexuality, race, religion and education. It looks at lives, like lines, that do not meet but which travel in proximity, simultaneously attracted and repelled. James’ short stories have been published in various journals and anthologies.

  1. Allergic sensitization

    DEFF Research Database (Denmark)

    van Ree, Ronald; Hummelshøj, Lone; Plantinga, Maud

    2014-01-01

    Allergic sensitization is the outcome of a complex interplay between the allergen and the host in a given environmental context. The first barrier encountered by an allergen on its way to sensitization is the mucosal epithelial layer. Allergic inflammatory diseases are accompanied by increased pe...

  2. Context Sensitive Modeling of Cancer Drug Sensitivity.

    Directory of Open Access Journals (Sweden)

    Bo-Juen Chen

    Full Text Available Recent screening of drug sensitivity in large panels of cancer cell lines provides a valuable resource towards developing algorithms that predict drug response. Since more samples provide increased statistical power, most approaches to prediction of drug sensitivity pool multiple cancer types together without distinction. However, pan-cancer results can be misleading due to the confounding effects of tissues or cancer subtypes. On the other hand, independent analysis for each cancer-type is hampered by small sample size. To balance this trade-off, we present CHER (Contextual Heterogeneity Enabled Regression, an algorithm that builds predictive models for drug sensitivity by selecting predictive genomic features and deciding which ones should-and should not-be shared across different cancers, tissues and drugs. CHER provides significantly more accurate models of drug sensitivity than comparable elastic-net-based models. Moreover, CHER provides better insight into the underlying biological processes by finding a sparse set of shared and type-specific genomic features.

  3. High basal Wnt signaling is further induced by PI3K/mTor inhibition but sensitive to cSRC inhibition in mammary carcinoma cell lines with HER2/3 overexpression

    International Nuclear Information System (INIS)

    Timmermans-Sprang, Elpetra P. M.; Gracanin, Ana; Mol, Jan A.

    2015-01-01

    Elevated basal, ligand-independent, Wnt signaling in some canine breast cancer cells is not caused by classical mutations in APC, β-Catenin or GSK3β but, at least partially, by enhanced LEF1 expression. We examined the expression and function of EGFR/HER-regulated pathways on the ligand-independent Wnt signaling. Twelve canine mammary tumor cell lines with previously reported differential basal Wnt activity were used. The expression levels of genes related to EGF-signaling were analyzed by cluster analysis. Cell lines with a combined overexpression of EGF-related genes and enhanced basal Wnt activity were treated with PI3K/mTor or cSRC inhibitors or transfected with a construct expressing wild-type PTEN. Subsequently, effects were measured on Wnt activity, cell proliferation, gene expression and protein level. High basal Wnt/LEF1 activity was associated with overexpression of HER2/3, ID1, ID2, RAC1 and HSP90 together with low to absent cMET and PTEN mRNA expression, suggesting a connection between Wnt- and HER-signaling pathways. Inhibition of the HER-regulated PI3K/mTor pathway using the dual PI3K/mTor inhibitor BEZ235 or the mTor inhibitor Everolimus® resulted in reduced cell proliferation. In the cell line with high basal Wnt activity, however, an unexpected further increased Wnt activity was found that could be greatly reduced after inhibition of the HER-regulated cSRC activity. Inhibition of the PI3K/mTor pathway was associated with enhanced expression of β-Catenin, Axin2, MUC1, cMET, EGFR and HER2 and a somewhat increased β-Catenin protein content, whereas cSRC inhibition was associated with slightly enhanced HER3 and SLUG mRNA expression. A high protein expression of HER3 was found only in a cell line with high basal Wnt activity. High basal Wnt activity in some mammary cancer cell lines is associated with overexpression of HER-receptor related genes and HER3 protein, and the absence of PTEN. Inhibition of the PI3K/mTor pathway further stimulated

  4. VT Digital Line Graph Miscellaneous Transmission Lines

    Data.gov (United States)

    Vermont Center for Geographic Information — (Link to Metadata) This datalayer is comprised of Miscellaineous Transmission Lines. Digital line graph (DLG) data are digital representations of cartographic...

  5. Climate Sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Lindzen, Richard [M.I.T.

    2011-11-09

    Warming observed thus far is entirely consistent with low climate sensitivity. However, the result is ambiguous because the sources of climate change are numerous and poorly specified. Model predictions of substantial warming aredependent on positive feedbacks associated with upper level water vapor and clouds, but models are notably inadequate in dealing with clouds and the impacts of clouds and water vapor are intimately intertwined. Various approaches to measuring sensitivity based on the physics of the feedbacks will be described. The results thus far point to negative feedbacks. Problems with these approaches as well as problems with the concept of climate sensitivity will be described.

  6. In chronic myeloid leukemia patients on second-line tyrosine kinase inhibitor therapy, deep sequencing of BCR-ABL1 at the time of warning may allow sensitive detection of emerging drug-resistant mutants.

    Science.gov (United States)

    Soverini, Simona; De Benedittis, Caterina; Castagnetti, Fausto; Gugliotta, Gabriele; Mancini, Manuela; Bavaro, Luana; Machova Polakova, Katerina; Linhartova, Jana; Iurlo, Alessandra; Russo, Domenico; Pane, Fabrizio; Saglio, Giuseppe; Rosti, Gianantonio; Cavo, Michele; Baccarani, Michele; Martinelli, Giovanni

    2016-08-02

    Imatinib-resistant chronic myeloid leukemia (CML) patients receiving second-line tyrosine kinase inhibitor (TKI) therapy with dasatinib or nilotinib have a higher risk of disease relapse and progression and not infrequently BCR-ABL1 kinase domain (KD) mutations are implicated in therapeutic failure. In this setting, earlier detection of emerging BCR-ABL1 KD mutations would offer greater chances of efficacy for subsequent salvage therapy and limit the biological consequences of full BCR-ABL1 kinase reactivation. Taking advantage of an already set up and validated next-generation deep amplicon sequencing (DS) assay, we aimed to assess whether DS may allow a larger window of detection of emerging BCR-ABL1 KD mutants predicting for an impending relapse. a total of 125 longitudinal samples from 51 CML patients who had acquired dasatinib- or nilotinib-resistant mutations during second-line therapy were analyzed by DS from the time of failure and mutation detection by conventional sequencing backwards. BCR-ABL1/ABL1%(IS) transcript levels were used to define whether the patient had 'optimal response', 'warning' or 'failure' at the time of first mutation detection by DS. DS was able to backtrack dasatinib- or nilotinib-resistant mutations to the previous sample(s) in 23/51 (45 %) pts. Median mutation burden at the time of first detection by DS was 5.5 % (range, 1.5-17.5 %); median interval between detection by DS and detection by conventional sequencing was 3 months (range, 1-9 months). In 5 cases, the mutations were detectable at baseline. In the remaining cases, response level at the time mutations were first detected by DS could be defined as 'Warning' (according to the 2013 ELN definitions of response to 2nd-line therapy) in 13 cases, as 'Optimal response' in one case, as 'Failure' in 4 cases. No dasatinib- or nilotinib-resistant mutations were detected by DS in 15 randomly selected patients with 'warning' at various timepoints, that later turned into optimal

  7. Radioecological sensitivity

    International Nuclear Information System (INIS)

    Howard, Brenda J.; Strand, Per; Assimakopoulos, Panayotis

    2003-01-01

    After the release of radionuclide into the environment it is important to be able to readily identify major routes of radiation exposure, the most highly exposed individuals or populations and the geographical areas of most concern. Radioecological sensitivity can be broadly defined as the extent to which an ecosystem contributes to an enhanced radiation exposure to Man and biota. Radioecological sensitivity analysis integrates current knowledge on pathways, spatially attributes the underlying processes determining transfer and thereby identifies the most radioecologically sensitive areas leading to high radiation exposure. This identifies where high exposure may occur and why. A framework for the estimation of radioecological sensitivity with respect to humans is proposed and the various indicators by which it can be considered have been identified. These are (1) aggregated transfer coefficients (Tag), (2) action (and critical) loads, (3) fluxes and (4) individual exposure of humans. The importance of spatial and temporal consideration of all these outputs is emphasized. Information on the extent of radionuclide transfer and exposure to humans at different spatial scales is needed to reflect the spatial differences which can occur. Single values for large areas, such as countries, can often mask large variation within the country. Similarly, the relative importance of different pathways can change with time and therefore assessments of radiological sensitivity are needed over different time periods after contamination. Radioecological sensitivity analysis can be used in radiation protection, nuclear safety and emergency preparedness when there is a need to identify areas that have the potential of being of particular concern from a risk perspective. Prior identification of radioecologically sensitive areas and exposed individuals improve the focus of emergency preparedness and planning, and contribute to environmental impact assessment for future facilities. The

  8. The U-line line balancing problem

    NARCIS (Netherlands)

    Miltenburg, G.J.; Wijngaard, J.

    1994-01-01

    The traditional line balancing (LB) problem considers a production line in which stations are arranged consecutively in a line. A balance is determined by grouping tasks into stations while moving forward (or backward) through a precedence network. Recently many production lines are being arranged

  9. Western Alaska ESI: FISHL (Fish Lines)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains sensitive biological resource data for anadromous fish species in Western Alaska. Vector lines in this data set represent species occurrences...

  10. Columbia River ESI: FISHL (Fish Lines)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains sensitive biological resource data for anadromous fish species in Columbia River. Vector lines in this data set represent locations of...

  11. Virginia ESI: HYDRO (Hydrography Lines and Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains vector lines and polygons representing coastal hydrography used in the creation of the Environmental Sensitivity Index (ESI) for Virginia. The...

  12. Program of telluric lines monitoring

    Directory of Open Access Journals (Sweden)

    Vince I.

    2006-01-01

    Full Text Available A new observational program of telluric lines monitoring was introduced at Belgrade Astronomical Observatory. The ultimate goal of this program is to investigate the properties of Earth’s atmosphere through modeling the observed profiles of telluric lines. The program is intend to observe infrared molecular oxygen lines that were selected according to spectral sensitivity of the available CCD camera. In this paper we give the initial and the final selection criteria for spectral lines included in the program the description of equipment and procedures used for observations and reduction, a review of preliminary observational results with the estimated precision, and a short discussion on the comparison of the theoretical predictions and the measurements.

  13. Multiple Lines of Evidence

    Energy Technology Data Exchange (ETDEWEB)

    Amidan, Brett G. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Venzin, Alexander M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Bramer, Lisa M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2015-06-03

    This paper discusses the process of identifying factors that influence the contamination level of a given decision area and then determining the likelihood that the area remains unacceptable. This process is referred to as lines of evidence. These lines of evidence then serve as inputs for the stratified compliance sampling (SCS) method, which requires a decision area to be divided into strata based upon contamination expectations. This is done in order to focus sampling efforts more within stratum where contamination is more likely and to use the domain knowledge about these likelihoods of the stratum remaining unacceptable to buy down the number of samples necessary, if possible. Two different building scenarios were considered as an example (see Table 3.1). SME expertise was elicited concerning four lines of evidence factors (see Table 3.2): 1) amount of contamination that was seen before decontamination, 2) post-decontamination air sampling information, 3) the applied decontaminant information, and 4) the surface material. Statistical experimental design and logistic regression modelling were used to help determine the likelihood that example stratum remained unacceptable for a given example scenario. The number of samples necessary for clearance was calculated by applying the SCS method to the example scenario, using the estimated likelihood of each stratum remaining unacceptable as was determined using the lines of evidence approach. The commonly used simple random sampling (SRS) method was also used to calculate the number of samples necessary for clearance for comparison purposes. The lines of evidence with SCS approach resulted in a 19% to 43% reduction in total number of samples necessary for clearance (see Table 3.6). The reduction depended upon the building scenario, as well as the level of percent clean criteria. A sensitivity analysis was also performed showing how changing the estimated likelihoods of stratum remaining unacceptable affect the number

  14. The innominate line

    International Nuclear Information System (INIS)

    Whelan, M.A.; Myung, K.H.; Bergeron, R.T.

    1984-01-01

    The innominate line continues to be of value in evaluating the integrity of the sphenoid bone since plain skull radiographs remain a primary screening tool for metastatic disease, seizure disorder and headache. The detection of lesions involving the sphenoid bone can be difficult. The accuracy of the radionulcide scan is reduced because of confusion caused by uptake in the adjacent nasal and sinus mucosa. On computed tomography, the sections through the base of the skull and orbit can contain many artifictual densities caused by a combination of bone, soft tissue and sinus air interfaces. In addition, routine settings of window width and level on CT scan are designed to best demonstrate the soft tissues, and bony lesions can easily be missed. Thus, disruption of the ''integrity'' of this line on plain films, particularly the Caldwell projection, can be a sensitive first indicator of disease involving the sphenoid bone. Such a determination on plain film leads to more accurate CT scanning, in that attention will be given to the skull base and scans will be imaged with both soft tissue and bone windows. (orig./MG)

  15. Development of a Handheld Line Information Reader and Generator for Efficient Management of Optical Communication Lines.

    Science.gov (United States)

    Lee, Jaeyul; Kwon, Hyungwoo; Song, Jaewon; Jeon, Mansik; Kim, Jeehyun

    2017-08-24

    A handheld line information reader and a line information generator were developed for the efficient management of optical communication lines. The line information reader consists of a photo diode, trans-impedance amplifier, voltage amplifier, microcontroller unit, display panel, and communication modules. The line information generator consists of a laser diode, laser driving circuits, microcontroller unit, and communication modules. The line information reader can detect the optical radiation field of the test line by bending the optical fiber. To enhance the sensitivity of the line information reader, an additional lens was used with a focal length of 4.51 mm. Moreover, the simulation results obtained through BeamPROP ® software from Synopsys, Inc. demonstrated a stronger optical radiation field of the fiber due to a longer transmission wavelength and larger bending angle of the fiber. Therefore, the developed devices can be considered as useful tools for the efficient management of optical communication lines.

  16. Sensitive Media

    Directory of Open Access Journals (Sweden)

    Malinowska Anna

    2017-12-01

    Full Text Available The paper engages with what we refer to as “sensitive media,” a concept associated with developments in the overall media environment, our relationships with media devices, and the quality of the media themselves. Those developments point to the increasing emotionality of the media world and its infrastructures. Mapping the trajectories of technological development and impact that the newer media exert on human condition, our analysis touches upon various forms of emergent affect, emotion, and feeling in order to trace the histories and motivations of the sensitization of “the media things” as well as the redefinition of our affective and emotional experiences through technologies that themselves “feel.”

  17. Sex-dependent behavior, neuropeptide profile and antidepressant response in rat model of depression

    DEFF Research Database (Denmark)

    Sanchez, Connie; El Khoury, Aram; Hassan, Moustapha

    2018-01-01

    A plethora of animal models of depression is described in the literature, aiming at mimicking different aspects of depression. Understanding the link between depression and stress has been and remains a major focus area for development of animal models, but lines of research with a more mechanistic...... focus targeting deficiencies in neurotransmitter systems or dysfunctional neuronal circuitries and neuroinflammation are also pursued vigorously. The main objectives of the present study were systematically to evaluate strain and sex characteristics of a genetic animal model, the Flinders Sensitive Line...... (FSL)/ Flinders Resistant Line (FRL), by applying behavioral, molecular and pharmacological measures relevant to depression, and compare it with the outbred Sprague Dawley rat. In addition, we aimed at comparing across strains and sex the expression of NPY, CRF, CGRP in brain regions critically...

  18. Spent Pot Lining Characterization Framework

    Science.gov (United States)

    Ospina, Gustavo; Hassan, Mohamed I.

    2017-09-01

    Spent pot lining (SPL) management represents a major concern for aluminum smelters. There are two key elements for spent pot lining management: recycling and safe storage. Spent pot lining waste can potentially have beneficial uses in co-firing in cement plants. Also, safe storage of SPL is of utmost importance. Gas generation of SPL reaction with water and ignition sensitivity must be studied. However, determining the feasibility of SPL co-firing and developing the required procedures for safe storage rely on determining experimentally all the necessary SPL properties along with the appropriate test methods, recognized by emissions standards and fire safety design codes. The applicable regulations and relevant SPL properties for this purpose are presented along with the corresponding test methods.

  19. Sensitive Ceramics

    DEFF Research Database (Denmark)

    2014-01-01

    Sensitive Ceramics is showing an interactive digital design tool for designing wall like composition with 3d ceramics. The experiment is working on two levels. One which has to do with designing compositions and patterns in a virtual 3d universe based on a digital dynamic system that responds on ...... with realizing the modules in ceramics by 3d printing directly in porcelain with a RapMan printer that coils up the 3d shape in layers. Finally the ceramic modules are mounted in a laser cut board that reflects the captured composition of the movement of the hands....

  20. Stability of the LHC transfer lines

    CERN Document Server

    Kain, V; Bartmann, W; Bracco, C; Goddard, B; Meddahi, M; Uythoven, J; Wenninger, J

    2011-01-01

    The LHC is filled from the SPS through two 3 km transfer lines. The injected beam parameters need to be well under control for luminosity performance, machine protection and operational efficiency. Small fractions of beam loss on the transfer line collimation system create showers which can trigger the sensitive LHC beam loss monitor system nearby and cause a beam abort during filling. The stability of the transfer line trajectory through the collimators is particularly critical in this respect. This paper will report on the transfer line trajectory stability during the proton run in 2011, correlations with injection losses, correction frequency and the most likely sources for the observed oscillations.

  1. Cable line engineering

    International Nuclear Information System (INIS)

    Jang, Hak Sin; Kim, Sin Yeong

    1998-02-01

    This book is about cable line engineering. It is comprised of nine chapters, which deals with summary of cable communication such as way, process of cable communication and optical communication, Line constant of transmission on primary constant, reflection and crosstalk, communication cable line of types like flat cable, coaxial cable and loaded cable, Install of communication line with types and facility of aerial line, construction method of communication line facility, Measurement of communication line, Carrier communication of summary, PCM communication with Introduction, regeneration relay system sampling and quantization and Electric communication service and general information network with mobile communication technique and satellite communication system.

  2. Ketamine is a potent antidepressant in two rodent models of depression

    DEFF Research Database (Denmark)

    Mathe, A.; Sousa, V.; Fischer, C. W.

    2013-01-01

    pathophysiological factor and converging evidence indicates that other systems, such as the glutamatergic are of paramount importance. Indeed, work at the Yale University, NIMH, and Icahn School of Medicine at Mount Sinai demonstrated the marked antidepressant effects of intravenously infused ketamine to treatment...... resistant patients diagnosed with major depressive disorder. In order to better understand the mechanisms of ketamine effects we decided to test it on animal models. Methods: All experiments were approved by the Karolinska Institutet's Committee for Animal Protection. Two rat models, bred at the Karolinska...... Institutet, the Flinders Sensitive Line (FSL) and their controls, the Flinders Resistant Line (FRL), and the SERT KO (homozygous, heterozygous, and the wild type rats) were used. Male animals were injected 10 mg ketamine/kg body weight or vehicle and the Open Field Test (OF) and Forced Swim Test (FST...

  3. Increased numbers of orexin/hypocretin neurons in a genetic rat depression model

    DEFF Research Database (Denmark)

    Mikrouli, Elli; Wörtwein, Gitta; Soylu, Rana

    2011-01-01

    The Flinders Sensitive Line (FSL) rat is a genetic animal model of depression that displays characteristics similar to those of depressed patients including lower body weight, decreased appetite and reduced REM sleep latency. Hypothalamic neuropeptides such as orexin/hypocretin, melanin......-concentrating hormone (MCH) and cocaine and amphetamine regulated transcript (CART), that are involved in the regulation of both energy metabolism and sleep, have recently been implicated also in depression. We therefore hypothesized that alterations in these neuropeptide systems may play a role in the development...... of the FSL phenotype with both depressive like behavior, metabolic abnormalities and sleep disturbances. In this study, we first confirmed that the FSL rats displayed increased immobility in the Porsolt forced swim test compared to their control strain, the Flinders Resistant Line (FRL), which is indicative...

  4. Gene-environment interaction affects substance P and neurokinin A in the entorhinal cortex and periaqueductal grey in a genetic animal model of depression: implications for the pathophysiology of depression

    DEFF Research Database (Denmark)

    Husum, Henriette; Wörtwein, Gitta; Andersson, Weronika

    2008-01-01

    Evidence implies a role for corticotropin-releasing hormone (CRH) and tachykinins, e.g. substance P (SP) and neurokinin A (NKA) in the pathophysiology of depression. We have previously shown that SP- and NKA-like immunoreactivity (-LI) concentrations were altered in the frontal cortex and striatum...... of the congenitally 'depressed' Flinders Sensitive Line (FSL) compared to the Flinders Resistant Line (FRL) control rats. It is also known that environmental stress may affect brain levels of tachykinins. In view of these results we decided to superimpose maternal deprivation, an early life environmental stressor......, onto the genetically predisposed 'depressed' FSL rats and the FRL control rats and use this paradigm as a model of gene-environment interaction. The adult animals were sacrificed, adrenal glands and brains dissected out and SP-, NKA- and CRH-LI levels were determined in ten discrete brain regions...

  5. Detecção da citotoxicidade de materiais biocompatíveis nas linhagens celulares MRC-5, HeLa e RC-IAL MRC-5, HeLa and RC-IAL cell lines sensitivity for detection of cytotoxicity of biocompatible materials

    Directory of Open Access Journals (Sweden)

    Aurea S. Cruz

    1992-04-01

    Full Text Available A sensibilidade de uma linhagem celular diplóide e duas heteroplóides, para a detecção de citotoxicidade através do método de difusão em camada de ágar sobre culturas celulares, foi avaliada experimentalmente com solução de ácido ascórbico em diferentes concentrações e, na prática, frente a 562 amostras de 21 diferentes materiais industriais enviados para análise na Seção de Culturas Celulares do Instituto Adolfo Lutz. A linhagem celular heteroplóide designada RC-IAL apresentou, em relação às linhagens MRC-5 e HeLa, maior sensibilidade porque revelou a presença de efeito citotóxico nas menores concentrações utilizadas (10 e 25 ug/ml do ácido ascórbico e apresentou maior diâmetro do halo citotóxico em 15 amostras e igual diâmetro em 16 das 43 amostras (7,6% que resultaram positivas. Nas 43 amostras positivas, a linhagem MRC-5 não revelou citotoxicidade em 3 amostras de espuma e 1 de resina acrílica. O polivinilcloreto (PVC e o polietileno, raramente revelaram positividade, enquanto plástico, algodão e resinas acrílicas revelaram citotoxicidade ao redor de 5%. Em vista dos resultados é discutida a proposta da utilização da linhagem RC-IAL e HeLa para a continuidade das futuras análises solicitadas ao Instituto Adolfo LutzThe sensitivity of diploid and heteroploid cell lines for detection of cytotoxicity using the agar diffusion method on cell culture, was tested with ascorbic acid solution of different concentrations. A total of 562 samples of 21 various materials were tested. The heteroploid cell line, RC-IAL, showed in relation to the MRC-5 and HeLa cell lines, greater sensitivity because it showed the presence of cytotoxic effect with the lowest concentration used (10 and 25ug/ml of ascorbic acid and showed greater diameter of cytotoxic halo in 15 samples and equal diameter in 16 of the 43 positive samples (7.6%. Out of 43 positive samples, the MRC-5 line did not show cytotoxicity in 3 sponge samples and

  6. Temperature diagnostic line ratios of Fe XVII

    International Nuclear Information System (INIS)

    Raymond, J.C.; Smith, B.W.; Los Alamos National Lab., NM)

    1986-01-01

    Based on extensive calculations of the excitation rates of Fe XVII, four temperature-sensitive line ratios are investigated, paying special attention to the contribution of resonances to the excitation rates and to the contributions of dielectronic recombination satellites to the observed line intensities. The predictions are compared to FPCS observations of Puppis A and to Solar Maximum Mission (SMM) and SOLEX observations of the sun. Temperature-sensitive line ratios are also computed for emitting gas covering a broad temperature range. It is found that each ratio yields a differently weighted average for the temperature and that this accounts for some apparent discrepancies between the theoretical ratios and solar observations. The effects of this weighting on the Fe XVII temperature diagnostics and on the analogous Fe XXIV/Fe XXV satellite line temperature diagnostics are discussed. 27 references

  7. Radiation sensitivity of human malignant lymphocytes

    International Nuclear Information System (INIS)

    Seshadri, R.; Matthews, C.; Morley, A.A.

    1985-01-01

    A simple and rapid in vitro technique to assess the sensitivity of human malignant lymphocytes to roentgen irradiation is described. A variety of established malignant lymphocyte cell lines were cloned in microwells and clone survival was used as the end-point. The survival of the clonogenic malignant lymphocyte down to a fraction of approximately 0.001 could be measured accurately. Except for a T-cell line, the radiation sensitivities of the cell lines were similar to that of normal T-lymphocytes. (orig.)

  8. Bridging Culture On-Line: Strategies for Teaching Cultural Sensitivity.

    Science.gov (United States)

    Wendler, M. Cecilia; Struthers, Roxanne

    2002-01-01

    An online cross-cultural health course for nurses sought to provide access to cultural experiences by culturally congruent use of a minority visiting scholar and required participation in cultural enrichment activities. Course and faculty evaluations were designed to be appropriate for the asynchronous environment. (Contains 25 references.) (SK)

  9. VT Electric Transmission Line Corridors - corridor lines

    Data.gov (United States)

    Vermont Center for Geographic Information — (Link to Metadata) The ELTRN layer depicts electric transmission line corridors in Vermont. Various methods have been used to digitize features. The data layer...

  10. Homotopic Polygonal Line Simplification

    DEFF Research Database (Denmark)

    Deleuran, Lasse Kosetski

    This thesis presents three contributions to the area of polygonal line simplification, or simply line simplification. A polygonal path, or simply a path is a list of points with line segments between the points. A path can be simplified by morphing it in order to minimize some objective function...

  11. Asymmetries of the solar Ca II lines

    International Nuclear Information System (INIS)

    Heasley, J.N.

    1975-01-01

    A theoretical study of the influence of propagating acoustic pulses in the solar chromosphere upon the line profiles of the Ca II resonance and infrared triplet lines has been made. The major objective has been to explain the observed asymmetries seen in the cores of the H and K lines and to predict the temporal behavior of the infrared lines caused by passing acoustic or shock pulses. The velocities in the pulses, calculated from weak shock theory, have been included consistently in the non-LTE calculations. The results of the calculations show that these lines are very sensitive to perturbations in the background atmosphere caused by the pulses. Only minor changes in the line shapes result from including the velocities consistently in the line source function calculations. The qualitative changes in the line profiles vary markedly with the strength of the shock pulses. The observed differences in the K line profiles seen on the quiet Sun can be explained in terms of a spectrum of pulses with different wavelengths and initial amplitudes in the photosphere. (Auth.)

  12. In vitro screening for aryl hydrocarbon receptor agonistic activity in 200 pesticides using a highly sensitive reporter cell line, DR-EcoScreen cells, and in vivo mouse liver cytochrome P450-1A induction by propanil, diuron and linuron.

    Science.gov (United States)

    Takeuchi, Shinji; Iida, Mitsuru; Yabushita, Hisatoshi; Matsuda, Tadashi; Kojima, Hiroyuki

    2008-12-01

    The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that regulates genes involved in xenobiotic metabolism, cellular proliferation and differentiation. In this study, we have developed a highly sensitive AhR-mediated reporter cell line, DR-EcoScreen cells, which are mouse hepatoma Hepa1c1c7 cells stably transfected with a reporter plasmid containing seven copies of dioxin-responsive element. Using these DR-EcoScreen cells, we performed the reporter gene assay and characterized the AhR agonistic activities of 200 pesticides (29 organochlorines, 11 diphenyl ethers, 56 organophosphorus pesticides, 12 pyrethroids, 22 carbamates, 12 acid amides, 7 triazines, 6 ureas, and 45 others). Eleven of the 200 pesticides (acifluorfen-methyl, bifenox, chlorpyrifos, isoxathion, quinalphos, chlorpropham, diethofencarb, propanil, diuron, linuron, and prochloraz) showed AhR-mediated transcriptional activity. In particular, three herbicides (propanil, diuron, and linuron) have a common chemical structure and showed more potent agonistic activity than other pesticides. To investigate the in vivo effects, we examined the gene expression of AhR-inducible cytochrome P450 1As (CYP1As) in the liver of female C57BL/6 mice intraperitoneally injected with these three herbicides (300 mg kg(-1)) by quantitative RT-PCR, resulting in induction of significant high levels of CYP1A1 and CYP1A2 mRNAs. This indicates that propanil, diuron and linuron possess AhR-mediated transactivation effect in vivo as well as in vitro. Through the present study, we demonstrated that DR-EcoScreen cells are useful for sensitive, rapid and simple identification of AhR agonists among a large number of environmental chemicals.

  13. Generalized tolerance sensitivity and DEA metric sensitivity

    OpenAIRE

    Neralić, Luka; E. Wendell, Richard

    2015-01-01

    This paper considers the relationship between Tolerance sensitivity analysis in optimization and metric sensitivity analysis in Data Envelopment Analysis (DEA). Herein, we extend the results on the generalized Tolerance framework proposed by Wendell and Chen and show how this framework includes DEA metric sensitivity as a special case. Further, we note how recent results in Tolerance sensitivity suggest some possible extensions of the results in DEA metric sensitivity.

  14. Generalized tolerance sensitivity and DEA metric sensitivity

    Directory of Open Access Journals (Sweden)

    Luka Neralić

    2015-03-01

    Full Text Available This paper considers the relationship between Tolerance sensitivity analysis in optimization and metric sensitivity analysis in Data Envelopment Analysis (DEA. Herein, we extend the results on the generalized Tolerance framework proposed by Wendell and Chen and show how this framework includes DEA metric sensitivity as a special case. Further, we note how recent results in Tolerance sensitivity suggest some possible extensions of the results in DEA metric sensitivity.

  15. The selectively bred high alcohol sensitivity (HAS) and low alcohol sensitivity (LAS) rats differ in sensitivity to nicotine.

    Science.gov (United States)

    de Fiebre, NancyEllen C; Dawson, Ralph; de Fiebre, Christopher M

    2002-06-01

    Studies in rodents selectively bred to differ in alcohol sensitivity have suggested that nicotine and ethanol sensitivities may cosegregate during selective breeding. This suggests that ethanol and nicotine sensitivities may in part be genetically correlated. Male and female high alcohol sensitivity (HAS), control alcohol sensitivity, and low alcohol sensitivity (LAS) rats were tested for nicotine-induced alterations in locomotor activity, body temperature, and seizure activity. Plasma and brain levels of nicotine and its primary metabolite, cotinine, were measured in these animals, as was the binding of [3H]cytisine, [3H]epibatidine, and [125I]alpha-bungarotoxin in eight brain regions. Both replicate HAS lines were more sensitive to nicotine-induced locomotor activity depression than the replicate LAS lines. No consistent HAS/LAS differences were seen on other measures of nicotine sensitivity; however, females were more susceptible to nicotine-induced seizures than males. No HAS/LAS differences in nicotine or cotinine levels were seen, nor were differences seen in the binding of nicotinic ligands. Females had higher levels of plasma cotinine and brain nicotine than males but had lower brain cotinine levels than males. Sensitivity to a specific action of nicotine cosegregates during selective breeding for differential sensitivity to a specific action of ethanol. The differential sensitivity of the HAS/LAS rats is due to differences in central nervous system sensitivity and not to pharmacokinetic differences. The differential central nervous system sensitivity cannot be explained by differences in the numbers of nicotinic receptors labeled in ligand-binding experiments. The apparent genetic correlation between ethanol and nicotine sensitivities suggests that common genes modulate, in part, the actions of both ethanol and nicotine and may explain the frequent coabuse of these agents.

  16. Familial melanoma associated with dominant ultraviolet radiation sensitivity

    International Nuclear Information System (INIS)

    Ramsay, R.G.; Chen, P.; Imray, F.P.; Kidson, C.; Lavin, M.F.; Hockey, A.

    1982-01-01

    Sensitivity to ultraviolet radiation was studied in lymphoblastoid cell lines derived from 32 members of two families with histories of multiple primary melanomas in several generations. As assayed by colony formation in agar or by trypan blue exclusion following irradiation, cellular sensitivity showed a bimodal distribution. All persons with melanoma or multiple moles were in the sensitive group, while some family members exhibited responses similar to those of controls. Cells from four cases of sporadic melanoma showed normal levels of sensitivity. The data are consistent with a dominantly inherited ultraviolet light sensitivity associated with these examples of familial melanoma. Spontaneous and ultraviolet light-induced sister chromatid exchange frequencies were similar to those in control cell lines. No defect in excision repair was detected in any of the above cell lines, but the sensitive group showed postirradiation inhibition of DNA replication intermediate between controls and an excision-deficient xeroderma pigmentosum cell line

  17. Directed line liquids

    International Nuclear Information System (INIS)

    Kamien, R.D.

    1992-01-01

    This thesis is devoted to the study of ensembles of dense directed lines. These lines are principally to be thought of as polymers, though they also have the morphology of flux lines in high temperature superconductors, strings of colloidal spheres in electrorheological fluids and the world lines of quantum mechanical bosons. The authors discuss how directed polymer melts, string-like formations in electrorheological and ferro-fluids, flux lines in high temperature superconductors and the world lines of quantum mechanical bosons all share similar descriptions. They study a continuous transition in all of these systems, and then study the critical mixing properties of binary mixtures of directed polymers through the renormalization group. They predict the exponents for a directed polymer blend consolute point and a novel two-phase superfluid liquid-gas critical point

  18. Series Transmission Line Transformer

    Science.gov (United States)

    Buckles, Robert A.; Booth, Rex; Yen, Boris T.

    2004-06-29

    A series transmission line transformer is set forth which includes two or more of impedance matched sets of at least two transmissions lines such as shielded cables, connected in parallel at one end ans series at the other in a cascading fashion. The cables are wound about a magnetic core. The series transmission line transformer (STLT) which can provide for higher impedance ratios and bandwidths, which is scalable, and which is of simpler design and construction.

  19. Covariant electromagnetic field lines

    Science.gov (United States)

    Hadad, Y.; Cohen, E.; Kaminer, I.; Elitzur, A. C.

    2017-08-01

    Faraday introduced electric field lines as a powerful tool for understanding the electric force, and these field lines are still used today in classrooms and textbooks teaching the basics of electromagnetism within the electrostatic limit. However, despite attempts at generalizing this concept beyond the electrostatic limit, such a fully relativistic field line theory still appears to be missing. In this work, we propose such a theory and define covariant electromagnetic field lines that naturally extend electric field lines to relativistic systems and general electromagnetic fields. We derive a closed-form formula for the field lines curvature in the vicinity of a charge, and show that it is related to the world line of the charge. This demonstrates how the kinematics of a charge can be derived from the geometry of the electromagnetic field lines. Such a theory may also provide new tools in modeling and analyzing electromagnetic phenomena, and may entail new insights regarding long-standing problems such as radiation-reaction and self-force. In particular, the electromagnetic field lines curvature has the attractive property of being non-singular everywhere, thus eliminating all self-field singularities without using renormalization techniques.

  20. Position sensitive x-ray detector

    International Nuclear Information System (INIS)

    Macchione, E.L.A.

    1990-01-01

    A multi ware position sensitive gas counter for X-ray detection was developed in our laboratory, making use of commercial delay-lines for position sensing. Six delay-line chips (50 ns delay each, 40 Mhz cut-off frequency) cover a total sensitive length of 150 mm leading to a delay-risetime ratio that allows for a high-resolution position detection. Tests using the 5,9 keV X-ray line from a 55 Fe source and integral linearity better than 0,1% and a maximal differential linearity of ±4,0% were obtained operating the detector with an Ar-C H 4 (90%-10%) gas mixture at 700 torr. Similar tests were performed, using the 8,04 keV line from a Cu x-ray tube. A total resolution of 330 μm, and the same integral and differential linearities were obtained. (author)

  1. Western Alaska ESI: STREAMS (River and Stream Lines)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains vector lines representing inland linear hydrography features used in the creation of the Environmental Sensitivity Index (ESI) for Western...

  2. Coastal Resources Atlas: Long Island: HYDRO (Hydrography Lines and Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains vector lines and polygons representing coastal hydrography used in the creation of the Environmental Sensitivity Index (ESI) for Long Island,...

  3. North Slope, Alaska ESI: HYDRO (Hydrography Lines and Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains vector lines and polygons representing coastal hydrography used in the creation of the Environmental Sensitivity Index (ESI) for the North...

  4. Columbia River ESI: HYDRO (Hydrography Lines and Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains vector lines and polygons representing coastal hydrography used in the creation of the Environmental Sensitivity Index (ESI) for Columbia...

  5. Bristol Bay, Alaska Subarea ESI: HYDRO (Hydrography Lines and Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains vector lines and polygons representing coastal hydrography used in the creation of the Environmental Sensitivity Index (ESI) for the Bristol...

  6. Minnesota County Boundaries - lines

    Data.gov (United States)

    Minnesota Department of Natural Resources — Minnesota county boundaries derived from a combination of 1:24,000 scale PLS lines, 1:100,000 scale TIGER, 1:100,000 scale DLG, and 1:24,000 scale hydrography lines....

  7. Database of emission lines

    Science.gov (United States)

    Binette, L.; Ortiz, P.; Joguet, B.; Rola, C.

    1998-11-01

    A widely accessible data bank (available through Netscape) and consiting of all (or most) of the emission lines reported in the litterature is being built. It will comprise objects as diverse as HII regions, PN, AGN, HHO. One of its use will be to define/refine existing diagnostic emission line diagrams.

  8. A position sensitive parallel plate avalanche counter

    International Nuclear Information System (INIS)

    Lombardi, M.; Tan Jilian; Potenza, R.; D'amico, V.

    1986-01-01

    A position sensitive parallel plate avalanche counter with a distributed constant delay-line-cathode (PSAC) is described. The strips formed on the printed board were served as the cathode and the delay line for readout of signals. The detector (PSAC) was operated in isobutane gas at the pressure range from 10 to 20 torr. The position resolution is better than 1 mm and the time resolution is about 350 ps, for 252 Cf fission-spectrum source

  9. Silencing of Taxol-Sensitizer Genes in Cancer Cells: Lack of Sensitization Effects

    International Nuclear Information System (INIS)

    Huang, Shang-Lang; Chao, Chuck C.-K.

    2015-01-01

    A previous genome-wide screening analysis identified a panel of genes that sensitize the human non-small-cell lung carcinoma cell line NCI-H1155 to taxol. However, whether the identified genes sensitize other cancer cells to taxol has not been examined. Here, we silenced the taxol-sensitizer genes identified (acrbp, atp6v0d2, fgd4, hs6st2, psma6, and tubgcp2) in nine other cancer cell types (including lung, cervical, ovarian, and hepatocellular carcinoma cell lines) that showed reduced cell viability in the presence of a sub-lethal concentration of taxol. Surprisingly, none of the genes studied increased sensitivity to taxol in the tested panel of cell lines. As observed in H1155 cells, SKOV3 cells displayed induction of five of the six genes studied in response to a cell killing dose of taxol. The other cell types were much less responsive to taxol. Notably, four of the five inducible taxol-sensitizer genes tested (acrbp, atp6v0d2, psma6, and tubgcp2) were upregulated in a taxol-resistant ovarian cancer cell line. These results indicate that the previously identified taxol-sensitizer loci are not conserved genetic targets involved in inhibiting cell proliferation in response to taxol. Our findings also suggest that regulation of taxol-sensitizer genes by taxol may be critical for acquired cell resistance to the drug

  10. Silencing of Taxol-Sensitizer Genes in Cancer Cells: Lack of Sensitization Effects

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Shang-Lang [Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan (China); Chao, Chuck C.-K., E-mail: cckchao@mail.cgu.edu.tw [Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan (China); Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan (China); Department of Medical Research and Development, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan (China)

    2015-06-16

    A previous genome-wide screening analysis identified a panel of genes that sensitize the human non-small-cell lung carcinoma cell line NCI-H1155 to taxol. However, whether the identified genes sensitize other cancer cells to taxol has not been examined. Here, we silenced the taxol-sensitizer genes identified (acrbp, atp6v0d2, fgd4, hs6st2, psma6, and tubgcp2) in nine other cancer cell types (including lung, cervical, ovarian, and hepatocellular carcinoma cell lines) that showed reduced cell viability in the presence of a sub-lethal concentration of taxol. Surprisingly, none of the genes studied increased sensitivity to taxol in the tested panel of cell lines. As observed in H1155 cells, SKOV3 cells displayed induction of five of the six genes studied in response to a cell killing dose of taxol. The other cell types were much less responsive to taxol. Notably, four of the five inducible taxol-sensitizer genes tested (acrbp, atp6v0d2, psma6, and tubgcp2) were upregulated in a taxol-resistant ovarian cancer cell line. These results indicate that the previously identified taxol-sensitizer loci are not conserved genetic targets involved in inhibiting cell proliferation in response to taxol. Our findings also suggest that regulation of taxol-sensitizer genes by taxol may be critical for acquired cell resistance to the drug.

  11. Wood pole overhead lines

    CERN Document Server

    Wareing, Brian

    2005-01-01

    This new book concentrates on the mechanical aspects of distribution wood pole lines, including live line working, environmental influences, climate change and international standards. Other topics include statutory requirements, safety, profiling, traditional and probabilistic design, weather loads, bare and covered conductors, different types of overhead systems, conductor choice, construction and maintenance. A section has also been devoted to the topic of lightning, which is one of the major sources of faults on overhead lines. The book focuses on the effects of this problem and the strate

  12. An analytical theory of transmission line shielding

    International Nuclear Information System (INIS)

    Pettersson, Per

    1993-01-01

    The classical electrogeometric model of shielding failure flashovers on transmission lines is investigated by analytical methods. Most of the basic elements that has appeared in the literature on the subject have been incorporated and put into a comprehensive model. These elements are: tower top geometry, structure height above ground, line insulation, lateral slope of ground, probability distribution of lightning currents, ratio of striking distances to ground wire and earth relative to conductor, and probability distribution of lightning leader approach angle to ground. Departing from a basic idealistic case, the sensitivity of the model to variations in these parameters is studied. Numerical examples are given. 8 refs, 8 figs, 1 tab

  13. Veterans Crisis Line

    Data.gov (United States)

    Department of Veterans Affairs — The caring responders at the Veterans Crisis Line are specially trained and experienced in helping Veterans of all ages and circumstances. Some of the responders are...

  14. Product line design

    Czech Academy of Sciences Publication Activity Database

    Anderson, S. P.; Celik, Levent

    2015-01-01

    Roč. 157, May (2015), s. 517-526 ISSN 0022-0531 Institutional support: RVO:67985998 Keywords : product line design * product differentiation * second-degree price discrimination Subject RIV: AH - Economics Impact factor: 1.097, year: 2015

  15. Kansas Electric Transmission Lines

    Data.gov (United States)

    Kansas Data Access and Support Center — This data set is a digital representation of the EletcircTransmission lines for the State of Kansas as maintained by the Kansas Corporation Commission. Data is...

  16. Electric Power Transmission Lines

    Data.gov (United States)

    Department of Homeland Security — Transmission Lines are the system of structures, wires, insulators and associated hardware that carry electric energy from one point to another in an electric power...

  17. SAF line powder operations

    International Nuclear Information System (INIS)

    Frederickson, J.R.; Horgos, R.M.

    1983-10-01

    An automated nuclear fuel fabrication line is being designed for installation in the Fuels and Materials Examination Facility (FMEF) near Richland, Washington. The fabrication line will consist of seven major process systems: Receiving and Powder Preparation; Powder Conditioning; Pressing and Boat Loading; Debinding, Sintering, and Property Adjustment; Boat Transport; Pellet Inspection and Finishing; and Pin Operations. Fuel powder processing through pellet pressing will be discussed in this paper

  18. Capital Improvements Business Line

    Science.gov (United States)

    2012-08-08

    NAVFAC Southwest Dan Waid Program & Business Mgmt NAVFAC SW Capital Improvements Business Line NAVFAC SW 8 August 2012 1 Report...REPORT TYPE 3. DATES COVERED 00-00-2012 to 00-00-2012 4. TITLE AND SUBTITLE Capital Improvements Business Line 5a. CONTRACT NUMBER 5b. GRANT...AVAILABILITY STATEMENT Approved for public release; distribution unlimited 13. SUPPLEMENTARY NOTES Presented at the 2012 Navy Gold Coast Small Business

  19. Nasca Lines, Peru

    Science.gov (United States)

    2001-01-01

    The Nasca Lines are located in the Pampa region of Peru, the desolate plain of the Peruvian coast 400 km south of Lima. The Lines were first spotted when commercial airlines began flying across the Peruvian desert in the 1920's. Passengers reported seeing 'primitive landing strips' on the ground below. The Lines were made by removing the iron-oxide coated pebbles which cover the surface of the desert. When the gravel is removed, they contrast with the light color underneath. In this way the lines were drawn as furrows of a lighter color. On the pampa, south of the Nasca Lines, archaeologists have now uncovered the lost city of the line-builders, Cahuachi. It was built nearly two thousand years ago and was mysteriously abandoned 500 years later. This ASTER sub-image covers an area of 14 x 18 km, was acquired on December 22, 2000, and is located at 14.7 degrees south latitude and 75.1 degrees west longitude. The U.S. science team is located at NASA's Jet Propulsion Laboratory, Pasadena, Calif. The Terra mission is part of NASA's Science Mission Directorate.

  20. Transmission line capital costs

    International Nuclear Information System (INIS)

    Hughes, K.R.; Brown, D.R.

    1995-05-01

    The displacement or deferral of conventional AC transmission line installation is a key benefit associated with several technologies being developed with the support of the U.S. Department of Energy's Office of Energy Management (OEM). Previous benefits assessments conducted within OEM have been based on significantly different assumptions for the average cost per mile of AC transmission line. In response to this uncertainty, an investigation of transmission line capital cost data was initiated. The objective of this study was to develop a database for preparing preliminary estimates of transmission line costs. An extensive search of potential data sources identified databases maintained by the Bonneville Power Administration (BPA) and the Western Area Power Administration (WAPA) as superior sources of transmission line cost data. The BPA and WAPA data were adjusted to a common basis and combined together. The composite database covers voltage levels from 13.8 to 765 W, with cost estimates for a given voltage level varying depending on conductor size, tower material type, tower frame type, and number of circuits. Reported transmission line costs vary significantly, even for a given voltage level. This can usually be explained by variation in the design factors noted above and variation in environmental and land (right-of-way) costs, which are extremely site-specific. Cost estimates prepared from the composite database were compared to cost data collected by the Federal Energy Regulatory Commission (FERC) for investor-owned utilities from across the United States. The comparison was hampered because the only design specifications included with the FERC data were voltage level and line length. Working within this limitation, the FERC data were not found to differ significantly from the composite database. Therefore, the composite database was judged to be a reasonable proxy for estimating national average costs

  1. LINE BROADENING AND THE SOLAR OPACITY PROBLEM

    Energy Technology Data Exchange (ETDEWEB)

    Krief, M.; Feigel, A.; Gazit, D., E-mail: menahem.krief@mail.huji.ac.il [The Racah Institute of Physics, The Hebrew University, 91904 Jerusalem (Israel)

    2016-06-20

    The calculation of line widths constitutes theoretical and computational challenges in the calculation of opacities of hot, dense plasmas. Opacity models use line broadening approximations that are untested at stellar interior conditions. Moreover, calculations of atomic spectra of the Sun indicate a large discrepancy in the K-shell line widths between several atomic codes and the Opacity-Project (OP). In this work, the atomic code STAR is used to study the sensitivity of solar opacities to line broadening. Variations in the solar opacity profile due to an increase of the Stark widths resulting from discrepancies with OP, are compared, in light of the solar opacity problem, with the required opacity variations of the present day Sun, as imposed by helioseismic and neutrino observations. The resulting variation profile is much larger than the discrepancy between different atomic codes, agrees qualitatively with the missing opacity profile, recovers about half of the missing opacity nearby the convection boundary, and has a little effect in the internal regions. Since it is hard to estimate quantitatively the uncertainty in the Stark widths, we show that an increase of all line widths by a factor of about ∼100 recovers quantitatively the missing opacity. These results emphasize the possibility that photoexcitation processes are not modeled properly, and more specifically, highlight the need for a better theoretical characterization of the line broadening phenomena at stellar interior conditions, and of the uncertainty due to the way it is implemented by atomic codes.

  2. Along the line

    DEFF Research Database (Denmark)

    Dinesen, Cort Ross

    2011-01-01

    Embarking on a work of art constitutes a reduction of information – because we grasp the diversity and plurality of the manifestations we encounter by abstracting them and transforming them into manageable concepts; as we do when we draw contour lines on the landscape – they are imaginary...... and invisible but an abstraction essential for noting a difference or marking a place on a map. In the same way, a stroke in a sketch or a line in the sand is a manifestation of our ability to draw a boundary that both includes and excludes information. Where the line makes the birth of an idea visible......, it expresses through movement our tendency to mark a difference by drawing attention to and enclosing a whole series of relations that confront our preconceived notions. It is in the process of transformation in which we reduce the complexity of how we work, and rethink our ideas anew by refining the very same...

  3. Spectral Line Shapes. Proceedings

    International Nuclear Information System (INIS)

    Zoppi, M.; Ulivi, L.

    1997-01-01

    These proceedings represent papers presented at the 13th International Conference on Spectral Line Shapes which was held in Firenze,Italy from June 16-21, 1996. The topics covered a wide range of subjects emphasizing the physical processes associated with the formation of line profiles: high and low density plasma; atoms and molecules in strong laser fields, Dopple-free and ultra-fine spectroscopy; the line shapes generated by the interaction of neutrals, atoms and molecules, where the relavant quantities are single particle properties, and the interaction-induced spectroscopy. There were 131 papers presented at the conference, out of these, 6 have been abstracted for the Energy Science and Technology database

  4. Stokes line width

    International Nuclear Information System (INIS)

    Nikiskov, A.I.; Ritus, V.I.

    1993-01-01

    The concept of Stokes line width is introduced for the asymptotic expansions of functions near an essential singularity. Explicit expressions are found for functions (switching functions) that switch on the exponentially small terms for the Dawson integral, Airy function, and the gamma function. A different, more natural representation of a function, not associated with expansion in an asymptotic series, in the form of dominant and recessive terms is obtained by a special division of the contour integral which represents the function into contributions of higher and lower saddle points. This division leads to a narrower, natural Stokes line width and a switching function of an argument that depends on the topology of the lines of steepest descent from the saddle point

  5. Overhead distribution line models for harmonics studies

    Energy Technology Data Exchange (ETDEWEB)

    Nagpal, M.; Xu, W.; Dommel, H.W.

    1994-01-01

    Carson's formulae and Maxwell's potential coefficients are used for calculating the per unit length series impedances and shunt capacitances of the overhead lines. The per unit length values are then used for building the models, nominal pi-circuit, and equivalent pi-circuit at the harmonic frequencies. This paper studies the accuracy of these models for presenting the overhead distribution lines in steady-state harmonic solutions at frequencies up to 5 kHz. The models are verified with a field test on a 25 kV distribution line and the sensitivity of the models to ground resistivity, skin effect, and multiple grounding is reported.

  6. VT Digital Line Graph Railroads

    Data.gov (United States)

    Vermont Center for Geographic Information — (Link to Metadata) This datalayer is comprised of major railroad lines for the state of Vermont. These railroad lines line up well along quadrangle boundaries, but...

  7. Ethylene responses in three Hydrangea lines

    DEFF Research Database (Denmark)

    Lauridsen, Uffe Bjerre; Müller, Renate; Lütken, Henrik Vlk

    2015-01-01

    Abstract The ornamental scrub Hydrangea is generally not considered to be particularly sensitive to the phytohormone ethylene. The present study aimed at testing ethylene sensitivity in three different Hydrangea lines: 1, 2 and 3 taking into account the effect of temperature. Ethylene response...... was measured as leaf epinasty and leaf drop. Data indicated that higher temperature accelerates the effect of 2 μl L-1 ethylene over a 12-day period, and if the inhibitor 1-methylcyclopopene 1-MCP is able to attenuate this effect. Breeding line 1 and 3 dropped 3.8±0.6 and 5.0±0.4 leaves on average......, respectively, during the 12-day experimental period. Non-treated controls of line 1 and 3 dropped 1.8±0.6 and 1.8±0.4 leaves, respectively. In contrast, line 2 did not show a significant response to ethylene treatment with a leaf drop of 2.1±0.3 leaves, compared to a leaf drop of 0.8±0.3 in non...

  8. Sprayed concrete linings

    Energy Technology Data Exchange (ETDEWEB)

    Hindle, D.

    1999-12-01

    Sprayed concrete, or shotcrete, was invented in the 1920s for preserving dinosaur skeletons and was used underground initially in coalmines for the preservation and fine proofing of timber supports. Its use as a support lining in rock tunnelling was developed in the 1950s and 60s. The article surveys equipment available from major manufacturers and suppliers of concrete spraying equipment (Aliva, Cifa, GIA, Industri, Ingersoll Rand, etc.), specialist cement and additive manufacturers (Castle, Cement, Moria Carbotech). manufacturers of lattice girders and fibre reinforcement, and manufacturers of instrumentation for tunnel linings. 5 tabs., 9 photos.

  9. Statistical evaluation and measuring strategy for extremely small line shifts

    International Nuclear Information System (INIS)

    Hansen, P.G.

    1978-01-01

    For a measuring situation limited by counting statistics, but where the level of precision is such that possible systematic errors are a major concern, it is proposed to determine the position of a spectral line from a measured line segment by applying a bias correction to the centre of gravity of the segment. This procedure is statistically highly efficient and not sensitive to small errors in assumptions about the line shape. The counting strategy for an instrument that takes data point by point is also considered. It is shown that an optimum (''two-point'') strategy exists; a scan of the central part of the line is 68% efficient by this standard. (Auth.)

  10. Chemical kinetic functional sensitivity analysis: Elementary sensitivities

    International Nuclear Information System (INIS)

    Demiralp, M.; Rabitz, H.

    1981-01-01

    Sensitivity analysis is considered for kinetics problems defined in the space--time domain. This extends an earlier temporal Green's function method to handle calculations of elementary functional sensitivities deltau/sub i//deltaα/sub j/ where u/sub i/ is the ith species concentration and α/sub j/ is the jth system parameter. The system parameters include rate constants, diffusion coefficients, initial conditions, boundary conditions, or any other well-defined variables in the kinetic equations. These parameters are generally considered to be functions of position and/or time. Derivation of the governing equations for the sensitivities and the Green's funciton are presented. The physical interpretation of the Green's function and sensitivities is given along with a discussion of the relation of this work to earlier research

  11. Glue-paste linings

    DEFF Research Database (Denmark)

    Fuster-López, Laura; Andersen, Cecil Krarup; Bouillon, Nicolas

    2017-01-01

    Glue-paste linings of (Western) canvas paintings have been performed with a variety of materials throughout history and are present in a very significant amount of artworks in collections in Europe and elsewhere. Cereal flours and animal glues were usually the main ingredients because they were r...

  12. Product line design

    Czech Academy of Sciences Publication Activity Database

    Anderson, S. P.; Celik, Levent

    2015-01-01

    Roč. 157, May (2015), s. 517-526 ISSN 0022-0531 R&D Projects: GA ČR(CZ) GA15-22540S Institutional support: PRVOUK-P23 Keywords : product line design * product differentiation * second-degree price discrimination Subject RIV: AH - Economics Impact factor: 1.097, year: 2015

  13. K-line photometry

    International Nuclear Information System (INIS)

    Henry, R.C.

    1979-01-01

    A brief review is given of more than a decade of work involving measurement of the strength of the K line of calcium in A-type stars. The effects of interstellar reddening are reexamined, and an improved estimate for the range in calcium abundance among field stars is obtained. (Auth.)

  14. SAF line pellet gaging

    International Nuclear Information System (INIS)

    Jedlovec, D.R.; Bowen, W.W.; Brown, R.L.

    1983-10-01

    Automated and remotely controlled pellet inspection operations will be utilized in the Secure Automated Fabrication (SAF) line. A prototypic pellet gage was designed and tested to verify conformance to the functions and requirements for measurement of diameter, surface flaws and weight-per-unit length

  15. Bike Map Lines

    Data.gov (United States)

    Town of Chapel Hill, North Carolina — Chapel Hill Bike Map Lines from KMZ file.This data came from the wiki comment board for the public, not an “official map” showing the Town of Chapel Hill's plans or...

  16. Drawing the Line

    DEFF Research Database (Denmark)

    Holm, Isak Winkel

    2016-01-01

    of judgement that distinguishes between the inside and outside of a political community, between citizens and zombies. Second, the chapter focuses on the rhetorics applied to draw the line between rights-bearers and the rightless. ‘Prophetic’ speech, echoing the language of the Old Testament prophets, is vital...

  17. Developing Green Line Products

    DEFF Research Database (Denmark)

    Muñoz-Marin, Ana Maria; Lassen, Astrid Heidemann; Poulsen, Søren Bolvig

    2011-01-01

    This publication is based on the Master thesis “User-driven ecoinnovation process: Towards the implementation of the Green product line at JELD-WEN” written by Ana Maria Muñoz-Marin as her Graduation Project for the MSc. Global Innovation Management degree. The company-based experiment was carried...

  18. Magnetic field line Hamiltonian

    International Nuclear Information System (INIS)

    Boozer, A.H.

    1984-03-01

    The magnetic field line Hamiltonian and the associated canonical form for the magnetic field are important concepts both for understanding toroidal plasma physics and for practical calculations. A number of important properties of the canonical or Hamiltonian representation are derived and their importance is explained

  19. Mixed Lubricated Line Contacts

    NARCIS (Netherlands)

    Faraon, I.C.

    2005-01-01

    The present work deals with friction in mixed lubricated line contacts. Components in systems are becoming smaller and due to, for instance power transmitted, partial contact may occur. In industrial applications, friction between the moving contacting surfaces cannot be avoided, therefore it is

  20. Lined canvas paintings

    DEFF Research Database (Denmark)

    Krarup Andersen, Cecil

    2013-01-01

    at 50% RH but increased the stress level severely in dry conditions and offered no support to the painting at 70-80 % RH. This means that the traditional glue-paste lining techniques and the wax-resin technique in high RH seem to limit the advisable RH fluctuation in a cultural institution. Conversely...

  1. LEAR: antiproton extraction lines

    CERN Multimedia

    Photographic Service

    1992-01-01

    Antiprotons, decelerated in LEAR to a momentum of 100 MeV/c (kinetic energy of 5.3 MeV), were delivered to the experiments in an "Ultra-Slow Extraction", dispensing some 1E9 antiprotons over times counted in hours. Beam-splitters and a multitude of beam-lines allowed several users to be supplied simultaneously.

  2. Labelling subway lines

    NARCIS (Netherlands)

    Garrido, M.A.; Iturriaga, C.; Márquez, A.; Portillo, J.R.; Reyes, P.; Wolff, A.; Eades, P.; Takaoka, T.

    2001-01-01

    Graphical features on map, charts, diagrams and graph drawings usually must be annotated with text labels in order to convey their meaning. In this paper we focus on a problem that arises when labeling schematized maps, e.g. for subway networks. We present algorithms for labeling points on a line

  3. Subjective poverty line definitions

    NARCIS (Netherlands)

    J. Flik; B.M.S. van Praag (Bernard)

    1991-01-01

    textabstractIn this paper we will deal with definitions of subjective poverty lines. To measure a poverty threshold value in terms of household income, which separates the poor from the non-poor, we take into account the opinions of all people in society. Three subjective methods will be discussed

  4. Building with a Line

    Science.gov (United States)

    Hubbert, Beth

    2011-01-01

    Architecture is a versatile, multifaceted area to study in the artroom with multiple age levels. It can easily stimulate a study of basic line, shape, and various other art elements and principles. It can then be extended into a more extensive study of architectural elements, styles, specific architects, architecture of different cultures, and…

  5. Biosynthesis: Reprogramming assembly lines

    Science.gov (United States)

    Menon, Binuraj R. K.; Jenner, Matthew

    2018-03-01

    Rational engineering of biosynthetic assembly lines for production of new compounds is an attractive prospect, yet it presents many challenges. Learning from biology, some of the rules for expanding the chemical diversity of non-ribosomal peptides have been uncovered in two recent studies.

  6. Magnetic field line Hamiltonian

    International Nuclear Information System (INIS)

    Boozer, A.H.

    1985-02-01

    The basic properties of the Hamiltonian representation of magnetic fields in canonical form are reviewed. The theory of canonical magnetic perturbation theory is then developed and applied to the time evolution of a magnetic field embedded in a toroidal plasma. Finally, the extension of the energy principle to tearing modes, utilizing the magnetic field line Hamiltonian, is outlined

  7. Defining line replaceable units

    NARCIS (Netherlands)

    Parada Puig, J. E.; Basten, R. J I

    2015-01-01

    Defective capital assets may be quickly restored to their operational condition by replacing the item that has failed. The item that is replaced is called the Line Replaceable Unit (LRU), and the so-called LRU definition problem is the problem of deciding on which item to replace upon each type of

  8. On-line moisture analysis

    International Nuclear Information System (INIS)

    Cutmore, N.G.; Mijak, D.G

    2002-01-01

    Measurement of the moisture content of iron ore has become a key issue for controlling moisture additions for dust suppression. In most cases moisture content is still determined by manual or automatic sampling of the ore stream, followed by conventional laboratory analysis by oven drying. Although this procedure enables the moisture content to be routinely monitored, it is too slow for control purposes. This has generated renewed interest in on-line techniques for the accurate and rapid measurement of moisture in iron ore on conveyors. Microwave transmission techniques have emerged over the past 40 years as the dominant technology for on-line measurement of moisture in bulk materials, including iron ores. Alternative technologies have their limitations. Infra-red analysers are used in a variety of process industries, but rely on the measurement of absorption by moisture in a very thin surface layer. Consequently such probes may be compromised by particle size effects and biased presentation of the bulk material. Nuclear-based analysers measure the total hydrogen content in the sample and do not differentiate between free and combined moisture. Such analysers may also be sensitive to material presentation and elemental composition. Very low frequency electromagnetic probes, such as capacitance or conductance probes, operate in the frequency region where the DC conductivity dominates much of the response, which is a function not only of moisture content but also of ionic composition and chemistry. These problems are overcome using microwave transmission techniques, which also have the following advantages, as a true bulk moisture analysis is obtained, because a high percentage of the bulk material is analysed; the moisture estimate is mostly insensitive to any biased presentation of moisture, for example due to stratification of bulk material with different moisture content and because no physical contact is made between the sensor and the bulk material. This is

  9. The last line effect explained

    NARCIS (Netherlands)

    Beller, M. (Moritz); Zaidman, A. (Andy); Karpov, A. (Andrey); R.A. Zwaan (Rolf)

    2017-01-01

    textabstractMicro-clones are tiny duplicated pieces of code; they typically comprise only few statements or lines. In this paper, we study the “Last Line Effect,” the phenomenon that the last line or statement in a micro-clone is much more likely to contain an error than the previous lines or

  10. The last line effect explained

    NARCIS (Netherlands)

    Beller, M.M.; Zaidman, A.E.; Karpov, Andrey; Zwaan, Rolf A.

    Micro-clones are tiny duplicated pieces of code; they typically comprise only few statements or lines. In this paper, we study the “Last Line Effect,” the phenomenon that the last line or statement in a micro-clone is much more likely to contain an error than the previous lines or statements. We do

  11. Radio recombination lines from H II regions

    International Nuclear Information System (INIS)

    Silverglate, P.R.

    1978-01-01

    Radio recombination lines have been observed from forty-six H II regions. The Arecibo 1000-foot radio telescope was used to provide high sensitivity and high angular resolution at 1400 MHz (gain approx. 7.7 0 K/Jy, HPBW = 3:2) and 2372 MHZ (gain approx. 6.3 0 K/Jy, HPBW = 2'). Observations were made at 1400 MHz in the frequency switching mode, and at 2372 MHz in the total power mode. Gaussians were fit to be observed lines to derive velocities, line widths, and line temperatures. From the velocities kinematic distances were derived. For eleven sources H I absorption measurements were also made. The absorption spectra enabled the kinematic distance ambiguity to be resolved for some sources. The absorption spectra themselves were found to have extremely sharp, non-gaussian edges. One explanation for these is a model where the interstellar medium contains many H I cloudlets with T/sub s/less than or equal to 100 0 K and turbulent velocities less than or equal to 3 km/s. The H I absorption spectrum is then a superposition of many narrow gaussian profiles. It was also found from a comparison of H I absorption velocities with radio recombination line velocities that peculiar motions exist in the interstellar medium with velocities of up to 10 km/s. Using the measured line temperatures and continuum temperatures, estimates were desired of emission measures, electron temperatures, and electron densities, using a non-LTE analysis. Non-LTE effects were important only for the hottest and densest H II regions. The non-LTE calculations were checked through a comparison derivation of electron temperatures using hydrogen beta lines

  12. Contact Line Dynamics

    Science.gov (United States)

    Kreiss, Gunilla; Holmgren, Hanna; Kronbichler, Martin; Ge, Anthony; Brant, Luca

    2017-11-01

    The conventional no-slip boundary condition leads to a non-integrable stress singularity at a moving contact line. This makes numerical simulations of two-phase flow challenging, especially when capillarity of the contact point is essential for the dynamics of the flow. We will describe a modeling methodology, which is suitable for numerical simulations, and present results from numerical computations. The methodology is based on combining a relation between the apparent contact angle and the contact line velocity, with the similarity solution for Stokes flow at a planar interface. The relation between angle and velocity can be determined by theoretical arguments, or from simulations using a more detailed model. In our approach we have used results from phase field simulations in a small domain, but using a molecular dynamics model should also be possible. In both cases more physics is included and the stress singularity is removed.

  13. Adaptive method of lines

    CERN Document Server

    Saucez, Ph

    2001-01-01

    The general Method of Lines (MOL) procedure provides a flexible format for the solution of all the major classes of partial differential equations (PDEs) and is particularly well suited to evolutionary, nonlinear wave PDEs. Despite its utility, however, there are relatively few texts that explore it at a more advanced level and reflect the method''s current state of development.Written by distinguished researchers in the field, Adaptive Method of Lines reflects the diversity of techniques and applications related to the MOL. Most of its chapters focus on a particular application but also provide a discussion of underlying philosophy and technique. Particular attention is paid to the concept of both temporal and spatial adaptivity in solving time-dependent PDEs. Many important ideas and methods are introduced, including moving grids and grid refinement, static and dynamic gridding, the equidistribution principle and the concept of a monitor function, the minimization of a functional, and the moving finite elem...

  14. Limit lines for risk

    International Nuclear Information System (INIS)

    Cox, D.C.; Baybutt, P.

    1982-01-01

    Approaches to the regulation of risk from technological systems, such as nuclear power plants or chemical process plants, in which potential accidents may result in a broad range of adverse consequences must take into account several different aspects of risk. These include overall or average risk, accidents posing high relative risks, the rate at which accident probability decreases with increasing accident consequences, and the impact of high frequency, low consequence accidents. A hypothetical complementary cumulative distribution function (CCDF), with appropriately chosen parametric form, meets all these requirements. The Farmer limit line, by contrast, places limits on the risks due to individual accident sequences, and cannot adequately account for overall risk. This reduces its usefulness as a regulatory tool. In practice, the CCDF is used in the Canadian nuclear licensing process, while the Farmer limit line approach, supplemented by separate qualitative limits on overall risk, is employed in the United Kingdom

  15. Draw the Line!

    DEFF Research Database (Denmark)

    present proceedings from the UPGEM conference "Draw the Line!" in Copenhagen May 2008. The proceedings include contributions by UPGEM researchers, conference speeches by other researchers, politicians and gender equality officers in which they relate their work and research with the research done in UPGEM......Draw the Line! International Conference, Copenhagen 2008 Papers, proceedings and recommendations is the second publication of the international three year long project "Understanding Puzzles in the Gendered European Map" (UPGEM), which is financed by the European Commission. In this publication we....... The UPGEM research has previously been published in national reports from each of the partner countries (Denmark, Estonia, Finland, Italy and Poland). In these individual national reports of universities as workplaces for male and female researchers we discuss scientific cultures in physics embedded...

  16. SLIA beam line design

    International Nuclear Information System (INIS)

    Petillo, J.; Chernin, D.; Kostas, C.; Mondelli, A.

    1990-01-01

    The Spiral Line Induction Accelerator (SLIA) is a multi-kiloampere compact electron accelerator. It uses linear induction accelerator modules on the straight sections of a racetrack spiral, with strong-focusing bends to recirculate the electrons. The strong focusing is provided by stellarator windings on the bends. Stellarator coils are used to provide the strong focusing on the bends. The matching of the electron beam from a diode through a series of accelerator modules and stellarator bends is a major issue in the design of this accelerator. The beam line design for a proof-of-concept SLIA experiment (10 kA, 7 MeV) to be carried out at Pulse Sciences, Inc. will be presented. The design will demonstrate beam matching from element to element in the focusing system, the design of an achromatic bend, and the requirements for avoiding collective instabilities

  17. Susceptibility testing of fish cell lines for virus isolation

    DEFF Research Database (Denmark)

    Ariel, Ellen; Skall, Helle Frank; Olesen, Niels Jørgen

    2009-01-01

    and laboratories, but also between lineages of the same cell line. To minimise the occurrence of false negatives in a cell culture based surveillance system, we have investigated methods, to select cell lineages that are relatively superior in their susceptibility to a panel of virus isolates. The procedures...... cell lineages, we increased the number of isolates of each virus, propagated stocks in a given cell line and tested all lineages of that line in use in the laboratory. Testing of relative cell line susceptibility between laboratories is carried out annually via the Inter-laboratory Proficiency Test...... sensitivity for surveillance purposes within a cell line and between laboratories.In terms of economic and practical considerations as well as attempting to approach a realistic test system, we suggest the optimal procedure for susceptibility testing of fish cell lines for virus isolation to be a combination...

  18. Remote mechanical C line

    International Nuclear Information System (INIS)

    Nuttall, K.R.; Gardner, P.R.

    1991-01-01

    Westinghouse Hanford Company is developing a desk-top simulation based training program on the operation of the Remote Mechanical C (RMC) Line process in the Plutonium Finishing Plant on the Hanford site, Richland, Washington. Simulations display aod contioually update current values of system parameters on computer graphics of RMC line equipment. Students are able to operate a variety of controllers to maintain proper system status. Programmed faults, selectable by the course instructor, can be used to test student responses to off-normal events. Prior to operation of the simulation, students are given computer-based tutorials on the function, processes, operation, and error conditions associated with individual components. By including the capability of operating each individual component - valves, heaters, agitators, etc. - the computer-based training (CBT) lessons become an interactive training manual. From one perspective RMC represents one step in the diffusion of the well-known and well-documented simulator training activities for nuclear reactor operators to other training programs, equally critical, perhaps, but less well scrutinized in the past. Because of the slowly responding nature of the actual process, RMC can retain many of the capabilities of practice and testing in a simulated work environment while avoiding the cost of a full scale simulator and the exposure and waste developed by practice runs of the RMC line. From another perspective RMC suggests training advances even beyond the most faithful simulators. For example, by integrating CBT lessons with the simulation, RMC permits students to focus in on specific processes occurring inside chosen components. In effect, the interactive training manual is available on-line with the simulation itself. Cost are also discussed

  19. Pink-line syndrome

    Digital Repository Service at National Institute of Oceanography (India)

    Ravindran J.; Raghukumar, C.; Manikandan, B.

    , a physiological crisis in the scleractinian coral Porites lutea. Marine biology 149: 347-356 7. Ravindran J, Raghukumar C (2006a) Histological observations on the scleractinian coral Porites lutea affected by pink-line syndrome. Current science... handbook: guidelines for assessment and monitoring. Currie Communications, Melbourne, Australia, 94p+App 10. Vargas-Angel B, Wheeler B (2009) Coral health and disease assessment in the US Pacific territories and affiliated states. Proc. 11th Coral Reef...

  20. Line managers as marketers.

    Science.gov (United States)

    Rynne, T J

    1986-09-01

    Many hospital administrators and boards of directors, having overcome their initial opposition to advertising and hired a marketing professional, are wondering why their marketing programs have not accomplished all that they had hoped. The answer lies in their perception of who is responsible for marketing. Marketing is not a specialty separate from the disciplines of management--it is a basic management skill. Its goal is to satisfy the customer by providing products and services that meet the customer's needs, wants, and preferences. Line managers must understand the hospital's customers and make the critical day-to-day differences in satisfying them. They are the hospital's front-line marketers, and the marketing department's role is to support them in this function. The marketing department should develop the line managers' marketing skills by furnishing them with the appropriate tools: formats, models, examples, and instructions. In addition, the marketing staff should provide such specialized services as marketing research, ad agency management, and development of communications.

  1. Evaluation of some bean lines tolerance to alkaline soil

    Directory of Open Access Journals (Sweden)

    Abeer A. Radi

    2012-01-01

    Full Text Available Introduction: In less arid climates, salts are less concentrated and sodium dominates in carbonate and bicarbonate forms, which enhance the formation of alkaline soils. The development and identification of salt-tolerant crop cultivars or lines would complement salt management programs to improve the productivity and yields of salt stressed plants.Materials and methods: This work was to study the evaluation of alkalinity tolerance of some bean lines grown under different levels of sodium carbonate (Na2CO3 to select the most alkalinity tolerant lines versus the most-sensitive ones out of 6 lines of the test plants.Results: The symptoms induced by alkalinity included reduction in root, shoot growth, and leaf area which were more severe in some bean lines. Potassium leakage was severely affected by alkalinity in some lines at all tested levels, while in some others a moderate damage was manifested only at the higher levels. The increase in Na2CO3 level was associated with a gradual fall in chlorophyll a and b biosynthesis of all the test bean lines. However, alkalinity at low and moderate levels had a favorable effect on the biosynthesis of carotenoids in all the test bean lines. The increase in Na2CO3 supply had a considerable stimulatory effect on sodium accumulation, while potassium accumulation fluctuated in organs of bean lines.Conclusion: Assiut 1104 out of all the different lines investigated was found to display the lowest sensitivity to alkalinity stress, while Assiut 12/104 was the most sensitive one.

  2. High resolution RGB color line scan camera

    Science.gov (United States)

    Lynch, Theodore E.; Huettig, Fred

    1998-04-01

    A color line scan camera family which is available with either 6000, 8000 or 10000 pixels/color channel, utilizes off-the-shelf lenses, interfaces with currently available frame grabbers, includes on-board pixel by pixel offset correction, and is configurable and controllable via RS232 serial port for computer controlled or stand alone operation is described in this paper. This line scan camera is based on an available 8000 element monochrome line scan camera designed by AOA for OEM use. The new color version includes improvements such as better packaging and additional user features which make the camera easier to use. The heart of the camera is a tri-linear CCD sensor with on-chip color balancing for maximum accuracy and pinned photodiodes for low lag response. Each color channel is digitized to 12 bits and all three channels are multiplexed together so that the resulting camera output video is either a 12 or 8 bit data stream at a rate of up to 24Megpixels/sec. Conversion from 12 to 8 bit, or user-defined gamma, is accomplished by on board user-defined video look up tables. The camera has two user-selectable operating modes; lows speed, high sensitivity mode or high speed, reduced sensitivity mode. The intended uses of the camera include industrial inspection, digital archiving, document scanning, and graphic arts applications.

  3. Resistivity tomography using line electrode; Sendenryugen wo tsukatta hiteiko tomography

    Energy Technology Data Exchange (ETDEWEB)

    Sugimoto, Y [Dia Consultants Company, Tokyo (Japan)

    1996-10-01

    Resistivity tomography (RT) using line electrode was studied. Although line electrode is available even for RT, in casing line electrode, only one kind of electrode data is obtained. The calculation method of potential and sensitivity distributions based on line electrode is not yet established. Since various data in various measurement arrangements are required for analysis of RT, the new measurement method was devised which measures resistivities while successively changing the tip depth of line electrode. Until now, although potential has been calculated under the assumption that outflow current per unit length of line electrode is uniform, this assumption is incorrect. The new potential distribution calculation method was thus proposed. Sensitivity distribution calculation for inverse analysis is also described. RT using line electrode could precisely obtain deep information which couldn`t be obtained only by measurement along the surface measuring line. Although RT is poorer in accuracy than the previous point electrode method, it will be probably improved by 3-electrode arrangement. RT is also useful in the case difficult to apply point electrode method. 3 refs., 10 figs.

  4. Structure sensitivity in adsorption

    DEFF Research Database (Denmark)

    Hammer, Bjørk; Nielsen, Ole Holm; Nørskov, Jens Kehlet

    1997-01-01

    The structure sensitivity of CO adsorption on different flat, stepped, kinked and reconstructed Pt surfaces is studied using large-scale density-functional calculations. We find an extremely strong structure sensitivity in the adsorption energy with variations up to 1 eV (or 100%) from one...... structure to the next. We propose a model to explain this behavior, and use it to discuss more generally the origin of structure sensitivity in heterogeneous catalysis....

  5. Fabrics Protect Sensitive Skin from UV Rays

    Science.gov (United States)

    2009-01-01

    Late Johnson Space Center engineer Dr. Robert Dotts headed a team to develop cool suits for children suffering from life-threatening sun sensitivities. Dotts hoped to develop ultraviolet-blocking technology in a fabric that -- unlike in a bulky space suit -- could remain comfortable, light, and breathable in the sun and heat. The team worked with SPF 4 US LLC (SPF) of Madison, Wisconsin to design ultraviolet-blocking cool suits, which protect sun-sensitive patients and enable them to experience life outdoors safely. Using knowledge gained during the NASA collaboration, SPF created an entire line of ultraviolet-blocking apparel.

  6. How sensitizing is chlorocresol?

    DEFF Research Database (Denmark)

    Andersen, Klaus Ejner; Hamann, K

    1984-01-01

    Chlorocresol is a biocide with widespread use in industry and pharmaceutical products. It is an occasional human contact sensitizer. The sensitizing potential of chlorocresol was judged strong using the guinea pig maximization test (GPMT) and doubtful in the less sensitive open epicutaneous test......% in pet. showed 11 reactions among 1462 patients tested, but none were explainable and reproducible during re-tests and provocative use tests, indicating that the GPMT overestimated the sensitization potential. The results from guinea pig allergy tests cannot stand alone but have to be validated by other...

  7. Sensitivity and uncertainty analysis

    CERN Document Server

    Cacuci, Dan G; Navon, Ionel Michael

    2005-01-01

    As computer-assisted modeling and analysis of physical processes have continued to grow and diversify, sensitivity and uncertainty analyses have become indispensable scientific tools. Sensitivity and Uncertainty Analysis. Volume I: Theory focused on the mathematical underpinnings of two important methods for such analyses: the Adjoint Sensitivity Analysis Procedure and the Global Adjoint Sensitivity Analysis Procedure. This volume concentrates on the practical aspects of performing these analyses for large-scale systems. The applications addressed include two-phase flow problems, a radiative c

  8. Coaxial transmission line - Equalization

    International Nuclear Information System (INIS)

    Bonnerue, J.L.; Fremont, Jacques; Haubtmann, Jack; Pillon, Gerard.

    1981-09-01

    The transmission of electrical signal through a coaxial line is not perfect and signal distortions are increased as much as the frequency spectrum is extended. We have designed and achieved passive filters (named equalizers) with transfer functions which are inverse of coaxial transfer functions. Doing so our attempt is to avoid definitive loss of information in the recorded data. The main feature of our equalization method lies in the fact it could be either an electrical or a numerical correction or both of them. Some examples in the use of this technique are also proposed [fr

  9. α-line systematics

    International Nuclear Information System (INIS)

    Caurier, E.; Zuker, A.P.

    1991-01-01

    A study of the α-line, defined as a set of differences (D α ) characterized binding energies of (N,Z) nuclei, is presented. The 2p2n-separation energies for even-even nuclei, odd-odd nuclei, even(Z)-odd(N) nuclei, odd(Z)-even(N) nuclei are presented. Trends and details in even-even nuclei, magic numbers of even-even and odd-odd nuclei are discussed. (G.P.) 1 ref.; 8 figs

  10. Temperature-insensitive laser frequency locking near absorption lines

    International Nuclear Information System (INIS)

    Kostinski, Natalie; Olsen, Ben A.; Marsland, Robert III; McGuyer, Bart H.; Happer, William

    2011-01-01

    Combined magnetically induced circular dichroism and Faraday rotation of an atomic vapor are used to develop a variant of the dichroic atomic vapor laser lock that eliminates lock sensitivity to temperature fluctuations of the cell. Operating conditions that eliminate first-order sensitivity to temperature fluctuations can be determined by low-frequency temperature modulation. This temperature-insensitive gyrotropic laser lock can be accurately understood with a simple model, that is in excellent agreement with observations in potassium vapor at laser frequencies in a 2 GHz range about the 770.1 nm absorption line. The methods can be readily adapted for other absorption lines.

  11. Signal processors for position-sensitive detectors

    Energy Technology Data Exchange (ETDEWEB)

    Hasegawa, Ken-ichi [Hosei Univ., Koganei, Tokyo (Japan). Coll. of Engineering

    1996-07-01

    Position-sensitive detectors (PSD) are widely used in following various fields: condensed matter studies, material engineering, medical radiology particle physics, astrophysics and industrial applications. X-ray diffraction analysis is one of the field where PSDs are the most important instruments. In this field, many types of PSAs are employed: position-sensitive proportional counters (PSPC), multi-wire proportional chambers (MWPC), imaging plates, image intensifiers combined CCD cameras and semiconductor array devices. Two readout systems used for PSDs, where one is a charge-division type with high stability and the other is an encoder with multiple delay, line readout circuits useful for fast counting, were reported in this paper. The multiple delay line encoding system can be applicable to high counting rate 1D and 2D gas proportional detectors. (G.K.)

  12. From Off-line to On-line Handwriting Recognition

    NARCIS (Netherlands)

    Lallican, P.; Viard-Gaudin, C.; Knerr, S.

    2004-01-01

    On-line handwriting includes more information on time order of the writing signal and on the dynamics of the writing process than off-line handwriting. Therefore, on-line recognition systems achieve higher recognition rates. This can be concluded from results reported in the literature, and has been

  13. Radiation resistant lining material

    International Nuclear Information System (INIS)

    Ouchi, Koki; Okagawa, Seigo; Tamaki, Hidehiro.

    1990-01-01

    Rigidity, viscoelasticity, flexibility, radiation resistance, leaching resistance, rust-proofness, endurance, etc. are required for the lining materials to wall surfaces and floor surfaces of facilities used under the effect of radiation rays and for the inner surface protection of vessels for radioactive wastes. The present invention provides radiation resistant lining material capable of satisfying such various requirements in a well-balanced manner. That is, the material contains (A) 100 parts by weight of rapidly curing cement, (B) 50 to 300 % by weight of aggregate, and (C) 80 to 120 parts by weight of polymer emulsion. As the specific example, the ingredient (A) is commercially available under the trade name of Jet Cement. The aggregate of the ingredient (B) has preferably from about 0.6 to 0.2 mm of size and is made of material, preferably, silicon or iron grains. As the ingredient (C), acrylic resin emulsion is preferred. As a result of example, these ingredient constitutions can satisfy each of the required performance described above. (I.S.)

  14. Strategic production line synchronisation

    Directory of Open Access Journals (Sweden)

    Hattingh, Teresa

    2016-08-01

    Full Text Available A study was conducted at the sole global producer of suspension struts for a particular vehicle manufacturer. This supplier is currently able to meet customer demand. However, it does so because of a large finished goods and work-in-progress (WIP inventory. The plant operates two production processes that are separated by a large buffer of WIP, which essentially decouples the production processes. This study aimed to reduce this WIP buffer; this would require the processes to become synchronised, bearing in mind that the reliability of delivery should not decrease. A tool that considers time, quality, and machine capacity was developed to assess the impact of line synchronisation on company performance figures. It was found that line synchronisation produced several benefits for the supplier, including batch size reduction, lower inventory levels, and associated shorter lead times. This further allowed the supplier to improve flow in the plant by introducing a pull system. Improved visual oversight could lead to further improved problem-solving and innovation.

  15. Position-sensitive proportional counter

    International Nuclear Information System (INIS)

    Kopp, M.K.

    1980-01-01

    A position-sensitive proportional counter circuit uses a conventional (low-resistance, metal-wire anode) counter for spatial resolution of an ionizing event along the anode, which functions as an RC line. A pair of preamplifiers at the anode ends act as stabilized active-capacitance loads, each comprising a series-feedback, low-noise amplifier and a unity-gain, shunt-feedback amplifier whose output is connected through a feedback capacitor to the series-feedback amplifier input. The stabilized capacitance loading of the anode allows distributed RC-line position encoding and subsequent time difference decoding by sensing the difference in rise times of pulses at the anode ends where the difference is primarily in response to the distributed capacitance along the anode. This allows the use of lower resistance wire anodes for spatial radiation detection which simplifies the counter construction of handling of the anodes, and stabilizes the anode resistivity at high count rates (>10 6 counts/sec). (author)

  16. HOT GAS LINES IN T TAURI STARS

    International Nuclear Information System (INIS)

    Ardila, David R.; Herczeg, Gregory J.; Gregory, Scott G.; Hillenbrand, Lynne A.; Ingleby, Laura; Bergin, Edwin; Bethell, Thomas; Calvet, Nuria; France, Kevin; Brown, Alexander; Edwards, Suzan; Johns-Krull, Christopher; Linsky, Jeffrey L.; Yang, Hao; Valenti, Jeff A.; Abgrall, Hervé; Alexander, Richard D.; Brown, Joanna M.; Espaillat, Catherine; Hussain, Gaitee

    2013-01-01

    For Classical T Tauri Stars (CTTSs), the resonance doublets of N V, Si IV, and C IV, as well as the He II 1640 Å line, trace hot gas flows and act as diagnostics of the accretion process. In this paper we assemble a large high-resolution, high-sensitivity data set of these lines in CTTSs and Weak T Tauri Stars (WTTSs). The sample comprises 35 stars: 1 Herbig Ae star, 28 CTTSs, and 6 WTTSs. We find that the C IV, Si IV, and N V lines in CTTSs all have similar shapes. We decompose the C IV and He II lines into broad and narrow Gaussian components (BC and NC). The most common (50%) C IV line morphology in CTTSs is that of a low-velocity NC together with a redshifted BC. For CTTSs, a strong BC is the result of the accretion process. The contribution fraction of the NC to the C IV line flux in CTTSs increases with accretion rate, from ∼20% to up to ∼80%. The velocity centroids of the BCs and NCs are such that V BC ∼> 4 V NC , consistent with the predictions of the accretion shock model, in at most 12 out of 22 CTTSs. We do not find evidence of the post-shock becoming buried in the stellar photosphere due to the pressure of the accretion flow. The He II CTTSs lines are generally symmetric and narrow, with FWHM and redshifts comparable to those of WTTSs. They are less redshifted than the CTTSs C IV lines, by ∼10 km s –1 . The amount of flux in the BC of the He II line is small compared to that of the C IV line, and we show that this is consistent with models of the pre-shock column emission. Overall, the observations are consistent with the presence of multiple accretion columns with different densities or with accretion models that predict a slow-moving, low-density region in the periphery of the accretion column. For HN Tau A and RW Aur A, most of the C IV line is blueshifted suggesting that the C IV emission is produced by shocks within outflow jets. In our sample, the Herbig Ae star DX Cha is the only object for which we find a P-Cygni profile in the C IV

  17. Hydrogen line formation in the quescent prominences

    International Nuclear Information System (INIS)

    Tsovookhuu, Ch.

    1980-01-01

    Equations of transfer and statistical equilibrium for hydronen atom with eight bound levels and continuum are solved simultaneously. A plane-parallel layer located perpendicular to the Sun surface is taken as a geometrical model. Input parameters of the physical model are optical thickness in the center of Hsub(α) line, electron temperature and concentration in the layer center are well as temperature and density gradients. Functions of sources, line profiles, total energies and the Balmer decrements, which are compared with observations and theoretical calculations made by other authors, have been calculated. The comparison shows that the results are quite acceptable and can be used when analyzing the spectrum and determining physical parameters of solar prominences. Dependence of different performances of the line (equivalent width, central intensity, halfwidth, depth of central depression etc.) on values of initial model parameters is investigated. Line halfwidth is more sensitive to the temperatuu value in the layer center, while central intensity - to the value of temperature gradient and a depth of central depression - to electron concentration. Calculated were shares of primary sources responsible for different excitation mechanism depending on total optical thickness as well as mean probabilities of quantum yield out of a medium which can be used during parametric accountancy of radiation diffusion in solar prominences [ru

  18. Line Spectrum of Intermediate Polars

    Directory of Open Access Journals (Sweden)

    Yonggi Kim

    1998-06-01

    Full Text Available Kim & Beuermann (1995, 1996 have developed a model for the propagation of X-rays from the accreting white dwarf through the infalling material and the re-emission of the energy deposited by photo-absorption in the optical (and UV spectral range. By using this model, we calculate the profiles of the Hγ emission-line spectrum of intermediate polars. Photoabsorption of X-rays by the infalling material is the dominant process in forming the observed energy-dependent rotational modulation of the X-ray flux. X-ray and optical modulations are sensitive to model parameters in different ways. In principle, these dependencies allow us to obtain improved insight into the accretion geometry of the intermediate polars. We present results of our calculations and compare them with the Hβ line spectrum (Kim & Beuermann 1996.

  19. Tuned cavity magnetometer sensitivity.

    Energy Technology Data Exchange (ETDEWEB)

    Okandan, Murat; Schwindt, Peter

    2009-09-01

    We have developed a high sensitivity (sensitivity levels.

  20. Cobalt sensitization and dermatitis

    DEFF Research Database (Denmark)

    Thyssen, Jacob P

    2012-01-01

    : This clinical review article presents clinical and scientific data on cobalt sensitization and dermatitis. It is concluded that cobalt despite being a strong sensitizer and a prevalent contact allergen to come up on patch testing should be regarded as a very complex metal to test with. Exposure...

  1. Multiple chemical sensitivity

    DEFF Research Database (Denmark)

    Tran, Marie Thi Dao; Arendt-Nielsen, Lars; Kupers, Ron

    2013-01-01

    BACKGROUND: Multiple Chemical Sensitivity (MCS) is a chronic condition characterized by recurrent, non-specific symptoms in response to chemically unrelated exposures in non-toxic concentrations. Although the pathophysiology of MCS remains unknown, central sensitization may be an important factor...

  2. Assessing Sensitiveness to Transport

    DEFF Research Database (Denmark)

    Lieb, Christoph; Suter, Stefan; Sánchez, Alfredo

    Summary The EU-project ASSET (ASessing SEnsitiveness to Transport) aims at developing and implementing a concise concept to assess transport sensitive areas (TSA) in a European context, i.e. areas in which transport leads to more serious impacts than in other areas. The aim of work package 2 (WP2...

  3. Finnish Teachers’ Ethical Sensitivity

    Directory of Open Access Journals (Sweden)

    Elina Kuusisto

    2012-01-01

    Full Text Available The study examined the ethical sensitivity of Finnish teachers (=864 using a 28-item Ethical Sensitivity Scale Questionnaire (ESSQ. The psychometric qualities of this instrument were analyzed, as were the differences in self-reported ethical sensitivity between practicing and student teachers and teachers of different subjects. The results showed that the psychometric qualities of the ESSQ were satisfactory and enabled the use of an explorative factor analysis. All Finnish teachers rated their level of ethical sensitivity as high, which indicates that they had internalized the ethical professionalism of teaching. However, practicing teachers’ assessments were higher than student teachers’. Moreover, science as a subject was associated with lower self-ratings of ethical sensitivity.

  4. Insulin sensitivity and albuminuria

    DEFF Research Database (Denmark)

    Pilz, Stefan; Rutters, Femke; Nijpels, Giel

    2014-01-01

    OBJECTIVE: Accumulating evidence suggests an association between insulin sensitivity and albuminuria, which, even in the normal range, is a risk factor for cardiovascular diseases. We evaluated whether insulin sensitivity is associated with albuminuria in healthy subjects. RESEARCH DESIGN...... AND METHODS: We investigated 1,415 healthy, nondiabetic participants (mean age 43.9 ± 8.3 years; 54.3% women) from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study, of whom 852 participated in a follow-up examination after 3 years. At baseline, insulin sensitivity...... was assessed by hyperinsulinemic-euglycemic clamps, expressed as the M/I value. Oral glucose tolerance test-based insulin sensitivity (OGIS), homeostasis model assessment of insulin resistance (HOMA-IR), and urinary albumin-to-creatinine ratio (UACR) were determined at baseline and follow-up. RESULTS...

  5. China's Bilateral Currency Swap Lines

    OpenAIRE

    Zhitao, Lin; Wenjie, Zhan; Cheung, Yin-Wong

    2016-01-01

    We study the determinants of China’s bilateral local currency swap lines that were established since the recent global finance crisis. It is found that economic factors, political considerations, and institutional characteristics including trade intensity, economic size, strategic partnership, free trade agreement, corruption, and stability affect the decision of signing a swap line agreement. Once a swap line agreement decision is made, the size of the swap line is then mainly affected by tr...

  6. Line pressure effects on differential pressure measurements

    International Nuclear Information System (INIS)

    Neff, G.G.; Evans, R.P.

    1982-01-01

    The performance of differential pressure transducers in experimental pressurized water reactor (PWR) systems was evaluated. Transient differential pressure measurements made using a simple calibration proportionality relating differential pressure to output voltage could have large measurement uncertainties. A more sophisticated calibration equation was derived to incorporate the effects of zero shifts and sensitivity shifts as pressure in the pressure sensing line changes with time. A comparison made between the original calibration proportionality equation and the derived compensation equation indicates that potential measurement uncertainties can be reduced

  7. A congestion line flow control in deregulated power system

    Directory of Open Access Journals (Sweden)

    Venkatarajan Shanmuga Sundaram

    2011-01-01

    Full Text Available Under open access, market-driven transactions have become the new independent decision variables defining the behavior of the power system. The possibility of transmission lines getting over-loaded is relatively more under deregulated operation because different parts of the system are owned by separate companies and in part operated under varying service charges. This paper discusses a two-tier algorithm for correcting the lone overloads in conjunction with the conventional power-flow methods. The method uses line flow sensitivities, which are computed by the East Decoupled Power-flow algorithm and can be adapted for on-line implementation.

  8. Mjollnir Rotational Line Scan Diagnostics.

    Science.gov (United States)

    1981-05-19

    using long cavity. M8 Removable Pellicle Beam Splitter for He-Ne Lineup Beam. Removed before HF or DF laser is turned on. 27 A 27 * A r of the chopper...three probe laser lines, however three lines were sequentially measured to verify the diagnostic equipment. Two of the three lines have been monitored

  9. CLO : The cell line ontology

    NARCIS (Netherlands)

    Sarntivijai, Sirarat; Lin, Yu; Xiang, Zuoshuang; Meehan, Terrence F.; Diehl, Alexander D.; Vempati, Uma D.; Schuerer, Stephan C.; Pang, Chao; Malone, James; Parkinson, Helen; Liu, Yue; Takatsuki, Terue; Saijo, Kaoru; Masuya, Hiroshi; Nakamura, Yukio; Brush, Matthew H.; Haendel, Melissa A.; Zheng, Jie; Stoeckert, Christian J.; Peters, Bjoern; Mungall, Christopher J.; Carey, Thomas E.; States, David J.; Athey, Brian D.; He, Yongqun

    2014-01-01

    Background: Cell lines have been widely used in biomedical research. The community-based Cell Line Ontology (CLO) is a member of the OBO Foundry library that covers the domain of cell lines. Since its publication two years ago, significant updates have been made, including new groups joining the CLO

  10. Parallel plate transmission line transformer

    NARCIS (Netherlands)

    Voeten, S.J.; Brussaard, G.J.H.; Pemen, A.J.M.

    2011-01-01

    A Transmission Line Transformer (TLT) can be used to transform high-voltage nanosecond pulses. These transformers rely on the fact that the length of the pulse is shorter than the transmission lines used. This allows connecting the transmission lines in parallel at the input and in series at the

  11. Topological Acoustic Delay Line

    Science.gov (United States)

    Zhang, Zhiwang; Tian, Ye; Cheng, Ying; Wei, Qi; Liu, Xiaojun; Christensen, Johan

    2018-03-01

    Topological protected wave engineering in artificially structured media is at the frontier of ongoing metamaterials research that is inspired by quantum mechanics. Acoustic analogues of electronic topological insulators have recently led to a wealth of new opportunities in manipulating sound propagation with strikingly unconventional acoustic edge modes immune to backscattering. Earlier fabrications of topological insulators are characterized by an unreconfigurable geometry and a very narrow frequency response, which severely hinders the exploration and design of useful devices. Here we establish topologically protected sound in reconfigurable phononic crystals that can be switched on and off simply by rotating its three-legged "atoms" without altering the lattice structure. In particular, we engineer robust phase delay defects that take advantage of the ultrabroadband reflection-free sound propagation. Such topological delay lines serve as a paradigm in compact acoustic devices, interconnects, and electroacoustic integrated circuits.

  12. Line broadening by focusing

    International Nuclear Information System (INIS)

    Brito, A.L. de; Jabs, A.

    1983-01-01

    It is pointed out that the spectral width of a quasi-monochromatic light beam broadens when the beam is focused. A quantitative formula for this broadening is derived from classical wave theory. The effect is shown to explain some experiments on laser beams done by E. Panarella which that author has explained under the ad-hoc hypothesis that the frequency of the photons changes along with the intensity of the light beam. The line broadening by focusing might also contribute to gas ionization by incident light when the ionization potential is well above the mean photon energy. Some remarks are made on some direct applications of the Heisenberg relations in comparison with our treatment. (Author) [pt

  13. Protease-sensitive synthetic prions.

    Directory of Open Access Journals (Sweden)

    David W Colby

    2010-01-01

    Full Text Available Prions arise when the cellular prion protein (PrP(C undergoes a self-propagating conformational change; the resulting infectious conformer is designated PrP(Sc. Frequently, PrP(Sc is protease-resistant but protease-sensitive (s prions have been isolated in humans and other animals. We report here that protease-sensitive, synthetic prions were generated in vitro during polymerization of recombinant (rec PrP into amyloid fibers. In 22 independent experiments, recPrP amyloid preparations, but not recPrP monomers or oligomers, transmitted disease to transgenic mice (n = 164, denoted Tg9949 mice, that overexpress N-terminally truncated PrP. Tg9949 control mice (n = 174 did not spontaneously generate prions although they were prone to late-onset spontaneous neurological dysfunction. When synthetic prion isolates from infected Tg9949 mice were serially transmitted in the same line of mice, they exhibited sPrP(Sc and caused neurodegeneration. Interestingly, these protease-sensitive prions did not shorten the life span of Tg9949 mice despite causing extensive neurodegeneration. We inoculated three synthetic prion isolates into Tg4053 mice that overexpress full-length PrP; Tg4053 mice are not prone to developing spontaneous neurological dysfunction. The synthetic prion isolates caused disease in 600-750 days in Tg4053 mice, which exhibited sPrP(Sc. These novel synthetic prions demonstrate that conformational changes in wild-type PrP can produce mouse prions composed exclusively of sPrP(Sc.

  14. Lu AA21004, a novel multimodal antidepressantwith activity exerted through serotonergic targets

    DEFF Research Database (Denmark)

    Mork, A.; Pehrson, A.; Montezinho, L. C. P.

    2012-01-01

    Background: Lu AA21004 is a multimodal antidepressant that functions as a 5-HT3 and 5-HT7 receptor antagonist, 5-HT1B receptor partial agonist, 5-HT1A receptor agonist and inhibitor of the 5-HT transporter in vitro. Here we investigated preclinical effects of Lu AA21004 1) on target occupancies, 2...... (5-HT), noradrenaline (NA), dopamine (DA), acetylcholine (ACh), histamine (Hist)] were measured by microdialysis. Antidepressant potential was assessed in the forced swim test using Flinders Sensitive Line (FSL) rats. Moreover, effects of Lu AA21004 on acquisition, consolidation and recall...

  15. Escitalopram reduces increased hippocampal cytogenesis in a genetic rat depression model

    DEFF Research Database (Denmark)

    Petersén, Asa; Wörtwein, Gitta; Gruber, Susanne H M

    2008-01-01

    to stressors, but, so far, not in models of depression. Here we report that the number of BrdU positive cells in hippocampus was (1) significantly higher in a rat model of depression, the Flinders Sensitive Line (FSL) compared to control FRL, (2) increased in both FSL and FRL following maternal separation, (3......) reduced by escitalopram treatment in maternally separated animals to the level found in non-separated animals. These results argue against the prevailing hypothesis that adult cytogenesis is reduced in depression and that the common mechanism underlying antidepressant treatments is to increase adult...

  16. The potential effectiveness of nanoparticles as radio sensitizers for radiotherapy

    Directory of Open Access Journals (Sweden)

    Mohammad Babaei

    2014-03-01

    Full Text Available Introduction: Application of nanoparticles as radio sensitizer is a promising field to improve efficiency of radiotherapy.Methods:This study was conducted to review nano radio sensitizers. PubMed, Ovid Medline, Science Direct, Scopus, ISI web of knowledge, and Springer databases were searched from 2000 to May 2013 to identify relevant studies. Search was restricted to English language. Results: We included any study that evaluated nanoparticles, volunteer of radio enhancement at radiotherapy on animals or cell lines. Nanoparticles can increase radio sensitivity of tumor cells. This effect was shown in vivo and in vitro, at kilovltage or megavoltage energies, in 24 reviewed studies. Focus of studies was on gold nanoparticles. Radio sensitizing effects of nanoparticles depend on nanoparticles’ size, type, concentration, intracellular localization, used irradiation energy and tested cell line.Conclusion: Literature suggests potency of nanoparticles for increasing cell radio sensitivity. Reviewed results are promising and warrant future clinical trials.

  17. Two-line hybrid rice male sterile line 'NHR111S' with a marker of green-revertible albino leaves

    International Nuclear Information System (INIS)

    Wu Wei; Liu Xin; Shu Xiaoli; Shu Qingyao; Xia Yingwu; Wu Dianxing

    2006-01-01

    NHR111S is a new two-line male sterile line with a marker of green-revertible albino leave that was bred from in vitro mutagens is of the thermo/photoperiod-sensitive male sterile line 'Guangzhan63S' by 60 Co γ-rays. It has the same desired agronomic traits, fertility characteristics and combining ability as characteristics of the parent. It is convenient to develop leaf color marker-aided elimination strategy in the multiplication and production of hybrid rice seeds. (authors)

  18. Fingerprinting the type of line edge roughness

    Science.gov (United States)

    Fernández Herrero, A.; Pflüger, M.; Scholze, F.; Soltwisch, V.

    2017-06-01

    Lamellar gratings are widely used diffractive optical elements and are prototypes of structural elements in integrated electronic circuits. EUV scatterometry is very sensitive to structure details and imperfections, which makes it suitable for the characterization of nanostructured surfaces. As compared to X-ray methods, EUV scattering allows for steeper angles of incidence, which is highly preferable for the investigation of small measurement fields on semiconductor wafers. For the control of the lithographic manufacturing process, a rapid in-line characterization of nanostructures is indispensable. Numerous studies on the determination of regular geometry parameters of lamellar gratings from optical and Extreme Ultraviolet (EUV) scattering also investigated the impact of roughness on the respective results. The challenge is to appropriately model the influence of structure roughness on the diffraction intensities used for the reconstruction of the surface profile. The impact of roughness was already studied analytically but for gratings with a periodic pseudoroughness, because of practical restrictions of the computational domain. Our investigation aims at a better understanding of the scattering caused by line roughness. We designed a set of nine lamellar Si-gratings to be studied by EUV scatterometry. It includes one reference grating with no artificial roughness added, four gratings with a periodic roughness distribution, two with a prevailing line edge roughness (LER) and another two with line width roughness (LWR), and four gratings with a stochastic roughness distribution (two with LER and two with LWR). We show that the type of line roughness has a strong impact on the diffuse scatter angular distribution. Our experimental results are not described well by the present modelling approach based on small, periodically repeated domains.

  19. Developing cultural sensitivity

    DEFF Research Database (Denmark)

    Ruddock, Heidi; Turner, deSalle

    2007-01-01

    . Background. Many countries are becoming culturally diverse, but healthcare systems and nursing education often remain mono-cultural and focused on the norms and needs of the majority culture. To meet the needs of all members of multicultural societies, nurses need to develop cultural sensitivity......Title. Developing cultural sensitivity: nursing students’ experiences of a study abroad programme Aim. This paper is a report of a study to explore whether having an international learning experience as part of a nursing education programme promoted cultural sensitivity in nursing students...... and incorporate this into caregiving. Method. A Gadamerian hermeneutic phenomenological approach was adopted. Data were collected in 2004 by using in-depth conversational interviews and analysed using the Turner method. Findings. Developing cultural sensitivity involves a complex interplay between becoming...

  20. Spontaneous baroreflex sensitivity

    DEFF Research Database (Denmark)

    Barthel, Petra; Bauer, Axel; Müller, Alexander

    2012-01-01

    Low baroreflex sensitivity (BRS) indicates poor prognosis after acute myocardial infarction. Noninvasive BRS assessment is complicated by nonstationarities and noise in electrocardiogram and pressure signals. Phase-rectified signal averaging is a novel signal processing technology overcoming thes...

  1. Radiation response of mouse lymphoid and myeloid cell lines. Pt. 1

    International Nuclear Information System (INIS)

    Radford, I.R.

    1994-01-01

    The sensitivity of 10 mouse lymphoid or myeloid cell lines to γ-ray- and DNA-associated 125 I-decay-induced clonogenic cell killing have been compared with their rate of loss of viability (membrane integrity) and with their putative cell type of origin. The increased sensitivity of haematopoietic cell lines to killing by DNA dsb may be related to their mode of death (apoptosis versus necrosis). Mode of cell death may thus be an important factor in determining the 'inherent radiosensitivity' of normal cells/tissues. Haematopoietic cell lines that undergo rapid interphase apoptotic death showed extreme sensitivity to DNA dsb. (author)

  2. Bipolar pulse forming line

    Science.gov (United States)

    Rhodes, Mark A.

    2008-10-21

    A bipolar pulse forming transmission line module for linear induction accelerators having first, second, third, fourth, and fifth planar conductors which form an interleaved stack with dielectric layers between the conductors. Each conductor has a first end, and a second end adjacent an acceleration axis. The first and second planar conductors are connected to each other at the second ends, the fourth and fifth planar conductors are connected to each other at the second ends, and the first and fifth planar conductors are connected to each other at the first ends via a shorting plate adjacent the first ends. The third planar conductor is electrically connectable to a high voltage source, and an internal switch functions to short a high voltage from the first end of the third planar conductor to the first end of the fourth planar conductor to produce a bipolar pulse at the acceleration axis with a zero net time integral. Improved access to the switch is enabled by an aperture through the shorting plate and the proximity of the aperture to the switch.

  3. On-line filtering

    International Nuclear Information System (INIS)

    Verkerk, C.

    1978-01-01

    Present day electronic detectors used in high energy physics make it possible to obtain high event rates and it is likely that future experiments will face even higher data rates than at present. The complexity of the apparatus increases very rapidly with time and also the criteria for selecting desired events become more and more complex. So complex in fact that the fast trigger system cannot be designed to fully cope with it. The interesting events become thus contaminated with multitudes of uninteresting ones. To distinguish the 'good' events from the often overwhelming background of other events one has to resort to computing techniques. Normally this selection is made in the first part of the analysis of the events, analysis normally performed on a powerful scientific computer. This implies however that many uninteresting or background events have to be recorded during the experiment for subsequent analysis. A number of undesired consequences result; and these constitute a sufficient reason for trying to perform the selection at an earlier stage, in fact ideally before the events are recorded on magnetic tape. This early selection is called 'on-line filtering' and it is the topic of the present lectures. (Auth.)

  4. PEARS Emission Line Galaxies

    Science.gov (United States)

    Pirzkal, Nor; Rothberg, Barry; Ly, Chun; Rhoads, James E.; Malhotra, Sangeeta; Grogin, Norman A.; Dahlen, Tomas; Meurer, Gerhardt R.; Walsh, Jeremy; Hathi, Nimish P.; hide

    2012-01-01

    We present a full analysis of the Probing Evolution And Reionization Spectroscopically (PEARS) slitless grism spectroscopic data obtained vl'ith the Advanced Camera for Surveys on HST. PEARS covers fields within both the Great Observatories Origins Deep Survey (GOODS) North and South fields, making it ideal as a random surveY of galaxies, as well as the availability of a wide variety of ancillary observations to support the spectroscopic results. Using the PEARS data we are able to identify star forming galaxies within the redshift volume 0 galaxies down to a limiting flux of approx 10 - 18 erg/s/sq cm . The ELRs have also been compared to the properties of the host galaxy, including morphology, luminosity, and mass. From this analysis we find three key results: 1) The computed line luminosities show evidence of a flattening in the luminosity function with increasing redshift; 2) The star forming systems show evidence of disturbed morphologies, with star formation occurring predominantly within one effective (half-light) radius. However, the morphologies show no correlation with host stellar mass; and 3) The number density of star forming galaxies with M(*) >= 10(exp 9) Solar M decreases by an order of magnitude at z<=0.5 relative to the number at 0.5 < z < 0.9 in support of the argument for galaxy downsizing.

  5. Combined echo offset (Dixon) and line volume chemical shift imaging as a clinical imaging protocol

    International Nuclear Information System (INIS)

    Listerud, J.; Chan, T.; Lenkinski, R.E.; Kressel, H.Y.; Chao, P.W.

    1989-01-01

    The authors have studied the sensitivity and specificity of the line-volume chemical-shift imaging (CSI) method as compared with the Dixon method they have recently implemented on a Signa, which supports a variety of options. Potential sources or error for the Dixon method include line broadening due to susceptibility, field inhomogeneity, and errors form olefinic resonances associated with fat, which behave like water in the Dixon regime. The authors investigate whether a combined Dixon/line-volume CSI method could be used to improve the placement of the line volume and to provide higher sensitivity and specificity than does the Dixon method alone

  6. Optimization of line configuration and balancing for flexible machining lines

    Science.gov (United States)

    Liu, Xuemei; Li, Aiping; Chen, Zurui

    2016-05-01

    Line configuration and balancing is to select the type of line and allot a given set of operations as well as machines to a sequence of workstations to realize high-efficiency production. Most of the current researches for machining line configuration and balancing problems are related to dedicated transfer lines with dedicated machine workstations. With growing trends towards great product variety and fluctuations in market demand, dedicated transfer lines are being replaced with flexible machining line composed of identical CNC machines. This paper deals with the line configuration and balancing problem for flexible machining lines. The objective is to assign operations to workstations and find the sequence of execution, specify the number of machines in each workstation while minimizing the line cycle time and total number of machines. This problem is subject to precedence, clustering, accessibility and capacity constraints among the features, operations, setups and workstations. The mathematical model and heuristic algorithm based on feature group strategy and polychromatic sets theory are presented to find an optimal solution. The feature group strategy and polychromatic sets theory are used to establish constraint model. A heuristic operations sequencing and assignment algorithm is given. An industrial case study is carried out, and multiple optimal solutions in different line configurations are obtained. The case studying results show that the solutions with shorter cycle time and higher line balancing rate demonstrate the feasibility and effectiveness of the proposed algorithm. This research proposes a heuristic line configuration and balancing algorithm based on feature group strategy and polychromatic sets theory which is able to provide better solutions while achieving an improvement in computing time.

  7. Isolation and cross-sensitivity of X-ray-sensitive mutants of V79-4 hamster cells

    International Nuclear Information System (INIS)

    Jones, N.J.; Cox, R.; Thacker, J.

    1987-01-01

    The V79-4 Chinese hamster line was mutagenized and surviving clones screened for X-ray sensitivity using a replica microwell technique. One slightly sensitive clone and 3 clearly sensitive clones were isolated from approximately 5000 screened, and designated irs 1 to irs 4. The 3 more sensitive clones showed different responses to the genotoxic agents mitomycin C (MMC), ethyl methanesulphonate (EMS) and ultraviolet light (UV). irs 1 showed considerable sensitivity to all the agents tested, in the order MMC >> EMS > UV. irs 2 and irs 3 had similar sensitivities to EMS and to UV (EMS > UV) but irs 3 was more sensitive than irs 2 to MMC. None of these mutants is identical in phenotype to previously published mutants. (Auth.)

  8. Alternate Double Single Track Lines

    Energy Technology Data Exchange (ETDEWEB)

    Moraga Contreras, P.; Grande Andrade, Z.; Castillo Ron, E.

    2016-07-01

    The paper discusses the advantages and shortcomings of alternate double single track (ADST) lines with respect to double track lines for high speed lines. ADST lines consists of sequences of double and single track segments optimally selected in order to reduce the construction and maintenance costs of railway lines and to optimize the timetables used to satisfy a given demand. The single tracks are selected to coincide with expensive segments (tunnels and viaducts) and the double tracks are chosen to coincide with flat areas and only where they are necessary. At the same time, departure times are adjusted for trains to cross at the cheap double track segments. This alternative can be used for new lines and also for existing conventional lines where some new tracks are to be constructed to reduce travel time (increase speed). The ADST proposal is illustrated with some examples of both types (new lines and where conventional lines exist), including the Palencia-Santander, the Santiago-Valparaíso-Viña del Mar and the Dublin-Belfast lines, where very important reductions (90 %) are obtained, especially where a railway infrastructure already exist. (Author)

  9. On line portal imaging

    International Nuclear Information System (INIS)

    Munro, Peter

    1997-01-01

    Purpose/Objective: The purpose of this presentation is to examine the various imaging devices that have been developed for portal imaging, describe some of the image registration methods that have been developed to determine geometric errors quantitatively, and discuss how portal imaging has been incorporated into clinical practice. Discussion: Verification of patient positioning has always been an important aspect of external beam radiation therapy. Over the past decade many portal imaging devices have been developed by individual investigators and most accelerator manufacturers now offer 'on-line' portal imaging systems. The commercial devices include T.V. camera-based systems, liquid ionisation chamber systems, and shortly, flat panel systems. The characteristics of these imaging systems will be discussed. In addition, other approaches such as the use of kilovoltage x-ray sources, video monitoring, and ultrasound have been proposed for improving patient positioning. Some of the advantages of these approaches will be discussed. One of the major advantages of on-line portal imaging is that many quantitative techniques have been developed to detect errors in patient positioning. The general approach is to register anatomic structures on a portal image with the same structures on a digitized simulator film. Once the anatomic structures have been registered, any discrepancies in the position of the patient can be identified. One problem is finding a common frame of reference for the simulator and portal images, since the location of the radiation field within the pixel matrix may differ for the two images. As a result, a common frame of reference has to be established before the anatomic structures in the images can be registered - generally by registering radiation field edges identified in the simulator and portal images. In addition, distortions in patient geometry or rotations out of the image plane can confound the image registration techniques. Despite the

  10. On line portal imaging

    International Nuclear Information System (INIS)

    Munro, Peter

    1996-01-01

    Purpose/Objective: The purpose of this presentation is to examine the various imaging devices that have been developed for portal imaging; describe some of the image registration methods that have been developed to determine geometric errors quantitatively; discuss some of the ways that portal imaging has been incorporated into routine clinical practice; describe quality assurance procedures for these devices, and discuss the use of portal imaging devices for dosimetry applications. Discussion: Verification of patient positioning has always been an important aspect of external beam radiation therapy. Over the past decade many portal imaging devices have been developed by individual investigators and most accelerator manufacturers now offer 'on-line' portal imaging systems. The commercial devices can be classified into three categories: T.V. camera-based systems, liquid ionisation chamber systems, and amorphous silicon systems. Many factors influence the quality of images generated by these portal imaging systems. These include factors which are unavoidable (e.g., low subject contrast), factors which depend upon the individual imaging device forming the image (e.g., dose utilisation, spatial resolution) as well as factors which depend upon the characteristics of the linear accelerator irradiating the imaging system (x-ray source size, image magnification). The characteristics of individual imaging systems, such as spatial resolution, temporal response, and quantum utilisation will be discussed. One of the major advantages of on-line portal imaging is that many quantitative techniques have been developed to detect errors in patient positioning. The general approach is to register anatomic structures on a portal image with the same structures on a digitized simulator film. Once the anatomic structures have been registered, any discrepancies in the position of the patient can be identified. However, the task is not nearly as straight-forward as it sounds. One problem

  11. Recent approaches for enhancing sensitivity in enantioseparations by CE.

    Science.gov (United States)

    Sánchez-Hernández, Laura; García-Ruiz, Carmen; Luisa Marina, María; Luis Crego, Antonio

    2010-01-01

    This article reviews the latest methodological and instrumental improvements for enhancing sensitivity in chiral analysis by CE. The review covers literature from March 2007 until May 2009, that is, the works published after the appearance of the latest review article on the same topic by Sánchez-Hernández et al. [Electrophoresis 2008, 29, 237-251]. Off-line and on-line sample treatment techniques, on-line sample preconcentration strategies based on electrophoretic and chromatographic principles, and alternative detection systems to the widely employed UV/Vis detection in CE are the most relevant approaches discussed for improving sensitivity. Microchip technologies are also included since they can open up great possibilities to achieve sensitive and fast enantiomeric separations.

  12. WHAT IF (Sensitivity Analysis

    Directory of Open Access Journals (Sweden)

    Iulian N. BUJOREANU

    2011-01-01

    Full Text Available Sensitivity analysis represents such a well known and deeply analyzed subject that anyone to enter the field feels like not being able to add anything new. Still, there are so many facets to be taken into consideration.The paper introduces the reader to the various ways sensitivity analysis is implemented and the reasons for which it has to be implemented in most analyses in the decision making processes. Risk analysis is of outmost importance in dealing with resource allocation and is presented at the beginning of the paper as the initial cause to implement sensitivity analysis. Different views and approaches are added during the discussion about sensitivity analysis so that the reader develops an as thoroughly as possible opinion on the use and UTILITY of the sensitivity analysis. Finally, a round-up conclusion brings us to the question of the possibility of generating the future and analyzing it before it unfolds so that, when it happens it brings less uncertainty.

  13. Sensitivity Analysis Without Assumptions.

    Science.gov (United States)

    Ding, Peng; VanderWeele, Tyler J

    2016-05-01

    Unmeasured confounding may undermine the validity of causal inference with observational studies. Sensitivity analysis provides an attractive way to partially circumvent this issue by assessing the potential influence of unmeasured confounding on causal conclusions. However, previous sensitivity analysis approaches often make strong and untestable assumptions such as having an unmeasured confounder that is binary, or having no interaction between the effects of the exposure and the confounder on the outcome, or having only one unmeasured confounder. Without imposing any assumptions on the unmeasured confounder or confounders, we derive a bounding factor and a sharp inequality such that the sensitivity analysis parameters must satisfy the inequality if an unmeasured confounder is to explain away the observed effect estimate or reduce it to a particular level. Our approach is easy to implement and involves only two sensitivity parameters. Surprisingly, our bounding factor, which makes no simplifying assumptions, is no more conservative than a number of previous sensitivity analysis techniques that do make assumptions. Our new bounding factor implies not only the traditional Cornfield conditions that both the relative risk of the exposure on the confounder and that of the confounder on the outcome must satisfy but also a high threshold that the maximum of these relative risks must satisfy. Furthermore, this new bounding factor can be viewed as a measure of the strength of confounding between the exposure and the outcome induced by a confounder.

  14. Sensitivities of ionic explosives

    Science.gov (United States)

    Politzer, Peter; Lane, Pat; Murray, Jane S.

    2017-03-01

    We have investigated the relevance for ionic explosive sensitivity of three factors that have been demonstrated to be related to the sensitivities of molecular explosives. These are (1) the maximum available heat of detonation, (2) the amount of free space per molecule (or per formula unit) in the crystal lattice and (3) specific features of the electrostatic potential on the molecular or ionic surface. We find that for ionic explosives, just as for molecular ones, there is an overall tendency for impact sensitivity to increase as the maximum detonation heat release is greater. This means that the usual emphasis upon designing explosives with large heats of detonation needs to be tempered somewhat. We also show that a moderate detonation heat release does not preclude a high level of detonation performance for ionic explosives, as was already demonstrated for molecular ones. Relating the free space per formula unit to sensitivity may require a modified procedure for ionic explosives; this will continue to be investigated. Finally, an encouraging start has been made in linking impact sensitivities to the electrostatic potentials on ionic surfaces, although limited so far to ammonium salts.

  15. Managing a sensitive project

    International Nuclear Information System (INIS)

    Etcheber, Pascal

    1998-01-01

    A 'sensitive' project needs to be managed differently from a 'normal' project. This statement might seem simple enough. However, it does not seem to be a simple task to prove it in twenty minutes. This paper is an attempt to share with the audience some of the experiences the company had dealing with sensitive projects. It describes what a sensitive project is, though of all people, the 'nuclear' should know. Then the common mistakes are described, that are made in the hoping that some personal experiences are recognised. Finally the company's strategy is shown, how we foster third party support and the main tools to be used. Ultimately, success is ensured by having a sufficient quantity of allies. A sensitive project does not die because it has too many opponents, but because it has too few allies. Finding and helping allies to act is the thrust of our activity. It enables sensitive projects which deserve to succeed to do so, where traditional management fails miserably

  16. Design of LEIR Transfer Lines

    CERN Document Server

    Carli, Ch; Hemery, J-Y

    2002-01-01

    The LEIR transfer lines are designed to transport the ion beam from the Linac 3 to LEIR and, after accumulation and acceleration from LEIR to the PS. A part of the transfer line is used for both, injection and extraction. Thus, it is natural to design injection and extraction optics in common. Beside optics constraints, the geometry of the existing machines (Linac 3, LEIR and PS) and transfer tunnels have to be respected. A new proposal for the LEIR transfer lines is presented.

  17. Detecting Weak Spectral Lines in Interferometric Data through Matched Filtering

    Science.gov (United States)

    Loomis, Ryan A.; Öberg, Karin I.; Andrews, Sean M.; Walsh, Catherine; Czekala, Ian; Huang, Jane; Rosenfeld, Katherine A.

    2018-04-01

    Modern radio interferometers enable observations of spectral lines with unprecedented spatial resolution and sensitivity. In spite of these technical advances, many lines of interest are still at best weakly detected and therefore necessitate detection and analysis techniques specialized for the low signal-to-noise ratio (S/N) regime. Matched filters can leverage knowledge of the source structure and kinematics to increase sensitivity of spectral line observations. Application of the filter in the native Fourier domain improves S/N while simultaneously avoiding the computational cost and ambiguities associated with imaging, making matched filtering a fast and robust method for weak spectral line detection. We demonstrate how an approximate matched filter can be constructed from a previously observed line or from a model of the source, and we show how this filter can be used to robustly infer a detection significance for weak spectral lines. When applied to ALMA Cycle 2 observations of CH3OH in the protoplanetary disk around TW Hya, the technique yields a ≈53% S/N boost over aperture-based spectral extraction methods, and we show that an even higher boost will be achieved for observations at higher spatial resolution. A Python-based open-source implementation of this technique is available under the MIT license at http://github.com/AstroChem/VISIBLE.

  18. Improving restorer line of hybrid rice by irradiation

    International Nuclear Information System (INIS)

    Guo Guangrong; Yi Weiping; Liu Wuquan

    1995-03-01

    The work for improving restorer line of hybrid rice has been done. The results showed the radiosensitivity of foreign varieties overtakes Chinese ones at average level. Because of their different blood relationship, there are various situation on foreign varieties, i.e. varieties from IR system are not sensitive, Shui-yun system are second and Miyang system are sensitive. The radiosensitivity for restorer lines of hybrid F 0 overtakes one for F 1 . According to this results. We have put forward the point of view 'Multi-gene type blend system'. M 2 mutant frequency of restorer line was investigated. The results showed: there was a little difference between the total mutant frequencies from the different varieties. But, there may be difference in some characters by over thirty times between them. So a problem, worthy to be further studied is proposed that do the differences of radiosensitivity between varieties relate to the mutant frequency of these characters? Various mutants were obtained by irradiation treatment, among which a few mutants changed to maintainer line because losing restorer genes, other more mutants still were restorer lines. New combinations developed by these new mutant restorer lines have strong heterosis. The optimum combinations have been utilized in rice production. (7 tabs.)

  19. Sensitizing properties of proteins

    DEFF Research Database (Denmark)

    Poulsen, Lars K.; Ladics, Gregory S; McClain, Scott

    2014-01-01

    The scope of allergy risk is diverse considering the myriad ways in which protein allergenicity is affected by physiochemical characteristics of proteins. The complexity created by the matrices of foods and the variability of the human immune system add additional challenges to understanding...... the relationship between sensitization potential and allergy disease. To address these and other issues, an April 2012 international symposium was held in Prague, Czech Republic, to review and discuss the state-of-the-science of sensitizing properties of protein allergens. The symposium, organized by the Protein...... Allergenicity Technical Committee of the International Life Sciences Institute's Health and Environmental Sciences Institute, featured presentations on current methods, test systems, research trends, and unanswered questions in the field of protein sensitization. A diverse group of over 70 interdisciplinary...

  20. Screening sensitivity theory

    International Nuclear Information System (INIS)

    Oblow, E.M.; Perey, F.G.

    1984-01-01

    A comprehensive rigorous theory is developed for screening sensitivity coefficients in largescale modeling applications. The theory uses Bayesian inference and group theory to establish a probabilistic framework for solving an underdetermined system of linear equations. The underdetermined problem is directly related to statistical screening sensitivity theory as developed in recent years. Several examples of the new approach to screening are worked out in detail and comparisons are made with statistical approaches to the problem. The drawbacks of these latter methods are discussed at some length

  1. Highly Sensitive Optical Receivers

    CERN Document Server

    Schneider, Kerstin

    2006-01-01

    Highly Sensitive Optical Receivers primarily treats the circuit design of optical receivers with external photodiodes. Continuous-mode and burst-mode receivers are compared. The monograph first summarizes the basics of III/V photodetectors, transistor and noise models, bit-error rate, sensitivity and analog circuit design, thus enabling readers to understand the circuits described in the main part of the book. In order to cover the topic comprehensively, detailed descriptions of receivers for optical data communication in general and, in particular, optical burst-mode receivers in deep-sub-µm CMOS are presented. Numerous detailed and elaborate illustrations facilitate better understanding.

  2. On line portal imaging

    International Nuclear Information System (INIS)

    Munro, Peter

    1995-01-01

    Purpose/Objective: The purpose of this presentation is to review the physics of imaging with high energy x-ray beams; examine the various imaging devices that have been developed for portal imaging; describe some of the image registration methods that have been developed to determine errors in patient positioning quantitatively; and discuss some of the ways that portal imaging has been incorporated into routine clinical practice. Verification of patient positioning has always been an important aspect of external beam radiation therapy. Checks of patient positioning have generally been done with film, however, film suffers from a number of drawbacks, such as poor image display and delays due to film development. Over the past decade many portal imaging devices have been developed by individual investigators and most accelerator manufacturers now offer 'on-line' portal imaging systems, which are intended to overcome the limitations of portal films. The commercial devices can be classified into three categories: T.V. camera-based systems, liquid ionisation chamber systems, and amorphous silicon systems. Many factors influence the quality of images generated by these portal imaging systems. These include factors which are unavoidable (e.g., low subject contrast), factors which depend upon the individual imaging device forming the image (e.g., dose utilisation, spatial resolution) as well as factors which depend upon the characteristics of the linear accelerator irradiating the imaging system (x-ray source size, image magnification). The fundamental factors which limit image quality and the characteristics of individual imaging systems, such as spatial resolution, temporal response, and quantum utilisation will be discussed. One of the major advantages of on-line portal imaging is that many quantitative techniques have been developed to detect errors in patient positioning. The general approach is to register anatomic structures on a portal image with the same

  3. Guam and the Northern Mariana Islands ESI: HYDRO (Hydrography Lines and Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains vector lines and polygons representing coastal hydrography used in the creation of the Environmental Sensitivity Index (ESI) for Guam and the...

  4. Rhode Island, Connecticut, New York, and New Jersey ESI: HYDRO (Hydrography Lines and Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains vector lines and polygons representing coastal hydrography used in the creation of the Environmental Sensitivity Index (ESI) for Rhode Island,...

  5. Cook Inlet and Kenai Peninsula, Alaska ESI: HYDRO (Hydrography Lines and Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains vector lines and polygons representing coastal hydrography used in the creation of the Environmental Sensitivity Index (ESI) for Cook Inlet...

  6. Self-Shielding Of Transmission Lines

    Energy Technology Data Exchange (ETDEWEB)

    Christodoulou, Christos [Univ. of New Mexico, Albuquerque, NM (United States)

    2017-03-01

    The use of shielding to contend with noise or harmful EMI/EMR energy is not a new concept. An inevitable trade that must be made for shielding is physical space and weight. Space was often not as much of a painful design trade in older larger systems as they are in today’s smaller systems. Today we are packing in an exponentially growing number of functionality within the same or smaller volumes. As systems become smaller and space within systems become more restricted, the implementation of shielding becomes more problematic. Often, space that was used to design a more mechanically robust component must be used for shielding. As the system gets smaller and space is at more of a premium, the trades starts to result in defects, designs with inadequate margin in other performance areas, and designs that are sensitive to manufacturing variability. With these challenges in mind, it would be ideal to maximize attenuation of harmful fields as they inevitably couple onto transmission lines without the use of traditional shielding. Dr. Tom Van Doren proposed a design concept for transmission lines to a class of engineers while visiting New Mexico. This design concept works by maximizing Electric field (E) and Magnetic Field (H) field containment between operating transmission lines to achieve what he called “Self-Shielding”. By making the geometric centroid of the outgoing current coincident with the return current, maximum field containment is achieved. The reciprocal should be true as well, resulting in greater attenuation of incident fields. Figure’s 1(a)-1(b) are examples of designs where the current centroids are coincident. Coax cables are good examples of transmission lines with co-located centroids but they demonstrate excellent field attenuation for other reasons and can’t be used to test this design concept. Figure 1(b) is a flex circuit design that demonstrate the implementation of self-shielding vs a standard conductor layout.

  7. Similarity law for Widom lines and coexistence lines.

    Science.gov (United States)

    Banuti, D T; Raju, M; Ihme, M

    2017-05-01

    The coexistence line of a fluid separates liquid and gaseous states at subcritical pressures, ending at the critical point. Only recently, it became clear that the supercritical state space can likewise be divided into regions with liquidlike and gaslike properties, separated by an extension to the coexistence line. This crossover line is commonly referred to as the Widom line, and is characterized by large changes in density or enthalpy, manifesting as maxima in the thermodynamic response functions. Thus, a reliable representation of the coexistence line and the Widom line is important for sub- and supercritical applications that depend on an accurate prediction of fluid properties. While it is known for subcritical pressures that nondimensionalization with the respective species critical pressures p_{cr} and temperatures T_{cr} only collapses coexistence line data for simple fluids, this approach is used for Widom lines of all fluids. However, we show here that the Widom line does not adhere to the corresponding states principle, but instead to the extended corresponding states principle. We resolve this problem in two steps. First, we propose a Widom line functional based on the Clapeyron equation and derive an analytical, species specific expression for the only parameter from the Soave-Redlich-Kwong equation of state. This parameter is a function of the acentric factor ω and compares well with experimental data. Second, we introduce the scaled reduced pressure p_{r}^{*} to replace the previously used reduced pressure p_{r}=p/p_{cr}. We show that p_{r}^{*} is a function of the acentric factor only and can thus be readily determined from fluid property tables. It collapses both subcritical coexistence line and supercritical Widom line data over a wide range of species with acentric factors ranging from -0.38 (helium) to 0.34 (water), including alkanes up to n-hexane. By using p_{r}^{*}, the extended corresponding states principle can be applied within

  8. Genetics Home Reference: warfarin sensitivity

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions Warfarin sensitivity Warfarin sensitivity Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Warfarin sensitivity is a condition in which individuals have ...

  9. Responses to cholinergic agonists of rats selectively bred for differential sensitivity to ethanol.

    Science.gov (United States)

    de Fiebre, C M; Romm, E; Collins, J T; Draski, L J; Deitrich, R A; Collins, A C

    1991-03-01

    Alcoholics are almost invariably heavy users of tobacco. Both alcoholism and smoking appear to be influenced by genetic factors but it is not known whether the same or different genes regulate the abuse of ethanol and nicotine. Recent studies have demonstrated that the long-sleep (LS) and short-sleep (SS) mouse lines, which were selectively bred for differences in ethanol-induced anesthesia ("sleep-time"), also differ in several effects of nicotine and the muscarinic agonist, oxotremorine. In order to determine whether or not these differences are due to chance, the relative sensitivities of rat lines which were selectively bred for differences in ethanol-induced sleep-time were determined. The high alcohol sensitivity (HAS) rat line was more sensitive to the locomotor and body temperature depressant effects of nicotine than was the low alcohol sensitivity (LAS) rat line. The control line (CAS) was intermediate in sensitivity. The rat lines did not differ in sensitivity to oxotremorine's hypothermia-producing effects. The numbers and affinities of two classes of brain nicotinic receptors were measured in eight brain regions. No differences among the rat lines were detected. These results suggest that ethanol elicits some of its depressant actions via an effect on brain nicotinic systems, but the differences in sensitivity to ethanol and nicotine are probably not due to differences in the number of brain nicotinic receptors. Perhaps this interaction explains the high correlation between alcoholism and smoking in humans.

  10. Transmission Delay Modeling of Packet Communication over Digital Subscriber Line

    Directory of Open Access Journals (Sweden)

    Jiri Vodrazka

    2013-01-01

    Full Text Available Certain multimedia and voice services, such as VoIP, IPTV, etc., are significantly delay sensitive and their performance is influenced by the overall transmission delay and its variance. One of the most common solutions used in access networks are xDSL lines, especially ADSL2+ or VDSL2. Although these subscriber lines also use packet communication, there are several differences and mechanisms, which influence their resulting delay. Their delay characteristics are also dependent on the individual settings of each xDSL provider, therefore we decided to investigate this area for typical commercially available lines in Czech Republic. Based on the measured values and experiments with real ADSL2+ lines we also developed a potential modeling method, which is presented in this article as well. The parameters for packet jitter based on the generalized Pareto distribution were modeled.

  11. Radiation response of haematopoietic cell lines of human origin

    International Nuclear Information System (INIS)

    Lehnert, S.; Rybka, W.B.; Suissa, S.; Giambattisto, D.

    1986-01-01

    Six human haematopoietic cell lines, five of leukaemic origin, including cells with myeloid, lymphoid and undifferentiated phenotype have been studied with respect to radiation response. The intrinsic radio-sensitivity of the cells varied widely, the D 0 s ranging from 0.53 to 1.39 Gy. Five of the cell lines showed some capacity to accumulate sublethal damage; in three of these, enhanced survival was demonstrated in split-dose experiments. One cell line (HL-60) was anomalous in that although little accumulation of sublethal damage was demonstrable, survival was enhanced by fractionation of the dose. Five of the six cell lines studied were of leukaemic origin. The results support the belief that, in contrast to the almost constant radiosensitivity of normal haematopoietic cell progenitors, leukaemic cell progenitors may show a wide range of radiosensitivities. (author)

  12. Fractions, Number Lines, Third Graders

    Science.gov (United States)

    Cramer, Kathleen; Ahrendt, Sue; Monson, Debra; Wyberg, Terry; Colum, Karen

    2017-01-01

    The Common Core State Standards for Mathematics (CCSSM) (CCSSI 2010) outlines ambitious goals for fraction learning, starting in third grade, that include the use of the number line model. Understanding and constructing fractions on a number line are particularly complex tasks. The current work of the authors centers on ways to successfully…

  13. Mechanical Behaviour of Lined Pipe

    NARCIS (Netherlands)

    Hilberink, A.

    2011-01-01

    Installing lined pipe by means of the reeling installation method seems to be an attractive combination, because it provides the opportunity of eliminating the demanding welds from the critical time offshore and instead preparing them onshore. However, reeling of lined pipe is not yet proven

  14. Marine line fish research programme

    CSIR Research Space (South Africa)

    SANCOR

    1979-04-01

    Full Text Available This report outlines the framework for a marine line fish programme under the aegis of the South African National Committee for Oceanographic Research (SANCOR). An attempt is made to assess the state of knowledge about South African marine line...

  15. A tangent subsolar merging line

    International Nuclear Information System (INIS)

    Crooker, N.U.; Siscoe, G.L.; Toffoletto, F.R.

    1990-01-01

    The authors describe a global magnetospheric model with a single subsolar merging line whose position is determined neither locally by the relative orientations and strengths of the merging fields nor globally by the orientation of a separator line--the governing parameters of most previous models--but by the condition of tangential contact between the external field and the magnetopause. As in previous models, the tilt of the merging line varies with IMF orientation, but here it also depends upon the ratio of Earth's magnetic flux that leaks out of the magnetopause to IMF flux that penetrates in. In the limiting case treated by Alekseyev and Belen'kaya, with no leakage of Earth's field and total IMF penetration, the merging line forms a great circle around a spherical magnetosphere where undeviated IMF lines lie tangent to its surface. This tangent merging line lies perpendicular to the IMF. They extend their work to the case of finite leakage and partial penetration, which distort the IMF into a draped pattern, thus changing the locus of tangency to the sphere. In the special case where the penetrating IMF flux is balanced by an equal amount of Earth flux leakage, the tangent merging line bisects the angle between the IMF and Earth's northward subsolar field. This result is identical to the local merging line model result for merging fields with equal magnitude. Here a global flux balance condition replaces the local equal magnitude condition

  16. PAYMENT CAPACITY SENSITIVITY FACTORS

    Directory of Open Access Journals (Sweden)

    Daniel BRÎNDESCU – OLARIU

    2014-11-01

    The results of the study facilitate the determination and classification of the main sensitivity factors for the payment capacity at sample level, the establishment of general benchmarks for the payment capacity (as no such benchmarks currently exist in the Romanian literature and the identification of the mechanisms through which the variation of different factors impacts the payment capacity.

  17. High-Sensitivity Spectrophotometry.

    Science.gov (United States)

    Harris, T. D.

    1982-01-01

    Selected high-sensitivity spectrophotometric methods are examined, and comparisons are made of their relative strengths and weaknesses and the circumstances for which each can best be applied. Methods include long path cells, noise reduction, laser intracavity absorption, thermocouple calorimetry, photoacoustic methods, and thermo-optical methods.…

  18. Sensitization of Parker fittings

    International Nuclear Information System (INIS)

    Wilber, W.W.

    1985-09-01

    At your request, ferrules from 316 SS Parker-Hannifen compression fittings at the FFTF have been examined and evaluated to determine the metallurgical condition as related to carbide precipitation in grain boundaries (known as sensitization) and the implications this may have with regard to corrosion resistance. To accomplish this, two ferrules from new stock, two ferrules from old stock and two ferrules that had seen service were examined metallurgically. The samples were prepared for optical metallography. They were viewed in both the etched and unetched condition and analyzed on the scanning electron microscope (SEM) for elemental content. It was confirmed that the ferrules from new stock had a 5 mil thick nitrided layer on the ferrule ID at the lead end and that the 316 SS ferrule material was in the sensitized condition, indicating low resistance to aqueous corrosion. The material from old stock had no nitride layer but was in the sensitized condition indicating low resistance to aqueous corrosion. The ferrules that had seen service had not been nitrided and were not sensitized indicating high resistance to aqueous corrosion

  19. Radiation-sensitive diacrylates

    International Nuclear Information System (INIS)

    Demajistre, R.

    1976-01-01

    Novel diacrylates are prepared by reacting a monohydroxylated acrylic monomer with a polyisocyanate. The reaction product may be polymerized by subjecting to ionizing irradiation, actinic light or to free radical catalysts to form a useful coating material. The diacrylates may also be copolymerized with other radiation sensitive materials. 6 claims, no drawings

  20. Multiple Chemical Sensitivity

    DEFF Research Database (Denmark)

    Junge, Anne Gram

    Et voksende antal mennesker i Danmark oplever at være overfølsomme over for dufte og kemikalier. Imidlertid er den tilskrevne diagnose Multiple Chemical Sensitivity (MCS) ikke medicinsk anerkendt i Danmark pga. mangel på organiske og patofysiologisk basis for symptomerne. Dette speciale bygger på...

  1. Radiation induced variations in photoperiod-sensitivity, thermo-sensitivity and the number of days to heading in rice

    International Nuclear Information System (INIS)

    Hsieh, S.C.

    1975-01-01

    Radiation induced semi-dwarf mutants derived from five japonica type varieties of rice were studied with regard to their photoperiod-sensitivity, thermo-sensitivity and the number of days to heading. The experiment was carried out under the natural conditions at Taipei. The coefficient of photoperiod-sensitivity and thermo-sensitivity as developed by Oka (1954) were estimated for the mutants in comparison with their original varieties. It was observed that these various physiological characters could be altered easily by mutations. Mutants showed wider ranges in both positive and negative directions than their original varieties in all physiological characters studied. Even though heading date depends on both photoperiod-sensitivity and thermo-sensitivity, it was estimated which of the two contributed more to the induced earliness in each mutant. This offers a basis for selecting early maturing lines of rice

  2. Unexpected lines due to hyperfine interaction

    International Nuclear Information System (INIS)

    Andersson, Martin

    2009-01-01

    Hyperfine interaction is often viewed as a small perturbation that only broadens or in some cases splits a line into many closely spaced lines. In this work, we present some cases where this picture is obsolete and where the hyperfine interaction makes drastic changes to spectra. Off-diagonal hyperfine interaction introduces a mixing between states which can differ in the J quantum number. In most cases this mixing is very small, but even so it could have a dramatic influence on the spectra. Some metastable levels are sensitive to the hyperfine interaction and we show this by presenting the results for hyperfine-dependent lifetimes of the 3d 9 4s 3 D 3 level along parts of the higher end of the Ni-like iso-electronic sequence. In the absence of a nuclear spin, this level can only decay through a magnetic-octupole transition, but in the presence of a nuclear spin, the off-diagonal hyperfine interaction introduces a mixing with the 3d 9 4s 3 D 2 level and a new electric-quadrupole transition channel is opened. It is shown that this new transition channel in many cases is the dominant one and that the lifetime of the 3 D 3 level is sensitive to hyperfine interaction all along the sequence. An example of other types of states that are sensitive to hyperfine interaction are those belonging to configurations of the type nsn'l' where l≥3. In such systems the levels are close in energy and the open s-shell gives rise to a strong hyperfine interaction. This in turn introduces a large mixing between the hyperfine levels and shows up in the spectra as a large intensity redistribution among the hyperfine lines. We present detailed results for the 4s4d 3 D 2 -4s4f 3 F 2 transitions in Ga ii, and show that by including the hyperfine interaction in a proper way, we could reproduce experimental spectra that had not been possible earlier.

  3. Teaching Braille Line Tracking Using Stimulus Fading

    Science.gov (United States)

    Scheithauer, Mindy C.; Tiger, Jeffrey H.

    2014-01-01

    Line tracking is a prerequisite skill for braille literacy that involves moving one's finger horizontally across a line of braille text and identifying when a line ends so the reader may reset his or her finger on the subsequent line. Current procedures for teaching line tracking are incomplete, because they focus on tracking lines with only…

  4. Comparison of responses of human melanoma cell lines to MEK and BRAF inhibitors

    Directory of Open Access Journals (Sweden)

    Clare Judith Stones

    2013-05-01

    Full Text Available The NRAS and BRAF genes are frequently mutated in melanoma, suggesting that the NRAS-BRAF-MEK-ERK signalling pathway is an important target for therapy. Two classes of drugs, one targeting activated BRAF and one targeting MEK, are currently undergoing clinical evaluation. We have analysed the NRAS and BRAF mutational status of a series of 44 early passage lines developed from New Zealand patients with metastatic melanoma. 41% of the lines analysed had BRAF mutations, 23% had NRAS mutations and 36% had neither. We then determined IC50 values (drug concentrations for 50% growth inhibition for CI-1040, a commonly used inhibitor of MEK kinase; trametinib, a clinical agent targeting MEK kinase; and vemurafenib, an inhibitor of mutant BRAF kinase. Cell lines with activating BRAF mutations were significantly more sensitive to vemurafenib than lines with NRAS mutations or lines lacking either mutation (p < 0.001. IC50 values for CI-1040 and trametinib were strongly correlated (r = 0.98 with trametinib showing ~100-fold greater potency. Cell lines sensitive to vemurafenib were also sensitive to CI-1040 and trametinib, but there was no relationship between IC50 values and NRAS mutation status. A small number of lines lacking a BRAF mutation were sensitive to CI-1040 but resistant to vemurafenib. We used western blotting to investigate the effect on ERK phosphorylation of CI-1040 in four lines, of vemurafenib in two lines and of trametinib in two lines. The results support the view that MEK inhibitors might be combined with BRAF inhibitors in the treatment melanomas of with activated BRAF. The high sensitivity to trametinib of some lines with wild-type BRAF status also suggests that MEK inhibitors could have a therapeutic effect against some melanomas as single agents.

  5. Discrimination of skin sensitizers from non-sensitizers by interleukin-1α and interleukin-6 production on cultured human keratinocytes.

    Science.gov (United States)

    Jung, Daun; Che, Jeong-Hwan; Lim, Kyung-Min; Chun, Young-Jin; Heo, Yong; Seok, Seung Hyeok

    2016-09-01

    In vitro testing methods for classifying sensitizers could be valuable alternatives to in vivo sensitization testing using animal models, such as the murine local lymph node assay (LLNA) and the guinea pig maximization test (GMT), but there remains a need for in vitro methods that are more accurate and simpler to distinguish skin sensitizers from non-sensitizers. Thus, the aim of our study was to establish an in vitro assay as a screening tool for detecting skin sensitizers using the human keratinocyte cell line, HaCaT. HaCaT cells were exposed to 16 relevant skin sensitizers and 6 skin non-sensitizers. The highest dose used was the dose causing 75% cell viability (CV75) that we determined by an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The levels of extracellular production of interleukin-1α (IL-1α) and IL-6 were measured. The sensitivity of IL-1α was 63%, specificity was 83% and accuracy was 68%. In the case of IL-6, sensitivity: 69%, specificity: 83% and accuracy: 73%. Thus, this study suggests that measuring extracellular production of pro-inflammatory cytokines IL-1α and IL-6 by human HaCaT cells may potentially classify skin sensitizers from non-sensitizers. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  6. Screening of ten advanced chickpea lines for blight and wilt resistance

    International Nuclear Information System (INIS)

    Jamil, F.F.; Haq, I.; Sarwar, N.; Alam, S.S.; Khan, J.A.; Hanif, M.; Khan, I.A.; Sarwar, M.; Haq, M.A.

    2002-01-01

    Ten advanced chickpea lines developed at NIAB were screened for resistance to Ascochyta blight and Fusarium wilt diseases in different sets of experiments conducted under controlled environment. Inoculation of plants by spore suspension of virulent strains of Ascochyta rabiei revealed that one line (97313) was resistant tolerant, two lines (97305, 97392) were tolerant, six lines (97306, 97310, 97311, 97303, 97302, 97393) were tolerant/susceptible and one line (97301) was susceptible. Screening of the same lines against Fusarium wilt by water culture method showed that two lines (97301, 97313) were moderately resistant, four lines (97302, 97303, 97306, 97393) were tolerant and the remaining four lines were susceptible. Screening through phytotoxic culture filtrates revealed that two lines (97302, 97313) were less sensitive to culture filtrates of Ascochyta rabiei and Fusarium oxysporum than the resistant check (CM88). These lines were also analyzed spectrophotometrically for peroxidase enzyme activity. Maximum enzyme activity was detected after 48 hours of inoculation with A. rabiei in three lines (97305, 97311, 97313) and resistant check (CM88) while enzyme activity in the remaining lines reached its maximum after 72 hours of inoculation which was comparable to the susceptible check (Pb-1). These studies lead to the conclusion that one line (97313) exhibited resistance against both the diseases and can be used as a source of resistance for further improvement of chickpea germplasm. (author)

  7. Atlas transmission line breakdown analysis

    CERN Document Server

    Nielsen, K E; Ballard, E O; Elizondo, J M; Gribble, R F; McCuistian, B T; Parsons, W M

    1999-01-01

    The Atlas facility will use 24 radially converging, vertically oriented and tapered, oil insulated, triplate transmission lines between the Marx generators and the central load region. Among the requirements of the transmission lines are low inductance and high reliability. The inter-conductor gap is nominally 2 cm and the lines taper from a height of 1.75 m at the Marx end to 0.32 m at the output end. The aluminum conductors, held together by 20 insulating spacers, are assembled and inserted as a unit into radial oil-filled steel tanks. The negative, high-voltage, center conductor is 2.54-cm thick and the outer ground conductors are 1.59-cm thick. All 24 triplate transmission lines connect to a transition section at near 1 m radius that couples the transmission lines to a disk/conical solid- dielectric-insulated power flow channel transmission line terminating at the load. Peak operating voltage on the lines can be as high as 240 kV with an effective stress time of 0.8 mu s. Testing of small sections of the ...

  8. Isolation and characterization of a radiosensitive Chinese hamster ovary cell line

    International Nuclear Information System (INIS)

    Fuller, L.F.

    1987-01-01

    A x-ray sensitive Chinese hamster ovary cell line was isolated using a semi-automated procedure in which mutagenized CHO cells were allowed to form colonies on top of agar, x-irradiated, then photographed at two later times. Comparison of the photographs allowed the identification of colonies which displayed significant growth arrest. One of the colonies identified in this manner produced a stable, radiosensitive line. This cell line is normal in x-ray induced inhibition of DNA synthesis, and single- and double-strand break repair, and is moderately sensitive to ethyl methane sulfonate and UV light. The sensitive line performs only half as much x-ray-induced repair replication as the parental line and this deficiency is believed to be the primary cause of its radiosensitivity. The sensitive line produces significantly higher numbers of x-ray-induced chromosome and chromatid aberrations including chromatid aberrations following exposure during the G 1 phase of the cell cycle. The line is hypomutable compared to the parental line with x-ray exposure inducing only one-third as many 6-thioguanine resistant colonies

  9. Chromatin structure and cellular radiosensitivity : A comparison of two human tumour cell lines

    NARCIS (Netherlands)

    Woudstra, EC; Roesink, JM; Rosemann, M; Brunsting, JF; Driessen, C; Orta, T; Konings, AWT; Peacock, JH; Kampinga, HH

    1996-01-01

    The role of variation in susceptibility to DNA damage induction was studied as a determinant for cellular radiosensitivity. Comparison of the radiosensitive HX142 and radioresistant RT112 cell lines previously revealed higher susceptibility to X-ray-induced DNA damage in the sensitive cell line

  10. PAYMENT CAPACITY SENSITIVITY FACTORS

    OpenAIRE

    Daniel BRÎNDESCU – OLARIU

    2014-01-01

    The current study focuses on the sensitivity of the corporate payment capacity. Through the nature of the subject, the research is based on simulating variations of the forecasted cash-flows of the companies included in the sample. The study employs 391 forecasted yearly cash-flows statements collected from 50 companies from Timis County (Romania), as well as the detailed hypotheses of the forecasts. The results of the study facilitate the determination and classification of the main se...

  11. Mutagenic sensitivity to triticales

    International Nuclear Information System (INIS)

    Reddy, V.R.K.

    1993-01-01

    The effect of gamma rays, ethyl methane sulphonate and their combined treatments on germination, survival, seedling height and sterility were studied in one winter Triticale var. 6TA 87 and one sprig Triticale var. cinnamon. Based on LD 50 , degree of reduction in seedling height and increase in seed and pollen sterility, it was concluded that Triticale var. cinnamon is highly sensitive and mutable compared to Triticale 6TA 876. (author). 5 refs., 2 tabs

  12. rf reference line for PEP

    International Nuclear Information System (INIS)

    Schwarz, H.D.; Weaver, J.N.

    1979-03-01

    A rf phase reference line in 6 segments around the 2200 meter circumference PEP storage ring is described. Each segment of the reference line is phase stabilized by its own independent feedback system, which uses an amplitude modulated reflection from the end of each line. The modulation is kept small and decoupled from the next segment to avoid crosstalk and significant modulation of the rf drive signal. An error evaluation of the system is made. The technical implementation and prototype performance are described. Prototype tests indicate that the phase error around the ring can be held below 1 degree with this relatively simple system

  13. rf reference line for PEP

    Energy Technology Data Exchange (ETDEWEB)

    Schwarz, H.D.; Weaver, J.N.

    1979-03-01

    A rf phase reference line in 6 segments around the 2200 meter circumference PEP storage ring is described. Each segment of the reference line is phase stabilized by its own independent feedback system, which uses an amplitude modulated reflection from the end of each line. The modulation is kept small and decoupled from the next segment to avoid crosstalk and significant modulation of the rf drive signal. An error evaluation of the system is made. The technical implementation and prototype performance are described. Prototype tests indicate that the phase error around the ring can be held below 1 degree with this relatively simple system.

  14. Status of ACCULINNA beam line

    CERN Document Server

    Rodin, A M; Bogdanov, D D; Golovkov, M S; Fomichev, A S; Sidorchuk, S I; Slepnev, R S; Wolski, R; Ter-Akopian, G M; Oganessian, Yu T; Yukhimchuk, A A; Perevozchikov, V V; Vinogradov, Yu I; Grishenchkin, S K; Demin, A M; Zlatoustovskii, S V; Kuryakin, A V; Filchagin, S V; Ilkaev, R I

    2003-01-01

    The separator ACCULINNA was upgraded to achieve new experimental requirements. The beam line was extended by new ion-optical elements beyond the cyclotron hall. The new arrangements yield much better background conditions. The intensities of sup 6 He and sup 8 He radioactive beams produced in fragmentation of 35 A MeV sup 1 sup 1 B ions were increased up to a factor of 10. The upgraded beam line was used in experiments to study the sup 5 H resonance states populated in the t+t reaction. A cryogenic liquid tritium target was designed and installed at the separator beam line.

  15. Interference and Sensitivity Analysis.

    Science.gov (United States)

    VanderWeele, Tyler J; Tchetgen Tchetgen, Eric J; Halloran, M Elizabeth

    2014-11-01

    Causal inference with interference is a rapidly growing area. The literature has begun to relax the "no-interference" assumption that the treatment received by one individual does not affect the outcomes of other individuals. In this paper we briefly review the literature on causal inference in the presence of interference when treatments have been randomized. We then consider settings in which causal effects in the presence of interference are not identified, either because randomization alone does not suffice for identification, or because treatment is not randomized and there may be unmeasured confounders of the treatment-outcome relationship. We develop sensitivity analysis techniques for these settings. We describe several sensitivity analysis techniques for the infectiousness effect which, in a vaccine trial, captures the effect of the vaccine of one person on protecting a second person from infection even if the first is infected. We also develop two sensitivity analysis techniques for causal effects in the presence of unmeasured confounding which generalize analogous techniques when interference is absent. These two techniques for unmeasured confounding are compared and contrasted.

  16. Tactual sensitivity in hypochondriasis.

    Science.gov (United States)

    Haenen, M A; Schmidi, A J; Schoenmakers, M; van den Hout, M A

    1997-01-01

    In his article on amplification, somatization and somatoform disorders Barsky [Psychosomatics 1992; 33:28-34] pointed out the importance of studying the perception and processing of somatic and visceral symptoms. Subsequently, it was demonstrated that hypochondriacal patients are not more accurately aware of cardiac activity than a group of non-hypochondriacal patients. Authors concluded that hypochondriacal somatic complaints do not result from an unusually fine discriminative ability to detect normal physiological sensations that non-hypochondriacal patients are unable to perceive. The aim of the present study was to investigate tactual sensitivity to non-painful stimuli in hypochondriacal patients and healthy subjects. Twenty-seven outpatients with DSM-III-R hypochondriasis and 27 healthy control subjects were compared. In all subjects the two-point discrimination threshold was measured, as well as subjective sensitivity to harmless bodily sensations as measured by the Somatosensory Amplification Scale. It was found that hypochondriacal patients reported more distress and discomfort with benign bodily sensations. The two-point discrimination threshold of hypochondriacal patients was not significantly lower in patients as compared to controls. Hypochondriacal subjects considered themselves more sensitive to benign bodily sensations without being better able to discriminate between two tactual bodily signals. These findings of the present study correspond quite closely to those reported earlier.

  17. Analysis of some coplanar transmission lines: coplanar coupled lines, coplanar coupled striplines, and coplanar coupled lines with rectangular microshield

    Science.gov (United States)

    Yuan, Naichang; He, Jianguo; Yao, Demiao; Dai, Qin; Lin, Weigan

    1995-06-01

    Two types of coplanar transmission lines, rectangular microshield coplanar coupled lines (RMCCL) and coplanar coupled rectangular microshield lines (CCRML), are proposed for MMIC applications. These are developed from coplanar coupled lines (CCL) and coplanar coupled strip lines (CCS). Analytic formulas are presented for calculating the quasistatic TEM parameters of these coupled lines by means of exact conformal mapping techniques. Numerical results are also presented to illustrate the properties of these coplanar transmission lines.

  18. On line protection systems for induction motors

    International Nuclear Information System (INIS)

    Colak, I.; Celik, H.; Sefa, I.; Demirbas, S.

    2005-01-01

    Protection of induction motors is very important since they are widely used in industry for many applications due to their high robustness, reliability, low cost and maintenance, high efficiency and long service life. So, protecting these motors is crucial for operations. This paper presents a combined protection approach for induction motors. To achieve this, the electrical values of the induction motor were measured with sensitivity ±1% through a data acquisition card and processed with software developed in Visual C++. An on line protection system for induction motors was achieved easily and effectively. The experimental results have shown that the induction motor was protected against the possible problems faced during the operation. The software developed for this protection provides flexible and reliable media for operators and their motors. It is expected that the motor protection achieved in this study might be faster than the classical techniques and also may be applied to larger motors easily after small modifications of the software

  19. Kinematic sensitivity of robot manipulators

    Science.gov (United States)

    Vuskovic, Marko I.

    1989-01-01

    Kinematic sensitivity vectors and matrices for open-loop, n degrees-of-freedom manipulators are derived. First-order sensitivity vectors are defined as partial derivatives of the manipulator's position and orientation with respect to its geometrical parameters. The four-parameter kinematic model is considered, as well as the five-parameter model in case of nominally parallel joint axes. Sensitivity vectors are expressed in terms of coordinate axes of manipulator frames. Second-order sensitivity vectors, the partial derivatives of first-order sensitivity vectors, are also considered. It is shown that second-order sensitivity vectors can be expressed as vector products of the first-order sensitivity vectors.

  20. Sensitizing pigment in the fly

    International Nuclear Information System (INIS)

    Vogt, K.; Kirschfeld, K.

    1983-01-01

    The sensitizing pigment hypothesis for the high UV sensitivity in fly photoreceptors (R1-6) is further substantiated by measurements of the polarisation sensitivity in the UV. The quantum yield of the energy transfer from sensitizing pigment to rhodopsin was estimated by electrophysiological measurements of the UV sensitivity and the rhabdomeric absorptance (at 490 nm) in individual receptor cells. The transfer efficiency is >=0.75 in receptors with an absorptance in the rhabdomeres of 0.55-0.95. This result suggests that the sensitizing pigment is bound in some way to the rhodopsin. A ratio of two molecules of sensitizing pigment per one rhodopsin is proposed. (orig.)

  1. Tuning of JET transmission line/antenna system during ICRH

    International Nuclear Information System (INIS)

    Oeberg, J.

    1993-05-01

    The launched toroidal wave spectrum for ICRH and ICRH current drive is controlled by the phasing of the antenna currents. This causes imbalance in the transmission lines, which makes it more difficult to use the full power of the ICRH generators. Further, the generators are sensitive to the amount of reflected power. To reduce the amount of reflected power the transmission lines have to be constantly tuned. To study the tuning three models of the antenna are developed and compared with experimental results. A method is suggested which enables better usage of the generated power using a power correction unit to evenly distribute the power load between the generators. 4 refs, 24 figs

  2. Phase sensitive multichannel OCT

    International Nuclear Information System (INIS)

    Trasischker, W.

    2015-01-01

    The main aim of this thesis was to develop and improve phase sensitive, multichannel methods for optical coherence tomography (OCT) using light in the 840 nm and 1040 nm regime. Conventional OCT provides purely structural information by illuminating the sample by one beam and recording the backscattered signal with one detection channel. Combination of this approach with a raster scan enables the acquisition of 2D and 3D structural information with a resolution in the micrometer regime. However, sometimes additional image contrast or information is desired. Amongst other approaches, this can be provided by a phase sensitive analysis of the interference pattern. Combining phase sensitivity with the illumination of the sample by more than one beam and/or by recording the data using more than one data acquisition channel allows for even more enhanced imaging. While phase sensitive OCT gives access to additional contrast and information, multichannel OCT can provide higher imaging speed, scan eld size and exible dierential measurements. Amongst the dierential, phase sensitive approaches, Doppler OCT (DOCT) and polarization sensitive OCT (PS-OCT) are two of the most promising OCT modalities. While the former targets information on the movement of backscattering particles, the latter measures alterations of the polarization state of the light induced by the sample. Both techniques provide additional image contrast and are, due to the non-invasive and fast character of OCT, well suited for in vivo imaging of the human eye. In the course of this thesis, two dierent multichannel, phase sensitive OCT systems will be presented. First, a D-OCT system with three dierent sampling beams is described. With a central wavelength of 840 nm these three beams are emitted by three individual laser sources. This eectively eliminates any cross talk and provides the full depth range for each channel. Furthermore, by illuminating the sample from three dierent directions, the absolute

  3. Ensemble Sensitivity Analysis of a Severe Downslope Windstorm in Complex Terrain: Implications for Forecast Predictability Scales and Targeted Observing Networks

    Science.gov (United States)

    2013-09-01

    observations, linear regression finds the straight line that explains the linear relationship of the sample. This line is given by the equation y = mx + b...SENSITIVITY ANALYSIS OF A SEVERE DOWNSLOPE WINDSTORM IN COMPLEX TERRAIN: IMPLICATIONS FOR FORECAST PREDICTABILITY SCALES AND TARGETED OBSERVING...SENSITIVITY ANALYSIS OF A SEVERE DOWNSLOPE WINDSTORM IN COMPLEX TERRAIN: IMPLICATIONS FOR FORECAST PREDICTABILITY SCALES AND TARGETED OBSERVING NETWORKS

  4. Animated construction of line drawings

    KAUST Repository

    Fu, Hongbo; Zhou, Shizhe; Liu, Ligang; Mitra, Niloy J.

    2011-01-01

    Revealing the sketching sequence of a line drawing can be visually intriguing and used for video-based storytelling. Typically this is enabled based on tedious recording of artists' drawing process. We demonstrate that it is often possible

  5. Animated construction of line drawings

    KAUST Repository

    Fu, Hongbo; Zhou, Shizhe; Liu, Ligang; Mitra, Niloy J.

    2011-01-01

    system produces plausible animated constructions of input line drawings, with no or little user intervention. We test our algorithm on a range of input sketches, with varying degree of complexity and structure, and evaluate the results via a user study

  6. Composite Materials in Overhead Lines

    DEFF Research Database (Denmark)

    Sørensen, Thomas Kjærsgaard; Holbøll, Joachim

    2009-01-01

    towers and recently conductors based on composite materials are available at transmission levels. In this paper it is investigated which composite based solutions are available in connection with complete overhead line systems including insulators, towers and conductors. The components are reviewed......The use of composite materials, e.g. fibreglass materials, in overhead transmission line systems is nothing new. Composite based insulators have been applied to transmission lines for over 30 years, mainly as suspension and post insulators and often as an option for special applications. Also...... with respect to solved and persisting known failures/problems of both mechanical and electrical nature. Major challenges related to extensive use of composite materials in an overhead line system are identified, as are possible benefits - both when using standard as well as customised composite components, e...

  7. Louisiana ESI: ROADS (Road Lines)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains the state maintained primary and secondary road network of Louisiana. Vector lines in the data set represent Interstates, U.S. Highways, and...

  8. Control Point Generated PLS - lines

    Data.gov (United States)

    Minnesota Department of Natural Resources — The Control Point Generated PLS layer contains line and polygon features to the 1/4 of 1/4 PLS section (approximately 40 acres) and government lot level. The layer...

  9. Railroad Lines, US, 2015, NAVTEQ

    Data.gov (United States)

    U.S. Environmental Protection Agency — NAVTEQ Railroads for the United States. The Railroads layer contains Railroad features published as lines and polylines. Attributes for this layer include the name...

  10. Base Flood Elevation (BFE) Lines

    Data.gov (United States)

    Department of Homeland Security — The Base Flood Elevation (BFE) table is required for any digital data where BFE lines will be shown on the corresponding Flood Insurance Rate Map (FIRM). Normally if...

  11. Radio and line transmission 2

    CERN Document Server

    Roddy, Dermot

    2013-01-01

    Radio and Line Transmission, Volume 2 gives a detailed treatment of the subject as well as an introduction to additional advanced subject matter. Organized into 14 chapters, this book begins by explaining the radio wave propagation, signal frequencies, and bandwidth. Subsequent chapters describe the transmission lines and cables; the aerials; tuned and coupled circuits; bipolar transistor amplifiers; field-effect transistors and circuits; thermionic valve amplifiers; LC oscillators; the diode detectors and modulators; and the superheterodyne receiver. Other chapters explore noise and interfere

  12. SAF line analytical chemistry system

    International Nuclear Information System (INIS)

    Gerber, E.W.; Sherrell, D.L.

    1983-10-01

    An analytical chemistry system dedicated to supporting the Secure Automated Fabrication (SAF) line is discussed. Several analyses are required prior to the fuel pellets being loaded into cladding tubes to assure certification requirements will be met. These analyses, which will take less than 15 minutes, are described. The automated sample transport system which will be used to move pellets from the fabriction line to the chemistry area is also described

  13. QSOs with narrow emission lines

    International Nuclear Information System (INIS)

    Baldwin, J.A.; Mcmahon, R.; Hazard, C.; Williams, R.E.

    1988-01-01

    Observations of two new high-redshift, narrow-lined QSOs (NLQSOs) are presented and discussed together with observations of similar objects reported in the literature. Gravitational lensing is ruled out as a possible means of amplifying the luminosity for one of these objects. It is found that the NLQSOs have broad bases on their emission lines as well as the prominent narrow cores which define this class. Thus, these are not pole-on QSOs. The FWHM of the emission lines fits onto the smoothly falling tail of the lower end of the line-width distribution for complete QSO samples. The equivalent widths of the combined broad and narrow components of the lines are normal for QSOs of the luminosity range under study. However, the NLQSOs do show ionization differences from broader-lined QSOs; most significant, the semiforbidden C III/C IV intensity ratio is unusually low. The N/C abundance ratio in these objects is found to be normal; the Al/C abundance ratio may be quite high. 38 references

  14. Polarization of Coronal Forbidden Lines

    Energy Technology Data Exchange (ETDEWEB)

    Li, Hao; Qu, Zhongquan [Yunnan Observatories, Chinese Academy of Sciences, Kunming, Yunnan 650011 (China); Landi Degl’Innocenti, Egidio, E-mail: sayahoro@ynao.ac.cn [Dipartimento di Astronomia e Scienza dello Spazio, Università di Firenze, Largo E. Fermi 2, I-50125 Firenze (Italy)

    2017-03-20

    Since the magnetic field is responsible for most manifestations of solar activity, one of the most challenging problems in solar physics is the diagnostics of solar magnetic fields, particularly in the outer atmosphere. To this end, it is important to develop rigorous diagnostic tools to interpret polarimetric observations in suitable spectral lines. This paper is devoted to analyzing the diagnostic content of linear polarization imaging observations in coronal forbidden lines. Although this technique is restricted to off-limb observations, it represents a significant tool to diagnose the magnetic field structure in the solar corona, where the magnetic field is intrinsically weak and still poorly known. We adopt the quantum theory of polarized line formation developed in the framework of the density matrix formalism, and synthesize images of the emergent linear polarization signal in coronal forbidden lines using potential-field source-surface magnetic field models. The influence of electronic collisions, active regions, and Thomson scattering on the linear polarization of coronal forbidden lines is also examined. It is found that active regions and Thomson scattering are capable of conspicuously influencing the orientation of the linear polarization. These effects have to be carefully taken into account to increase the accuracy of the field diagnostics. We also found that linear polarization observation in suitable lines can give valuable information on the long-term evolution of the magnetic field in the solar corona.

  15. Sensitivity Analysis of a Horizontal Earth Electrode under Impulse ...

    African Journals Online (AJOL)

    This paper presents the sensitivity analysis of an earthing conductor under the influence of impulse current arising from a lightning stroke. The approach is based on the 2nd order finite difference time domain (FDTD). The earthing conductor is regarded as a lossy transmission line where it is divided into series connected ...

  16. Achieving sensitive, high-resolution laser spectroscopy at CRIS

    Energy Technology Data Exchange (ETDEWEB)

    Groote, R. P. de [Instituut voor Kern- en Stralingsfysica, KU Leuven (Belgium); Lynch, K. M., E-mail: kara.marie.lynch@cern.ch [EP Department, CERN, ISOLDE (Switzerland); Wilkins, S. G. [The University of Manchester, School of Physics and Astronomy (United Kingdom); Collaboration: the CRIS collaboration

    2017-11-15

    The Collinear Resonance Ionization Spectroscopy (CRIS) experiment, located at the ISOLDE facility, has recently performed high-resolution laser spectroscopy, with linewidths down to 20 MHz. In this article, we present the modifications to the beam line and the newly-installed laser systems that have made sensitive, high-resolution measurements possible. Highlights of recent experimental campaigns are presented.

  17. The Far Infrared Lines of OH as Molecular Cloud Diagnostics

    Science.gov (United States)

    Smith, Howard A.

    2004-01-01

    Future IR missions should give some priority to high resolution spectroscopic observations of the set of far-IR transitions of OH. There are 15 far-IR lines arising between the lowest eight rotational levels of OH, and ISO detected nine of them. Furthermore, ISO found the OH lines, sometimes in emission and sometimes in absorption, in a wide variety of galactic and extragalactic objects ranging from AGB stars to molecular clouds to active galactic nuclei and ultra-luminous IR galaxies. The ISO/LWS Fabry-Perot resolved the 119 m doublet line in a few of the strong sources. This set of OH lines provides a uniquely important diagnostic for many reasons: the lines span a wide wavelength range (28.9 m to 163.2 m); the transitions have fast radiative rates; the abundance of the species is relatively high; the IR continuum plays an important role as a pump; the contribution from shocks is relatively minor; and, not least, the powerful centimeter-wave radiation from OH allows comparison with radio and VLBI datasets. The problem is that the large number of sensitive free parameters, and the large optical depths of the strongest lines, make modeling the full set a difficult job. The SWAS montecarlo radiative transfer code has been used to analyze the ISO/LWS spectra of a number of objects with good success, including in both the lines and the FIR continuum; the DUSTY radiative transfer code was used to insure a self-consistent continuum. Other far IR lines including those from H2O, CO, and [OI] are also in the code. The OH lines all show features which future FIR spectrometers should be able to resolve, and which will enable further refinements in the details of each cloud's structure. Some examples are given, including the case of S140, for which independent SWAS data found evidence for bulk flows.

  18. Optimal Transmission Line Switching under Geomagnetic Disturbances

    International Nuclear Information System (INIS)

    Lu, Mowen; Nagarajan, Harsha; Yamangil, Emre; Bent, Russell; Backhaus, Scott

    2017-01-01

    Recently, there have been increasing concerns about how geomagnetic disturbances (GMDs) impact electrical power systems. Geomagnetically-induced currents (GICs) can saturate transformers, induce hot spot heating and increase reactive power losses. These effects can potentially cause catastrophic damage to transformers and severely impact the ability of a power system to deliver power. To address this problem, we develop a model of GIC impacts to power systems that includes 1) GIC thermal capacity of transformers as a function of normal Alternating Current (AC) and 2) reactive power losses as a function of GIC. We also use this model to derive an optimization problem that protects power systems from GIC impacts through line switching, generator dispatch, and load shedding. We then employ state-of-the-art convex relaxations of AC power flow equations to lower bound the objective. We demonstrate the approach on a modified RTS96 system and UIUC 150-bus system and show that line switching is an effective means to mitigate GIC impacts. We also provide a sensitivity analysis of decisions with respect to GMD direction.

  19. 76 FR 51367 - China Shipping Container Lines Co., Ltd.; COSCO Container Lines Company Limited; Evergreen Line A...

    Science.gov (United States)

    2011-08-18

    ... FEDERAL MARITIME COMMISSION [Docket No. 11-12] China Shipping Container Lines Co., Ltd.; COSCO Container Lines Company Limited; Evergreen Line A Joint Service Agreement; Hanjin Shipping Co., Ltd... Maritime Commission (Commission) by China Shipping Container Lines Co., Ltd.; COSCO Container Lines Company...

  20. Grounding line processes on the Totten Glacier

    Science.gov (United States)

    Cook, S.; Watson, C. S.; Galton-Fenzi, B.; Peters, L. E.; Coleman, R.

    2017-12-01

    The Totten Glacier has been an area of recent interest due to its large drainage basin, much of which is grounded below sea level and has a history of large scale grounding line movement. Reports that warm water reaches the sub-ice shelf cavity have led to speculation that it could be vulnerable to future grounding line retreat. Over the Antarctic summer 2016/17 an array of 6 GPS and autonomous phase-sensitive radar (ApRES) units were deployed in the grounding zone of the Totten Glacier. These instruments measure changes in ice velocity and thickness which can be used to investigate both ice dynamics across the grounding line, and the interaction between ice and ocean in the subglacial cavity. Basal melt rates calculated from the ApRES units on floating ice range from 1 to 17 m/a. These values are significantly lower than previous estimates of basal melt rate produced by ocean modelling of the subglacial cavity. Meanwhile, GPS-derived velocity and elevation on the surface of the ice show a strong tidal signal, as does the vertical strain rate within the ice derived from internal layering from the ApRES instruments. These results demonstrate the significance of the complex grounding pattern of the Totten Glacier. The presence of re-grounding points has significant implications for the dynamics of the glacier and the ocean circulation within the subglacial cavity. We discuss what can be learned from our in situ measurements, and how they can be used to improve models of the glacier's future behaviour.

  1. Comparison of the effect of interferon on two human hepatoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Crespi, M; Schoub, B D; Lyons, S F; Chiu, M N [University of the Witwatersrand, Johannesburg (South Africa). Dept. of Virology

    1985-06-01

    Two human hepatoma cell lines, the PLC/PRF/5 and the Mahlavu cells, which differ in their production of the hepatitis B surface antigen (HBsAg), responded differently to interferon (IFN). After IFN treatment both cell lines were able to inhibit Sindbis virus replication. Oligo A synthetase (E enzyme) could be activated in the PLC/PRF/5 cells although they were not sensitive to exogenous 2 - 5 oligoadenylic acid (2 - 5 A). In contrast, the Mahlavu cells were sensitive to exogenous 2 - 5 A, but unable to activate the E enzyme. Both cell lines were unable to stimulate phosphorylation of the exogenous initiator factor eIF-2.

  2. In vivo radiation sensitivity of glioblastoma multiforme

    International Nuclear Information System (INIS)

    Taghian, Alphonse; Freeman, Jill; Suit, Herman; DuBois, Willem; Budach, Wilfried; Baumann, Michael

    1995-01-01

    Purpose: Human glioblastoma (GBM) is one of the most resistant tumors to radiation. In previous reports, we have demonstrated a wide range of radiation sensitivity of GBM in vitro; that is, SF 2 values of 0.2 to 0.8. The great sensitivity of some of the cell lines is not in accord with the almost invariably fatal clinical outcome of patients with GBM. The sensitivity of cells in vitro pertains to cells cultured in optimal nutritional conditions. The TCD 50 (the radiation dose necessary to control 50% of the tumors locally) determined in lab animals is analogous to the use of radiation with curative intent in clinical radiation oncology. The aim of the present study was (a) to evaluate the sensitivity of GBM in vivo relative to that of other tumor types and (b) assess the relationship between the single dose TCD 50 of the xenografts and the sensitivity of the corresponding cell lines in vitro. Methods and Materials: The TCD 50 assay was used to study twelve human tumor lines. Four previously published values were added. A total of 10 GBM, 4 squamous cell carcinoma (SCC), 1 soft tissue sarcoma (STS), and 1 cancer colon (CC) are included in the analysis. For further suppression of the residual immune system, all the animals received 6 Gy whole-body irradiation 1 day before transplantation. Local tumor irradiations were given as a single dose, under conditions of clamp hypoxia using a Cs irradiator. Results: The TCD 50 values for the 10 GBM xenografts varied between 32.5 and 75.2 Gy, with an average of 47.2 ± 13.1 Gy. The TCD 50 values for the SCC were similar to those of the GBM and ranged from 40.7 and 54.4 Gy, with a mean of 46.8 ± 6.4. The difference between the average TCD 50 of GBM and SCC was not significant. The STS and CC xenografts had TCD 50 values of 46.0 and 49.2 Gy, respectively. No correlation was found between the TCD 50 in vivo and the SF 2 or D 0 in vitro. Conclusions: Our data on GBM xenografts showed a wide range of sensitivities to single dose

  3. In vivo radiation sensitivity of glioblastoma multiforme

    Energy Technology Data Exchange (ETDEWEB)

    Taghian, Alphonse; Freeman, Jill; Suit, Herman; DuBois, Willem; Budach, Wilfried; Baumann, Michael

    1995-04-30

    Purpose: Human glioblastoma (GBM) is one of the most resistant tumors to radiation. In previous reports, we have demonstrated a wide range of radiation sensitivity of GBM in vitro; that is, SF{sub 2} values of 0.2 to 0.8. The great sensitivity of some of the cell lines is not in accord with the almost invariably fatal clinical outcome of patients with GBM. The sensitivity of cells in vitro pertains to cells cultured in optimal nutritional conditions. The TCD{sub 50} (the radiation dose necessary to control 50% of the tumors locally) determined in lab animals is analogous to the use of radiation with curative intent in clinical radiation oncology. The aim of the present study was (a) to evaluate the sensitivity of GBM in vivo relative to that of other tumor types and (b) assess the relationship between the single dose TCD{sub 50} of the xenografts and the sensitivity of the corresponding cell lines in vitro. Methods and Materials: The TCD{sub 50} assay was used to study twelve human tumor lines. Four previously published values were added. A total of 10 GBM, 4 squamous cell carcinoma (SCC), 1 soft tissue sarcoma (STS), and 1 cancer colon (CC) are included in the analysis. For further suppression of the residual immune system, all the animals received 6 Gy whole-body irradiation 1 day before transplantation. Local tumor irradiations were given as a single dose, under conditions of clamp hypoxia using a Cs irradiator. Results: The TCD{sub 50} values for the 10 GBM xenografts varied between 32.5 and 75.2 Gy, with an average of 47.2 {+-} 13.1 Gy. The TCD{sub 50} values for the SCC were similar to those of the GBM and ranged from 40.7 and 54.4 Gy, with a mean of 46.8 {+-} 6.4. The difference between the average TCD{sub 50} of GBM and SCC was not significant. The STS and CC xenografts had TCD{sub 50} values of 46.0 and 49.2 Gy, respectively. No correlation was found between the TCD{sub 50} in vivo and the SF{sub 2} or D{sub 0} in vitro. Conclusions: Our data on GBM

  4. Context Sensitive Health Informatics

    DEFF Research Database (Denmark)

    Kuziemsky, Craig; Nøhr, Christian; Aarts, Jos

    2013-01-01

    Context is a key consideration when designing and evaluating health information technology (HIT) and cannot be overstated. Unintended consequences are common post HIT implementation and even well designed technology may not achieve desired outcomes because of contextual issues. While context should...... be considered in the design and evaluation of health information systems (HISs) there is a shortcoming of empirical research on contextual aspects of HIT. This conference integrates the sociotechnical and Human-Centered-Design (HCD) approaches and showcases current research on context sensitive health...... informatics. The papers and presentations outlines theories and models for studying contextual issues and insights on how we can better design HIT to accommodate different healthcare contexts....

  5. Dye Sensitized Solar Cells

    Directory of Open Access Journals (Sweden)

    Di Wei

    2010-03-01

    Full Text Available Dye sensitized solar cell (DSSC is the only solar cell that can offer both the flexibility and transparency. Its efficiency is comparable to amorphous silicon solar cells but with a much lower cost. This review not only covers the fundamentals of DSSC but also the related cutting-edge research and its development for industrial applications. Most recent research topics on DSSC, for example, applications of nanostructured TiO2, ZnO electrodes, ionic liquid electrolytes, carbon nanotubes, graphene and solid state DSSC have all been included and discussed.

  6. Multiple Chemical Sensitivity

    DEFF Research Database (Denmark)

    Dantoft, Thomas Meinertz

    Multiple chemical sensitivity (MCS) is a chronic disorder characterized by reports of symptoms from various organ systems attributed by the individuals to exposure to common odors and airborne chemicals in doses far below those known to induce toxic effects. There exists a general lack of knowledge......, significantly reduced levels of IL-13 in the MCS group and no group differences in the allergen specific IgE measures. The differences were independent of factors such as sex, age, Body Mass Index, asthma, smoking, depression, anxiety and allergen-specific IgE. In conclusion, the study identified a distinct...

  7. Procedures for Sensitive Immunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Givol, D. [Department of Chemical Immunology, Weizmann Institute of Science, Rehovot (Israel)

    1970-02-15

    Sensitive immunoassay methods should be applied to small molecules of biological importance, which are non-immunogenic by themselves, such as small peptide hormones (e.g. bradykinin), plant hormones (e.g. indoleacetic acid), nucleotides and other small molecules. Methods of binding these small molecules, as haptens, to immunogenic carriers by various cross-linking agents are described (dicyclohexylcarbodiimide, tolylene-diisocyanate and glutaraldehyde), and the considerations involved in relation to the methods of binding and the specificity of the antibodies formed are discussed. Some uses of antibody bound to bromoacetyl cellulose as an immuno adsorbent convenient for assay of immunoglobulins are described. Finally, the sensitive immunoassay method of chemically modified phage is described. This includes methods of binding small molecules (such as the dinitrophenyl group, penicillin, indoleacetic acid) or proteins (such as insulin, immunoglobulins) to phages. Methods of direct chemical conjugation, or an indirect binding via anti-phage Fab, are described. The phage inactivation method by direct plating and its modifications (such as decision technique and complex inactivation) are compared with the more simple end-point titration method. The inhibition of phage inactivation has some advantages as it does not require radioactive material, or expensive radioactive counters, and avoids the need for separation between bound and unbound antigen. Hence, if developed, it could be used as an alternative to radioimmunoassay. (author)

  8. [Sensitization to Lyral].

    Science.gov (United States)

    Heras, F; Díaz-Recuero, J L; Cabello, M J; Conde-Salazar, L

    2006-01-01

    Lyral is a fragrance that is present in many cosmetic products. It has turned into an emergent allergen during the last years. In studies carried out in other European countries, the prevalence of sensitization to Lyral has been found to be 1.9-2.7 %, but it is unknown the prevalence in Spain, as well as the need to include it or not in the standard series of the Spanish Group of Contact Dermatitis (GEIDC). We have patch-tested to Lyral all patients with suspicion of contact dermatitis of any origin who attended our Service between April and May-2005. From a total of 170 patients included in our study, 2 of them had a sensitization to Lyral (1.2 %). One of these two patients had an axillae contact dermatitis caused by a deodorant containing Lyral. The other patient was a masseur-woman with a contact dermatitis on both hands, with periods of dissemination to upper extremities and trunk, and who used several cosmetics products for private reasons and during her job. Although the sample of this study is quite small, we think that the results allow to suspect that Lyral is one of the main allergens, or even the most important, in causing allergic contact dermatitis to fragrances in our environment. Therefore, we believe that we must raise the inclusion of Lyral in the standard series of GEIDC, either as independent allergen, or including it in a new mixture of fragrances.

  9. Proteomic Characterization of Inbreeding-Related Cold Sensitivity in Drosophila melanogaster

    DEFF Research Database (Denmark)

    Vermeulen, C.J.; Pedersen, Kamilla Sofie; Beck, Hans C.

    2013-01-01

    insight into the molecular interplay between intrinsic stress responses, inbreeding depression and temperature tolerance, we performed a proteomic characterization of a well-defined conditional inbreeding effect in a single line of Drosophila melanogaster, which suffers from extreme cold sensitivity...

  10. An X-ray gas position sensitive detector: construction and characterization

    International Nuclear Information System (INIS)

    Barbosa, A.F.; Gabriel, A.; Gabriel, A.; Craievich, A.

    1988-01-01

    A linear x-ray gas position sensitive detector with delay line readout has been constructed. The detector is described, characterized and used for detecting x-ray diffraction patterns from polycrystals. (author) [pt

  11. Thermal radiosensitization in heat- and radiation-sensitive mutants of CHO cells

    International Nuclear Information System (INIS)

    Kampinga, H.H.; Kanon, B.; Konings, A.W.T.; Stackhouse, M.A.; Bedford, J.S.

    1993-01-01

    In the current study, the extent of hyperthermic radiosensitization in a new γ-radiation-sensitive cell line, irs-20, recently isolated by Stackhouse and Bedford (1991) and a heat-sensitive mutant hs-36 (Harvey and Bedford 1988) was compared with the radiosensitization of their mutual parent CHO 10B12 cell line. The irs-20 and CHO 10B12 cells have comparable heat (43.5 o C) sensitivities, whereas hs-36 and CHO 10B12 show a similar sensitivity to γ- and X-rays. Radiosensitization due to pre-exposure to 43.5 o C heating of plateau phase cultures was found for all three cell lines, even after relatively mild heat treatment killing <20% of cells. Experiments using CHEF electrophoresis confirmed the dsb repair deficiency of the irs-20 cells (Stackhouse and Bedford 1992) and showed that heat inhibited dsb repair in all three cell lines. (Author)

  12. Building Bridges One Line at a Time

    Science.gov (United States)

    Grigsby, Cathy Murray

    2012-01-01

    In this article, first-grade students were taught the different kinds of lines that were part of the construction of various bridges--the curved lines of the arches of stone bridges, straight lines connecting the cables of a suspension bridge, vertical lines, horizontal lines, and so on. They gained practice in drawing structures and in fine brush…

  13. Linear morphoea follows Blaschko's lines.

    Science.gov (United States)

    Weibel, L; Harper, J I

    2008-07-01

    The aetiology of morphoea (or localized scleroderma) remains unknown. It has previously been suggested that lesions of linear morphoea may follow Blaschko's lines and thus reflect an embryological development. However, the distribution of linear morphoea has never been accurately evaluated. We aimed to identify common patterns of clinical presentation in children with linear morphoea and to establish whether linear morphoea follows the lines of Blaschko. A retrospective chart review of 65 children with linear morphoea was performed. According to clinical photographs the skin lesions of these patients were plotted on to standardized head and body charts. With the aid of Adobe Illustrator a final figure was produced including an overlay of all individual lesions which was used for comparison with the published lines of Blaschko. Thirty-four (53%) patients had the en coup de sabre subtype, 27 (41%) presented with linear morphoea on the trunk and/or limbs and four (6%) children had a combination of the two. In 55 (85%) children the skin lesions were confined to one side of the body, showing no preference for either left or right side. On comparing the overlays of all body and head lesions with the original lines of Blaschko there was an excellent correlation. Our data indicate that linear morphoea follows the lines of Blaschko. We hypothesize that in patients with linear morphoea susceptible cells are present in a mosaic state and that exposure to some trigger factor may result in the development of this condition.

  14. Prevalence and effects of multiple chemical sensitivities in Australia

    Directory of Open Access Journals (Sweden)

    Anne Steinemann

    2018-06-01

    Full Text Available Multiple chemical sensitivities (MCS is a medical condition associated with exposure to common chemical pollutants. The aims of this study are to assess the prevalence of MCS, its overlaps with asthma and fragrance sensitivity, and its health and societal effects in Australia. Data were collected in June 2016 using an on-line survey with a representative national sample (N = 1098 of adults (ages 18–65 in Australia. Results found that, across the country, 6.5% report medically diagnosed MCS, 18.9% report chemical sensitivity (being unusually sensitive to everyday chemicals and chemically formulated products, and 19.9% either or both. Among people with MCS, 74.6% also have diagnosed asthma or an asthma-like condition, and 91.5% have fragrance sensitivity, reporting health problems (such as migraine headaches when exposed to fragranced consumer products (such as air fresheners and cleaning supplies. In addition, among people with MCS, 77.5% are prevented from access to places because of fragranced products, 52.1% lost workdays or a job in the past year due to fragranced product exposure in the workplace, and 55.4% report health effects considered potentially disabling. Results indicate that MCS is a widespread disease, affecting an estimated 1 million adult Australians, with chemical sensitivity affecting another 2 million. Reducing chemical exposure to problematic sources, such as fragranced consumer products, is critical to reduce adverse effects. Keywords: MCS, Multiple chemical sensitivities, Chemical sensitivity, Asthma, Fragrance sensitivity, Fragranced consumer products

  15. Problems with the use of line shifts in plasmas

    International Nuclear Information System (INIS)

    Alexiou, Spiros

    2003-01-01

    In this work a nonperturbative semiclassical treatment with proper account of penetrating collisions and monopoles is used to illustrate the relative importance of penetration, close collisions and monopoles to the line shift. The main result of this work is that shifts are very sensitive, not linear in the density and even the sign of shifts may be affected by fairly fine effects, such as small deviations from thermal behavior

  16. Culture-sensitive psychotraumatology

    Science.gov (United States)

    Schnyder, Ulrich; Bryant, Richard A.; Ehlers, Anke; Foa, Edna B.; Hasan, Aram; Mwiti, Gladys; Kristensen, Christian H.; Neuner, Frank; Oe, Misari; Yule, William

    2016-01-01

    Background Although there is some evidence of the posttraumatic stress disorder (PTSD) construct's cross cultural validity, trauma-related disorders may vary across cultures, and the same may be true for treatments that address such conditions. Experienced therapists tailor psychotherapy to each patient's particular situation, to the nature of the patient's psychopathology, to the stage of therapy, and so on. In addition, culture-sensitive psychotherapists try to understand how culture enhances the meaning of their patient's life history, the cultural components of their illness and help-seeking behaviors, as well as their expectations with regard to treatment. We cannot take for granted that all treatment-seeking trauma survivors speak our language or share our cultural values. Therefore, we need to increase our cultural competencies. Methods The authors of this article are clinicians and/or researchers from across the globe, working with trauma survivors in various settings. Each author focused on one or more specific cultural aspects of working with trauma survivors and highlighted the following aspects. Results As a result of culture-specific individual and collective meanings linked to trauma and trauma-related disorders survivors may be exposed to (self-)stigma in the aftermath of trauma. Patients who are reluctant to talk about their traumatic experiences may instead be willing to write or use other ways of accessing the painful memories such as drawing. In other cultures, community and family cohesion are crucial elements of recovery. While awareness of culture-specific aspects is important, we also need to beware of premature cultural stereotyping. When disseminating empirically supported psychotherapies for PTSD across cultures, a number of additional challenges need to be taken into account: many low and middle income countries have very limited resources available and suffer from a poor health infrastructure. Conclusions In summary, culture-sensitive

  17. Effect of 17-AAG on radio-sensitivity of HeLa and V79 cells

    International Nuclear Information System (INIS)

    Pan Yanling; Hong Chengjiao; Zhang Baoguo

    2010-01-01

    In order to investigate the radio-sensitizing effect of 17-AAG, an inhibitor of Heat Shock Protein 90, on human Uterine Cervix Cancer HeLa and V79 cells, Clonogenic assay was used to observe the cell survival rate. The results show that 17-AAG can decrease obviously (p 0.05). This indicates that 17-AAG may enhance the radio-sensitivity of the HeLa cell line and has no effect on the V79 cell line. (authors)

  18. Use of lymphoblastoid cell lines to evaluate the hypersensitivity to ultraviolet radiation in Cockayne syndrome

    International Nuclear Information System (INIS)

    Otsuka, F.; Tarone, R.E.; Cayeux, S.; Robbins, J.H.

    1984-01-01

    Cockayne syndrome (CS) is a rare autosomal recessive disease characterized by acute sun sensitivity, cachectic dwarfism, and neurologic and skeletal abnormalities. Cultured skin fibroblasts from patients with this disease are known to be hypersensitive to the lethal effects of 254-nm UV radiation. The authors have studied the sensitivity of 254-nm UV radiation of lymphoblastoid lines derived from 3 typical CS patients, 1 atypical CS patient who had a very late age of onset of clinical manifestations, 2 patients who had both xeroderma pigmentosum (XP) and typical CS, and 3 heterozygous parents of these patients. Post-UV survival was determined by the trypan-blue dye-exclusion method. The lymphoblastoid lines from the 3 typical CS patients, the atypical CS patient, and the 2 patients with both CS and XP had decreased post-UV viability in comparison with lines from normal donors. Lines from the heterozygous parents had normal post-UV viability. The post-UV viability of the typical CS lines was similar to that of a XP complementation group C line. The relative post-UV viability of lymphoblastoid lines from the typical CS patients was similar to the relative post-UV survival of their fibroblast lines. The lymphoblastoid line from the atypical CS patient had a post-UV viability similar to that of the typical CS patients. Thus, the relative hypersensitivity of CS patients cells in vitro does not reflect the severity or age of onset of the patients clinical manifestations. The lymphoblastoid lines from the 2 patients who had both CS and XP were significantly more sensitive to the UV radiation than those from patients with only CS. Our studies demonstrate that lymphoblastoid lines from patients with CS are appropriate and useful cell lines for the study of the inherited hypersensitivity to UV radiation

  19. Standardization of beam line representations

    International Nuclear Information System (INIS)

    Carey, David C.

    1998-01-01

    Standardization of beam line representations means that a single set of data can be used in many situations to represent a beam line. This set of data should be the same no matter what the program to be run or the calculation to be made. We have concerned ourselves with three types of standardization: (1) The same set of data should be usable by different programs. (2) The inclusion of other items in the data, such as calculations to be done, units to be used, or preliminary specifications, should be in a notation similar to the lattice specification. (3) A single set of data should be used to represent a given beam line, no matter what is being modified or calculated. The specifics of what is to be modified or calculated can be edited into the data as part of the calculation. These three requirements all have aspects not previously discussed in a public forum. Implementations into TRANSPORT will be discussed

  20. Linear rotary optical delay lines

    Science.gov (United States)

    Guerboukha, Hichem; Qu, Hang; Skorobogatiy, Maksim

    2016-03-01

    We present a semi-analytical solution for the design of a high-speed rotary optical delay line that use a combination of two rotating curvilinear reflectors. We demonstrate that it is possible to design an infinite variety of the optical delay lines featuring linear dependence of the optical delay on the rotation angle. This is achieved via shape optimization of the rotating reflector surfaces. Moreover, a convenient spatial separation of the incoming and outgoing beams is possible. For the sake of example, we present blades that fit into a circle of 10cm diameter. Finally, a prototype of a rotary delay line is fabricated using CNC machining, and its optical properties are characterized.