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Sample records for wimp line sensitivity

  1. Development of Bubble Chambers with Sensitivity to WIMPs

    SciTech Connect

    Bond, Leonard J.; Collar, J. I.; Ely, James H.; Flake, Matthew; Hall, Jason M.; Jordan, David V.; Nakazawa, Dante; Raskin, Aza; Sonnenschein, Andrew; O'Sullivan, Kevin

    2005-01-10

    Bubble nucleation in moderately superheated liquids can be triggered by nuclear recoils from WIMPs. This phenomenon is the basis for superheated droplet detectors. The droplet technique is currently limited by insensitivity to spin-independent interactions, due to lack of heavy elements in the usual target liquids, and sensitivity to contamination of the gel by alpha emitters. As an alternative, we have developed a new type of homogeneous bubble chamber, which can contain heavy liquids, including CF3Br, CF3I, and C3F8. Detectors of this type may be scalable to large size at modest cost and could have very low backgrounds. We discuss results obtained with a 12 ml prototype and plans for a 1 liter chamber.

  2. Development of Bubble Chambers with Sensitivity to WIMPs

    SciTech Connect

    Bond, Leonard J.; Collar, J. I.; Ely, James H.; Flake, Matthew; Hall, Jason M.; Jordan, David V.; Nakazawa, Dante; Raskin, Aza; Sonnenschein, Andrew; Sullivan, Kelly O.

    2005-05-01

    Bubble nucleation in moderately superheated liquids can be triggered by nuclear recoils from WIMPs. This phenomenon is the basis for superheated droplet detectors. The droplet technique is currently limited by insensitivity to spin-independent interactions, due to lack of heavy elements in the usual target liquids, and sensitivity to contamination of the gel by alpha emitters. As an alternative, we have developed a new type of homogeneous bubble chamber, which can contain heavy liquids, including CF3Br, CF3I, and C3F8. Detectors of this type may be scalable to large size at modest cost and could have very low backgrounds. We discuss results obtained with a 12 ml prototype and plans for a 1 liter chamber.

  3. Positron line radiation from halo WIMP annihilations as a dark matter signature

    NASA Technical Reports Server (NTRS)

    Turner, Michael S.; Wilczek, Frank

    1989-01-01

    We suggest a new signature for dark matter annihilation in the halo: high energy positron line radiation. Because the cosmic ray positron spectrum falls rapidly with energy, e+'s from halo WIMP annihilations can be a significant, clean signal for very massive WIMP's (approx. greater than 30 GeV). In the case that the e+e- annihilation channel has an appreciable branch, the e+ signal should be above background in a future detector, such as have been proposed for ASTROMAG, and of potential importance as a dark matter signature. A significant e+e- branching ratio can occur for neutralinos or Dirac neutrinos. High-energy, continuum positron radiation may also be an important signature for massive neutralino annihilations, especially near or above the threshold of the W+W- and ZoZo annihilation channels.

  4. Extending the Sensitivity to the Detection of WIMP Dark Matter with an Improved Understanding of the Limiting Neutron Backgrounds

    SciTech Connect

    Kamat, Sharmila

    2005-01-01

    The Cryogenic Dark Matter Search (CDMS) uses position-sensitive Germanium and Silicon crystals in the direct detection of Weakly Interacting Massive Particles (WIMPs) believed to constitute most of the dark matter in the Universe. WIMP interactions with matter being rare, identifying and eliminating known backgrounds is critical for detection. Event-by-event discrimination by the detectors rejects the predominant gamma and beta backgrounds while Monte Carlo simulations help estimate, and subtract, the contribution from the neutrons. This thesis describes the effort to understand neutron backgrounds as seen in the two stages of the CDMS search for WIMPs. The first stage of the experiment was at a shallow site at the Stanford Underground Facility where the limiting background came from high-energy neutrons produced by cosmic-ray muon interactions in the rock surrounding the cavern. Simulations of this background helped inform the analysis of data from an experimental run at this site and served as input for the background reduction techniques necessary to set new exclusion limits on the WIMP-nucleon cross-section, excluding new parameter space for WIMPs of masses 8-20 GeV/c{sup 2}. This thesis considers the simulation methods used as well as how various event populations in the data served as checks on the simulations to allow them to be used in the interpretation of the WIMP-search data. The studies also confirmed the presence of a limiting neutron background at the shallow site, necessitating the move to the 713-meter deep Soudan Underground Facility. Similar computer-based studies helped quantify the neutron background seen at the deeper site and informed the analysis of the data emerging from the first physics run of the experiment at Soudan. In conjunction with the WIMP-search and calibration data, the simulations confirmed that increased depth considerably reduced the neutron backgrounds seen, greatly improving the sensitivity to WIMP detection. The data run set an upper limit of 4 x 10{sup -43} on the WIMP-nucleon cross section for a WIMP mass of 60 GeV/c{sup 2} . Upper limits to the rate of background neutrons have also been determined.

  5. A high efficiency veto to increase the sensitivity of ZEPLIN-III, a WIMP detector

    SciTech Connect

    Barnes, E. J.

    2009-09-08

    An active veto detector to complement the ZEPLIN-III two phase Xenon, direct dark matter device is described. The proposed design consists of 52 plastic scintillator segments, individually read out by high efficiency photomultipliers, coupled to a Gd loaded passive polypropylene shield. Experimental work was performed to determine the plastic scintillator characteristics which were used to inform a complete end-to-end Monte Carlo simulation of the expected performance of the new instrument, both operating alone and as an active veto detector for ZEPLIN-III. The veto device will be capable of tagging over 65% of coincident nuclear recoil events in the energy range of interest in ZEPLIN-III, and over 12% for gamma ray rejection, while contributing no significant additional background. In addition it will also provide valuable diagnostic capabilities. The inclusion of the veto to ZEPLIN-III will aid to significantly improve the sensitivity to spin independent WIMP-nucleon cross sections below 10{sup -8} pb.

  6. Leptophilic effective WIMPs

    NASA Astrophysics Data System (ADS)

    Chang, Spencer; Edezhath, Ralph; Hutchinson, Jeffrey; Luty, Markus

    2014-07-01

    Effective weakly interacting massive particle (WIMP) models are minimal extensions of the standard model that explain the relic density of dark matter by the "WIMP miracle." In this paper we consider the phenomenology of effective WIMPs with trilinear couplings to leptons and a new "lepton partner" particle. The observed relic abundance fixes the strength of the cubic coupling, so the parameters of the models are defined by the masses of the WIMP and lepton partner particles. This gives a simple parameter space where collider and direct detection experiments can be compared under well-defined physical minimality assumptions. The most sensitive collider probe is the search for leptons+MET, while the most sensitive direct detection channel is scattering from nuclei arising from loop diagrams. Collider and direct detection searches are highly complementary: colliders give the only meaningful constraint when dark matter is its own antiparticle, while direct detection is generally more sensitive if the dark matter is not its own antiparticle.

  7. Effective WIMPs

    NASA Astrophysics Data System (ADS)

    Hutchinson, Jeffrey Paul

    The 'WIMP miracle' for the relic abundance of thermal dark matter motivates weak scale dark matter with renormalizable couplings to standard model particles. This work examines minimal models with such couplings that explain dark matter as a thermal relic. The models contain a singlet dark matter particle with cubic renormalizable couplings between standard model particles and 'partner' particles with the same gauge quantum numbers as the standard model particle. The dark matter has spin 0, 1/2, or 1, and may or may not be its own antiparticle. Each model has 3 parameters: the masses of the dark matter and standard model partners, and the cubic coupling. Requiring the correct relic abundance gives a 2-dimensional parameter space where collider and direct detection constraints can be directly compared. This work focuses on the case of dark matter interactions with quarks and leptons. For quark models, collider and direct detection searches are remarkably complementary. Direct detection limits for the cases where the dark matter is not its own antiparticle require dark matter masses to be in the multi-TeV range, where they are extremely difficult to probe in collider experiments. The models where dark matter is its own antiparticle are strongly constrained by collider searches for monojet and jets +MET signals. These models are constrained by direct detection mainly near the limit where the dark matter and partner masses are nearly degenerate, where collider searches become more difficult. In the lepton case, the most sensitive collider probe is the search for leptons + MET, while the most sensitive direct detection channel is scattering off nuclei arising from loop diagrams. Here too collider and direct detection searches are highly complementary: colliders give the only meaningful constraint when dark matter is its own antiparticle, while direct detection is generally more sensitive if the dark matter is not its own antiparticle.

  8. Low-Mass WIMP Sensitivity and Statistical Discrimination of Electron and Nuclear Recoils by Varying Luke-Neganov Phonon Gain in Semiconductor Detectors

    NASA Astrophysics Data System (ADS)

    Pyle, M.; Bauer, D. A.; Cabrera, B.; Hall, J.; Schnee, R. W.; Basu Thakur, R.; Yellin, S.

    2012-06-01

    Amplifying the phonon signal in a semiconductor dark matter detector can be accomplished by operating at high voltage bias and converting the electrostatic potential energy into Luke-Neganov phonons. This amplification method has been validated at up to | E|=40 V/cm without producing leakage in CDMS II Ge detectors, allowing sensitivity to a benchmark WIMP with mass M χ =8 GeV/c2 and σ=1.8×10-42 cm2 (with significant sensitivity for M χ >2 GeV/c2) assuming flat electronic recoil backgrounds near threshold. Furthermore, for the first time we show that differences in Luke-Neganov gain for nuclear and electronic recoils can be used to discriminate statistically between low-energy background and a hypothetical WIMP signal by operating at two distinct voltage biases. Specifically, 99% of events have p-value <10-8 for a simulated 20 kg-day experiment with a benchmark WIMP signal with M χ =8 GeV/c2 and σ=3.3×10-41 cm2.

  9. Effective WIMPs

    NASA Astrophysics Data System (ADS)

    Chang, Spencer; Edezhath, Ralph; Hutchinson, Jeffrey; Luty, Markus

    2014-01-01

    The "WIMP miracle" for the relic abundance of thermal dark matter motivates weak scale dark matter with renormalizable couplings to standard model particles. We study minimal models with such couplings that explain dark matter as a thermal relic. The models contain a singlet dark matter particle with cubic renormalizable couplings between standard model particles and "partner" particles with the same gauge quantum numbers as the standard model particle. The dark matter has spin 0, 1/2, or 1, and may or may not be its own antiparticle. Each model has 3 parameters: the masses of the dark matter and standard model partners, and the cubic coupling. Requiring the correct relic abundance gives a 2-dimensional parameter space where collider and direct detection constraints can be directly compared. We focus on the case of dark matter interactions with colored particles. We find that collider and direct detection searches are remarkably complementary for these models. Direct detection limits for the cases where the dark matter is not its own antiparticle require dark matter masses to be in the multi-TeV range, where they are extremely difficult to probe in collider experiments. The models where dark matter is its own antiparticle are strongly constrained by collider searches for monojet and jets+MET signals. These models are constrained by direct detection mainly near the limit where the dark matter and partner masses are nearly degenerate, where collider searches become more difficult.

  10. Probing light WIMPs with directional detection experiments

    NASA Astrophysics Data System (ADS)

    Morgan, Ben; Green, Anne M.

    2012-10-01

    The CoGeNT and CRESST WIMP direct detection experiments have recently observed excesses of nuclear recoil events, while the DAMA/LIBRA experiment has a long-standing annual modulation signal. It has been suggested that these excesses may be due to light masses of mχ˜5-10GeV, weakly interacting massive particles (WIMPs). The Earth’s motion with respect to the Galactic rest frame leads to a directional dependence in the WIMP scattering rate, providing a powerful signal of the Galactic origin of any recoil excess. We investigate whether direct detection experiments with directional sensitivity have the potential to observe this anisotropic scattering rate with the elastically scattering light WIMPs proposed to explain the observed excesses. We find that the number of recoils required to detect an anisotropic signal from light WIMPs at 5σ significance varies from 7 to more than 190 over the set of target nuclei and energy thresholds expected for directional detectors. Smaller numbers arise from configurations where the detector is only sensitive to recoils from the highest-speed, and hence most anisotropic, WIMPs. However, the event rate above the threshold is very small in these cases, leading to the need for large experimental exposures to accumulate even a small number of events. To account for this sensitivity to the tail of the WIMP velocity distribution, whose shape is not well known, we consider two exemplar halo models spanning the range of possibilities. We also note that for an accurate calculation, the Earth’s orbital speed must be averaged over. We find that the exposures required to detect 10 GeV WIMPs at a WIMP-proton cross section of 10-4pb are of order 103kgday for a 20 keV energy threshold, within reach of planned directional detectors. Lower WIMP masses require higher exposures and/or lower energy thresholds for detection.

  11. Vector WIMP miracle

    NASA Astrophysics Data System (ADS)

    Abe, Tomohiro; Kakizaki, Mitsuru; Matsumoto, Shigeki; Seto, Osamu

    2012-07-01

    Weakly interacting massive particle (WIMP) is well known to be a good candidate for dark matter, and it is also predicted by many new physics models beyond the standard model at the TeV scale. We found that, if the WIMP is a vector particle (spin-one particle) which is associated with some gauge symmetry broken at the TeV scale, the Higgs mass is often predicted to be 120-125 GeV, which is very consistent with the result of Higgs searches recently reported by ATLAS and CMS Collaborations at the Large Hadron Collider experiment. In this Letter, we consider the vector WIMP using a non-linear sigma model in order to confirm this result as general as possible in a bottom-up approach. Near-future prospects to detect the vector WIMP at both direct and indirect detection experiments of dark matter are also discussed.

  12. Nonthermal 'WIMP miracle'

    SciTech Connect

    Acharya, Bobby Samir; Kane, Gordon; Watson, Scott; Kumar, Piyush

    2009-10-15

    Light scalar fields with only gravitational strength couplings are typically present in UV complete theories of physics beyond the standard model. In the early universe it is natural for these fields to dominate the energy density, and their subsequent decay - if prior to big bang nucleosynthesis - will typically yield some dark matter particles in their decay products. In this paper we make the observation that a Nonthermal 'WIMP Miracle' may result: that is, in the simplest solution to the cosmological moduli problem, nonthermally produced WIMPs can naturally account for the observed dark matter relic density.

  13. WIMP Dark Matter Limit-Direct Detection Data and Sensitivity Plots from the Cryogenic Dark Matter Search II and the University of California at Santa Barbara

    DOE Data Explorer

    Expectations for non-baryonic dark matter are founded principally in Big Bang nucleosynthesis calculations, which indicate that the missing mass of the universe is not likely to be baryonic. The supersymmetric standard model (SUSY) offers a promising framework for expectations of particle species which could satisfy the observed properties of dark matter. WIMPs are the most likely SUSY candidate for a dark matter particle. The High Energy Physics Group at University of California, Santa Barbara, is part of the CDMSII Collaboration and have provided the Interactive Plotter for WIMP Dark Matter Limit-Direct Detection Data on their website. They invite other collaborations working on dark matter research to submit datasets and, as a result, have more than 150 data sets now available for use with the plotting tool. The published source of the data is provided with each data set.

  14. Median recoil direction as a WIMP directional detection signal

    NASA Astrophysics Data System (ADS)

    Green, Anne M.; Morgan, Ben

    2010-03-01

    Direct detection experiments have reached the sensitivity to detect dark matter weakly interacting massive particles (WIMPs). Demonstrating that a putative signal is due to WIMPs, and not backgrounds, is a major challenge, however. The direction dependence of the WIMP scattering rate provides a potential WIMP “smoking gun.” If the WIMP distribution is predominantly smooth, the Galactic recoil distribution is peaked in the direction opposite to the direction of Solar motion. Previous studies have found that, for an ideal detector, of order 10 WIMP events would be sufficient to reject isotropy, and rule out an isotropic background. We examine how the median recoil direction could be used to confirm the WIMP origin of an anisotropic recoil signal. Specifically, we determine the number of events required to confirm the direction of solar motion as the median inverse recoil direction at 95% confidence. We find that for zero background 31 events are required, a factor of ˜2 more than are required to simply reject isotropy. We also investigate the effect of a nonzero isotropic background. As the background rate is increased the number of events required increases, initially fairly gradually and then more rapidly, once the signal becomes subdominant. We also discuss the effect of features in the speed distribution at large speeds, as found in recent high resolution simulations, on the median recoil direction.

  15. Median recoil direction as a WIMP directional detection signal

    SciTech Connect

    Green, Anne M.; Morgan, Ben

    2010-03-15

    Direct detection experiments have reached the sensitivity to detect dark matter weakly interacting massive particles (WIMPs). Demonstrating that a putative signal is due to WIMPs, and not backgrounds, is a major challenge, however. The direction dependence of the WIMP scattering rate provides a potential WIMP 'smoking gun'. If the WIMP distribution is predominantly smooth, the Galactic recoil distribution is peaked in the direction opposite to the direction of Solar motion. Previous studies have found that, for an ideal detector, of order 10 WIMP events would be sufficient to reject isotropy, and rule out an isotropic background. We examine how the median recoil direction could be used to confirm the WIMP origin of an anisotropic recoil signal. Specifically, we determine the number of events required to confirm the direction of solar motion as the median inverse recoil direction at 95% confidence. We find that for zero background 31 events are required, a factor of {approx}2 more than are required to simply reject isotropy. We also investigate the effect of a nonzero isotropic background. As the background rate is increased the number of events required increases, initially fairly gradually and then more rapidly, once the signal becomes subdominant. We also discuss the effect of features in the speed distribution at large speeds, as found in recent high resolution simulations, on the median recoil direction.

  16. The fraternal WIMP miracle

    SciTech Connect

    Craig, Nathaniel; Katz, Andrey

    2015-10-27

    We identify and analyze thermal dark matter candidates in the fraternal twin Higgs model and its generalizations. The relic abundance of fraternal twin dark matter is set by twin weak interactions, with a scale tightly tied to the weak scale of the Standard Model by naturalness considerations. As such, the dark matter candidates benefit from a “fraternal WIMP miracle”, reproducing the observed dark matter abundance for dark matter masses between 50 and 150 GeV. However, the couplings dominantly responsible for dark matter annihilation do not lead to interactions with the visible sector. The direct detection rate is instead set via fermionic Higgs portal interactions, which are likewise constrained by naturalness considerations but parametrically weaker than those leading to dark matter annihilation. The predicted direct detection cross section is close to current LUX bounds and presents an opportunity for the next generation of direct detection experiments.

  17. The fraternal WIMP miracle

    NASA Astrophysics Data System (ADS)

    Craig, Nathaniel; Katz, Andrey

    2015-10-01

    We identify and analyze thermal dark matter candidates in the fraternal twin Higgs model and its generalizations. The relic abundance of fraternal twin dark matter is set by twin weak interactions, with a scale tightly tied to the weak scale of the Standard Model by naturalness considerations. As such, the dark matter candidates benefit from a ``fraternal WIMP miracle'', reproducing the observed dark matter abundance for dark matter masses between 50 and 150 GeV . However, the couplings dominantly responsible for dark matter annihilation do not lead to interactions with the visible sector. The direct detection rate is instead set via fermionic Higgs portal interactions, which are likewise constrained by naturalness considerations but parametrically weaker than those leading to dark matter annihilation. The predicted direct detection cross section is close to current LUX bounds and presents an opportunity for the next generation of direct detection experiments.

  18. The CASPAR recoil discrimination detector for WIMP searches with calcium and fluorine.

    NASA Astrophysics Data System (ADS)

    Tovey, D. R.; Peak, C. D.; Roberts, J. W.; Spooner, N. J. C.

    1999-01-01

    The authors present results of development work on the CASPAR ('cocktail with alkali-halide scintillating particles') WIMP dark matter detector. The results of Monte Carlo simulations and neutron-scattering tests indicate that even a modest sized detector should provide improved spin-dependent WIMP sensitivity.

  19. The WIMP Forest: Indirect Detection of a Chiral Square

    SciTech Connect

    Bertone, Gianfranco; Jackson, C.B.; Shaughnessy, Gabe; Tait, Tim M.P.; Vallinotto, Alberto

    2009-04-01

    The spectrum of photons arising from WIMP annihilation carries a detailed imprint of the structure of the dark sector. In particular, loop-level annihilations into a photon and another boson can in principle lead to a series of lines (a WIMP forest) at energies up to the WIMP mass. A specific model which illustrates this feature nicely is a theory of two universal extra dimensions compactified on a chiral square. Aside from the continuum emission, which is a generic prediction of most dark matter candidates, we find a 'forest' of prominent annihilation lines that, after convolution with the angular resolution of current experiments, leads to a distinctive (2-bump plus continuum) spectrum, which may be visible in the near future with the Fermi Gamma-Ray Space Telescope (formerly known as GLAST).

  20. Nano-booms — A new class of WIMP detectors

    NASA Astrophysics Data System (ADS)

    Drukier, A. K.; Fagaly, R. L.; Bielski, R.

    2014-07-01

    Weakly Interacting Massive Particles (WIMPs) can constitute a large fraction of the dark matter (DM) in the universe. The importance of coherent scattering and detection of annual modulation effect (AME), diurnal modulation effect (DME) and direction sensitive AME was documented. In particular, DAMA/NaI and DAMA/LIBRA have released data collected during 14 annual cycles, which support in model independent way, the presence of DM particles in the galactic halo. There is a clear evidence of AME signature in DAMA data. Recently, positive hints have also been reported by CoGeNT on AME signature in Ge, while CREST-II and CDMS-Si have published some events in excess of estimated background; these events are compatible with WIMP-like candidates. If these results would be analyzed all together in some WIMP scenario, one could derive: MDM < 10 GeV/c2. Current generation of detectors is far from being optimal or in some cases even reliable when MDM approaches 5 GeV/c2. We propose a detector, which can detect the direction of incoming WIMPs. This paper focus on a particular implementation of the new class of nano-explosive DM detectors. The local heating ignites an explosion, which release chemical energy stored in such a nano-grain. Use of two component nano-explosive permits to amplify the bolometric effect due to WIMP-candidates. The energy available becomes 100,000-fold larger than the energy initially deposited by DM candidate. This leads to a sonic-boom, which can be detected remotely. This new class of nano-explosive detectors may be especially important in detection of WIMPs with very low mass, say MDM = O(5 GeV/c2). We describe a configuration, which leads to explosive-triode, and permits detection of the direction of incoming WIMPs.

  1. Probing WIMP particle physics and astrophysics with direct detection and neutrino telescope data

    NASA Astrophysics Data System (ADS)

    Kavanagh, Bradley J.; Fornasa, Mattia; Green, Anne M.

    2015-05-01

    With positive signals from multiple direct detection experiments, it will, in principle, be possible to measure the mass and cross sections of weakly interacting massive particle (WIMP) dark matter. Recent work has shown that, with a polynomial parametrization of the WIMP speed distribution, it is possible to make an unbiased measurement of the WIMP mass, without making any astrophysical assumptions. However, direct detection experiments are not sensitive to low-speed WIMPs and, therefore, any model-independent approach will lead to a bias in the cross section. This problem can be solved with the addition of measurements of the flux of neutrinos from the Sun. This is because the flux of neutrinos produced from the annihilation of WIMPs which have been gravitationally captured in the Sun is sensitive to low-speed WIMPs. Using mock data from next-generation direct detection experiments and from the IceCube neutrino telescope, we show that the complementary information from IceCube on low-speed WIMPs breaks the degeneracy between the cross section and the speed distribution. This allows unbiased determinations of the WIMP mass and spin-independent and spin-dependent cross sections to be made, and the speed distribution to be reconstructed. We use two parametrizations of the speed distribution: binned and polynomial. While the polynomial parametrization can encompass a wider range of speed distributions, this leads to larger uncertainties in the particle physics parameters.

  2. Light WIMPs in the Sun: Constraints from helioseismology

    SciTech Connect

    Cumberbatch, Daniel T.; Guzik, Joyce A.; Silk, Joseph; Watson, L. Scott; West, Stephen M.

    2010-11-15

    We calculate solar models including dark matter (DM) weakly interacting massive particles (WIMPs) of mass 5-50 GeV and test these models against helioseismic constraints on sound speed, convection-zone depth, convection-zone helium abundance, and small separations of low-degree p-modes. Our main conclusion is that both direct detection experiments and particle accelerators may be complemented by using the Sun as a probe for WIMP DM particles in the 5-50 GeV mass range. The DM most sensitive to this probe has suppressed annihilations and a large spin-dependent elastic scattering cross section. For the WIMP cross section parameters explored here, the lightest WIMP masses <10 GeV are ruled out by constraints on core sound speed and low-degree frequency spacings. For WIMP masses 30-50 GeV, the changes to the solar structure are confined to the inner 4% of the solar radius and so do not significantly affect the solar p-modes. Future helioseismology observations, most notably involving g-modes, and future solar neutrino experiments may be able to constrain the allowable DM parameter space in a mass range that is of current interest for direct detection.

  3. Event rates for WIMP detection

    SciTech Connect

    Vergados, J. D.; Moustakidis, Ch. C.; Oikonomou, V.

    2006-11-28

    The event rates for the direct detection of dark matter for various types of WIMPs are presented. In addition to the neutralino of SUSY models, we considered other candidates (exotic scalars as well as particles in Kaluza-Klein and technicolour theories) with masses in the TeV region. Then one finds reasonable branching ratios to excited states. Thus the detection of the WIMP can be made not only by recoil measurements, by measuring the de-excitation {gamma}-rays as well.

  4. CDMS WIMP detector Fabrication Optimization

    NASA Astrophysics Data System (ADS)

    Jastram, Andrew

    2012-03-01

    Less than 20% of the matter content in the Universe is made up of what we know as ordinary matter, the rest is dominated by Dark Matter. The major candidate constituent of Dark Matter is the Weakly Interacting Massive Particle (WIMP). The Cryogenic Dark Matter Search (CDMS) experiment uses photo-lithographically patterned Ge detectors with Transition Edge Sensors (TES) that are operated at 50mK temperature, to look for possible recoil with the slow moving WIMPs in our galaxy. This talk will present recent advances in the detector technology with a new dedicated nano-fabrication facility set up at Texas A&M University.

  5. Direct WIMP searches with XENON100 and XENON1T

    NASA Astrophysics Data System (ADS)

    Alfredo Davide, Ferella

    2015-05-01

    The XENON100 experiment is the second phase of the XENON direct Dark Matter search program. It consists of an ultra-low background double phase (liquid-gas) xenon filled time projection chamber with a total mass of 161 kg (62 in the target region and 99 in the active shield), installed at the Laboratori Nazionali del Gran Sasso (LNGS). Here the results from the 224.6 live days of data taken between March 2011 and April 2012 are reported. The experiment set one of the most stringent limits on the WIMP-nucleon spin-independent cross section to date (2 × 10-45 cm2 for a 55 Gev/c2 WIMP mass at 90 % confidence level) and the most stringent on the spin-dependent WIMP-neutron interaction (3.5 × 10-40 for a 45 GeV/c2 WIMP mass). With the same dataset, XENON100 excludes also solar axion coupling to electrons at gAe > 7.7 × 10-12 for a mass of mAxion <1 keV/c2 and galactic axion couplings by gAe > 1 × 10-12 at a mass range of mAxion = 5-10 keV/c2 (both 90 % C.L.). Moreover an absolute spectral comparison between simulated and measured nuclear recoil distributions of light and charge signals from a 241AmBe source demonstrates a high level of detector and systematics understanding. Finally, the third generation of the XENON experiments, XENON1T, is the first tonne scale direct WIMP search experiment currently under construction. The commissioning phase of XENON1T is expected to start in early 2015 followed, a few months after, by the first science run. The experiment will reach sensitivities on the WIMP-nucleon spin-independent cross section down to 2 ×10-47 cm2 after two years of data taking.

  6. A WIMP Dark Matter Detector Using MKIDs

    NASA Astrophysics Data System (ADS)

    Golwala, S.; Gao, J.; Moore, D.; Mazin, B.; Eckart, M.; Bumble, B.; Day, P.; Leduc, H. G.; Zmuidzinas, J.

    2008-04-01

    We are pursuing the development of a phonon- and ionization-mediated WIMP dark matter detector employing microwave kinetic inductance detectors (MKIDs) in the phonon-sensing channel. Prospective advantages over existing detectors include: improved reconstruction of the phonon signal and event position; simplified readout wiring and cold electronics; and simplified and more reliable fabrication. We have modeled a simple design using available MKID sensitivity data and anticipate energy resolution as good as existing phonon-mediated detectors and improved position reconstruction. We are doing preparatory experimental work by fabricating strip absorber architectures. Measurements of diffusion length, trapping efficiency, and MKID sensitivity with these devices will enable us to design a 1 cm2×2 mm prototype device to demonstrate phonon energy resolution and position reconstruction.

  7. Photon spectra from WIMP annihilation

    SciTech Connect

    Cembranos, J. A. R.; Cruz-Dombriz, A. de la; Dobado, A.; Maroto, A. L.; Lineros, R. A.

    2011-04-15

    If the present dark matter in the Universe annihilates into standard model particles, it must contribute to the fluxes of cosmic rays that are detected on the Earth and, in particular, to the observed gamma-ray fluxes. The magnitude of such a contribution depends on the particular dark matter candidate, but certain features of the produced photon spectra may be analyzed in a rather model-independent fashion. In this work we provide the complete photon spectra coming from WIMP annihilation into standard model particle-antiparticle pairs obtained by extensive Monte Carlo simulations. We present results for each individual annihilation channel and provide analytical fitting formulas for the different spectra for a wide range of WIMP masses.

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

    SciTech Connect

    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.

  9. MOON for double beta decays and X-rays from WIMP nuclear interactions

    NASA Astrophysics Data System (ADS)

    Ejiri, H.

    2006-07-01

    Neutrino-less double beta decays (0νββ) and direct observation of cold dark matter (DM) are of great interest for studying fundamental properties of neutrinos and weakly interacting massive particles (WIMPs). These are crucial for particle physics and cosmology beyond the standard electro-weak theory. The present seminar in the Erice neutrino school reports briefly (1) the effective neutrino mass studied by 0νββ, (2) the unique features and the present status of MOON (Molybdenum Observatory Of Neutrinos) for high-sensitivity 0νββ studies with 100Mo in the quasi-degenerate and inverted hierarchy regions, and (3) the direct detection of WIMPs by measuring atomic X-rays following inner-shell ionization by WIMPs nuclear interactions. The MOON project is carried out in collaboration with the MOON collaboration, and the X-ray work from WIMPs is done with Ch.C. Moustakidis and J.D. Vergados.

  10. WIMP annihilation and cooling of neutron stars

    SciTech Connect

    Kouvaris, Chris

    2008-01-15

    We study the effect of WIMP annihilation on the temperature of a neutron star. We shall argue that the released energy due to WIMP annihilation inside the neutron stars might affect the temperature of stars older than 10x10{sup 6} years, flattening out the temperature at {approx}10{sup 4} K for a typical neutron star.

  11. Sites of ozone sensitivity in diverse maize inbred lines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tropospheric ozone (O3) is an air pollutant that costs ~$14-26 billion in global crop losses and is projected to worsen in the future. Potential sites of O3 sensitivity in maize were tested by growing 200 inbred lines, including the nested association mapping population founder lines, under ambient...

  12. WIMPs at the galactic center

    DOE PAGESBeta

    Agrawal, Prateek; Batell, Brian; Fox, Patrick J.; Harnik, Roni

    2015-05-07

    Simple models of weakly interacting massive particles (WIMPs) predict dark matter annihilations into pairs of electroweak gauge bosons, Higgses or tops, which through their subsequent cascade decays produce a spectrum of gamma rays. Intriguingly, an excess in gamma rays coming from near the Galactic center has been consistently observed in Fermi data. A recent analysis by the Fermi collaboration confirms these earlier results. Taking into account the systematic uncertainties in the modelling of the gamma ray backgrounds, we show for the first time that this excess can be well fit by these final states. In particular, for annihilations to (WW,more » ZZ, hh, tt¯), dark matter with mass between threshold and approximately (165, 190, 280, 310) GeV gives an acceptable fit. The fit range for bb¯ is also enlarged to 35 GeV ≲ mχ ≲ 165 GeV. These are to be compared to previous fits that concluded only much lighter dark matter annihilating into b, τ, and light quark final states could describe the excess. We demonstrate that simple, well-motivated models of WIMP dark matter including a thermal-relic neutralino of the MSSM, Higgs portal models, as well as other simplified models can explain the excess.« less

  13. WIMPs at the galactic center

    SciTech Connect

    Agrawal, Prateek; Batell, Brian; Fox, Patrick J.; Harnik, Roni

    2015-05-07

    Simple models of weakly interacting massive particles (WIMPs) predict dark matter annihilations into pairs of electroweak gauge bosons, Higgses or tops, which through their subsequent cascade decays produce a spectrum of gamma rays. Intriguingly, an excess in gamma rays coming from near the Galactic center has been consistently observed in Fermi data. A recent analysis by the Fermi collaboration confirms these earlier results. Taking into account the systematic uncertainties in the modelling of the gamma ray backgrounds, we show for the first time that this excess can be well fit by these final states. In particular, for annihilations to (WW, ZZ, hh, tt¯), dark matter with mass between threshold and approximately (165, 190, 280, 310) GeV gives an acceptable fit. The fit range for bb¯ is also enlarged to 35 GeV ≲ mχ ≲ 165 GeV. These are to be compared to previous fits that concluded only much lighter dark matter annihilating into b, τ, and light quark final states could describe the excess. We demonstrate that simple, well-motivated models of WIMP dark matter including a thermal-relic neutralino of the MSSM, Higgs portal models, as well as other simplified models can explain the excess.

  14. WIMPs at the galactic center

    NASA Astrophysics Data System (ADS)

    Agrawal, Prateek; Batell, Brian; Fox, Patrick J.; Harnik, Roni

    2015-05-01

    Simple models of weakly interacting massive particles (WIMPs) predict dark matter annihilations into pairs of electroweak gauge bosons, Higgses or tops, which through their subsequent cascade decays produce a spectrum of gamma rays. Intriguingly, an excess in gamma rays coming from near the Galactic center has been consistently observed in Fermi data. A recent analysis by the Fermi collaboration confirms these earlier results. Taking into account the systematic uncertainties in the modelling of the gamma ray backgrounds, we show for the first time that this excess can be well fit by these final states. In particular, for annihilations to (WW, ZZ, hh, tbar t), dark matter with mass between threshold and approximately (165, 190, 280, 310) GeV gives an acceptable fit. The fit range for bbar b is also enlarged to 35 GeV lesssim mχ lesssim 165 GeV. These are to be compared to previous fits that concluded only much lighter dark matter annihilating into b, τ, and light quark final states could describe the excess. We demonstrate that simple, well-motivated models of WIMP dark matter including a thermal-relic neutralino of the MSSM, Higgs portal models, as well as other simplified models can explain the excess.

  15. WIMPs at the galactic center

    SciTech Connect

    Agrawal, Prateek; Batell, Brian; Fox, Patrick J.; Harnik, Roni

    2015-05-07

    Simple models of weakly interacting massive particles (WIMPs) predict dark matter annihilations into pairs of electroweak gauge bosons, Higgses or tops, which through their subsequent cascade decays produce a spectrum of gamma rays. Intriguingly, an excess in gamma rays coming from near the Galactic center has been consistently observed in Fermi data. A recent analysis by the Fermi collaboration confirms these earlier results. Taking into account the systematic uncertainties in the modelling of the gamma ray backgrounds, we show for the first time that this excess can be well fit by these final states. In particular, for annihilations to (WW, ZZ, hh, tt{sup -bar}), dark matter with mass between threshold and approximately (165, 190, 280, 310) GeV gives an acceptable fit. The fit range for bb{sup -bar} is also enlarged to 35 GeV≲m{sub χ}≲165 GeV. These are to be compared to previous fits that concluded only much lighter dark matter annihilating into b, τ, and light quark final states could describe the excess. We demonstrate that simple, well-motivated models of WIMP dark matter including a thermal-relic neutralino of the MSSM, Higgs portal models, as well as other simplified models can explain the excess.

  16. Problems for the WIMP Hypothesis?

    NASA Astrophysics Data System (ADS)

    Vandenberg, Don A.; Stetson, Peter B.

    If stars accrete WIMPs (Weakly Interacting Massive Particles) over their lifetimes, then they are predicted to develop and sustain central isothermal cores. This investigation examines whether stellar models with small ( 0.1 M) isothermal cores can be reconciled with a nu,ber of observations. Specifically, we examine how well they can match the properties of the well-observed binary AI Phoenicis, whether they can explain the gap feature in the old open cluster M67, and whether they can provide a satisfactory fit to the observed composite luminosity function of M68/M92/NGC 6397. We find that the hypothesis of an isothermal core is not easily rejected: of the three tests considered here, only the M67 comparison appears to pose some considerable difficulties for it. Interestingly, the luminosity function data seem to favor the isothermal-core models over their canonical counterparts.

  17. Soft collinear effective theory for heavy WIMP annihilation

    NASA Astrophysics Data System (ADS)

    Bauer, Martin; Cohen, Timothy; Hill, Richard J.; Solon, Mikhail P.

    2015-01-01

    In a large class of models for Weakly Interacting Massive Particles (WIMPs), the WIMP mass M lies far above the weak scale m W . This work identifies universal Sudakov-type logarithms ? log2(2 M/m W ) that spoil the naive convergence of perturbation theory for annihilation processes. An effective field theory (EFT) framework is presented, allowing the systematic resummation of these logarithms. Another impact of the large separation of scales is that a long-distance wavefunction distortion from electroweak boson exchange leads to observable modifications of the cross section. Careful accounting of momentum regions in the EFT allows the rigorous disentanglement of this so-called Sommerfeld enhancement from the short-distance hard annihilation process. The WIMP is described as a heavy-particle field, while the electroweak gauge bosons are treated as soft and collinear fields. Hard matching coefficients are computed at renormalization scale ? 2 M , then evolved down to ? m W , where electroweak symmetry breaking is incorporated and the matching onto the relevant quantum mechanical Hamiltonian is performed. The example of an SU(2) W triplet scalar dark matter candidate annihilating to line photons is used for concreteness, allowing the numerical exploration of the impact of next-to-leading order corrections and log resummation. For M ? 3 TeV, the resummed Sommerfeld enhanced cross section is reduced by a factor of 3 with respect to the treelevel fixed order result.

  18. A review of WIMP baryogenesis mechanisms

    NASA Astrophysics Data System (ADS)

    Cui, Yanou

    2015-12-01

    It was recently proposed that weakly interacting massive particles (WIMP) may provide new ways of generating the observed baryon asymmetry in the early universe, as well as addressing the cosmic coincidence between dark matter (DM) and baryon abundances. This suggests a new possible connection between weak scale new particle physics and modern cosmology. This review summarizes the general ideas and simple model examples of the two recently proposed WIMP baryogenesis mechanisms: baryogenesis from WIMP DM annihilation during thermal freeze-out, and baryogenesis from metastable WIMP decay after thermal freeze-out. This review also discusses the interesting phenomenology of these models, in particular, the experimental signals that can be probed in the intensity frontier experiments and the large hadron collider (LHC) experiments.

  19. Radiation sensitivity of Merkel cell carcinoma cell lines

    SciTech Connect

    Leonard, J.H.; Ramsay, J.R.; Birrell, G.W.

    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.

  20. WIMP abundance and lepton (flavour) asymmetry

    SciTech Connect

    Stuke, Maik; Schwarz, Dominik J.; Starkman, Glenn E-mail: dschwarz@physik.uni-bielefeld.de

    2012-03-01

    We investigate how large lepton asymmetries affect the evolution of the early universe at times before big bang nucleosynthesis and in particular how they influence the relic density of WIMP dark matter. In comparison to the standard calculation of the relic WIMP abundance we find a decrease, depending on the lepton flavour asymmetry. We find an effect of up to 20 per cent for lepton flavour asymmetries l{sub f} = O(0.1)

  1. Twin Higgs WIMP dark matter

    NASA Astrophysics Data System (ADS)

    García García, Isabel; Lasenby, Robert; March-Russell, John

    2015-09-01

    Dark matter (DM) without a matter asymmetry is studied in the context of twin Higgs (TH) theories in which the LHC naturalness problem is addressed. These possess a twin sector related to the Standard Model (SM) by a (broken) Z2 symmetry, and interacting with the SM via a specific Higgs portal. We focus on the minimal realization of the TH mechanism, the fraternal twin Higgs, with only a single generation of twin quarks and leptons, and the S U (3 )'×S U (2 )' gauge group. We show that a variety of natural twin-WIMP DM candidates are present (directly linked to the weak scale by naturalness), the simplest and most attractive being the τ' lepton with a mass mτ'>mHiggs/2 , although spin-1 W'± DM and multicomponent DM are also possible (twin baryons are strongly disfavored by tuning). We consider in detail the dynamics of the possibly (meta)stable glueballs in the twin sector, the nature of the twin QCD phase transition, and possible new contributions to the number of relativistic degrees of freedom, Δ Neff . Direct detection signals are below current bounds but accessible in near-future experiments. Indirect detection phenomenology is rich and requires detailed studies of twin hadronization and fragmentation to twin glueballs and quarkonia and their subsequent decay to SM, and possible light twin sector states.

  2. Improved WIMP-search reach of the CDMS II germanium data

    DOE PAGESBeta

    Agnese, R.

    2015-10-12

    CDMS II data from the five-tower runs at the Soudan Underground Laboratory were reprocessed with an improved charge-pulse fitting algorithm. Two new analysis techniques to reject surface-event backgrounds were applied to the 612 kg days germanium-detector weakly interacting massive particle (WIMP)-search exposure. An extended analysis was also completed by decreasing the 10 keV analysis threshold to ~5 keV, to increase sensitivity near a WIMP mass of 8 GeV/c2. After unblinding, there were zero candidate events above a deposited energy of 10 keV and six events in the lower-threshold analysis. This yielded minimum WIMP-nucleon spin-independent scattering cross-section limits of 1.8×10–44 andmore » 1.18×10–41 at 90% confidence for 60 and 8.6 GeV/c2 WIMPs, respectively. This improves the previous CDMS II result by a factor of 2.4 (2.7) for 60 (8.6) GeV/c2 WIMPs.« less

  3. Improved WIMP-search reach of the CDMS II germanium data

    SciTech Connect

    Agnese, R.

    2015-10-12

    CDMS II data from the five-tower runs at the Soudan Underground Laboratory were reprocessed with an improved charge-pulse fitting algorithm. Two new analysis techniques to reject surface-event backgrounds were applied to the 612 kg days germanium-detector weakly interacting massive particle (WIMP)-search exposure. An extended analysis was also completed by decreasing the 10 keV analysis threshold to ~5 keV, to increase sensitivity near a WIMP mass of 8 GeV/c2. After unblinding, there were zero candidate events above a deposited energy of 10 keV and six events in the lower-threshold analysis. This yielded minimum WIMP-nucleon spin-independent scattering cross-section limits of 1.8×10–44 and 1.18×10–41 at 90% confidence for 60 and 8.6 GeV/c2 WIMPs, respectively. This improves the previous CDMS II result by a factor of 2.4 (2.7) for 60 (8.6) GeV/c2 WIMPs.

  4. Improved WIMP-search reach of the CDMS II germanium data

    SciTech Connect

    Agnese, R.; Anderson, A. J.; Asai, M.; Balakishiyeva, D.; Barker, D.; Basu Thakur, R.; Bauer, D. A.; Billard, J.; Borgland, A.; Bowles, M. A.; Brandt, D.; Brink, P. L.; Bunker, R.; Cabrera, B.; Caldwell, D. O.; Calkins, R.; Cerdeno, D. G.; Chagani, H.; Chen, Y.; Cooley, J.; Cornell, B.; Crewdson, C. H.; Cushman, Priscilla B.; Daal, M.; Di Stefano, P. C.; Doughty, T.; Esteban, L.; Fallows, S.; Figueroa-Feliciano, E.; Godfrey, G. L.; Golwala, S. R.; Hall, Jeter C.; Harris, H. R.; Hertel, S. A.; Hofer, T.; Holmgren, D.; Hsu, L.; Huber, M. E.; Jardin, D. M.; Jastram, A.; Kamaev, O.; Kara, B.; Kelsey, M. H.; Kennedy, A.; Kiveni, M.; Koch, K.; Leder, A.; Loer, B.; Lopez Asamar, E.; Lukens, P.; Mahapatra, R.; Mandic, V.; McCarthy, K. A.; Mirabolfathi, N.; Moffatt, R. A.; Oser, S. M.; Page, K.; Page, W. A.; Partridge, R.; Pepin, M.; Phipps, A.; Prasad, K.; Pyle, M.; Qiu, H.; Rau, W.; Redl, P.; Reisetter, A.; Ricci, Y.; Rogers, H. E.; Saab, T.; Sadoulet, B.; Sander, J.; Schneck, K.; Schnee, R. W.; Scorza, S.; Serfass, B.; Shank, B.; Speller, D.; Toback, D.; Upadhyayula, S.; Villano, A. N.; Welliver, B.; Wilson, J. S.; Wright, D. H.; Yang, X.; Yellin, S.; Yen, J. J.; Young, B. A.; Zhang, J.

    2015-10-31

    CDMS II data from the five-tower runs at the Soudan Underground Laboratory were reprocessed with an improved charge-pulse fitting algorithm. Two new analysis techniques to reject surface-event backgrounds were applied to the 612 kg days germanium-detector weakly interacting massive particle (WIMP)-search exposure. An extended analysis was also completed by decreasing the 10 keV analysis threshold to ~5 keV, to increase sensitivity near a WIMP mass of 8 GeV/c2. After unblinding, there were zero candidate events above a deposited energy of 10 keV and six events in the lower-threshold analysis. This yielded minimum WIMP-nucleon spin-independent scattering cross-section limits of 1.8×10-44 and 1.18×10-41 at 90% confidence for 60 and 8.6 GeV/c2 WIMPs, respectively. This improves the previous CDMS II result by a factor of 2.4 (2.7) for 60 (8.6) GeV/c2 WIMPs.

  5. Improved WIMP-search reach of the CDMS II germanium data

    NASA Astrophysics Data System (ADS)

    Agnese, R.; Anderson, A. J.; Asai, M.; Balakishiyeva, D.; Barker, D.; Basu Thakur, R.; Bauer, D. A.; Billard, J.; Borgland, A.; Bowles, M. A.; Brandt, D.; Brink, P. L.; Bunker, R.; Cabrera, B.; Caldwell, D. O.; Calkins, R.; Cerdeño, D. G.; Chagani, H.; Chen, Y.; Cooley, J.; Cornell, B.; Crewdson, C. H.; Cushman, P.; Daal, M.; Di Stefano, P. C. F.; Doughty, T.; Esteban, L.; Fallows, S.; Figueroa-Feliciano, E.; Godfrey, G. L.; Golwala, S. R.; Hall, J.; Harris, H. R.; Hertel, S. A.; Hofer, T.; Holmgren, D.; Hsu, L.; Huber, M. E.; Jardin, D.; Jastram, A.; Kamaev, O.; Kara, B.; Kelsey, M. H.; Kennedy, A.; Kiveni, M.; Koch, K.; Leder, A.; Loer, B.; Lopez Asamar, E.; Lukens, P.; Mahapatra, R.; Mandic, V.; McCarthy, K. A.; Mirabolfathi, N.; Moffatt, R. A.; Oser, S. M.; Page, K.; Page, W. A.; Partridge, R.; Pepin, M.; Phipps, A.; Prasad, K.; Pyle, M.; Qiu, H.; Rau, W.; Redl, P.; Reisetter, A.; Ricci, Y.; Rogers, H. E.; Saab, T.; Sadoulet, B.; Sander, J.; Schneck, K.; Schnee, R. W.; Scorza, S.; Serfass, B.; Shank, B.; Speller, D.; Toback, D.; Upadhyayula, S.; Villano, A. N.; Welliver, B.; Wilson, J. S.; Wright, D. H.; Yang, X.; Yellin, S.; Yen, J. J.; Young, B. A.; Zhang, J.; SuperCDMS Collaboration

    2015-10-01

    CDMS II data from the five-tower runs at the Soudan Underground Laboratory were reprocessed with an improved charge-pulse fitting algorithm. Two new analysis techniques to reject surface-event backgrounds were applied to the 612 kg days germanium-detector weakly interacting massive particle (WIMP)-search exposure. An extended analysis was also completed by decreasing the 10 keV analysis threshold to ˜5 keV , to increase sensitivity near a WIMP mass of 8 GeV /c2 . After unblinding, there were zero candidate events above a deposited energy of 10 keV and six events in the lower-threshold analysis. This yielded minimum WIMP-nucleon spin-independent scattering cross-section limits of 1.8 ×10-44 and 1.18 ×10-41 at 90% confidence for 60 and 8.6 GeV /c2 WIMPs, respectively. This improves the previous CDMS II result by a factor of 2.4 (2.7) for 60 (8.6 ) GeV /c2 WIMPs.

  6. Improved Constraints on Wimps From the International Germanium Experiment IGEX

    SciTech Connect

    Morales, A.; Aalseth, Craig E.; Avignone, Frank T.; Brodzinski, Ronald L.; Cebrian, S.; Garcia, Eduardo M.; Irastorza, I. G.; Kirpichnikov, I. V.; Klimenko, A. A.; Miley, Harry S.; Morales, J.; De Solorzano, A. O.; Osetrov, S. B.; Pogosov, V. S.; Puimedon, J.; Reeves, James H.; Sarsa, M. ..; Smolnikov, A. A.; Tamanyan, A. G.; Vasenko, A. A.; Vasiliev, S. I.; Villar, Jose A.

    2002-04-18

    One IGEX 76Ge double-beta decay detector is currently operating in the Canfranc Underground Laboratory in a search for dark matter WIMPs, through the Ge nuclear recoil produced by the WIMP elastic scattering.

  7. Can we discover dual-component thermal WIMP dark matter?

    NASA Astrophysics Data System (ADS)

    Profumo, Stefano; Sigurdson, Kris; Ubaldi, Lorenzo

    2009-12-01

    We address the question of whether the upcoming generation of dark matter search experiments and colliders will be able to discover if the dark matter in the Universe has two components of weakly interacting massive particles (WIMPs). We outline a model-independent approach, and we study the specific cases of (1) direct detection with low-background 1 ton noble-gas detectors and (2) a 0.5 TeV center of mass energy electron-positron linear collider. We also analyze the case of indirect detection via two gamma-ray lines, which would provide a verification of such a discovery, although multiple gamma-ray lines can in principle originate from the annihilation of a single dark matter particle. For each search ``channel'', we outline a few assumptions to relate the very small set of parameters we consider (defining the masses of the two WIMPs and their relative abundance in the overall dark matter density) with the relevant detection rates. We then draw general conclusions on which corners of a generic dual-component dark matter scenario can be explored with current and next generation experiments. We find that in all channels the ideal setup is one where the relative mass splitting between the two WIMP species is of order 1, and where the two dark matter components contribute in a ratio close to 1:1 to the overall dark matter content of the Universe. Interestingly, in the case of direct detection, future experiments might detect multiple states even if only ~ 10% of the energy-density of dark matter in the Universe is in the subdominant species.

  8. Non-thermal WIMPs as dark radiation

    SciTech Connect

    Queiroz, Farinaldo S.

    2014-06-24

    It has been thought that only light species could behave as radiation and account for the dark radiation observed recently by Planck, WMAP9, South Pole and ATACAMA telescopes. In this work we will show GeV scale WIMPs can plausibly account for the dark radiation as well. Heavy WIMPs might mimic the effect of a half neutrino species if some fraction of them are produced non-thermally after their thermal freeze-out. In addition, we will show how BBN, CMB and Structure Formation bounds might be circumvented.

  9. Photon spectra from quark generation by WIMPs

    SciTech Connect

    Cembranos, J. A. R.; Cruz-Dombriz, A.; Maroto, A. L.; Dobado, A.; Lineros, R.

    2011-05-23

    If the present dark matter (DM) in the Universe annihilates into Standard Model (SM) particles, it must contribute to the gamma ray fluxes that are detected on the Earth. The magnitude of such contribution depends on the particular DM candidate, but certain features of these spectra may be analyzed in a model-independent fashion. In this work we provide the fitting formula valid for the simulated photon spectra from WIMP annihilation into light quark-anti quark (qq-bar) channels in a wide range of WIMP masses. We illustrate our results for the cc-bar channel.

  10. Soft collinear effective theory for heavy WIMP annihilation

    SciTech Connect

    Bauer, Martin; Cohen, Timothy; Hill, Richard J.; Solon, Mikhail P.

    2015-01-19

    In a large class of models for Weakly Interacting Massive Particles (WIMPs), the WIMP mass M lies far above the weak scale mW . This work identifies universal Sudakov-type logarithms ~ α log2(2 M/mW) that spoil the naive convergence of perturbation theory for annihilation processes. An effective field theory (EFT) framework is presented, allowing the systematic resummation of these logarithms. Another impact of the large separation of scales is that a long-distance wavefunction distortion from electroweak boson exchange leads to observable modifications of the cross section. Careful accounting of momentum regions in the EFT allows the rigorous disentanglement of this so-called Sommerfeld enhancement from the short-distance hard annihilation process. In addition, the WIMP is described as a heavy-particle field, while the electroweak gauge bosons are treated as soft and collinear fields. Hard matching coefficients are computed at renormalization scale μ ~ 2 M , then evolved down to μ ~ mW , where electroweak symmetry breaking is incorporated and the matching onto the relevant quantum mechanical Hamiltonian is performed. The example of an SU(2)W triplet scalar dark matter candidate annihilating to line photons is used for concreteness, allowing the numerical exploration of the impact of next-to-leading order corrections and log resummation. As a result, for M ≃ 3 TeV, the resummed Sommerfeld enhanced cross section is reduced by a factor of ~ 3 with respect to the treelevel fixed order result.

  11. Soft collinear effective theory for heavy WIMP annihilation

    DOE PAGESBeta

    Bauer, Martin; Cohen, Timothy; Hill, Richard J.; Solon, Mikhail P.

    2015-01-19

    In a large class of models for Weakly Interacting Massive Particles (WIMPs), the WIMP mass M lies far above the weak scale mW . This work identifies universal Sudakov-type logarithms ~ α log2(2 M/mW) that spoil the naive convergence of perturbation theory for annihilation processes. An effective field theory (EFT) framework is presented, allowing the systematic resummation of these logarithms. Another impact of the large separation of scales is that a long-distance wavefunction distortion from electroweak boson exchange leads to observable modifications of the cross section. Careful accounting of momentum regions in the EFT allows the rigorous disentanglement of thismore » so-called Sommerfeld enhancement from the short-distance hard annihilation process. In addition, the WIMP is described as a heavy-particle field, while the electroweak gauge bosons are treated as soft and collinear fields. Hard matching coefficients are computed at renormalization scale μ ~ 2 M , then evolved down to μ ~ mW , where electroweak symmetry breaking is incorporated and the matching onto the relevant quantum mechanical Hamiltonian is performed. The example of an SU(2)W triplet scalar dark matter candidate annihilating to line photons is used for concreteness, allowing the numerical exploration of the impact of next-to-leading order corrections and log resummation. As a result, for M ≃ 3 TeV, the resummed Sommerfeld enhanced cross section is reduced by a factor of ~ 3 with respect to the treelevel fixed order result.« less

  12. Searches for WIMP Annihilation with GLAST

    SciTech Connect

    Wai, L.; ,

    2005-06-21

    We describe signatures for WIMP annihilation in the gamma ray sky which can be observed by the GLAST mission, scheduled for launch in 2007. We review the search regions, which range from galactic substructure in the Milky Way all the way out to cosmological sources.

  13. Oh to Be Rid of Administrative Wimps!

    ERIC Educational Resources Information Center

    Weissberg, Robert

    2007-01-01

    Contemporary university administrators are usually wimps, and timidity in facing easily enraged campus radicals only invites outrageous demands which, in turn, subvert intellectual life. This must be changed. For much of human history leaders had to display physical valor and this trait should be restored to the college administrator job…

  14. Molecular mechanisms of alkylation sensitivity in Indian muntjac cell lines.

    PubMed

    Musk, S R; Hatton, D H; Bouffler, S D; Margison, G P; Johnson, R T

    1989-07-01

    The responses of two Indian muntjac cell lines to two monofunctional alkylating agents were investigated. An SV40-transformed line (SVM) had an increased sensitivity to cell killing when compared to the other, euploid line (DM) after exposure both to methyl nitrosourea (MNU) and to dimethylsulphate (DMS) and also exhibited higher frequencies of sister chromatid exchanges (SCEs) following alkylation. The hypersensitivity of SVM to DMS correlates with the defective repair of single-strand breaks that results in the generation of long-lived breaks in the DNA following exposure, leading eventually to the formation of chromosome aberrations. In contrast no difference is seen in the formation of long-lived breaks in the DNA of SVM and DM after treatment with biologically relevant doses of MNU; in this case hypersensitivity may be due to the loss of O6-alkylguanine-DNA-alkyltransferase activity. The conclusion that the hypersensitivites of SVM to MNU and to DMS have different molecular bases is supported by transfection of SVM with plasmids containing the protein coding region of the Escherichia coli ada+ gene; subsequent expression within the cell corrects its hypersensitivity to the cytotoxic and SCE-inducing effects of MNU but has very little influence upon the lethality, SCE induction or the repair of long-lived DNA strand breaks after exposure to DMS. PMID:2544312

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

    NASA Astrophysics Data System (ADS)

    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 pulses. The detectors and existing electronics can therefore be used to yield imaging instruments for neutron and gamma-rays, in the case of silicon. For CZT, we would prefer to utilize current sensing to be able to clearly isolate the effects of the various charge-transport non-idealities, the full realization of which awaits the fabrication of the custom-designed TIA chip.

  16. On-line parameter estimation using a high sensitivity estimator

    NASA Technical Reports Server (NTRS)

    Mishne, D.; Bryson, A. E., Jr.

    1978-01-01

    An on-line parameter identification method is presented. The method is based on a recursive formulation of the maximum likelihood method, with a significant modification on the gains of the state estimator. In the conventional maximum likelihood method, the Kalman gains are used in the state estimator. This produces unbiased, minimum variance parameter estimates in the presence of process noise and measurement noise, but it also slows the convergence rate when the identification is done on-line. Here we suggest choosing the gains to maximize a measure of the sensitivities of the state estimates to parameter variations. One such criterion is to minimize the trace of the inverse information matrix. This increases the convergence rate significantly. After one or two time constants, the gains are switched to the Kalman values to assure unbiased, minimum-variance estimates. The state estimate will initially be nonoptimal, and may not be adequate for control purposes. In this case, a parallel Kalman filter which uses the identifier's parameter estimates can be used. This method is applied here for the identification of a simple first-order system, and for the identification of short-period stability derivatives of an F-8 aircraft from simulated data.

  17. Differentiating hidden sector dark matter from light WIMPs with Germanium detectors

    NASA Astrophysics Data System (ADS)

    Foot, R.

    2013-06-01

    Light WIMP dark matter and hidden sector dark matter have been proposed to explain the DAMA, CoGeNT and CRESST-II data. Both of these approaches feature spin independent elastic scattering of dark matter particles on nuclei. Light WIMP dark matter invokes a single particle species which interacts with ordinary matter via contact interactions. By contrast hidden sector dark matter is typically multi-component and is assumed to interact via the exchange of a massless mediator. Such hidden sector dark matter thereby predicts a sharply rising nuclear recoil spectrum, dR/dER∼1/ER2 due to this dynamics, while WIMP dark matter predicts a spectrum which depends sensitively on the WIMP mass, mχ. We compare and contrast these two very different possible origins of the CoGeNT low energy excess. In the relevant energy range, the recoil spectra predicted by these two theories approximately agree provided mχ ≃ 8.5 GeV - close to the value favoured from fits to the CoGeNT and CDMS low energy data. Forthcoming experiments including C-4, CDEX, and the MAJORANA demonstrator, are expected to provide reasonably precise measurements of the low energy Germanium recoil spectrum, including the annual modulation amplitude, which should differentiate between these two theoretical possibilities.

  18. Output-sensitive 3D line integral convolution.

    PubMed

    Falk, Martin; Weiskopf, Daniel

    2008-01-01

    We propose an output-sensitive visualization method for 3D line integral convolution (LIC) whose rendering speed is largely independent of the data set size and mostly governed by the complexity of the output on the image plane. Our approach of view-dependent visualization tightly links the LIC generation with the volume rendering of the LIC result in order to avoid the computation of unnecessary LIC points: early-ray termination and empty-space leaping techniques are used to skip the computation of the LIC integral in a lazy-evaluation approach; both ray casting and texture slicing can be used as volume-rendering techniques. The input noise is modeled in object space to allow for temporal coherence under object and camera motion. Different noise models are discussed, covering dense representations based on filtered white noise all the way to sparse representations similar to oriented LIC. Aliasing artifacts are avoided by frequency control over the 3D noise and by employing a 3D variant of MIPmapping. A range of illumination models is applied to the LIC streamlines: different codimension-2 lighting models and a novel gradient-based illumination model that relies on precomputed gradients and does not require any direct calculation of gradients after the LIC integral is evaluated. We discuss the issue of proper sampling of the LIC and volume-rendering integrals by employing a frequency-space analysis of the noise model and the precomputed gradients. Finally, we demonstrate that our visualization approach lends itself to a fast graphics processing unit (GPU) implementation that supports both steady and unsteady flow. Therefore, this 3D LIC method allows users to interactively explore 3D flow by means of high-quality, view-dependent, and adaptive LIC volume visualization. Applications to flow visualization in combination with feature extraction and focus-and-context visualization are described, a comparison to previous methods is provided, and a detailed performance analysis is included. PMID:18467757

  19. New class of biological detectors for WIMPs

    NASA Astrophysics Data System (ADS)

    Drukier, A. K.; Cantor, Ch.; Chonofsky, M.; Church, G. M.; Fagaly, R. L.; Freese, K.; Lopez, A.; Sano, T.; Savage, C.; Wong, W. P.

    2014-07-01

    Weakly Interacting Massive Particles (WIMPs) may constitute a large fraction of the matter in the Universe. There are excess events in the data of DAMA/LIBRA, CoGeNT, CRESST-II, and recently CDMS-Si, which could be consistent with WIMP masses of approximately 10 GeV/c2. However, for MDM > 10 GeV/c2 null results of the CDMS-Ge, XENON, and LUX detectors may be in tension with the potential detections for certain dark matter scenarios and assuming a certain light response. We propose the use of a new class of biological dark matter (DM) detectors to further examine this light dark matter hypothesis, taking advantage of new signatures with low atomic number targets. Two types of biological DM detectors are discussed here: DNA-based detectors and enzymatic reactions (ER) based detectors. In the case of DNA-based detectors, we discuss a new implementation. In the case of ER detectors, there are four crucial phases of the detection process: (a) change of state due to energy deposited by a particle; (b) amplification due to the release of energy derived from the action of an enzyme on its substrate; (c) sustainable but nonexplosive enzymatic reaction; (d) self-termination due to the denaturation of the enzyme, when the temperature is raised. This paper provides information of how to design as well as optimize these four processes.

  20. WIMP-Search Results from the Second CDMSlite Run

    SciTech Connect

    Agnese, R.

    2015-09-08

    The CDMS low ionization threshold experiment (CDMSlite) uses cryogenic germanium detectors operated at a relatively high bias voltage to amplify the phonon signal in the search for weakly interacting massive particles (WIMPs). Our results are presented from the second CDMSlite run with an exposure of 70 kg days, which reached an energy threshold for electron recoils as low as 56 eV. Furthermore, a fiducialization cut reduces backgrounds below those previously reported by CDMSlite. New parameter space for the WIMP-nucleon spin-independent cross section is excluded forWIMP masses between 1.6 and 5.5 GeV/c2.

  1. TREX-DM: a low background Micromegas-based TPC for low mass WIMP detection

    NASA Astrophysics Data System (ADS)

    Iguaz, F. J.; Garza, J. G.; Aznar, F.; Castel, J. F.; Cebrián, S.; Dafni, T.; García, J. A.; Gómez, H.; González-Diaz, D.; Irastorza, I. G.; Lagraba, A.; Luzón, G.; Peiró, A.; Rodríguez, A.

    2015-11-01

    Dark Matter experiments are recently focusing their detection techniques in low-mass WIMPs, which requires the use of light elements and low energy threshold. In this context, we present the TREX-DM experiment, a low background Micromegas-based TPC for low-mass WIMP detection. Its main goal is the operation of an active detection mass ~0.300 kg, with an energy threshold below 0.4 keVee and fully built with previously selected radiopure materials. This article describes the actual setup, the first results of the comissioning in Ar+2%iC4H10 at 1.2 bar and the future updates for a possible physics run at the Canfranc Underground Laboratory in 2016. A first background model is also presented, based on Geant4 simulations and a muon/electron discrimination method. In a conservative scenario, TREX-DM could be sensitive to DAMA/LIBRA and other hints of positive WIMPs signals, with some space for improvement with a neutron/electron discrimination method or the use of other light gases.

  2. 9-{beta}-arabinofuranosyladenine preferentially sensitizes radioresistant squamous cell carcinoma cell lines to x-rays

    SciTech Connect

    Heaton, D.; Mustafi, R.; Schwartz, J.L. |

    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.

  3. Understanding WIMP-baryon interactions with direct detection: a roadmap

    SciTech Connect

    Gluscevic, Vera; Peter, Annika H.G. E-mail: apeter@physics.osu.edu

    2014-09-01

    We study prospects of dark-matter direct-detection searches for probing non-relativistic effective theory for WIMP-baryon scattering. We simulate a large set of noisy recoil-energy spectra for different scattering scenarios (beyond the standard momentum-independent contact interaction), for Generation 2 and futuristic experiments. We analyze these simulations and quantify the probability of successfully identifying the operator governing the scattering, if a WIMP signal is observed. We find that the success rate depends on a combination of factors: the WIMP mass, the mediator mass, the type of interaction, and the experimental energy window. For example, for a 20 GeV WIMP, Generation 2 is only likely to identify the right operator if the interaction is Coulomb-like, and is unlikely to do so in any other case. For a WIMP with a mass of 200 GeV or higher, success is almost guaranteed. We also find that, regardless of the scattering model and the WIMP parameters, a single Generation 2 experiment is unlikely to successfully discern the momentum dependence of the underlying operator on its own, but prospects improve drastically when experiments with different target materials and energy windows are analyzed jointly. Furthermore, we examine the quality of parameter estimation and degeneracies in the multi-dimensional parameter space of the effective theory. We find in particular that the resulting WIMP mass estimates can be severely biased if data are analyzed assuming the standard (momentum-independent) operator while the actual operator has momentum-dependence. Finally, we evaluate the ultimate reach of direct detection, finding that the prospects for successful operator selection prior to reaching the irreducible backgrounds are excellent, if the signal is just below the current limits, but slim if Generation 2 does not report WIMP detection.

  4. Efficient sensitivity analysis of photonic structures with transmission line modeling

    NASA Astrophysics Data System (ADS)

    Ahmed, Osman S.; Bakr, Mohamed H.; Swillam, Mohamed A.; Li, Xun

    2012-10-01

    We introduce a memory efficient approach for the reduction of the required memory storage in time domain transmission line modeling (TLM)-based adjoint variable method (AVM). The proposed approach is based on manipulating the TLM scattering matrices to remove all redundant calculations. The required memory overhead for our approach is drastically reduced to only 10% of that of the original TLM-based AVM. This represents the ultimate memory reduction preserving the same accuracy of previously reported AVM approaches. Utilizing this approach, we can conduct AVM calculations for dielectric bulk structures 10 times larger. Our algorithm has been verified by comparison to the expensive finite difference approaches.

  5. Heavy WIMP through Higgs portal at the LHC

    NASA Astrophysics Data System (ADS)

    Endo, Motoi; Takaesu, Yoshitaro

    2015-04-01

    The LHC constraints on Higgs-portal WIMPs are studied. Scalar, vector and anti-symmetric tensor fields are considered. They are assumed to be heavier than a half of the Higgs boson mass. We investigate 8 TeV LHC results on signatures of the vector boson fusion, mono-jet and associated production of the Z boson, which proceed via virtual exchange of the Higgs boson. We show that the vector boson fusion channel gives the most stringent constraints on Higgs-portal interactions for all the WIMP models investigated here. The upper limits on vector and tensor Higgs-portal couplings can be 0.43 and 0.16 for the WIMP mass of 65 GeV, respectively. However, they are rapidly weakened for heavier WIMP masses, allowing O (1) couplings for masses heavier than ∼ 100 GeV. Constraints for scalar WIMPs are very weak. Prospects of the 14 TeV LHC are also discussed. We show that the constraints on the tensor and vector couplings would be improved by a factor of ∼ 1.5- 2, depending on the search channels. It would be still challenging to constrain scalar WIMPs.

  6. Bridging culture on-line: Strategies for teaching cultural sensitivity.

    PubMed

    Wendler, M Cecilia; Struthers, Roxanne

    2002-01-01

    The demand for on-line learning experiences is greatly increasing, especially for place-bound students living in rural areas. Faculty at the University of Wisconsin-Eau Claire School of Nursing responded to the need for coursework focusing on cultural competence by offering an elective course at both the undergraduate and graduate level through asynchronous delivery systems. To accomplish this, specific strategies were used in the course on cross-cultural health. These approaches were thoughtfully developed to bridge cultures in an on-line environment for students who do not have cross-cultural experiences easily accessible within their home communities. Strategies included: (1) culturally congruent use of a minority visiting scholar who is a leader in professional nursing and a traditional woman healer within her Native American community to provide wisdom, information, and support to students and faculty, in the novel role of guest listener; (2) requiring participation in cultural enrichment activities, designed to assist the student in discovering the similarities and differences among diverse peoples in their lives; and (3) developing course and faculty evaluations that are congruent with the asynchronous learning environment. PMID:12486638

  7. Gossypium lines resistant to Rotylenchulus reniformis vary in sensitivity to the herbicide fluometuron

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reniform nematode (Rotylenchulus reniformis) resistance is being transferred to Gossypium hirsutum from its distant relatives. Reports of fluometuron damage to LONREN lines with nematode resistance from G. longicalyx raised concerns about introducing herbicide sensitivity from other nematode resista...

  8. Detecting Dark Matter annihilation lines with Fermi

    SciTech Connect

    Ylinen, Tomi; Edmonds, Yvonne; Bloom, Elliott D.; Conrad, Jan; /Royal Inst. Tech., Stockholm /Kalmar U. /KIPAC, Menlo Park /SLAC /Stockholm U.

    2009-05-15

    Dark matter constitutes one of the most intriguing but so far unresolved issues in physics today. In many extensions of the Standard Model the existence of a stable Weakly Interacting Massive Particle (WIMP) is predicted. The WIMP is an excellent dark matter particle candidate and one of the most interesting scenarios include an annihilation of two WIMPs into two gamma-rays. If the WIMPs are assumed to be non-relativistic, the resulting photons will both have an energy equal to the mass of the WIMP and manifest themselves as a monochromatic spectral line in the energy spectrum. This type of signal would represent a 'smoking gun' for dark matter, since no other known astrophysical process should be able to produce it. In these proceedings we give an overview of the different approaches to a search for dark matter lines that the Fermi-LAT collaboration is pursuing and the various challenges involved.

  9. Antimanic drug sensitizes breast cancer cell line to ionizing radiation.

    PubMed

    Rouhani, Maryam; Goliaei, Bahram; Khodagholi, Fariba; Nikoofar, Alireza

    2014-01-01

    Breast cancer is one of the most prevalent types of cancer among women. Lithium chloride (LiCl) is an FDA-approved drug for bipolar disorder. Breast cancer is reported to occur with higher rate in women with bipolar disorder. The effect of LiCl on the response of breast cancer cells to ionizing radiation has not been studied. We studied the effect of LiCl on the radiosensitivity of radioresistant T47D breast cancer cell line. Treatment of T47D cells with 20 mM LiCl for 24 hours decreased the radioresistance of these cells indicated by clonogenic survival assay. Comet assay demonstrated decreased DNA repair in LiCl-treated cells. LiCl treatment also decreased the meiotic recombination 11 (Mre11) mRNA level. Mre11 is an essential protein for DNA repair whose transcription is regulated by β-catenin protein. Western blot analysis indicated that the β-catenin protein level was decreased in LiCl-treated cells. LiCl increased glycogen synthase kinase-3β (GSK-3β) protein that is involved in β-catenin degradation. The results demonstrated that LiCl could radiosensitize T47D cells by decreasing DNA repair, partially through Mre11 repression. GSK-3β/β-catenin/Mre11 pathway might be the connection between LiCl treatment and the decreased DNA repair in T47D cells. PMID:24448371

  10. BBN and the CMB constrain neutrino coupled light WIMPs

    NASA Astrophysics Data System (ADS)

    Nollett, Kenneth M.; Steigman, Gary

    2015-04-01

    In the presence of a light weakly interacting massive particle (WIMP) with mass mχ≲30 MeV , there are degeneracies among the nature of the WIMP (fermion or boson), its couplings to the standard model particles (to electrons, positrons, and photons, or only to neutrinos), its mass mχ, and the number of equivalent (additional) neutrinos, Δ Nν. These degeneracies cannot be broken by the cosmic microwave background (CMB) constraint on the effective number of neutrinos, Neff. However, since big bang nucleosynthesis (BBN) is also affected by the presence of a light WIMP and equivalent neutrinos, complementary BBN and CMB constraints can help to break some of these degeneracies. In a previous paper [K. M. Nollett and G. Steigman, Phys. Rev. D 89, 083508 (2014)] the combined BBN and Planck [P. A. R. Ade et al. (Planck Collaboration), Astron. Astrophys. 571, A16 (2014)] CMB constraints were used to explore the allowed ranges for mχ, Δ Nν, and Neff in the case where the light WIMPs annihilate electromagnetically (EM) to photons and/or e± pairs. In this paper the BBN predictions for the primordial abundances of deuterium and 4He (along with 3He and 7Li) in the presence of a light WIMP that only couples (annihilates) to neutrinos [either standard model (SM) only or both SM and equivalent] are calculated. Recent observational estimates of the relic abundances of D and 4He are used to limit the light WIMP mass, the number of equivalent neutrinos, the effective number of neutrinos, and the present Universe baryon density (ΩBh2 ). Allowing for a neutrino coupled light WIMP and Δ Nν equivalent neutrinos, the combined BBN and CMB data provide lower limits to the WIMP mass that depend very little on the nature of the WIMP (Majorana or Dirac fermion, real or complex scalar boson), with a best fit mχ≳35 MeV , equivalent to no light WIMP at all. The analysis here excludes all neutrino coupled WIMPs with masses below a few MeV, with specific limits varying from 4 to 9 MeV depending on the nature of the WIMP. In the absence of a light WIMP (either EM or neutrino coupled), BBN alone prefers Δ Nν =0.50 ±0.23 , favoring neither the absence of equivalent neutrinos (Δ Nν=0 ), nor the presence of a fully thermalized sterile neutrino (Δ Nν=1 ). This result is consistent with the CMB constraint, Neff=3.30 ±0.27 [1], constraining "new physics" between BBN and recombination. Combining the BBN and CMB constraints gives Δ Nν =0.35 ±0.16 and Neff=3.40 ±0.16 . As a result, while BBN and the CMB combined require Δ Nν ≥0 at ˜98 % confidence, they disfavor Δ Nν ≥1 at >99 % confidence. Adding the possibility of a neutrino-coupled light WIMP extends the allowed range slightly downward for Δ Nν and slightly upward for Neff simultaneously, while leaving the best-fit values unchanged.

  11. Annihilation Lines from Dark Matter with the Fermi-LAT

    NASA Astrophysics Data System (ADS)

    Ylinen, Tomi

    2010-06-01

    Dark matter is today one of the most intriguing but so far unresolved issues in physics. Many extensions of the Standard Model of particle physics predict a stable Weakly Interacting Massive Particle (WIMP) that may annihilate directly into two gamma-rays. If the WIMPs are non-relativistic, the gamma-rays from this channel will have an energy equal to the mass of the WIMP. The signature caused by this annihilation is a spectral line, smeared out only by the energy resolution of the detector. The signal would be a ``smoking gun'' for dark matter, since no other astrophysical source should be able to produce it. We present here the preliminary results from the search for a dark matter line on a limited data set from the Fermi Large Area Telescope (LAT), the main instrument onboard the Fermi Gamma-ray Space Telescope, which was successfully launched on June 11, 2008. The Fermi-LAT is a pair-conversion detector for gamma-rays with an energy range from 20 MeV to 300 GeV and has an unprecedented resolution and sensitivity.

  12. Annihilation Lines from Dark Matter with the Fermi-LAT

    SciTech Connect

    Ylinen, Tomi

    2010-06-23

    Dark matter is today one of the most intriguing but so far unresolved issues in physics. Many extensions of the Standard Model of particle physics predict a stable Weakly Interacting Massive Particle (WIMP) that may annihilate directly into two gamma-rays. If the WIMPs are non-relativistic, the gamma-rays from this channel will have an energy equal to the mass of the WIMP. The signature caused by this annihilation is a spectral line, smeared out only by the energy resolution of the detector. The signal would be a ''smoking gun'' for dark matter, since no other astrophysical source should be able to produce it. We present here the preliminary results from the search for a dark matter line on a limited data set from the Fermi Large Area Telescope (LAT), the main instrument onboard the Fermi Gamma-ray Space Telescope, which was successfully launched on June 11, 2008. The Fermi-LAT is a pair-conversion detector for gamma-rays with an energy range from 20 MeV to 300 GeV and has an unprecedented resolution and sensitivity.

  13. WIMP search with the final year of CDMS II data

    SciTech Connect

    Hsu, L.; /Fermilab

    2010-07-01

    The Cryogenic Dark Matter Search (CDMS) has pioneered the use of ionization and athermal phonon signals to discriminate between candidate (nuclear recoil) and background (electron recoil) events in Ge crystals cooled to {approx}50 mK. The yield and timing information allows for the maximization of discovery potential by adjusting the expected background in the signal region to less than one event. A blind analysis on 612 kg-days of raw exposure from the CDMS II experiment was performed. Two events with an expected background of {approx}0.9 events were observed. No statistically significant evidence for WIMP interactions is reported. Combining this data with previously analyzed CDMS II data sets an upper limit on the WIMP-nucleon spin-independent cross-section of 3.8 x 10{sup -44} cm{sup 2} for a WIMP of mass 70 GeV/c{sup 2}.

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

    NASA Technical Reports Server (NTRS)

    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.

  15. Drug-Resistant Urothelial Cancer Cell Lines Display Diverse Sensitivity Profiles to Potential Second-Line Therapeutics12

    PubMed Central

    Vallo, Stefan; Michaelis, Martin; Rothweiler, Florian; Bartsch, Georg; Gust, Kilian M.; Limbart, Dominik M.; Rödel, Franz; Wezel, Felix; Haferkamp, Axel; Cinatl, Jindrich

    2015-01-01

    Combination chemotherapy with gemcitabine and cisplatin in patients with metastatic urothelial cancer of the bladder frequently results in the development of acquired drug resistance. Availability of cell culture models with acquired resistance could help to identify candidate treatments for an efficient second-line therapy. Six cisplatin- and six gemcitabine-resistant cell lines were established. Cell viability assays were performed to evaluate the sensitivity to 16 different chemotherapeutic substances. The activity of the drug transporter ATP-binding cassette transporter, subfamily B, member 1 (ABCB1, a critical mediator of multidrug resistance in cancer) was evaluated using fluorescent ABCB1 substrates. For functional assessment, cells overexpressing ABCB1 were generated by transduction with a lentiviral vector encoding for ABCB1, while zosuquidar was used for selective inhibition. In this study, 8 of 12 gemcitabine- or cisplatin-resistant cell lines were cross-resistant to carboplatin, 5 to pemetrexed, 4 to methotrexate, 3 to oxaliplatin, 5-fluorouracil, and paclitaxel, and 2 to cabazitaxel, larotaxel, docetaxel, topotecan, doxorubicin, and mitomycin c, and 1 of 12 cell lines was cross-resistant to vinflunine and vinblastine. In one cell line with acquired resistance to gemcitabine (TCC-SUPrGEMCI20), cross-resistance seemed to be mediated by ABCB1 expression. Our model identified the vinca alkaloids vinblastine and vinflunine, in Europe an already approved second-line therapeutic for metastatic bladder cancer, as the most effective compounds in urothelial cancer cells with acquired resistance to gemcitabine or cisplatin. These results demonstrate that this in vitro model can reproduce clinically relevant results and may be suitable to identify novel substances for the treatment of metastatic bladder cancer. PMID:26055179

  16. Update on light WIMP limits: LUX, lite and light

    SciTech Connect

    Nobile, Eugenio Del; Gelmini, Graciela B.; Huh, Ji-Haeng; Gondolo, Paolo E-mail: gelmini@physics.ucla.edu E-mail: jhhuh@physics.ucla.edu

    2014-03-01

    We reexamine the current direct dark matter data including the recent CDMSlite and LUX data, assuming that the dark matter consists of light WIMPs, with mass close to 10 GeV/c{sup 2} with spin-independent and isospin-conserving or isospin-violating interactions. We compare the data with a standard model for the dark halo of our galaxy and also in a halo-independent manner. In our standard-halo analysis, we find that for isospin-conserving couplings, CDMSlite and LUX together exclude the DAMA, CoGeNT, CDMS-II-Si, and CRESST-II possible WIMP signal regions. For isospin-violating couplings instead, we find that a substantial portion of the CDMS-II-Si region is compatible with all exclusion limits. In our halo-independent analysis, we find that for isospin-conserving couplings, the situation is of strong tension between the positive and negative results, as it was before the LUX and CDMSlite bounds, which turn out to exclude the same possible WIMP signals as previous limits. For isospin-violating couplings, we find that LUX and CDMS-II-Si bounds together exclude or severely constrain the DAMA, CoGeNT and CRESST-II possible WIMP signals.

  17. Investigation of polarization reflectometry sensitivity to detecting new events in fiber optical lines

    NASA Astrophysics Data System (ADS)

    Dashkov, Michael V.; Dmitriev, Eugeniy V.

    2015-03-01

    The investigation of polarization reflectometry sensitivity to detection and localization of new events in fiber optical lines is carried out. The results of numerical simulation and experimental measurements are represented. The estimation of localization accuracy for different events depending on polarization characteristic is represented. The algorithm of data processing and method for measurement using polarization controller are represented.

  18. 3-Bromopyruvate induces necrotic cell death in sensitive melanoma cell lines

    SciTech Connect

    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.

  19. Detecting dark matter WIMPs in the Draco dwarf: A multiwavelength perspective

    SciTech Connect

    Colafrancesco, Sergio; Profumo, Stefano; Ullio, Piero

    2007-01-15

    We explore the possible signatures of dark matter pair annihilations in the nearby dwarf spheroidal galaxy Draco. After investigating the mass models for Draco in the light of available observational data, we carefully model the dark matter density profile, taking advantage of numerical simulations of hierarchical structure formation. We then analyze the gamma-ray and electron/positron yield expected for weakly interacting dark matter particle (WIMP) models, including an accurate treatment of the propagation of the charged particle species. We show that unlike in larger dark matter structures - such as galaxy clusters - spatial diffusion plays here an important role. While Draco would appear as a pointlike gamma-ray source, synchrotron emission from electrons and positrons produced by WIMP annihilations features a spatially extended structure. Depending upon the cosmic ray propagation setup and the size of the magnetic fields, the search for a diffuse radio emission from Draco can be a more sensitive indirect dark matter search probe than gamma rays. Finally, we show that available data are consistent with the presence of a black hole at the center of Draco: if this is indeed the case, very significant enhancements of the rates for gamma rays and other emissions related to dark matter annihilations are expected.

  20. Constraints on low-mass WIMP interactions on 19F from PICASSO

    NASA Astrophysics Data System (ADS)

    Archambault, S.; Behnke, E.; Bhattacharjee, P.; Bhattacharya, S.; Dai, X.; Das, M.; Davour, A.; Debris, F.; Dhungana, N.; Farine, J.; Gagnebin, S.; Giroux, G.; Grace, E.; Jackson, C. M.; Kamaha, A.; Krauss, C.; Kumaratunga, S.; Lafrenière, M.; Laurin, M.; Lawson, I.; Lessard, L.; Levine, I.; Levy, C.; MacDonald, R. P.; Marlisov, D.; Martin, J.-P.; Mitra, P.; Noble, A. J.; Piro, M.-C.; Podviyanuk, R.; Pospisil, S.; Saha, S.; Scallon, O.; Seth, S.; Starinski, N.; Stekl, I.; Wichoski, U.; Xie, T.; Zacek, V.

    2012-05-01

    Recent results from the PICASSO dark matter search experiment at SNOLAB are reported. These results were obtained using a subset of 10 detectors with a total target mass of 0.72 kg of 19F and an exposure of 114 kgd. The low backgrounds in PICASSO allow recoil energy thresholds as low as 1.7 keV to be obtained which results in an increased sensitivity to interactions from Weakly Interacting Massive Particles (WIMPs) with masses below 10 GeV/c2. No dark matter signal was found. Best exclusion limits in the spin dependent sector were obtained for WIMP masses of 20 GeV/c2 with a cross section on protons of σpSD=0.032 pb (90% C.L.). In the spin independent sector close to the low mass region of 7 GeV/c2 favoured by CoGeNT and DAMA/LIBRA, cross sections larger than σpSI=1.41×10-4 pb (90% C.L.) are excluded.

  1. W. K. H. Panofsky Prize Talk: The Search for WIMP Dark Matter: CDMS Detectors

    NASA Astrophysics Data System (ADS)

    Cabrera, Blas

    2013-04-01

    As described in the accompanying talk by Bernard Sadoulet, the CDMS (cryogenic dark matter search) program has succeeded in pushing down by several orders of magnitude the sensitivity in the search for dark matter in the form of weakly interacting particles or WIMPs. In this talk we describe the technology that has enabled the CDMS detectors made of Ge and Si crystals to discriminate on an event by event basis electron recoils (most backgrounds from gammas) from nuclear recoils (the expected WIMP signal and neutrons). This rejection is accomplished by simultaneously measuring the ionization (electrons and holes in the semiconductor) and the phonons (lattice heat). To achieve the phonon measurement, the crystals are cooled to 0.05 K which allows the use of ultra low noise superconducting circuits. The phonon energy is collected at the surface of the crystals using Al films which absorb athermal phonons and produce quasiparticle excitations from the dissociated Cooper pairs. These excitations diffuse until the are trapped in superconducting tungsten transition edge sensors (TESs). The major advance of voltage biased TESs which are self biased in their transition region through negative feedback has been adopted very successfully for xray spectroscopy, gamma ray spectroscopy and CMB (cosmic microwave background) instruments. The most recent advance detectors called iZIPs (interleaved z-dependent ionization and phonon) provide a large improvement in surface electron rejection and remove that background for the next 200 kg Ge experiment and even for future ton scale experiments.

  2. Phosphoproteomics data classify hematological cancer cell lines according to tumor type and sensitivity to kinase inhibitors

    PubMed Central

    2013-01-01

    Background Tumor classification based on their predicted responses to kinase inhibitors is a major goal for advancing targeted personalized therapies. Here, we used a phosphoproteomic approach to investigate biological heterogeneity across hematological cancer cell lines including acute myeloid leukemia, lymphoma, and multiple myeloma. Results Mass spectrometry was used to quantify 2,000 phosphorylation sites across three acute myeloid leukemia, three lymphoma, and three multiple myeloma cell lines in six biological replicates. The intensities of the phosphorylation sites grouped these cancer cell lines according to their tumor type. In addition, a phosphoproteomic analysis of seven acute myeloid leukemia cell lines revealed a battery of phosphorylation sites whose combined intensities correlated with the growth-inhibitory responses to three kinase inhibitors with remarkable correlation coefficients and fold changes (> 100 between the most resistant and sensitive cells). Modeling based on regression analysis indicated that a subset of phosphorylation sites could be used to predict response to the tested drugs. Quantitative analysis of phosphorylation motifs indicated that resistant and sensitive cells differed in their patterns of kinase activities, but, interestingly, phosphorylations correlating with responses were not on members of the pathway being targeted; instead, these mainly were on parallel kinase pathways. Conclusion This study reveals that the information on kinase activation encoded in phosphoproteomics data correlates remarkably well with the phenotypic responses of cancer cells to compounds that target kinase signaling and could be useful for the identification of novel markers of resistance or sensitivity to drugs that target the signaling network. PMID:23628362

  3. A quantitative proteomics-based signature of platinum sensitivity in ovarian cancer cell lines

    PubMed Central

    Fan, Gaofeng; Wrzeszczynski, Kazimierz O.; Fu, Cexiong; Pappin, Darryl J.; Lucito, Robert; Tonks, Nicholas K.; Su, Gang

    2014-01-01

    Although DNA encodes the molecular instructions that underlie control of cell function, it is the proteins that are primarily responsible for implementing those instructions. Therefore, quantitative analyses of the proteome would be expected to yield insights into important candidates for the detection and treatment of disease. We present an iTRAQ (Isobaric Tagging for Relative and Absolute Quantification)-based proteomic analysis of 10 ovarian cancer cell lines and 2 normal ovarian surface epithelial cell lines. We profiled the abundance of 2659 cellular proteins, of which 1273 were common to all 12 cell lines. Of the 1273, 75 proteins exhibited elevated expression, and 164 proteins had diminished expression in the cancerous cells compared to the normal cell lines. The iTRAQ expression profiles allowed us to segregate cell lines based upon sensitivity and resistance to carboplatin. Importantly, we observed no substantial correlation between protein abundance and RNA expression or epigenetic, DNA methylation data. Furthermore, we could not discriminate between sensitivity and resistance to carboplatin on the basis of RNA expression and DNA methylation data alone. This study illustrates the importance of proteomics-based discovery for defining the basis for the carboplatin response in ovarian cancer and highlights candidate proteins, particularly involved in cellular redox regulation, homologous recombination and DNA damage repair, that otherwise could not have been predicted from whole genome and expression data sources alone. PMID:25406946

  4. Digital signal processing algorithms for power and line parameter measurements with low sensitivity to frequency change

    SciTech Connect

    Perunicic, B.; Levi, S. ); Kezunovic, M.; Soljanin, E. )

    1990-04-01

    This paper introduces a new approach to definition of digital signal processing algorithms using bilinear form representation. The new algorithms are used to calculate power and line parameter values based on the current and voltage samples. The bilinear form approach provides a convenient methodology for optimal design of digital signal processing algorithms. This feature is utilized to design digital algorithms for power and line parameter measurements with low sensitivity to system frequency change. Several different algorithms are defined and their performance to system frequency change. Various sampling rates and different data windows are utilized to define several test cases.

  5. A Search for WIMP Dark Matter using an Optimized Chi-square Technique on the Final Data from the Cryogenic Dark Matter Search Experiment (CDMS II)

    NASA Astrophysics Data System (ADS)

    Manungu Kiveni, Joseph

    2012-06-01

    During the last two decades, cosmology has become a precision observational science thanks (in part) to the incredible number of experiments performed to better understand the composition of the universe. The large amount of data accumulated strongly indicates that the bulk of the universe's matter is in the form of non-baryonic matter that does not interact electromagnetically. Combined evidence from the dynamics of galaxies and galaxy clusters confirms that most of the mass in the universe is not composed of any known form of matter. Measurements of the cosmic microwave background, big bang nucleosynthesis and many other experiments indicate that ˜80% of the matter in the universe is dark, non-relativistic and cold. The dark matter resides in the halos surrounding galaxies, galaxy clusters and other large-scale structures. Weakly Interacting Massive Particles (WIMPs) are well motivated class of dark matter candidates that arise naturally in supersymmetric extensions to the Standard Model of particles physics, and can be produced as non-relativistic thermal relics in the early universe with about the right density to account for the missing mass. The Cryogenic Dark Matter Search (CDMS) experiment seeks to directly detect the keV-scale energy deposited by WIMPs in the galactic halo when they scatter from nuclei in the crystalline detectors made of germanium and silicon. These detectors, called Z-sensitive Ionization and Phonon detectors (ZIPs) are operated at ˜ 45 mK and simultaneously measure the ionization and the (athermal) phonons produced by particle interactions. The ratio of ionization and phonon energies allows discrimination of a low rate of nuclear recoils (expected for WIMPs) from an overwhelming rate of electron recoils (expected for most backgrounds). Phonon-pulse shape and timing enables further suppression of lower-rate interactions at the detector surfaces. This dissertation describes the results of a WIMP search using CDMS II data sets accumulated at the Soudan Underground Laboratory in Minnesota. Results from the original analysis of these data were published in 2009; two events were observed in the signal region with an expected leakage of 0.9 events. Further investigation revealed an issue with the ionization-pulse reconstruction algorithm leading to a software upgrade and a subsequent reanalysis of the data. As part of the reanalysis, I performed an advanced discrimination technique to better distinguish (potential) signal events from backgrounds using a 5-dimensional chi-square method. This data-analysis technique combines the event information recorded for each WIMP-search event to derive a background-discrimination parameter capable of reducing the expected background to less than one event, while maintaining high efficiency for signal events. Furthermore, optimizing the cut positions of this 5-dimensional chi-square parameter for the 14 viable germanium detectors yields an improved expected sensitivity to WIMP interactions relative to previous CDMS results. This dissertation describes my improved (and optimized) discrimination technique and the results obtained from a blind application to the reanalyzed CDMS II WIMP-search data. This analysis achieved the best expected sensitivity of the three techniques developed for the reanalysis and so was chosen as the primary timing analysis whose limit will be quoted in a on-going publication paper which is currently in preparation. For this analysis, a total raw exposure of 612.17 kg-days are analyzed for this work. No candidate events was observed, and a corresponding upper limit on the WIMP-nucleon scattering cross section as a function of WIMP mass is defined. These data set a 90% upper limit on spin-independent WIMP-nucleon elastic-scattering cross section of 3.19 × 10-44 cm2 for a WIMP mass of 60 GeV c 2. Combining this result with all previous CDMS II data gives an upper limit of 1.96 ×10-44 cm2 for a WIMP of mass 60 GeV/c2 (a factor of 2 better than the original analysis). At the moment this analysis is being written, the WIMP-search results obtained with the reanalyzed CDMS II data occupies the second most stringent limits on WIMP-nucleon scattering, after XENON100, excluding previously unexplored parameter space. Interesting parameter space is excluded for WIMP-nucleon cross section as function of WIMP masse under standard assumptions, the parameter space favored by interpretations of other experiments's data as low-mass WIMP signals due to an excess of low energy events and annual modulation is partially excluded for DAMA/LIBRA and CoGeNT.

  6. Individual in-vitro sensitivities of human pancreatic carcinoma cell lines to photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Moesta, K. T.; Dmytrijuk, Andrew; Schlag, Peter M.; Mang, Thomas S.

    1992-06-01

    Photodynamic therapy (PDT) is a promising alternative in the treatment of pancreatic cancer in man, due to the low sensitivity of the normal pancreas to PDT as shown in preclinical studies. Investigations on four human pancreatic cancer lines (MIA PaCa-2, PaCa 1, PaCa 3, and CAPAN 2) in vitro demonstrated a considerable variety in PDT-sensitivity proportional to the degree of differentiation, which was related to photosensitizer-uptake (PhotofrinTM). The well differentiated pancreatic tumor line Capan 2 showed a close relationship between high cell density and increased PDT-resistance. The Photofrin uptake of Capan 2 at high cell densities could be increased by short trypsinization prior to photosensitizer exposure. The data supports the hypothesis that a complex intercellular organization reduces the cell surface available for photosensitizer uptake and may cause the relative PDT resistance of normal pancreatic tissues and highly differentiated tumors.

  7. Distribution of sensitivity to 4-nitroquinoline 1-oxide among Japanese lymphoblastoid cell lines

    SciTech Connect

    Kiyohara, Chikako; Hirohata, Tomio; Nagayama, Junya ); Kuratsune, Masanori Nakamura Junior Coll., Fukuoka )

    1991-01-01

    The processes through which the UV-mimic chemical carcinogen, 4-nitroquinoline 1-oxide (4NQO), leads to the DNA lesions are well characterized in E. coli, where the formation of stable 4NQO-purine adducts is critical. The DNA excision-repair mechanisms similar to those for E. coli occur in normal human cells. Xeroderma pigmentosum (XP) is an example of a rare recessive autosomal skin disorder which is characterized biochemically as a DNA repair-deficient disease. The fluorescein diacetate (FDA) method was recently used to determine the sensitivity of lymphoblastoid cell lines 4NQO. Viable cells take up, non-fluorescent chemical, FDA and convert it to, a fluorescent molecule, fluorescein by intracellular esterases. DNA damage produced by 4NQO could be evaluated on the basis of the cell lethality by this FDA method. In the present study the authors describe the distribution of sensitivity to 4NQO among lymphoblastoid cell lines established from Japanese.

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

    SciTech Connect

    Denne, B.; Hinnov, E.

    1984-04-01

    Relative intensity measurements of various line pairs resulting from magnetic dipole transitions within the configurations s/sup 2/p/sup 2/ and s/sup 2/p/sup 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/sup 2/p/sup 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.

  9. Intensity ratio measurements for density sensitive lines of highly charged Fe ions

    NASA Astrophysics Data System (ADS)

    Ali, Safdar; Shimizu, Erina; Sakaue, Hiroyuki A.; Kato, Daiji; Murakami, Izumi; Yamamoto, Norimasa; Hara, Hirohisa; Watanabe, Tetsuya; Nakamura, Nobuyuki

    2015-07-01

    Intensity ratio of density sensitive emission lines emitted from Fe ions in the extreme ultraviolet region is important for astrophysics applications. We report high-resolution intensity ratio measurements for Fe ions performed at Tokyo EBIT laboratory by employing a flat-field grazing incidence spectrometer. The experimental intensity ratios of Fe X and Fe XII are plotted as a function of electron density for different electron beam currents. The experimental results are compared with the predicted intensity ratios from the model calculations.

  10. WIMP dark matter direct-detection searches in noble gases

    NASA Astrophysics Data System (ADS)

    Baudis, Laura

    2014-09-01

    Cosmological observations and the dynamics of the Milky Way provide ample evidence for an invisible and dominant mass component. This so-called dark matter could be made of new, colour and charge neutral particles, which were non-relativistic when they decoupled from ordinary matter in the early universe. Such weakly interacting massive particles (WIMPs) are predicted to have a non-zero coupling to baryons and could be detected via their collisions with atomic nuclei in ultra-low background, deep underground detectors. Among these, detectors based on liquefied noble gases have demonstrated tremendous discovery potential over the last decade. After briefly introducing the phenomenology of direct dark matter detection, I will review the main properties of liquefied argon and xenon as WIMP targets and discuss sources of background. I will then describe existing and planned argon and xenon detectors that employ the so-called single- and dual-phase detection techniques, addressing their complementarity and science reach.

  11. Recombinant adenovirus-p53 (Gendicine) sensitizes a pancreatic carcinoma cell line to radiation

    PubMed Central

    Li, Jinluan; Pan, Jianji; Zhu, Xianggao; Su, Ying; Bao, Lingling; Qiu, Sufang; Zou, Changyan; Tham, Ivan W.K.

    2013-01-01

    Objective In this study, we examine the effects of recombinant adenovirus-p53 (rAd-p53) on the pancreatic carcinoma cell line SW1990. Specifically, we determine if expression of rAd-p53 sensitizes these cells to radiation. Methods Following transfection of SW1990 cells with rAd-p53, we measured expression of P53, P21 and Bax by immunocytochemistry. Both transfected and control cell lines were irradiated with a range of doses, and the survival fractions (SF) were calculated. Dose survival curves were constructed and modeled for comparison. Results Transfection of SW1990 cells with rAd-p53 resulted in increased expression of P53, P21 and Bax in a time-dependent manner. At 96 h after transfection, 89.92% of cells expressed P53, 56.8% expressed P21, and 76.50% expressed Bax. The SF following radiation was lower in the rAd-p53 transfected cells compared to the control cells, suggesting that rAd-p53 sensitizes SW1990 cells to radiation (D0 for the experimental and control groups was 2.199 and 2.462, respectively). Conclusions Use of the adenoviral vector is an effective means of transfecting SW1990 cells with wild-type P53, and this sensitizes the cell line to irradiation. This work suggests that combining rAd-p53 with radiation therapy in pancreatic cancer may be therapeutically beneficial. PMID:24385699

  12. [Establishment and characterization of human ovarian fibrosarcoma cell line and its sensitivity to anticancer agents].

    PubMed

    Kiyozuka, Y; Nishimura, H; Iwanaga, S; Yakushiji, M; Ito, K; Nakano, S; Tamori, N; Adachi, S; Noda, T; Imai, S

    1992-04-01

    We succeeded in establishing a cell line (KEN-3) for subculture from a fibrosarcoma which originated in the ovary in a girl aged 17 years. Its characteristics and sensitivity to anticancer agents are reported in this paper. 1. Characteristics of established cell line. Lined cells consist of multinucleated giant cells mixed among many spindle-shaped cells. They grow in small colonies and have none of the pavement-like arrangement characteristic of epithelial tumor cells. The number of chromosomes ranged from 45 to 128 (mode: pseudo-triploidy region, 65). The doubling time, cellular density and plating efficiency were 76.9 hours, 5.4 x 10(5)/cm2 and 30.2%, respectively. Concerning tumor markers, CEA and sialyl SSEA-1 were only produced in small quantities. Subculture was possible subcutaneously in the nude mouse with no capacity for the production of ascites. 2. Susceptibility to anticancer agents and GP170 expression. The in vitro susceptibility to about 12 types of anticancer agents was investigated with the MTT assay. IC50/PPC was shown to be less than 1 for Adriamycin only. The sensitivity to CDDP (IC50/PPC: 4.8) was low, and no sensitivity was observed at all to DTIC, which is used frequently for mesenchymal tumors. GP170 (mdr-1 products) was positive in established cells in immunohistochemical stain. PMID:1351514

  13. RNA-seq reveals determinants for irinotecan sensitivity/resistance in colorectal cancer cell lines

    PubMed Central

    Li, Xin-Xiang; Zheng, Hong-Tu; Peng, Jun-Jie; Huang, Li-Yong; Shi, De-Bing; Liang, Lei; Cai, San-Jun

    2014-01-01

    Irinotecan is a topoisomerase I inhibitor approved worldwide as a first- and second-line chemotherapy for advanced or recurrent colorectal cancer (CRC). Although irinotecan showed significant survival advantage for patients, a relatively low response rate and severe adverse effects demonstrated the urgent need for biomarkers searching to select the suitable patients who can benefit from irinotecan-based therapy and avoid the adverse effects. In present work, the irinotecan response (IC50 doses) of 20 CRC cell lines were correlated with the basal expression profiles investigated by RNA-seq to figure out genes responsible for irinotecan sensitivity/resistance. Genes negatively or positively correlated to irinotecan sensitivity were given after biocomputation, and 7 (CDC20, CTNNAL1, FZD7, CITED2, ABR, ARHGEF7, and RNMT) of them were validated in two CRC cell lines by quantitative real-time PCR, several of these 7 genes has been proposed to promote cancer cells proliferation and hence may confer CRC cells resistance to irinotecan. Our work might provide potential biomarkers and therapeutic targets for irinotecan sensitivity in CRC cells. PMID:24966994

  14. Differential sensitivities to lactate transport inhibitors of breast cancer cell lines.

    PubMed

    Morais-Santos, Filipa; Miranda-Gonçalves, Vera; Pinheiro, Sílvia; Vieira, André F; Paredes, Joana; Schmitt, Fernando C; Baltazar, Fátima; Pinheiro, Céline

    2014-02-01

    The tumour microenvironment is known to be acidic due to high glycolytic rates of tumour cells. Monocarboxylate transporters (MCTs) play a role in extracellular acidification, which is widely known to be involved in tumour progression. Recently, we have described the upregulation of MCT1 in breast carcinomas and its association with poor prognostic variables. Thus, we aimed to evaluate the effect of lactate transport inhibition in human breast cancer cell lines. The effects of α-cyano-4-hydroxycinnamate, quercetin and lonidamine on cell viability, metabolism, proliferation, apoptosis, migration and invasion were assessed in a panel of different breast cancer cell lines. MCT1, MCT4 and CD147 were differently expressed among the breast cancer cell lines and, as expected, different sensitivities were observed for the three inhibitors. Interestingly, in the most sensitive cell lines, lactate transport inhibition induced a decrease in cell proliferation, migration and invasion, as well as an increase in cell death. Results were validated by silencing MCT1 expression using siRNA. The results obtained here support targeting of lactate transport as a strategy to treat breast cancer, with a special emphasis on the basal-like subtype, which so far does not have a specific molecular therapy. PMID:24174370

  15. Hypoxic Conditions Promote Gemcitabine Sensitivity in a Pancreatic Cancer Stem Cell Line.

    PubMed

    Imaizumi, Akira; Onishi, Hideya; Yamasaki, Akio; Kawamoto, Makoto; Umebayashi, Masayo; Morisaki, Takashi; Hasumi, Kenichiro

    2016-02-01

    Development of an effective therapeutic strategy for refractory pancreatic cancer must consider whether chemosensitivity can be induced in chemoresistant cells. We established a pancreatic cancer stem cell-rich cell line using TIG-1 feeder cells and leukemia inhibitory factor (LIF)-rich SNL76/7 conditioned medium. We generated a cell line, namely YNPC031312-B, following isolation of cells from the malignant ascites of a patient with gemcitabine-resistant pancreatic cancer. A YNPC031312-B-Hypoxia cell line was established by maintaining YNPC031312-B cells under tumor-like hypoxic conditions (1% O2). Both cell lines exhibited a pancreatic cancer stem cell phenotype: YNPC031312-B cells were CD24(+)CD44(-)CD133(+)epithelial cell adhesion molecule (EpCAM)(+)alkaline phosphatase(+)Octamer-binding transcription factor (OCT)3/4+and YNPC031312-B-Hypoxia cells were CD24(+)CD44(+)CD133(+)EpCAM(+). YNPC031312-B-Hypoxia cells were larger, had superior migratory ability, and higher gemcitabine sensitivity compared to YNPC031312-B cells. The use of LIF or other factors with similar bioactivity under hypoxic conditions may contribute to the phenotypic change to gemcitabine sensitivity. Our results may aid development of new therapeutic strategies targeting refractory pancreatic cancer. PMID:26851020

  16. Sensitivity of the 65-nm poly line printability to sPSM manufacturing errors

    NASA Astrophysics Data System (ADS)

    Belova, Nadya; Jensen, John V.; Croffie, Ebo H.; Callan, Neal P.

    2004-12-01

    A methodology and a Monte Carlo simulation flow with integrated LSI Logic's OPC package, Molotof, was applied to the 65nm poly line sensitivity analysis. Strong phase shift mask (sPSM) manufacturing specifications were optimized to obtain image critical dimensions (CD) and image placement errors (IPE) complying with technology design rules. Reticle manufacturing statistical errors of phase depth, phase width, and phase intensity imbalance were used to generate a virtual sPSM for imaging poly lines. A criterion for qualifying reticle specification is to obtain all latent image CDs and IPEs within a design rule allowed range for a given mask specification. The approach allows for computing reticle and litho budgets into CD imaging performance. We present simulation and empirical results of statistical analysis of the 65nm poly line (clear field) printability, and a method for optimizing a strong phase shift reticle specification. Sensitivity to a single parameter variation and full statistical analysis of the 65nm poly line imaging performance affected by manufacturing errors is presented. The optimum reticle specification, yielded 100% of critical dimensions and image placement errors, was found in simulation and confirmed by empirical data.

  17. Hyaluronan oligomers sensitize chronic myeloid leukemia cell lines to the effect of Imatinib.

    PubMed

    Lompardía, Silvina Laura; Díaz, Mariángeles; Papademetrio, Daniela Laura; Mascaró, Marilina; Pibuel, Matías; Álvarez, Elida; Hajos, Silvia Elvira

    2016-04-01

    Chronic myeloid leukemia is a myeloproliferative syndrome characterized by the presence of the Philadelphia chromosome (Ph), generated by a reciprocal translocation occurring between chromosomes 9 and 22 [t(9;22)(q34;q11)]. As a consequence, a fusion gene (bcr-abl) encoding a constitutively active kinase is generated. The first-line treatment consists on BCR-ABL inhibitors such as Imatinib, Nilotinib and Dasatinib. Nevertheless, such treatment may lead to the selection of resistant cells. Therefore, finding molecules that enhance the anti-proliferative effect of first-line drugs is of value. Hyaluronan oligomers (oHA) are known to be able to sensitize several tumor cells to chemotherapy. We have previously demonstrated that oHA can revert Vincristine resistance in mouse lymphoma and human leukemia cell lines. However, little is known about the role of oHA in hematological malignancies. The aim of this work was to determine whether oHA are able to modulate the anti-proliferative effect of Imatinib in chronic myeloid leukemia (CML) cell lines. The effect on apoptosis and senescence as well as the involvement of signaling pathways were also evaluated. For this purpose, the human CML cell lines K562 and Kv562 (resistant) were used. We demonstrated that oHA sensitized both cell lines to the anti-proliferative effect of Imatinib increasing apoptosis and senescence. Moreover, this effect would be accomplished through the down-regulation of the PI3K signaling pathway. These findings highlight the potential of oHA when used as a co-adjuvant therapy for chronic myeloid leukemia. PMID:26582603

  18. No WIMP mini-spikes in dwarf spheroidal galaxies

    NASA Astrophysics Data System (ADS)

    Wanders, Mark; Bertone, Gianfranco; Volonteri, Marta; Weniger, Christoph

    2015-04-01

    The formation of black holes inevitably affects the distribution of dark and baryonic matter in their vicinity, leading to an enhancement of the dark matter density, called spike, and if dark matter is made of WIMPs, to a strong enhancement of the dark matter annihilation rate. Spikes at the center of galaxies like the Milky Way are efficiently disrupted by baryonic processes, but mini-spikes can form and survive undisturbed at the center of dwarf spheroidal galaxies. We show that Fermi LAT satellite data allow to set very stringent limits on the existence of mini-spikes in dwarf galaxies: for thermal WIMPs with mass between 100 GeV and 1 TeV, we obtain a maximum black hole mass between 100 and 1000 Msolar, ruling out black holes masses extrapolated from the M-? relationship in a large region of the parameter space. We also performed Monte Carlo simulations of merger histories of black holes in dwarf spheroidals in a scenario where black holes form from the direct collapse of primordial gas in early halos, and found that this specific formation scenario is incompatible at the 84% CL with dark matter being in the form of thermal WIMPs.

  19. Can WIMP dark matter overcome the nightmare scenario?

    NASA Astrophysics Data System (ADS)

    Kanemura, Shinya; Matsumoto, Shigeki; Nabeshima, Takehiro; Okada, Nobuchika

    2010-09-01

    Even if new physics beyond the standard model indeed exists, the energy scale of new physics might be beyond the reach at the Large Hadron Collider (LHC), and the LHC could find only the Higgs boson but nothing else. This is the so-called “nightmare scenario.” On the other hand, the existence of the dark matter has been established from various observations. One of the promising candidates for thermal relic dark matter is a stable and electric charge-neutral weakly interacting massive particle (WIMP) with mass below the TeV scale. In the nightmare scenario, we introduce a WIMP dark matter singlet under the standard model gauge group, which only couples to the Higgs doublet at the lowest order, and investigate the possibility that such WIMP dark matter can be a clue to overcome the nightmare scenario via various phenomenological tests such as the dark matter relic abundance, the direct detection experiments for the dark matter particle, and the production of the dark matter particle at the LHC.

  20. Can WIMP dark matter overcome the nightmare scenario?

    SciTech Connect

    Kanemura, Shinya; Nabeshima, Takehiro; Matsumoto, Shigeki; Okada, Nobuchika

    2010-09-01

    Even if new physics beyond the standard model indeed exists, the energy scale of new physics might be beyond the reach at the Large Hadron Collider (LHC), and the LHC could find only the Higgs boson but nothing else. This is the so-called ''nightmare scenario.'' On the other hand, the existence of the dark matter has been established from various observations. One of the promising candidates for thermal relic dark matter is a stable and electric charge-neutral weakly interacting massive particle (WIMP) with mass below the TeV scale. In the nightmare scenario, we introduce a WIMP dark matter singlet under the standard model gauge group, which only couples to the Higgs doublet at the lowest order, and investigate the possibility that such WIMP dark matter can be a clue to overcome the nightmare scenario via various phenomenological tests such as the dark matter relic abundance, the direct detection experiments for the dark matter particle, and the production of the dark matter particle at the LHC.

  1. Simultaneous inhibition of ATR and PARP sensitizes colon cancer cell lines to irinotecan

    PubMed Central

    Abu-Sanad, Atlal; Wang, Yunzhe; Hasheminasab, Fatemeh; Panasci, Justin; Noë, Alycia; Rosca, Lorena; Davidson, David; Amrein, Lilian; Sharif-Askari, Bahram; Aloyz, Raquel; Panasci, Lawrence

    2015-01-01

    Enhanced DNA damage repair is one mechanism involved in colon cancer drug resistance. Thus, targeting molecular components of repair pathways with specific small molecule inhibitors may improve the efficacy of chemotherapy. ABT-888 and VE-821, inhibitors of poly-ADP-ribose-polymerase (PARP) and the serine/threonine-kinase Ataxia telangiectasia related (ATR), respectively, were used to treat colon cancer cell lines in combination with the topoisomerase-I inhibitor irinotecan (SN38). Our findings show that each of these DNA repair inhibitors utilized alone at nontoxic single agent concentrations resulted in sensitization to SN38 producing a 1.4–3 fold reduction in the 50% inhibitory concentration (IC50) of SN38 in three colon cancer cell lines. When combined together, nontoxic concentrations of ABT-888 and VE-821 produced a 4.5–27 fold reduction in the IC50 of SN38 with the HCT-116 colon cancer cells demonstrating the highest sensitization as compared to LoVo and HT-29 colon cancer cells. Furthermore, the combination of all three agents was associated with maximal G2 −M arrest and enhanced DNA-damage (γH2AX) in all three colon cancer cell lines. The mechanism of this enhanced sensitization was associated with: (a) maximal suppression of SN38 induced PARP activity in the presence of both inhibitors and (b) ABT-888 producing partial abrogation of the VE-821 enhancement of SN38 induced DNA-PK phosphorylation, resulting in more unrepaired DNA damage; these alterations were only present in the HCT-116 cells which have reduced levels of ATM. This novel combination of DNA repair inhibitors may be useful to enhance the activity of DNA damaging chemotherapies such as irinotecan and help produce sensitization to this drug in colon cancer. PMID:26257651

  2. Improving bioreactor cultivation conditions for sensitive cell lines by dynamic membrane aeration.

    PubMed

    Frahm, Björn; Brod, Helmut; Langer, Uwe

    2009-01-01

    Although the importance of animal cell culture for the industrial (large scale) production of pharmaceutical products is continuously increasing, the sensibility of the cells towards their cultivation environment is still a challenging issue. In comparison to microbial cultures, cell cultures which are not protected by a cell wall are much more sensitive to shear stress and foam formation. Reactor design as well as the selection of 'robust' cell lines is particularly important for these circumstances. Nevertheless, even 'sensitive' cell lines are selected for certain pharmaceutical processes due to various reasons. These sensitive cell lines have even higher requirements regarding their cultivation environment. Important characteristics for the corresponding reactor design are a high (volumetric) gas mass transfer coefficient, low volumetric power input, low shear stress, low susceptibility to bio-fouling, the ability to cultivate sticky cells and sufficient mixing properties. Membrane aeration has been a long-known possibility to meet some of these requirements, but has not often been applied in recent years. The reasons lie mainly in low gas mass transfer rates, a limited installable volume-specific membrane surface area, restrictions in scalability and problems with membrane fouling. The dynamic membrane aeration bioreactor aeration is a simple concept for bubble-free oxygen supply of such sensitive cultures. It overcomes limitations and draw-backs of previous systems. Consisting of an oscillating, centrally arranged rotor (stirrer) that is wrapped with silicone membrane tubing, it enables doubling the gas mass transfer at the same shear stress in the investigated cultivation scales of 12, 20, 100, and 200 L. Continuous cultivation at these scales allows the same product output as fed-batch cultivation does at tremendously larger reactor volumes. Apart from introducing this novel technology, the presentation comprises selected cultivation results obtained for blood coagulation factor VIII in continuous mode and a therapeutic monoclonal antibody in fed-batch mode in comparison to reference trials. PMID:19319654

  3. Search for pseudoscalar-mediated WIMPs in t →c transitions with missing energy

    NASA Astrophysics Data System (ADS)

    Jia, Lian-Bao

    2015-10-01

    The recent astronomical observation of GeV gamma-ray excess from the Galactic center was suggested due to a b b ¯ mode in the tens GeV of weakly interacting massive particle (WIMP) pair annihilations, and this mode was also explored by the new dwarf galaxy observation. Considering the case where the WIMP pair mass is below the top quark mass, a pseudoscalar ϕ is studied in this article, which mediates the interactions between the standard model fermions and fermionic WIMPs and the neutral flavor-changing interactions in standard model fermion sectors. The b b ¯ mode is favored in WIMP pair annihilations, while the WIMP-nucleus scattering is highly suppressed in direct detection. Alternative schemes of t →c decay and single top production are employed to search the WIMPs. Assuming the mass of the WIMPs is around 5-60 GeV and with reasonable inputs by the constraints, the branching ratio Bt →c χ ¯ χ of a top quark decaying into a charm quark and a WIMP pair is derived of order 1 0-8- 1 0-5 ; thus, careful studies in the future on top physics may help to gain a better understanding of WIMPs.

  4. Light WIMPs, equivalent neutrinos, BBN, and the CMB

    NASA Astrophysics Data System (ADS)

    Steigman, Gary; Nollett, Kenneth M.

    Recent updates to the observational determinations of the primordial abundances of helium (4He) and deuterium are compared to the predictions of BBN to infer the universal ratio of baryons to photons, eta 10 equiv 1010(n_B/ngamma )0 (or, the present Universe baryon mass density parameter, {Ω_B h^{2} = eta 10/273.9) as well as to constrain the effective number of neutrinos ({N_eff) and the number of equivalent neutrinos ({ΔN_ν}). These BBN results are compared to those derived independently from the Planck CMB data. In the absence of a light WIMP ({m_χ} ⪆ 20 MeV), {N_eff = 3.05(1 + ensuremath {DeltaN_ nu }/3). In this case, there is excellent agreement between BBN and the CMB but, the joint fit reveals that {ΔN_ν} = 0.40±0.17, disfavoring standard big bang nucleosynthesis (SBBN) ({ΔN_ν} = 0) at ˜ 2.4 sigma , as well as a sterile neutrino ({ΔN_ν} = 1) at ˜ 3.5 sigma . In the presence of a light WIMP ({m_χ} ⪉ 20 MeV), the relation between {N_eff and {ΔN_&nu}; depends on the WIMP mass, leading to degeneracies among {N_eff, {ΔN_ν}, and {m_χ}. The complementary and independent BBN and CMB data can break some of these degeneracies. Depending on the nature of the light WIMP (Majorana or Dirac fermion, real or complex scalar) the joint BBN + CMB analyses set a lower bound to {m_χ} in the range 0.5 - 5 MeV (mchi /me ⪆ 1 - 10) and, they identify best fit values for {m_χ} in the range 5 - 10 MeV. The joint BBN + CMB analyses find a best fit value for the number of equivalent neutrinos, {ΔN_ν} ≈ 0.65, nearly independent of the nature of the WIMP. The best fit still disfavors the absence of dark radiation ({ΔN_ν} = 0 at ˜ 95% confidence), while allowing for the presence of a sterile neutrino ({ΔN_ν} = 1 at ⪉ 1 sigma ). For all cases considered here, the lithium problem persists. These results, presented at the Rencontres de l'Observatoire de Paris 2013 - ESO Workshop and summarized in these proceedings, are based on \\citet{kngs}.

  5. Neutrino flavor ratios as diagnostic of solar WIMP annihilation

    NASA Astrophysics Data System (ADS)

    Lehnert, Ralf; Weiler, Thomas J.

    2008-06-01

    We consider the neutrino (and antineutrino) flavors arriving at the Earth for neutrinos produced in the annihilation of weakly interacting massive particles (WIMPs) in the sun’s core. Solar-matter effects on the flavor propagation of the resulting ≳GeV neutrinos are studied analytically within a density-matrix formalism. Matter effects, including mass-state level crossings, influence the flavor fluxes considerably. The exposition herein is somewhat pedagogical, in that it starts with adiabatic evolution of single flavors from the sun’s center, with θ13 set to zero, and progresses to fully realistic processing of the flavor ratios expected in WIMP decay, from the sun’s core to the Earth. In the fully realistic calculation, nonadiabatic level crossing is included, as are possible nonzero values for θ13 and the CP-violating phase δ. Because of resonance enhancement in matter, nonzero values of θ13 even smaller than a degree can noticeably affect flavor propagation. Both normal and inverted neutrino-mass hierarchies are considered. Our main conclusion is that measuring flavor ratios (in addition to energy spectra) of ≳GeV solar neutrinos can provide discrimination between WIMP models. In particular, we demonstrate the flavor differences at the Earth for neutrinos from the two main classes of WIMP final states, namely W+W- and 95%bb¯+5%τ+τ-. Conversely, if WIMP properties were to be learned from production in future accelerators, then the flavor ratios of ≳GeV solar neutrinos might be useful for inferring θ13 and the mass hierarchy. From the full calculations, we find (and prove) some general features: a flavor-democratic flux produced at the sun’s core arrives at the Earth still flavor democratic; for maximal θ32 but arbitrary θ21 and θ13, the replacement δ→π-δ leaves the νe flavor spectra unaltered but interchanges νμ and ντ spectra at the Earth; and, only for neutrinos in the inverted hierarchy and antineutrinos in the normal hierarchy is the dependence on the mixing phase δ not suppressed to order δm212/δm322.

  6. Mutation and repair in an ultraviolet-sensitive Chinese hamster ovary cell line

    SciTech Connect

    Wood, R.D.

    1981-11-01

    An ultraviolet (UV) light-sensitive mutant of Chinese hamster ovary cells (CHO) has been isolated and characterized with respect to a number of post-irradiation responses. The UV-sensitive mutant, termed 43-3B, has the same growth rate and chromosome number as the wild-type CHO-9. 43-3B is hypersensitive to the lethal effects of UV light (D/sub 0/ of 0.3 J/m/sup 2/ as compared to 3.2 J/m/sup 2/ for the wild-type). A marked UV-hypermutability is observed in 43-3B as compared to the wild-type, as measured with markers for induced resistance to 6-thioguanine, ouabain, and diphtheria toxin. A factor of 38 to 65 more mutations are induced per unit fluence in 43-3B than in CHO-9. The UV-sensitive mutant is also sensitive to killing by simulated solar light, although the D/sub 0/ ratio is not as great as for germicidal UV. 43-3B exhibits only about 17% of the wild-type level of UV-stimulated DNA repair synthesis, as measured by autoradiography of G/sub 1/ phase cells. A much reduced ability to recover control rates of semiconservative DNA synthesis after UV irradiation was observed in the repair-deficient 43-3B cell line. Recovery of colony-forming ability between fractionated UV exposures was observed in the wild-type CHO-9, but little recovery was seen in 43-3B. The present investigation demonstrates that a sensitive/wild-type pair of CHO cell lines can be used in comparative studies to determine the involvement of repair in a wide range of post-irradiation phenomena.

  7. Drug sensitivity patterns of HHV8 carrying body cavity lymphoma cell lines

    PubMed Central

    2011-01-01

    Background Primary effusion lymphoma (PEL) is a rare KSHV/HHV8-associated high-grade non-Hodgkin's lymphoma (NHL) of B-cell origin, characterized by serous effusions in body cavities. Most patients are HIV-infected men with severe immunosuppression and other HHV8-associated diseases such as Kaposi's sarcoma (KS). The prognosis for those infected is poor, with a median survival of less than 6 months in most cohorts. Sustained complete remission is rare. High-dose chemotherapy regimens are used to improve remission rate and survival. The aim of the present study was to compare the drug sensitivity pattern of the available primary effusion (body cavity based) lymphoma-derived cell lines in order to find additional, potentially effective drugs that are not included in current chemotherapy treatment protocols. Methods We have analyzed 11 cell lines against 27 frequently used cytostatic drugs in short term (3 days) survival assays using automated high throughput confocal microscopy. Results All cell lines showed a distinct, individual drug sensitivity pattern. Considering the in vitro used and clinically achieved drug concentration, Vinorelbine, Paclitaxel, Epirubicin and Daunorubicin were the most effective drugs. Conclusions We suggest that inclusion of the above drugs into PEL chemotherapy protocols may be justified. The heterogeneity in the drug response pattern however indicated that assay-guided individualized therapy might be required to optimize therapeutic response. PMID:21992895

  8. Search for gamma-ray spectral lines with the Fermi Large Area Telescope and dark matter implications

    NASA Astrophysics Data System (ADS)

    Ackermann, M.; Ajello, M.; Albert, A.; Allafort, A.; Baldini, L.; Barbiellini, G.; Bastieri, D.; Bechtol, K.; Bellazzini, R.; Bissaldi, E.; Bloom, E. D.; Bonamente, E.; Bottacini, E.; Brandt, T. J.; Bregeon, J.; Brigida, M.; Bruel, P.; Buehler, R.; Buson, S.; Caliandro, G. A.; Cameron, R. A.; Caraveo, P. A.; Casandjian, J. M.; Cecchi, C.; Charles, E.; Chaves, R. C. G.; Chekhtman, A.; Chiang, J.; Ciprini, S.; Claus, R.; Cohen-Tanugi, J.; Conrad, J.; Cutini, S.; D'Ammando, F.; de Angelis, A.; de Palma, F.; Dermer, C. D.; Digel, S. W.; Di Venere, L.; Drell, P. S.; Drlica-Wagner, A.; Essig, R.; Favuzzi, C.; Fegan, S. J.; Ferrara, E. C.; Focke, W. B.; Franckowiak, A.; Fukazawa, Y.; Funk, S.; Fusco, P.; Gargano, F.; Gasparrini, D.; Germani, S.; Giglietto, N.; Giordano, F.; Giroletti, M.; Glanzman, T.; Godfrey, G.; Gomez-Vargas, G. A.; Grenier, I. A.; Guiriec, S.; Gustafsson, M.; Hadasch, D.; Hayashida, M.; Hill, A. B.; Horan, D.; Hou, X.; Hughes, R. E.; Inoue, Y.; Izaguirre, E.; Jogler, T.; Kamae, T.; Knödlseder, J.; Kuss, M.; Lande, J.; Larsson, S.; Latronico, L.; Longo, F.; Loparco, F.; Lovellette, M. N.; Lubrano, P.; Malyshev, D.; Mayer, M.; Mazziotta, M. N.; McEnery, J. E.; Michelson, P. F.; Mitthumsiri, W.; Mizuno, T.; Moiseev, A. A.; Monzani, M. E.; Morselli, A.; Moskalenko, I. V.; Murgia, S.; Nakamori, T.; Nemmen, R.; Nuss, E.; Ohsugi, T.; Okumura, A.; Omodei, N.; Orienti, M.; Orlando, E.; Ormes, J. F.; Paneque, D.; Perkins, J. S.; Pesce-Rollins, M.; Piron, F.; Pivato, G.; Rainò, S.; Rando, R.; Razzano, M.; Razzaque, S.; Reimer, A.; Reimer, O.; Romani, R. W.; Sánchez-Conde, M.; Schulz, A.; Sgrò, C.; Siegal-Gaskins, J.; Siskind, E. J.; Snyder, A.; Spandre, G.; Spinelli, P.; Suson, D. J.; Tajima, H.; Takahashi, H.; Thayer, J. G.; Thayer, J. B.; Tibaldo, L.; Tinivella, M.; Tosti, G.; Troja, E.; Uchiyama, Y.; Usher, T. L.; Vandenbroucke, J.; Vasileiou, V.; Vianello, G.; Vitale, V.; Winer, B. L.; Wood, K. S.; Wood, M.; Yang, Z.; Zaharijas, G.; Zimmer, S.

    2013-10-01

    Weakly interacting massive particles (WIMPs) are a theoretical class of particles that are excellent dark matter candidates. WIMP annihilation or decay may produce essentially monochromatic γ rays detectable by the Fermi Large Area Telescope (LAT) against the astrophysical γ-ray emission of the Galaxy. We have searched for spectral lines in the energy range 5-300 GeV using 3.7 years of data, reprocessed with updated instrument calibrations and an improved energy dispersion model compared to the previous Fermi-LAT Collaboration line searches. We searched in five regions selected to optimize sensitivity to different theoretically motivated dark matter density distributions. We did not find any globally significant lines in our a priori search regions and present 95% confidence limits for annihilation cross sections of self-conjugate WIMPs and decay lifetimes. Our most significant fit occurred at 133 GeV in our smallest search region and had a local significance of 3.3 standard deviations, which translates to a global significance of 1.5 standard deviations. We discuss potential systematic effects in this search, and examine the feature at 133 GeV in detail. We find that the use both of reprocessed data and of additional information in the energy dispersion model contributes to the reduction in significance of the linelike feature near 130 GeV relative to significances reported in other works. We also find that the feature is narrower than the LAT energy resolution at the level of 2 to 3 standard deviations, which somewhat disfavors the interpretation of the 133 GeV feature as a real WIMP signal.

  9. Measurement and Modeling of Density-Sensitive Lines of Fe XIII in the Extreme Ultraviolet

    SciTech Connect

    Yamamoto, N; Kato, T; Beiersdorfer, P; Lepson, J K

    2008-01-17

    We present an analysis of the spectral emission of Fe XIII near 200 {angstrom}. High resolution spectra were recorded at two densities ({approx} x 10{sup 11} and {approx} 10{sup 13} cm{sup -3}) in the laboratory and compared to collisional radiative model calculations based on the CHIANTI data base as well as to models using atomic data from distorted-wave and R-matrix calculations. The Fe XIII lines in this wavelength range are sensitive indicators of plasma density below {approx} 10{sup 11} cm{sup -3}. The laboratory data thus test the calculations in the astrophysically high-density limit. Significant differences between the measurements and models were found for several line ratios. Differences in the wavelengths employed in the different models also changed the agreement with the measurements. Best agreement was found in the comparisons with CHIANTI.

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

    SciTech Connect

    Emter, Roger; Ellis, Graham; Natsch, Andreas

    2010-06-15

    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.

  11. Goodbye to WIMPs: A Scalable Interface for ALMA Operations

    NASA Astrophysics Data System (ADS)

    Schwarz, J.; Pietriga, E.; Schilling, M.; Grosbol, P.

    2011-07-01

    The operators of the ALMA Observatory will monitor and control more than 50 mm/submm radio antennas and their associated instrumentation from an operations site that is separated from this hardware by 35-50 km. Software that enables them to identify trouble spots and react to failures quickly in this environment will be critical to the safe and efficient functioning of the observatory. Early commissioning of ALMA uses a operator interface implemented with a standard window, icon, menu, pointing device (WIMP) toolkit. Early experience indicates that this paradigm will not scale well as the number of antennas approaches its full complement. Operators lose time as they manipulate overlapping or tabbed windows to drill-down to detailed diagnostic data, losing a feeling for "where they are" in the process. The WIMP model reaches its limits when there is so much information to present to users that they cannot focus on details while maintaining a view from above. To simplify the operators' tasks and let them concentrate on the real issues at hand rather than continually re-organizing their use of screen space, we are replacing the existing top-level interface with a multi-scale interface that takes advantage of semantic zooming, dynamic network visualization and other advanced filtering, navigation and visualization features. Following the first of several planned participatory design workshops, we have developed prototypes to show how users' needs can be met with the kinds of navigation that become possible when the restrictions of the WIMP model are lifted. Cycles of design and implementation coupled with active user feedback will characterize this project up through deployment.

  12. Equivalent neutrinos, light WIMPs, and the chimera of dark radiation

    NASA Astrophysics Data System (ADS)

    Steigman, Gary

    2013-05-01

    According to conventional wisdom, in the standard model (SM) of particle physics and cosmology the “effective number of neutrinos” measured in the late Universe is Neff=3 (more precisely, 3.046). For extensions of the standard model allowing for the presence of ΔNν “equivalent neutrinos” (or “dark radiation”), it is generally the case that Neff>3. These canonical results are reconsidered, demonstrating that a measurement of Neff>3 can be consistent with ΔNν=0 (“dark radiation without dark radiation”). Conversely, a measurement consistent with Neff=3 is not inconsistent with the presence of dark radiation (ΔNν>0). In particular, if there is a light weakly interacting massive particle (WIMP) that annihilates to photons after the SM neutrinos have decoupled, the photons are heated beyond their usual heating from e± annihilation, reducing the late time ratio of neutrino and photon temperatures (and number densities), leading to Neff<3. This opens the window for one or more equivalent neutrinos, including “sterile neutrinos,” to be consistent with Neff=3. By reducing the neutrino number density in the present Universe, this also allows for more massive neutrinos, relaxing the current constraints on the sum of the neutrino masses. In contrast, if the light WIMP couples only to the SM neutrinos and not to the photons and e± pairs, its late time annihilation heats the neutrinos but not the photons, resulting in Neff>3 even in the absence of equivalent neutrinos or dark radiation. A measurement of Neff>3 is no guarantee of the presence of equivalent neutrinos or dark radiation. In the presence of a light WIMP and/or equivalent neutrinos, there are degeneracies among the light WIMP mass and its nature (fermion or boson, as well as its couplings to neutrinos and photons), the number and nature (fermion or boson) of the equivalent neutrinos, and their decoupling temperature (the strength of their interactions with the SM particles). As the analysis here reveals, there’s more to a measurement of Neff than meets the eye.

  13. [Detection of genetic determinants that define the difference of near-isogenic Triticum aestivum L. Lines in photoperiodic sensitivity].

    PubMed

    Kiseleva, A A; Eggi, E E; Koshkin, V A; Sitnikov, M N; Roder, M; Salina, E A; Potokina, E K

    2014-07-01

    Identification of genetic determinants that define different degrees of line sensitivity to the photoperiod was conducted on material of near-isogenic lines of the soft hexaploid wheat Triticum aestivum L. using SSR markers and markers specific to the Vrn and Ppd genes. It was established that the Ppd-s line contains a dominant Ppd-Dla allele located on chromosome 2D. This allele is characterized by a vast deletion in the gene promoter region. For two other lines (Ppd-m and Ppd-w), introgression of the Ppd-B1 gene on chromosome 2B was shown from the parental Sonora variety, which is slightly sensitive to the length of the day; however, the previously described Ppd-Bla. 1 allele was not found. Another polymorphism that can cause weak photoperiodic sensitivity, an increased amount of the Ppd-B1 gene copies, was detected for these lines. PMID:25720138

  14. Dihydropyridine-sensitive and omega-conotoxin-sensitive calcium channels in a mammalian neuroblastoma-glioma cell line.

    PubMed Central

    Kasai, H; Neher, E

    1992-01-01

    1. Pharmacological and kinetic properties of high-voltage-activated (HVA) Ca2+ channel currents were studied using the whole-cell and perforated patch-clamp methods in a mouse neuroblastoma and rat glioma hybrid cell line, NG108-15, differentiated by dibutyryl cyclic AMP or by prostaglandin E1 and theophylline. 2. The HVA currents were separated into two components by use of two organic Ca2+ channel antagonists, omega-conotoxin GVIA (omega CgTX) and a dihydropyridine (DHP) compound, nifedipine. One current component, IDHP, was blocked by nifedipine (Kd = 8.2 nM) and was resistant to omega CgTX. Conversely, the other component, I omega CgTX, was irreversibly blocked by omega CgTX and was resistant to DHPs. Thus, IDHP could be studied in isolation by a short application of omega CgTX, while I omega CgTX could be studied in the presence of nifedipine. 3. The voltage for half-activation of IDHP was smaller than that of I omega CgTX by 13 mV. IDHP was activated at potentials that were subthreshold for voltage-dependent K+ currents of the cell, whereas I omega CgTX was not. 4. Time courses of activation and deactivation of IDHP were faster than those of I omega CgTX. 5. Voltage-dependent inactivation was small for both IDHP and I omega CgTX at any potential. 6. Ca(2+)-dependent inactivation of IDHP was faster and more prominent than that of I omega CgTX. The time course of the Ca(2+)-dependent inactivation of IDHP, but not I omega CgTX, was slowed as the membrane potential was made more positive between -20 and 30 mV, although amplitude of the current was increased. 7. Alkaline earth metal ions carried the two components of IHVA in the same order: Ba2+ greater than Sr2+ greater than Ca2+. 8. Metal ions blocked the two components of IHVA in the same order of potency: Gd3+ greater than La3+ greater than Cd2+ greater than Cu2+ greater than Mn2+ greater than Ni2+. 9. An alkylating agent, N-ethylmaleimide (NEM, 0.1 mM), selectively augmented IDHP by 30%. 10. During the course of cellular differentiation induced by dibutyryl cyclic AMP, IDHP appeared earlier than I omega CgTX. 11. These results indicate that two classes of Ca2+ channels contribute to the HVA currents of this cell line. The DHP-sensitive channel is more apt to generate Ca2+ spikes and Ca2+ plateau potentials than the omega CgTX-sensitive channel. PMID:1375634

  15. On-Line Monitoring of Nitrogenase Activity in Cyanobacteria by Sensitive Laser Photoacoustic Detection of Ethylene

    PubMed Central

    Zuckermann, H.; Staal, M.; Stal, L. J.; Reuss, J.; te Lintel, Hekkert S.; Harren, F.; Parker, D.

    1997-01-01

    A new and extremely sensitive method for measuring nitrogenase activity through acetylene reduction is presented. Ethylene produced by nitrogenase-mediated reduction of acetylene is detected by using laser photoacoustics (LPA). This method possesses a detection limit making it 3 orders of magnitude more sensitive than traditional gas chromatographic analysis. Photoacoustic detection is based on the strong and unique absorption pattern of ethylene in the CO(inf2) laser wavelength region (9 to 11 (mu)m). The high sensitivity allowed on-line monitoring of nitrogenase activity in a culture of the heterocystous cyanobacterium Nodularia spumigena, which was isolated from a water bloom in the Baltic Sea. This setup makes it unnecessary to take subsamples from the culture and avoids long incubations in sealed vials. The fast response of the LPA technique allows measurement of real-time dynamic changes of nitrogenase activity. The method was used to analyze in vivo saturation of nitrogenase by acetylene in N. spumigena. It is demonstrated that 20% acetylene does not saturate nitrogenase and that the degree of saturation depends on light intensity. With concentrations of acetylene as low as 2.5% it is possible to assess the degree of saturation and to extrapolate to total nitrogenase activity. In N. spumigena nitrogenase activity becomes independent of light intensity above 20 to 80 (mu)mol of photons m(sup-2) s(sup-1) at 20% O(inf2). PMID:16535725

  16. SYSTEMATIC ASSESSMENT OF ANALYTICAL METHODS FOR DRUG SENSITIVITY PREDICTION FROM CANCER CELL LINE DATA*

    PubMed Central

    Jang, In Sock; Neto, Elias Chaibub; Guinney, Justin; Friend, Stephen H.; Margolin, Adam A.

    2014-01-01

    Large-scale pharmacogenomic screens of cancer cell lines have emerged as an attractive pre-clinical system for identifying tumor genetic subtypes with selective sensitivity to targeted therapeutic strategies. Application of modern machine learning approaches to pharmacogenomic datasets have demonstrated the ability to infer genomic predictors of compound sensitivity. Such modeling approaches entail many analytical design choices; however, a systematic study evaluating the relative performance attributable to each design choice is not yet available. In this work, we evaluated over 110,000 different models, based on a multifactorial experimental design testing systematic combinations of modeling factors within several categories of modeling choices, including: type of algorithm, type of molecular feature data, compound being predicted, method of summarizing compound sensitivity values, and whether predictions are based on discretized or continuous response values. Our results suggest that model input data (type of molecular features and choice of compound) are the primary factors explaining model performance, followed by choice of algorithm. Our results also provide a statistically principled set of recommended modeling guidelines, including: using elastic net or ridge regression with input features from all genomic profiling platforms, most importantly, gene expression features, to predict continuous-valued sensitivity scores summarized using the area under the dose response curve, with pathway targeted compounds most likely to yield the most accurate predictors. In addition, our study provides a publicly available resource of all modeling results, an open source code base, and experimental design for researchers throughout the community to build on our results and assess novel methodologies or applications in related predictive modeling problems. PMID:24297534

  17. In-line interferometer for direction-sensitive displacement measurements by optical feedback detection

    SciTech Connect

    Tarun, Alvarado; Jecong, Julius; Saloma, Caesar

    2005-12-01

    We demonstrate a compact in-line interferometer for direction-sensitive displacement measurement by optical feedback detection with a semiconductor laser (SL) light source. Two reflected beams from a semitransparent reference mirror and a reflecting test object interfere in the SL medium, causing a variation in its output power. The reference mirror is located between the SL output facet and the test object. The performance of the interferometer is investigated numerically and experimentally to determine its optimal operating conditions. We have verified the operating conditions where the behavior of the SL output power profile could indicate accurately the displacement magnitude and direction of the moving test object. The profile behavior is robust against variations in optical feedback and scale of the interferometer configuration.

  18. Plasma diagnostic techniques in the ultraviolet - The C III density-sensitive lines in the sun

    NASA Technical Reports Server (NTRS)

    Dupree, A. K.; Foukal, P. V.; Jordan, C.

    1976-01-01

    Spectra and spectroheliograms of the C III transitions at 977 and 1176 A are obtained with the Harvard extreme-ultraviolet spectrometer on Skylab. Analysis of the intensities of these lines, and of their density-sensitive ratio, indicates a wide range of temperature gradients and electron densities in the transition region of various solar features. From values of the observed ratio, we suggest necessary revisions to the excitation rates, and propose a relationship between the ratio and density. The significantly higher ratio found in active regions indicates a density increase of about a factor 2 relative to the network. In the quiet sun, there is no significant difference in density between network and cell interiors, but the uncertainty is as large as a factor 3. The very central 10% of the areas of cell interiors shows a significantly higher density than the mean value for cell interiors.

  19. Stress hormones and abiotic stresses have different effects on antioxidants in maize lines with different sensitivity.

    PubMed

    Kellos, T; Tímár, I; Szilágyi, V; Szalai, G; Galiba, G; Kocsy, G

    2008-09-01

    The effect of stress hormones and abiotic stress treatments on reactive oxygen species and on antioxidants was compared in two maize (Zea mays L.) lines (Penjalinan and Z7) having different stress tolerance. Following treatment with abscisic acid, salicylic acid or hydrogen peroxide, the amount of hydrogen peroxide and lipid peroxides increased, while after osmotic stress or cultivation in continuous darkness, the levels were unchanged or decreased. The higher amount of lipid peroxides in Penjalinan indicated its greater sensitivity compared to Z7. The level of the examined antioxidants was increased by nearly all treatments. Glutathione and cysteine contents were higher after salicylic acid, hydrogen peroxide and polyethylene glycol treatments and lower after application of abscisic acid, NaCl and growth in darkness in Z7 than in Penjalinan. The activity of glutathione reductase, ascorbate peroxidase, catalase and glutathione S-transferase was higher after almost all treatments in Z7. The expression of the glutathione synthetase (EC 6.3.2.3) gene was not affected by the treatments, while the level of gamma-glutamylcysteine synthetase (EC 6.3.2.2) and glutathione reductase (EC 1.6.4.2) transcripts increased after most treatments. The two stress hormones and the stress treatments resulted in different changes in antioxidant levels in the two maize lines, which indicates the specific, stress tolerance-dependent response of plants to the various growth regulators and adverse environmental effects that were examined. PMID:18761495

  20. Inhibition of geranylgeranylation mediates sensitivity to CHOP-induced cell death of DLBCL cell lines

    SciTech Connect

    Ageberg, Malin; Rydstroem, Karin; Linden, Ola; Linderoth, Johan; Jerkeman, Mats; Drott, Kristina

    2011-05-01

    Prenylation is a post-translational hydrophobic modification of proteins, important for their membrane localization and biological function. The use of inhibitors of prenylation has proven to be a useful tool in the activation of apoptotic pathways in tumor cell lines. Rab geranylgeranyl transferase (Rab GGT) is responsible for the prenylation of the Rab family. Overexpression of Rab GGTbeta has been identified in CHOP refractory diffuse large B cell lymphoma (DLBCL). Using a cell line-based model for CHOP resistant DLBCL, we show that treatment with simvastatin, which inhibits protein farnesylation and geranylgeranylation, sensitizes DLBCL cells to cytotoxic treatment. Treatment with the farnesyl transferase inhibitor FTI-277 or the geranylgeranyl transferase I inhibitor GGTI-298 indicates that the reduction in cell viability was restricted to inhibition of geranylgeranylation. In addition, treatment with BMS1, a combined inhibitor of farnesyl transferase and Rab GGT, resulted in a high cytostatic effect in WSU-NHL cells, demonstrated by reduced cell viability and decreased proliferation. Co-treatment of BMS1 or GGTI-298 with CHOP showed synergistic effects with regard to markers of apoptosis. We propose that inhibition of protein geranylgeranylation together with conventional cytostatic therapy is a potential novel strategy for treating patients with CHOP refractory DLBCL.

  1. Widespread Molecular Patterns Associated with Drug Sensitivity in Breast Cancer Cell Lines, with Implications for Human Tumors

    PubMed Central

    Creighton, Chad J.

    2013-01-01

    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 patterns. PMID:24386073

  2. The Sensitivity of West African Squall Line Water Budgets to Land Cover

    NASA Technical Reports Server (NTRS)

    Mohr, Karen I.; Baker, R. David; Tao, Wei-Kuo; Famiglietti, James S.; Starr, David OC. (Technical Monitor)

    2001-01-01

    This study used a two-dimensional coupled land/atmosphere (cloud-resolving) model to investigate the influence of land cover on the water budgets of squall lines in the Sahel. Study simulations used the same initial sounding and one of three different land covers, a sparsely vegetated semi-desert, a grassy savanna, and a dense evergreen broadleaf forest. All simulations began at midnight and ran for 24 hours to capture a full diurnal cycle. In the morning, the latent heat flux, boundary layer mixing ratio, and moist static energy in the boundary layer exhibited notable variations among the three land covers. The broadleaf forest had the highest latent heat flux, the shallowest, moistest, slowest growing boundary layer, and significantly more moist static energy per unit area than the savanna and semi-desert. Although all simulations produced squall lines by early afternoon, the broadleaf forest had the most intense, longest-lived squall lines with 29% more rainfall than the savanna and 37% more than the semi-desert. The sensitivity of the results to vegetation density, initial sounding humidity, and grid resolution was also assessed. There were greater differences in rainfall among land cover types than among simulations of the same land cover with varying amounts of vegetation. Small changes in humidity were equivalent in effect to large changes in land cover, producing large changes in the condensate and rainfall. Decreasing the humidity had a greater effect on rainfall volume than increasing the humidity. Reducing the grid resolution from 1.5 km to 0.5 km decreased the temperature and humidity of the cold pools and increased the rain volume.

  3. Pancreatic cancer cell lines deficient in argininosuccinate synthetase are sensitive to arginine deprivation by arginine deiminase

    PubMed Central

    Bowles, Tawnya L.; Kim, Randie; Galante, Joseph; Parsons, Colin M.; Virudachalam, Subbulakshmi; Kung, Hsing-Jien; Bold, Richard J.

    2009-01-01

    Eukaryotic cells can synthesize the non-essential amino acid arginine from aspartate and citrulline using the enzyme argininosuccinate synthetase (ASS). It has been observed that ASS is under-expressed in various types of cancers ASS, for which arginine become auxotrophic. Arginine deiminase (ADI) is a prokaryotic enzyme that metabolizes arginine to citrulline and has been found to inhibit melanoma and hepatoma cancer cells deficient of ASS. We tested the hypothesis that pancreatic cancers have low ASS expression and therefore arginine deprivation by ADI will inhibit cell growth. ASS expression was examined in 47 malignant and 20 non-neoplastic pancreatic tissues as well as a panel of human pancreatic cancer cell lines. Arginine deprivation was achieved by treatment with a recombinant form of ADI formulated with polyethylene glycol (PEG-ADI). Effects on caspase activation, cell growth and cell death were examined. Furthermore, the effect of PEG-ADI on the in vivo growth of pancreatic xenografts was examined. Eighty-seven percent of the tumors lacked ASS expression; 5 of 7 cell lines similarly lacked ASS expression. PEG-ADI specifically inhibited growth of those cell lines lacking ASS. PEG-ADI treatment induced caspase activation and induction of apoptosis. PEG-ADI was well tolerated in mice despite complete elimination of plasma arginine; tumor growth was inhibited by ∼50%. Reduced expression of ASS occurs in pancreatic cancer and predicts sensitivity to arginine deprivation achieved by PEG-ADI treatment. Therefore, these findings suggest that arginine deprivation by ADI could provide a beneficial strategy for the treatment of pancreatic cancer, a malignancy in which new therapy is desperately needed. PMID:18661517

  4. Comparison of anthracycline concentrations in S180 cell lines of varying sensitivity.

    PubMed

    Siegfried, J M; Tritton, T R; Sartorelli, A C

    1983-08-01

    Sublines of sarcoma 180 (S180) of varying sensitivity to adriamycin (ADR) have been selected in culture. The degree of resistance of these sublines ranged from 6- to 125-fold above that of parent S180 cells. ADR-resistant sublines demonstrated comparable degrees of cross-resistance to daunomycin (DNR), marcellomycin and AD 32, but each subline showed a uniform degree of tolerance toward actinomycin D and vincristine. Compared to the anthracycline-sensitive parent tumor, a 40% decrease in the intracellular steady-state level of [3H]-daunomycin was observed in all sublines regardless of the degree of resistance. The level of cell-associated DNR and ADR observed after administration of equipotent concentrations of drug was different for each cell line and increased in proportion to the drug concentration. Thus, altered drug permeability appeared to be of minimal importance in the expression of high levels of resistance. In addition, the extent of DNR metabolism by the anthracycline-resistant sublines was not sufficiently different from that seen in parent S180 cells to account for the observed tolerance to these agents. PMID:6684559

  5. Evaluation of the drug sensitivity and expression of 16 drug resistance-related genes in canine histiocytic sarcoma cell lines.

    PubMed

    Asada, Hajime; Tomiyasu, Hirotaka; Goto-Koshino, Yuko; Fujino, Yasuhito; Ohno, Koichi; Tsujimoto, Hajime

    2015-06-01

    Canine histiocytic sarcoma (HS) is an aggressive tumor type originating from histiocytic cell lineages. This disease is characterized by poor response to chemotherapy and short survival time. Therefore, it is of critical importance to identify and develop effective antitumor drugs against HS. The objectives of this study were to examine the drug sensitivities of 10 antitumor drugs. Using a real-time RT-PCR system, the mRNA expression levels of 16 genes related to drug resistance in 4 canine HS cell lines established from dogs with disseminated HS were determined and compared to 2 canine lymphoma cell lines (B-cell and T-cell). These 4 canine HS cell lines showed sensitivities toward microtubule inhibitors (vincristine, vinblastine and paclitaxel), comparable to those in the canine B-cell lymphoma cell line. Moreover, it was shown that P-gp in the HS cell lines used in this study did not have enough function to efflux its substrate. Sensitivities to melphalan, nimustine, methotrexate, cytarabine, doxorubicin and etoposide were lower in the 4 HS cell lines than in the 2 canine lymphoma cell lines. The data obtained in this study using cultured cell lines could prove helpful in the developing of advanced and effective chemotherapies for treating dogs that are suffering from HS. PMID:25715778

  6. Evaluation of the drug sensitivity and expression of 16 drug resistance-related genes in canine histiocytic sarcoma cell lines

    PubMed Central

    ASADA, Hajime; TOMIYASU, Hirotaka; GOTO-KOSHINO, Yuko; FUJINO, Yasuhito; OHNO, Koichi; TSUJIMOTO, Hajime

    2015-01-01

    Canine histiocytic sarcoma (HS) is an aggressive tumor type originating from histiocytic cell lineages. This disease is characterized by poor response to chemotherapy and short survival time. Therefore, it is of critical importance to identify and develop effective antitumor drugs against HS. The objectives of this study were to examine the drug sensitivities of 10 antitumor drugs. Using a real-time RT-PCR system, the mRNA expression levels of 16 genes related to drug resistance in 4 canine HS cell lines established from dogs with disseminated HS were determined and compared to 2 canine lymphoma cell lines (B-cell and T-cell). These 4 canine HS cell lines showed sensitivities toward microtubule inhibitors (vincristine, vinblastine and paclitaxel), comparable to those in the canine B-cell lymphoma cell line. Moreover, it was shown that P-gp in the HS cell lines used in this study did not have enough function to efflux its substrate. Sensitivities to melphalan, nimustine, methotrexate, cytarabine, doxorubicin and etoposide were lower in the 4 HS cell lines than in the 2 canine lymphoma cell lines. The data obtained in this study using cultured cell lines could prove helpful in the developing of advanced and effective chemotherapies for treating dogs that are suffering from HS. PMID:25715778

  7. The radiation-sensitizing effect of flavopiridol in the esophageal cancer cell line Eca109

    PubMed Central

    YAO, YUAN; SHI, JINGBIN; ZHANG, ZHUO; ZHANG, FENG; MA, RUILAN; ZHAO, YAN

    2013-01-01

    Flavopiridol is a cyclin-dependent kinase inhibitor. It has shown an antitumor effect against several cancers. In the present study, the radiation-sensitizing effect of flavopiridol was investigated in an esophageal squamous carcinoma cell line, Eca109. The growth inhibitory rate of Eca109 with flavopiridol was determined using the MTT and the radio-sensitizing rate using clonogenic survival assays. The cell cycle distribution and the rate of apoptosis were measured using flow cytometry. The proteins cyclin D1, ERK/pERK, caspase-3, Bax and Bcl-2 were detected using western blot analysis to elucidate the mechanism of the radiosensitization effect. MTT assay showed that flavopiridol inhibited the survival rate of Eca109 cells and the effect was dose-dependent. Its IC50 was 193.3 nmol/l. The result of the clonogenic survival revealed that flavopiridol enhanced the radiosensitivity of Eca109 cells and the sensitization enhancement ratio (SER) was 1.194 at 0.2×IC50. Moreover, we detected that the cells treated with flavorpiridol were arrested at the G2/M phase and the apoptosis caused by radiation was increased. In addition, the proteins caspase-3 and Bax in cells treated with flavopiridol were upregulated, while cyclin D1 and Bcl-2 were downregulated. In conclusion, flavopiridol may enhance the radiosensitivity of Eca109 cells and the radiosensitizing effect of flavopiridol may be mediated by decreasing the levels of the cyclin D1 protein, thus increasing the percentage of cells at G2/M phase. PMID:23833659

  8. Constraints on low-mass WIMPs from the EDELWEISS-III dark matter search

    NASA Astrophysics Data System (ADS)

    Armengaud, E.; Arnaud, Q.; Augier, C.; Benoît, A.; Benoît, A.; Bergé, L.; Bergmann, T.; Billard, J.; Blümer, J.; de Boissière, T.; Bres, G.; Broniatowski, A.; Brudanin, V.; Camus, P.; Cazes, A.; Chapellier, M.; Charlieux, F.; Dumoulin, L.; Eitel, K.; Filosofov, D.; Foerster, N.; Fourches, N.; Garde, G.; Gascon, J.; Gerbier, G.; Giuliani, A.; Grollier, M.; Gros, M.; Hehn, L.; Hervé, S.; Heuermann, G.; Humbert, V.; De Jésus, M.; Jin, Y.; Jokisch, S.; Juillard, A.; Kéfélian, C.; Kleifges, M.; Kozlov, V.; Kraus, H.; Kudryavtsev, V. A.; Le-Sueur, H.; Lin, J.; Mancuso, M.; Marnieros, S.; Menshikov, A.; Navick, X.-F.; Nones, C.; Olivieri, E.; Pari, P.; Paul, B.; Piro, M.-C.; Poda, D. V.; Queguiner, E.; Robinson, M.; Rodenas, H.; Rozov, S.; Sanglard, V.; Schmidt, B.; Scorza, S.; Siebenborn, B.; Tcherniakhovski, D.; Vagneron, L.; Weber, M.; Yakushev, E.; Zhang, X.

    2016-05-01

    We present the results of a search for elastic scattering from galactic dark matter in the form of Weakly Interacting Massive Particles (WIMPs) in the 4–30 GeV/c2 mass range. We make use of a 582 kg-day fiducial exposure from an array of 800 g Germanium bolometers equipped with a set of interleaved electrodes with full surface coverage. We searched specifically for ~ 2.5–20 keV nuclear recoils inside the detector fiducial volume. As an illustration the number of observed events in the search for 5 (resp. 20) GeV/c2 WIMPs are 9 (resp. 4), compared to an expected background of 6.1 (resp. 1.4). A 90% CL limit of 4.3 × 10‑40 cm2 (resp. 9.4 × 10‑44 cm2) is set on the spin-independent WIMP-nucleon scattering cross-section for 5 (resp. 20) GeV/c2 WIMPs. This result represents a 41-fold improvement with respect to the previous EDELWEISS-II low-mass WIMP search for 7 GeV/c2 WIMPs. The derived constraint is in tension with hints of WIMP signals from some recent experiments, thus confirming results obtained with different detection techniques.

  9. Generalized spin-dependent WIMP-nucleus interactions and the DAMA modulation effect

    NASA Astrophysics Data System (ADS)

    Scopel, Stefano; Yoon, Kook-Hyun; Yoon, Jong-Hyun

    2015-07-01

    Guided by non-relativistic Effective Field Theory (EFT) we classify the most general spin-dependent interactions between a fermionic Weakly Interacting Massive Particle (WIMP) and nuclei, and within this class of models we discuss the viability of an interpretation of the DAMA modulation result in terms of a signal from WIMP elastic scatterings using a halo-independent approach. We find that, although several relativistic EFT's can lead to a spin-dependent cross section, in some cases with an explicit, non-negligible dependence on the WIMP incoming velocity, three main scenarios can be singled out in the non-relativistic limit which approximately encompass them all, and that only differ by their dependence on the transferred momentum. For two of them compatibility between DAMA and other constraints is possible for a WIMP mass below 30 GeV, but only for a WIMP velocity distribution in the halo of our Galaxy which departs from a Maxwellian. This is achieved by combining a suppression of the WIMP effective coupling to neutrons (to evade constraints from xenon and germanium detectors) to an explicit quadratic or quartic dependence of the cross section on the transferred momentum (that leads to a relative enhancement of the expected rate off sodium in DAMA compared to that off fluorine in droplet detectors and bubble chambers). For larger WIMP masses the same scenarios are excluded by scatterings off iodine in COUPP.

  10. Extended Source Gamma-Ray Emission from WIMP Annihilation in the Sagittarius Dwarf Elliptical Galaxy (SULI paper)

    SciTech Connect

    Vasu-Devan, Vidya; /Columbia U. /SLAC

    2006-01-04

    The proximity of the dark matter dominated Sagittarius Dwarf Elliptical Galaxy (position (l,b) = 5.6{sup o}, -14{sup o}) allows it to act as an ideal laboratory for the exploration of extended gamma-ray emission from Weakly Interacting Massive Particle (WIMP) annihilation processes in a dark matter-dominated system. Since the matter in our universe is predominantly dark, exploring such processes as WIMP annihilation will lead to a better understanding of cosmology. In order to study this gamma-ray emission, a model for the diffuse background gamma-radiation in the dwarf galaxy's region is extracted from the Energetic Gamma Ray Experiment Telescope (EGRET) data. After validating this model and comparing it to the EGRET diffuse model, the background model is added to effective bleeding-contamination from external point sources and multiple models for the signal-above-background emission. Various models of this emission are tested: (a) no source located in region, (b) unidentified point source 3EG J1847-3219 from the Third EGRET Catalog responsible for the emission and (c) extended emission resulting from WIMP annihilation responsible for the signal above background. These models are created through the employment of Monte Carlo simulation methods, utilizing the response functions of the EGRET instrument to simulate the point spread function, energy dispersion and effects of variable effective area depending on angle of incidence. Energy spectra for point sources are generated from the best predictions of spectral indices listed in the Third EGRET Catalog and the spectrum for the extended dark matter source is generated from Pythia high energy annihilation simulations. Hypothesis testing is conducted to assess the goodness-of-fit of these models to the data taken by EGRET. Additionally, we hope to expand our analysis by employing the response functions of the imminent Gamma Ray Large Area Space Telescope (GLAST) to our models. This extension should highlight the sensitivity disparities between GLAST and EGRET and show GLAST's potential enhancement of this analysis. This process will allow for forecasting of extended WIMP annihilation emission signatures for the GLAST detector.

  11. Simultaneous Generation of WIMP Miracle-like Densities of Baryons and Dark Matter

    NASA Astrophysics Data System (ADS)

    McDonald, John

    2012-09-01

    The observed density of dark matter is of the magnitude expected for a thermal relic weakly-interacting massive particle (WIMP). In addition, the observed baryon density is within an order of magnitude of the dark matter density. This suggests that the baryon density is physically related to a typical thermal relic WIMP dark matter density. We present a model which simultaneously generates thermal relic WIMP-like densities for both baryons and dark matter by modifying a large initial baryon asymmetry. Production of unstable scalars carrying baryon number at the LHC would be a clear signature of the model.

  12. Limits on spin-dependent wimp-nucleon interactions from the cryogenic dark matter search

    SciTech Connect

    Akerib, D.S.; Armel-Funkhouser, M.S.; Attisha, M.J.; Bailey, C.N.; Baudis, L.; Bauer, Daniel A.; Brink, P.L.; Brusov, P.P.; Bunker, R.; Cabrera, B.; Caldwell, D.O.; Chang, C.L.; Cooley, J.; Crisler, M.B.; Cushman, P.; Daal, M.; DeJongh, F.; Dixon, R.; Dragowsky, M.R.; Driscoll, D.D.; Duong, L.; /Case Western Reserve U. /UC, Berkeley /Brown U. /Florida U. /Fermilab /Stanford U., Phys. Dept. /UC, Santa Barbara /Minnesota U. /Caltech /Colorado U., Denver /LBL, Berkeley /Santa Clara U.

    2005-09-01

    The Cryogenic Dark Matter Search (CDMS) is an experiment to detect weakly interacting massive particles (WIMPs) based on their interactions with Ge and Si nuclei. We report the results of an analysis of data from the first two runs of CDMS at the Soudan Underground Laboratory in terms of spin-dependent WIMP-nucleon interactions on {sup 73}Ge and {sup 29}Si. These data exclude new regions of spin-dependent WIMP-nucleon interaction parameter space, including regions relevant to spin-dependent interpretations of the annual modulation signal reported by the DAMA/NaI experiment.

  13. Gravitationally induced particle production and its impact on the WIMP abundance

    NASA Astrophysics Data System (ADS)

    Baranov, I.; Lima, J. A. S.

    2015-12-01

    A large set of independent astronomical observations have provided a strong evidence for nonbaryonic dark matter in the Universe. One of the most investigated candidates is an unknown long-lived Weakly Interacting Massive Particle (WIMP) which was in thermal equilibrium with the primeval plasma. Here we investigate the WIMP abundance based on the relativistic kinetic treatment for gravitationally induced particle production recently proposed in the literature (Lima and Baranov, 2014) [16]. The new evolution equation is deduced and solved both numerically and through a semi-analytical approach. The predictions of the WIMP observables are discussed and compared with the ones obtained in the standard approach.

  14. WIMP dark matter as radiative neutrino mass messenger

    NASA Astrophysics Data System (ADS)

    Hirsch, M.; Lineros, R. A.; Morisi, S.; Palacio, J.; Rojas, N.; Valle, J. W. F.

    2013-10-01

    The minimal seesaw extension of the Standard SU(3) c ?SU(2) L ?U(1) Y Model requires two electroweak singlet fermions in order to accommodate the neutrino oscillation parameters at tree level. Here we consider a next to minimal extension where light neutrino masses are generated radiatively by two electroweak fermions: one singlet and one triplet under SU(2)L. These should be odd under a parity symmetry and their mixing gives rise to a stable weakly interactive massive particle (WIMP) dark matter candidate. For mass in the GeV-TeV range, it reproduces the correct relic density, and provides an observable signal in nuclear recoil direct detection experiments. The fermion triplet component of the dark matter has gauge interactions, making it also detectable at present and near future collider experiments.

  15. Highly-sensitive micellar electrokinetic chromatographic analysis of dioxin-related compounds using on-line concentration.

    PubMed

    Otsuka, K; Hayashibara, H; Yamauchi, S; Quirino, J P; Terabe, S

    1999-08-20

    An application study of an on-line concentration technique of neutral analytes for micellar electrokinetic chromatography (MEKC) was carried out in environmental analysis to enhance the UV detection sensitivity. Several dioxins and related compounds, such as dibenzofuran, dibenzo-p-dioxin, 2,3- and 2,7-dichlorodibenzo-p-dioxins, and 2,3,7-trichlorodibenzo-p-dioxin, were used as test solutes. For a highly sensitive separation and detection, cyclodextrin-modified MEKC (CD-MEKC) under acidic conditions was employed as a separation mode and stacking using reverse migrating micelles and a water plug (SRW) as an on-line concentration technique. Almost a 200-fold gain in detection sensitivity was obtained for the model compounds in SRW-CD-MEKC compared to that in normal CD-MEKC without on-line concentration and the limit of detection was found to be around 0.1 ppm for each solute. PMID:10486748

  16. Development of Sensitivity Analysis Algorithm for a Straight-Line Beam Structure by the Transfer Stiffness Coefficient Method

    NASA Astrophysics Data System (ADS)

    Moon, Deok-Hong; Choi, Myung-Soo

    This paper describes the sensitivity analysis algorithm extending the concept of the transfer stiffness coefficient method (TSCM) which is suitable to analyze accurately vibrations of complex and large structures on a personal computer with small computer memories. This sensitivity analysis algorithm is based on the concept transferring the sensitivities of the stiffness coefficient with respect to design parameters. In this paper, the free vibration analysis algorithm by the TSCM for a straight-line structure is shortly introduced and the free vibration sensitivity analysis algorithm is formulated by the present method. To demonstrate the validity of the present method, a straight-line beam structure with various boundary conditions is proposed as a numerical example. Eigenvalues and eigenvectors and their derivatives for the beam obtained by the present method are compared with those of the Fox's method and the reanalysis on a personal computer.

  17. Generating a "Humanized" Drosophila S2 Cell Line Sensitive to Pharmacological Inhibition of Kinesin-5

    PubMed Central

    Ye, Anna A.; Maresca, Thomas J.

    2016-01-01

    Kinetochores are large protein-based structures that assemble on centromeres during cell division and link chromosomes to spindle microtubules. Proper distribution of the genetic material requires that sister kinetochores on every chromosome become bioriented by attaching to microtubules from opposite spindle poles before progressing into anaphase. However, erroneous, non-bioriented attachment states are common and cellular pathways exist to both detect and correct such attachments during cell division. The process by which improper kinetochore-microtubule interactions are destabilized is referred to as error correction. To study error correction in living cells, incorrect attachments are purposely generated via chemical inhibition of kinesin-5 motor, which leads to monopolar spindle assembly, and the transition from mal-orientation to biorientation is observed following drug washout. The large number of chromosomes in many model tissue culture cell types poses a challenge in observing individual error correction events. Drosophila S2 cells are better subjects for such studies as they possess as few as 4 pairs of chromosomes. However, small molecule kinesin-5 inhibitors are ineffective against Drosophila kinesin-5 (Klp61F). Here we describe how to build a Drosophila cell line that effectively replaces Klp61F with human kinesin-5, which renders the cells sensitive to pharmacological inhibition of the motor and suitable for use in the cell-based error correction assay. PMID:26863489

  18. WIMP Gamma Rays From the Galactic Center with GLAST and Accelerator Comparison

    SciTech Connect

    Morselli, Aldo; Lionetto, Andrea; Nuss, Eric

    2007-07-12

    We will describe the prospects for detecting gamma-rays from WIMP's annihilation in the Galactic Center and we compare this search with the possibilities at LHC and with space antimatter experiments like PAMELA.

  19. Search for dark matter WIMPs using upward through-going muons in Super-Kamiokande

    SciTech Connect

    Desai, S.; Earl, M.; Kearns, E.; Stone, J.L.; Sulak, L.R.; Walter, C.W.; Wang, W.; Ashie, Y.; Fukuda, S.; Fukuda, Y.; Ishihara, K.; Itow, Y.; Koshio, Y.; Minamino, A.; Miura, M.; Moriyama, S.; Nakahata, M.; Namba, T.; Nambu, R.; Obayashi, Y.

    2004-10-15

    We present the results of indirect searches for Weakly Interacting Massive Particles (WIMPs), with 1679.6 live days of data from the Super-Kamiokande detector using neutrino-induced upward through-going muons. The search is performed by looking for an excess of high energy muon neutrinos from WIMP annihilations in the Sun, the core of the Earth, and the Galactic Center, as compared to the number expected from the atmospheric neutrino background. No statistically significant excess was seen. We calculate the flux limits in various angular cones around each of the above celestial objects. We obtain conservative model-independent upper limits on the WIMP-nucleon cross section as a function of WIMP mass, and compare these results with the corresponding results from direct dark matter detection experiments.

  20. On-line liquid chromatography-mass spectrometry with dilution line to achieve large volume urine injection for the improvement of sensitivity.

    PubMed

    Liu, Min; Yan, Wei; Lin, Jin-Ming; Hashi, Yuki; Liu, Li-Bin; Wei, Yanlin

    2008-07-11

    A unique automated on-line high-performance liquid chromatography-mass spectrometry (LC-MS) method was developed allowing injection of a large volume of urine for the improvement of sensitivity using estrogens as analytes. The urine sample was precipitated by acetonitrile (sample:acetonitrile, 1:2, v/v) to remove most proteins. Then the supernatant was directly delivered at 0.3 mL/min by a pump, which broke through the limit of autosampler with fixed loop. Then the sample was loaded onto a restricted access media (RAM) pre-column after on-line dilution with NH(4)Ac solution which was delivered by another pump under high flow-rate. After the addition of on-line dilution line, the content of organic solvent in the sample aliquot was sharply decreased so that the analytes were effectively trapped by pre-column. In addition, another 6-port valve was added to selectively deliver the effluent containing analytes into MS, which minimized the pollution of the MS and matrix effect. After optimization of the condition of extraction method, 3 mL sample (containing 1 mL urine) could be successfully enriched. The injection volume increased 10 times compared with conventional on-line LC-MS methods for biofluid analysis, significantly improving sensitivity. Moreover, no obvious increase of column pressure was observed after 300 injections. The method was validated by spiking urine. Linearity was determined by sample which was in the range of 1-500 ng/mL. The process efficiency ranged from 70.2 to 106% with RSDs less than 15% with the exception of a few analytes. The limit of detection (LOD) and quantification (LOQ) ranged from 0.3 to 2 ng/mL and 1 to 8 ng/mL, respectively, corresponding a decrease of 1-2 orders of magnitude compared with those of off-line and on-line methods. PMID:18533167

  1. RUNX3 confers sensitivity to pheophorbide a-photodynamic therapy in human oral squamous cell carcinoma cell lines.

    PubMed

    Moon, Sook; Bae, Jung Yoon; Son, Hwa-Kyung; Lee, Doo Young; Park, Gyeongju; You, Hyun; Ko, Hyojin; Kim, Yong-Chul; Kim, Jin

    2015-02-01

    Photodynamic therapy (PDT) with photosensitizer is one of the promising modalities for cancer treatment. For clinical use of PDT, screening process should be preceded to enhance sensitivity to PDT. Thus, we investigated a molecular biomarker to determine the sensitivity to pheophorbide a (Pa)-PDT in immortalized human oral keratinocytes (IHOK) and oral squamous cell carcinoma (OSCC) cell lines. Two IHOK and several OSCC cell lines were used. After Pa-PDT, cell viability was reduced by more than 50%, and reactive oxygen species were generated in IHOK and OSCC cell lines. Additionally, apoptosis occurred in PDT-treated cells. IHOK(S) and IHOK(P), the two IHOK cell lines derived from the same source, showed a difference in cytotoxicity after Pa-PDT. To explain this difference in cytotoxicity, we looked at the expression of Wnt signaling-related genes in these two cell lines, for the morphology of IHOK(S) which was spindle like and elongated and distinct from IHOK(P) and the parent cell. Among the relevant genes, runt-related transcription factor 3 (RUNX3), an apoptosis-related gene, was selected as a potential marker that confers sensitivity to PDT. We found that the cytotoxicity by Pa-PDT was proportional to RUNX3 expression in OSCC cell lines. Additionally, knockdown of RUNX3 expression reduced cytotoxicity by Pa-PDT, suggesting that RUNX3 might be a biomarker to determine sensitivity to Pa-PDT. This was the first study to find a new target molecule that enhances Pa-PDT effects in IHOK and OSCC cell lines. Hence, the development of a PDT-dependent biomarker could provide a novel approach to improve the effects of PDT on oral precancerous and cancerous lesions. PMID:23700080

  2. Protein profiles reveal diverse responsive signaling pathways in kernels of two maize inbred lines with contrasting drought sensitivity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Drought stress is a major factor which 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 lines (B73 and Lo964) with contrasting drought sensitivity were...

  3. Hepatic drug metabolizing profile of Flinders Sensitive Line rat model of depression.

    PubMed

    Kotsovolou, Olga; Ingelman-Sundberg, Magnus; Lang, Matti A; Marselos, Marios; Overstreet, David H; Papadopoulou-Daifoti, Zoi; Johanson, Inger; Fotopoulos, Andrew; Konstandi, Maria

    2010-08-16

    The Flinders Sensitive Line (FSL) rat model of depression exhibits some behavioral, neurochemical, and pharmacological features that have been reported in depressed patients and has been very effective in screening antidepressants. Major factor that determines the effectiveness and toxicity of a drug is the drug metabolizing capacity of the liver. Therefore, in order to discriminate possible differentiation in the hepatic drug metabolism between FSL rats and Sprague-Dawley (SD) controls, their hepatic metabolic profile was investigated in this study. The data showed decreased glutathione (GSH) content and glutathione S-transferase (GST) activity and lower expression of certain major CYP enzymes, including the CYP2B1, CYP2C11 and CYP2D1 in FSL rats compared to SD controls. In contrast, p-nitrophenol hydroxylase (PNP), 7-ethoxyresorufin-O-dealkylase (EROD) and 16alpha-testosterone hydroxylase activities were higher in FSL rats. Interestingly, the wide spread environmental pollutant benzo(alpha)pyrene (B(alpha)P) induced CYP1A1, CYP1A2, CYP2B1/2 and ALDH3c at a lesser extend in FSL than in SD rats, whereas the antidepressant mirtazapine (MIRT) up-regulated CYP1A1/2, CYP2C11, CYP2D1, CYP2E1 and CYP3A1/2, mainly, in FSL rats. The drug also further increased ALDH3c whereas suppressed GSH content in B(alpha)P-exposed FSL rats. In conclusion, several key enzymes of the hepatic biotransformation machinery are differentially expressed in FSL than in SD rats, a condition that may influence the outcome of drug therapy. The MIRT-induced up-regulation of several drug-metabolizing enzymes indicates the critical role of antidepressant treatment that should be always taken into account in the designing of treatment and interpretation of insufficient pharmacotherapy or drug toxicity. PMID:20595028

  4. Relationship between expression of topoisomerase II isoforms and intrinsic sensitivity to topoisomerase II inhibitors in breast cancer cell lines.

    PubMed Central

    Houlbrook, S.; Addison, C. M.; Davies, S. L.; Carmichael, J.; Stratford, I. J.; Harris, A. L.; Hickson, I. D.

    1995-01-01

    Topoisomerase II is a key target for many anti-cancer drugs used to treat breast cancer. In human cells there are two closely related, but differentially expressed, topoisomerase II isoforms, designated topoisomerase II alpha and beta. Here, we report the production of a new polyclonal antibody raised against a fragment of the C-terminal domain of the 180 kDa form of topoisomerase II (the beta isoform), which does not cross-react with the 170 kDa form (the alpha isoform). Using this antibody, together with a polyclonal antibody specific for the 170 kDa isoform of topoisomerase II, we have examined the relationship between the sensitivity of a panel of human breast cancer cell lines to different classes of topoisomerase II inhibitors and cellular levels of the topoisomerase II alpha and beta proteins. We found that sensitivity to amsacrine showed a correlation with the level of expression of topoisomerase II alpha protein, and that sensitivity to etoposide showed a similar correlation with the level of expression of topoisomerase II beta protein. There was also a relationship between sensitivity of these cell lines to mitoxantrone and the cellular level of both isoforms of topoisomerase II. No relationship was found between the level of mRNA for topoisomerase II alpha or beta, and either sensitivity of breast cancer cell lines to topoisomerase II inhibitors or the level of topoisomerase II protein expression. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:8519659

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

    PubMed

    Stap, J; Aten, J A

    1990-11-01

    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 showed a higher sensitivity for the induction of proliferative death than RUC rat ureter carcinoma cells and V79 Chinese hamster cells which had a similar radiation sensitivity. The frequencies of micro-nucleated cells were measured at 48 hours after the treatment. It was determined by time-lapse cinematography that almost all the cells in the treated cultures had divided at that time. Our results indicate that for these cell lines the correlation between the effectiveness for cell killing and the induction of micro-nuclei was the same, within the experimental errors. PMID:2260014

  6. Sensitivity of malignant rhabdoid tumor cell lines to PD 0332991 is inversely correlated with p16 expression

    SciTech Connect

    Katsumi, Yoshiki; Iehara, Tomoko; Miyachi, Mitsuru; Yagyu, Shigeki; Tsubai-Shimizu, Satoko; Kikuchi, Ken; Tamura, Shinichi; Kuwahara, Yasumichi; Tsuchiya, Kunihiko; Kuroda, Hiroshi; Sugimoto, Tohru; Houghton, Peter J.; Hosoi, Hajime

    2011-09-16

    Highlights: {yields} PD 0332991 (PD) could suppress four of five malignant rhabdoid tumor (MRT) cell lines. {yields} The sensitivity of the MRT cell lines to PD was inversely correlated with p16 expression (r = 0.951). {yields} p16 expression in MRT could be used to predict its sensitivity to PD. {yields} PD may be an attractive agent for patients with MRT whose tumors express low levels of p16. -- Abstract: Malignant rhabdoid tumor (MRT) is a rare and highly aggressive neoplasm of young children. MRT is characterized by inactivation of integrase interactor 1 (INI1). Cyclin-dependent kinase 4 (CDK4), which acts downstream of INI1, is required for the proliferation of MRT cells. Here we investigated the effects of PD 0332991 (PD), a potent inhibitor of CDK4, against five human MRT cell lines (MP-MRT-AN, KP-MRT-RY, G401, KP-MRT-NS, KP-MRT-YM). In all of the cell lines except KP-MRT-YM, PD inhibited cell proliferation >50%, (IC{sub 50} values 0.01 to 0.6 {mu}M) by WST-8 assay, and induced G1-phase cell cycle arrest, as shown by flow cytometry and BrdU incorporation assay. The sensitivity of the MRT cell lines to PD was inversely correlated with p16 expression (r = 0.951). KP-MRT-YM cells overexpress p16 and were resistant to the growth inhibitory effect of PD. Small interfering RNA against p16 significantly increased the sensitivity of KP-MRT-YM cells to PD (p < 0.05). These results suggest that p16 expression in MRT could be used to predict its sensitivity to PD. PD may be an attractive agent for patients with MRT whose tumors express low levels of p16.

  7. Background optimization for a new spherical gas detector for very light WIMP detection

    NASA Astrophysics Data System (ADS)

    Dastgheibi Fard, Ali

    The Spherical gaseous detector (or Spherical Proportional Counter, SPC) is a novel type of par- ticle detector, with a broad range of applications. Its main features include a very low energy threshold independent of the volume (due to its very low capacitance), a good energy resolution, robustness and a single detection readout channel, in its simplest version. Applications range from radon emanation gas monitoring, neutron flux and gamma counting and spectroscopy to dark matter searches, in particular low mass WIMPs and coherent neutrino scattering measure- ment. Laboratories interested in these various applications share expertise within the NEWS (New Experiments With Sphere) network. SEDINE, a low background prototype installed at underground site of Laboratoire Souterrain de Modane is currently being operated and aims at measuring events at very low energy threshold, around 100 eV. We will present the energy cali- bration with 37Ar, the surface background reduction, the measurement of detector background at sub-keV energies, and show anticipated sensitivities for light dark matter search.

  8. 47 CFR 69.713 - Common line, traffic-sensitive, and tandem-switched transport services.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., traffic-sensitive, and tandem-switched transport services. (a) Scope. This paragraph governs requests for... §§ 69.152, 69.153, and 69.154. (2) Services in the traffic-sensitive basket, as described in § 61.42(d)(2) of this chapter. (3) The traffic-sensitive components of tandem-switched transport services,...

  9. Dye sensitized photovoltaic miniaturized solar cells, used as optical sensors for line of sight detection

    NASA Astrophysics Data System (ADS)

    Cesar, Cortes Torres Carlos; Sampei, Kota; Miho, Ogawa; Masataka, Ozawa; Norihisa, Miki

    2014-11-01

    Dye sensitized photovoltaic devices have been studied as transparent and low-cost solar cells. Our group have miniaturized the cells and used them as transparent optical sensors. This paper reports the design and fabrication of the cells and avoids the cross talk among cells, which was found recently and such effect provokes hardware instability. We use these optical sensors as an eye tracking device. The sensor array detects the difference in the intensity of light reflected from the pupil and the sclera and then determines the pupil position. Each sensor consists of two electrodes and electrolyte; hence our device conformed by only four semi-circular shaped sensors on eyeglasses can detect the view angle in both horizontal and vertical directions. Manufacturing process gives us freedom to easily re-arrange, add or remove sensors. In our prior work we had good performance in stand-alone configuration. We used specialized equipment from National Instruments for our measurements. However we found that: A cell is not 100% independent from the others, is affected by the absence or presence of light at the neighbour cells. When our device is connected to other electronic devices (for data processing), all cells have the same voltage among them; therefore, all cells behave the same way when any of them is affected by light. The root cause is, due to all sensors were interconnected via a micro channel and filled with electrolyte, due to its conductive properties, electrolyte does neither need electrodes nor physical paths to conduct electricity, so it creates a liquid wire between sensors, hence the gap between them become inexistent, consequently when our device is connected to other electronic devices, due to this unique channel and by sharing a common electronic ground, this connection provokes the voltage to be the same among all sensors in the array. Our device becomes four separate voltage lines in a parallel circuit. The device was also in short circuit provoked by some overlapping paths, despite that such paths were in different layers and separated by an adhesive film of 100pm thickness, such thickness was not large enough to creates a successful dielectric to isolate the paths.

  10. Cataloging antineoplastic agents according to their effectiveness against platinum-resistant and platinum-sensitive ovarian carcinoma cell lines

    PubMed Central

    Ishiguro, Kimiko; Zhu, Yong-Lian; Lin, Z. Ping; Penketh, Philip G.; Shyam, Krishnamurthy; Zhu, Rui; Baumann, Raymond P.; Sartorelli, Alan C.; Rutherford, Thomas J.; Ratner, Elena S.

    2016-01-01

    Although epithelial ovarian cancers (EOCs) are initially treated with platinum-based chemotherapy, EOCs vary in platinum responsiveness. Cataloging antineoplastic agents according to their effectiveness against platinum-resistant and platinum-sensitive EOC cell lines is valuable for development of therapeutic strategies to avoid platinum inefficacy and to exploit platinum sensitivity. TOV-21G devoid of FANCF expression, OV-90 and SKOV-3 were employed as examples of platinum-sensitive, platinum-intermediate and platinum-resistant cell lines, respectively. Antineoplastic agents examined included mitomycin C, doxorubicin, etoposide, gemcitabine, chlorambucil, paclitaxel, triapine and X-rays. Their effectiveness against cell lines was analyzed by clonogenic assays. Cytotoxic profiles of mitomycin C and carboplatin were similar, with mitomycin C exhibiting greater potency and selectivity against TOV-21G than carboplatin. Cytotoxic profiles of doxorubicin, etoposide and X-rays overlapped with that of carboplatin, while OV-90 overexpressing Rad51 was more resistant to chlorambucil than SKOV-3. The efficacy of paclitaxel and triapine was independent of platinum sensitivity or resistance. Consistent with these cytotoxic profiles, cisplatin/mitomycin C, triapine, and paclitaxel differed in the capacity to induce phosphorylation of H2AX, and produced unique inhibitory patterns of DNA/RNA syntheses in HL-60 human leukemia cells. Paclitaxel and triapine in combination produced additive antitumor effects in M109 murine lung carcinoma. In conclusion, mitomycin C is potentially more effective against Fanconi anemia pathway-deficient EOCs than carboplatin. Doxorubicin and etoposide, because of their overlapping cytotoxic properties with carboplatin, are unlikely to be efficacious against platinum-refractory EOCs. Paclitaxel and triapine are effective regardless of platinum sensitivity status, and promising in combination for both platinum-sensitive and platinum-refractory EOCs. PMID:27076919

  11. 47 CFR 69.713 - Common line, traffic-sensitive, and tandem-switched transport services.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...-switched transport services. 69.713 Section 69.713 Telecommunication FEDERAL COMMUNICATIONS COMMISSION..., traffic-sensitive, and tandem-switched transport services. (a) Scope. This paragraph governs requests for...)(2) of this chapter. (3) The traffic-sensitive components of tandem-switched transport services,...

  12. Secluded WIMPs, dark QED with massive photons, and the galactic center gamma-ray excess

    NASA Astrophysics Data System (ADS)

    Fortes, E. C. F. S.; Pleitez, V.; Stecker, F. W.

    2016-02-01

    We discuss a particular secluded WIMP dark matter model consisting of neutral fermions as the dark matter candidate and a Proca-Wentzel (PW) field as a mediator. In the model that we consider here, dark matter WIMPs interact with standard model (SM) particles only through the PW field of ∼MeV-multi-GeV mass particles. The interactions occur via a U(1)‧ mediator, Vμ‧, which couples to the SM by kinetic mixing with U(1) hypercharge bosons, Bμ‧. One important difference between our model and other such models in the literature is the absence of an extra singlet scalar, so that the parameter with dimension of mass MV2is not related to a spontaneous symmetry breaking. This QED based model is also renormalizable. The mass scale of the mediator and the absence of the singlet scalar can lead to interesting astrophysical signatures. The dominant annihilation channels are different from those usually considered in previous work. We show that the GeV-energy γ-ray excess in the galactic center region, as derived from Fermi-LAT Gamma-ray Space Telescope data, can be attributed to such secluded dark matter WIMPs, given parameters of the model that are consistent with both the cosmological dark matter density and the upper limits on WIMP spin-independent elastic scattering. Secluded WIMP models are also consistent with suggested upper limits on a DM contribution to the cosmic-ray antiproton flux.

  13. Mutation in CSA creates a new photoperiod-sensitive genic male sterile line applicable for hybrid rice seed production

    PubMed Central

    Zhang, Hui; Xu, Chenxi; He, Yi; Zong, Jie; Yang, Xijia; Si, Huamin; Sun, Zongxiu; Hu, Jianping; Liang, Wanqi; Zhang, Dabing

    2013-01-01

    Rice is a major staple food worldwide. Making hybrid rice has proved to be an effective strategy to significantly increase grain yield. Current hybrid rice technologies rely on male sterile lines and have been used predominantly in indica cultivars. However, intrinsic problems exist in the implementation of these technologies, such as limited germplasms and unpredictable conversions from sterility to fertility in the field. Here, we describe a photoperiod-controlled male sterile line, carbon starved anther (csa), which contains a mutation in an R2R3 MYB transcription regulator of pollen development. This mutation was introduced into indica and japonica rice, and it rendered male sterility under short-day conditions and male fertility under long-day conditions in both lines. Furthermore, F1 plants of csa and a restorer line JP69 exhibited heterosis (hybrid vigor), suggesting the feasibility of using this mutation to create hybrid rice. The csa-based photoperiod-sensitive male sterile line allows the establishment of a stable two-line hybrid system, which promises to have a significant impact on agriculture. PMID:23256151

  14. Clofazimine and B4121 sensitize an intrinsically resistant human colon cancer cell line to P-glycoprotein substrates.

    PubMed

    van Rensburg, C E; Joone, G K; O'Sullivan, J F

    2000-01-01

    The potential of B4121 to sensitize three intrinsically resistant human colon cancer cell lines (CaCo2, ATCC HTB 37; COLO 32 DM, ATCC CCL 220; HT-29, ATCC HTB 38) to vinblastine, doxorubicin, daunorubicin, paclitaxel, taxotere and cisplatin at a non-toxic, therapeutically relevant concentration of 0.25 microg/ml was compared with that of clofazimine at a similar concentration. The cell line expressing high levels of P-glycoprotein (P-gp), COLO 320 DM, was susceptible to chemosensitization by the experimental agents for the P-gp substrates (paclitaxel, taxotere, daunorubicin, vinblastine and doxorubicin) but not for cisplatin. CaCo2 cells expressed lower levels of P-gp and were only marginally susceptible to sensitization by any one of these drugs, except in the case of sensitization by B4121 for doxorubicin and taxotere, whereas the HT-29, a P-gp negative cell line, was unaffected. The riminophenazines, especially B4121, might prove useful as combination treatment in circumventing P-gp mediated resistance of colon cancers. PMID:10601617

  15. Lines

    ERIC Educational Resources Information Center

    Mires, Peter B.

    2006-01-01

    National Geography Standards for the middle school years generally stress the teaching of latitude and longitude. There are many creative ways to explain the great grid that encircles our planet, but the author has found that students in his college-level geography courses especially enjoy human-interest stories associated with lines of latitude…

  16. Wimp searches with gamma rays in the Fermi era: Challenges, methods and results

    SciTech Connect

    Conrad, J.; Cohen-Tanugi, J.

    2015-12-15

    The launch of the gamma-ray telescope Fermi Large Area Telescope (Fermi-LAT) started a pivotal period in indirect detection of dark matter. By outperforming expectations, for the first time a robust and stringent test of the paradigm of weakly interacting massive particles (WIMPs) is within reach. In this paper, we discuss astrophysical targets for WIMP detection and the challenges they present, review the analysis tools which have been employed to tackle these challenges, and summarize the status of constraints on and the claimed detections in the WIMP parameter space. Methods and results will be discussed in comparison to Imaging Air Cherenkov Telescopes. We also provide an outlook on short term and longer term developments.

  17. Limits on dark matter WIMPs using upward-going muons in the MACRO detector

    SciTech Connect

    Bellotti, R.; Cafagna, F.; Calicchio, M.; Castellano, M.; De Benedictis, L.; De Cataldo, G.; De Marzo, C.; Erriquez, O.; Favuzzi, C.; Fusco, P.; Giglietto, N.; Guarnaccia, P.; Mazziotta, M.N.; Montaruli, T.; Raino, A.; Spinelli, P.; Bernardini, E.; Cecchini, S.; Dekhissi, H.; Derkaoui, J.; Giacomelli, G.; Giorgini, M.; Lari, T.; Maaroufi, F.; Mandrioli, G.; Manzoor, S.; Margiotta Neri, A.; Ouchrif, M.; Patrizii, L.; Popa, V.; Rastelli, A.; Serra-Lugaresi, P.; Sioli, M.; Spurio, M.; Togo, V.; Ugolotti, D.; Habig, A.; Kearns, E.; Orth, C.; Scholberg, K.; Stone, J.L.; Sulak, L.R.; Walter, C.W.; Barish, B.C.; Choudhary, B.C.; Huang, Y.; Katsavounidis, E.; Katsavounidis, I.; Kim, H.; Kyriazopoulou, S.; Longley, N.P.; Michael, D.G.; Mikheyev, S.; Peck, C.W.; Lane, C.; Steinberg, R.; Battistoni, G.; Bilokon, H.; Bloise, C.; Carboni, M.; Chiarella, V.; Forti, C.; Iarocci, E.; Marini, A.; Patera, V.; Ronga, F.; Satta, L.; Sciubba, A.; Spinetti, M.; Antolini, R.; Aramo, C.; Bernardini, E.; Di Credico, A.; Gray, L.; Grillo, A.; Gustavino, C.; Lari, T.; Mikheyev, S.; Palamara, O.; Rastelli, A.; Reynoldson, J.; Scapparone, E.; Bower, C.; Heinz, R.; Miller, L.; Mufson, S.; Musser, J.; De Mitri, I.; Monacelli, P.; Petrera, S.; and others

    1999-10-01

    We perform an indirect search for weakly interacting massive particles (WIMPs) using the MACRO detector to look for neutrino-induced upward-going muons resulting from the annihilation of WIMPs trapped in the Sun and Earth. The search is conducted in various angular cones centered on the Sun and Earth to accommodate a range of WIMP masses. No significant excess over the background from atmospheric neutrinos is seen. We set experimental flux limits on the upward-going muon fluxes from the Sun and the Earth. These limits are used to constrain neutralino particle parameters from supersymmetric theory, including those suggested by recent results from DAMA-NaI. {copyright} {ital 1999} {ital The American Physical Society}

  18. 750 GeV dark pion: Cousin of a dark G -parity odd WIMP

    NASA Astrophysics Data System (ADS)

    Bai, Yang; Berger, Joshua; Lu, Ran

    2016-04-01

    We point out a potential common origin of the recently observed 750 GeV diphoton resonance and a weakly interacting massive particle (WIMP) candidate. In a dark QCD sector with an unbroken dark G parity, the diphoton resonance could be a dark G -even pion, while the WIMP could be the lightest dark G -odd pion. Both particles are Standard Model gauge singlets and have the same decay constant. For the dark pion decay constant of around 500 GeV, both the diphoton excess at the LHC and the dark matter thermal abundance can be accommodated in our model. Our model predicts additional dark G -even and dark G -odd color-octet pions within reach of the 13 TeV LHC runs. For the 5 +5 ¯ model, compatible with the grand unified theories, the WIMP mass is predicted to be within (613,750) GeV.

  19. Supersymmetry and dark matter post LHC8: Why we may expect both axion and WIMP detection

    SciTech Connect

    Baer, Howard

    2014-01-01

    In the post-LHC8 era, it is perceived that what is left of SUSY model parameter space is highly finetuned in the EW sector (EWFT). We discuss how conventional measures overestimate EWFT in SUSY theory. Radiatively-driven natural SUSY (RNS) models maintain the SUSY GUT paradigm with low EWFT at 10% level, but are characterized by light higgsinos ~100–300 GeV and a thermal underabundance of WIMP dark matter. Implementing the SUSY DFSZ solution to the strong CP problem explains the small μ parameter but indicates dark matter should be comprised mainly of axions with a small admixture of higgsino-like WIMPs. While RNS might escape LHC14 searches, we would expect ultimately direct detection of both WIMPs and axions. An e⁺e⁻ collider with √(s)~500–600 GeV should provide a thorough search for the predicted light higgsinos.

  20. In vivo and in vitro chemotherapy sensitivity testing for human kidney tumor lines: a comparative study

    SciTech Connect

    Kurth, K.H.; Romijn, J.C.; Kappendijk, M.; Weissglas, M.G.; van Dongen, J.W.

    1988-01-01

    In vivo and in vitro chemosensitivity testing has been applied to kidney carcinoma tumor lines. Serially transplantable tumors were implanted subcutaneously in nude mice and the animals were treated with cytostatic drugs. The results of this in vivo assay were compared with the results obtained with the subrenal capsule assay, the DNA precursor assay (/sup 3/H-thymidine), and the colony-formation assay, utilizing the same tumor line in each case. Higher rates of resistant tumors were found in the in vivo assays than in the in vitro assays. The SRC assay and the DNA assay had the highest predictive value, as judged from comparison with the results obtained with the source tumor (human kidney carcinoma tumor line).

  1. Effect of GFP expression on the sensitivity of glioma cell lines to photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Khatami, S.; Rendon, A.; Yoshimitsu, M.; Medin, J.; Lilge, L.

    2005-09-01

    Enhanced green fluorescent protein (EGFP)-expressing cells are customarily used in a variety of in vitro and in vivo studies and assays to ease visualization and localization. Nonetheless, the effects of EGFP expression on cellular responsivity to Photodynamic therapy (PDT), a combination therapy combining a photoactive drug and light, have yet to be characterized. To address this effect, rat astrocytoma cells (CNS-1), a lentivirus-transduced EGFP variant (CNS-1 GFP), human glioblastoma (U-87), and the transfected EGFP variant (U-87 GFP) are analyzed in terms of cell survival following PDT mediated by two different photoactive drugs. Cell survival is quantified via colony forming assays and Alamar blue assays, as a function of light dose, using the photosensitizers Photofrin (1ug ml-1 for 24h) and ALA (200ug ml-1 for 5h). Furthermore, effect of GFP expression on the responsivity to Cisplatin, a DNA-binding chemotherapeutic agent is determined for these cell lines. Our results show that EGFP expression does not affect the responsivity of Photofrin-PDT in comparison to parental cell lines (non GFP expressing cells), but does alter that of ALA-PDT. No change in responsivity is observed for Cisplatin treatment for either cell line. These results can be explained by oxidative stress induced by EGFP expression. This work will establish under which circumstances it is appropriate to use EGFP-expressing cell lines in the context of PDT preclinical research in vivo and in vitro.

  2. DIFFERENTIAL CYTOTOXIC SENSITIVITY IN MOUSE AND HUMAN CELL LINES EXPOSED TO ORGANOPHOSPHATE INSECTICIDES

    EPA Science Inventory

    Cell lines were used to examine the differential interspecies response (i.e., species selectivity) to organophosphates (OPs). aseline activities of the major target esterase i.e., cholinesterase (ChE), carboxylesterase (CbxE), neurotoxic esterase (NTE) were assayed in mouse and v...

  3. EBV and not HPV sensitizes tobacco-associated head and neck cancer cell line FaDu to radiotherapy.

    PubMed

    Anandharaj, Arunkumar; Ekshyyan, Oleksandr; Jia, Yali; Rong, Xiaohua; Harrison, Lynn; Shi, Runhua; Scott, Rona S; Nathan, Cherie-Ann O

    2016-04-01

    Conclusion EBV radiosensitized the p53 mutant tobacco associated head and neck cell line, FaDu. Objectives In the head and neck, HPV is a major risk factor associated with tonsil and base of tongue cancers, while a majority of undifferentiated nasopharyngeal cancers are positive for EBV. Clinically, head and neck tumors positive for HPV or EBV are more radiosensitive than tumors associated with tobacco and alcohol. This study aimed to evaluate whether viral infections can sensitize tobacco-associated head and neck squamous cell carcinoma cell line that harbors multiple mutations, especially TP53, to radiotherapy. Method Four FaDu cell lines (vector control - FaDu-DN; FaDu expressing HPV16 E6/E7 - FaDu-HPV; FaDu infected with EBV - FaDu-EBV; and FaDu-HPV infected with EBV - FaDu-HE) were evaluated for their radiation sensitivity using clonogenic assay. Cell cycle, protein expression, apoptosis, and cellular senescence were analyzed. Results FaDu-EBV and FaDu-HE exhibited significantly increased radiosensitivity in comparison with the control cell line. Radiation-induced cell cycle arrest was altered in all cell lines expressing viral genes. The observed distribution of cells at G1 and S phases was associated with a significant increase in expression of p21 protein along with decreased levels of pAKT/AKT and pERK/ERK ratio (p < 0.05) and increased cellular senescence (p < 0.05). PMID:26635065

  4. High sensitivity detection of NO2 employing off-axis integrated cavity output spectroscopy coupled with multiple line integrated spectroscopy

    NASA Astrophysics Data System (ADS)

    Rao, Gottipaty N.; Karpf, Andreas

    2011-05-01

    We report on the development of a new sensor for NO2 with ultrahigh sensitivity of detection. This has been accomplished by combining off-axis integrated cavity output spectroscopy (OA-ICOS) (which can provide large path lengths of the order of several km in a small volume cell) with multiple line integrated absorption spectroscopy (MLIAS) (where we integrate the absorption spectra over a large number of rotational-vibrational transitions of the molecular species to further improve the sensitivity). Employing an external cavity tunable quantum cascade laser operating in the 1601 - 1670 cm-1 range and a high-finesse optical cavity, the absorption spectra of NO2 over 100 transitions in the R-band have been recorded. From the observed linear relationship between the integrated absorption vs. concentration of NO2, we report an effective sensitivity of detection of 10 ppt for NO2. To the best of our knowledge, this is among the most sensitive levels of detection of NO2 to date. A sensitive sensor for the detection of NO2 will be helpful to monitor the ambient air quality, combustion emissions from the automobiles, power plants, aircraft and for the detection of nitrate based explosives (which are commonly used in improvised explosives (IEDs)). Additionally such a sensor would be valuable for the study of complex chemical reactions that undergo in the atmosphere resulting in the formation of photochemical smog, tropospheric ozone and acid rain.

  5. X-ray emission-line spectra of photoionized plasmas - Density sensitivity of the Fe L-shell series

    NASA Technical Reports Server (NTRS)

    Liedahl, Duane A.; Kahn, Steven M.; Osterheld, Albert L.; Goldstein, William H.

    1992-01-01

    The circumsource environments of accretion-powered X-ray sources are likely to support relatively dense (greater than 10 exp 11/cu cm) photoionized X-ray emission-line regions. The Fe L-shell ions provide a versatile class of plasma diagnostics in this regime, their multielectron structures resulting in diverse spectral phenomena. Attention is given to the spectral response of Fe L-shell ions to variations in electron density over the range 10 exp 11 to 10 exp 16/cu cm. It is found that density-sensitive line ratios exist in the wavelength interval 12-17 A for the ions Fe XVII-XXI. The prominent role of radiative recombination in the population kinetics distinguishes the density-sensitive Fe lines in photoionized plasmas from those which operate in coronal equilibrium plasmas. The results of detailed atomic modeling of these ions are presented and applications to spectroscopic observations of accretion-driven X-ray sources are discussed.

  6. Breast Cancer Cell Lines Exhibit Differential Sensitivities to Microtubule-targeting Drugs Independent of Doubling Time

    PubMed Central

    RISINGER, APRIL L.; DYBDAL-HARGREAVES, NICHOLAS F.; MOOBERRY, SUSAN L.

    2016-01-01

    Background Microtubule-targeting agents (MTAs) are a mainstay in breast cancer treatment, yet patient responses differ. The underlying mechanisms of these differences are unknown. While MTAs are mitotic inhibitors, recent evidence highlights that non-mitotic effects of these drugs can contribute to their anticancer effects. It is critical to identify the non-mitotic mechanisms that could contribute to differences among MTAs. However, it is not clear whether rapidly dividing cells in culture are optimal tools to address these mechanistic questions in interphase cells. Materials and Methods Detailed concentration response curves for five MTAs in a panel of diverse breast cancer cell lines were generated. Results Substantial differences among both drugs and cell lines, consistent with the clinical scenario, were observed. Importantly, these differences do not correlate with cell doubling time. Conclusion The interphase actions of MTAs are critical to the full spectrum of their effects in cancer cells, even in cell culture models. PMID:26504006

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

    SciTech Connect

    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/..mu..m to over 1000 keV/..mu..m. All Ataxia survival curves were exponential functions of the dose. Their radiosensitivity reached peak values at 100 to 200 keV/..mu..m. 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. Isolation and characterization of a UV-sensitive hypermutable aphidicolin-resistant Chinese hamster cell line

    SciTech Connect

    Chang, C.C.; Boezi, J.A.; Warren, S.T.; Sabourin, C.L.; Liu, P.K.; Glatzer, L.; Trosko, J.E.

    1981-01-01

    Aphidicolin is a specific inhibitor of DNA polymerase alpha and blocks DNA synthesis in vivo. The inhibition of purified alpha-polymerase has been shown to be competitive with dCTP but not with the other three deoxynucleoside triphosphates (dNTPs). In order to study the various roles that the alpha-polymerase might play in DNA replication and/or repair, we have attempted to isolate Chinese hamster V79 cells that are resistant to aphidicolin. Four resistant mutants were isolated from BrdU--black light- and UV-mutagenized cells. None of the mutants isolated contains an alpha-polymerase that is resistant, in crude extract measurements, to aphidicolin. Three mutants isolated, however, were found to be resistant to araC. Two mutants tested were found to be sensitive to cytidine and have elevated levels of dCTP or all 4 dNTPs. These results indicate that they are nucleotide pool mutants instead of alpha-polymerase mutants. One mutant, aphr-4, is characterized by the following: (1) high level of dCTP; (2) thymidine (or CdR, UdR) auxotrophic; (3) sensitive to thymidine (and AdR, GdR); (4) slow-growing; (5) cytidine sensitive; (6) UV sensitive and hypermutable at the ouabain-resistant locus; and (7) a ninefold increase in frequency of chromatid gaps and breaks when cells are exposed to BrdU-containing medium. Revertants of aphr-4 which are partially aphidicolin-resistant and retain the first three characteristics listed above, but not the others, have been isolated. The appearance of this type of revertant indicates that either aphr-4 or its ''revertant'' is a double mutant.

  9. High-pressure Xenon Gas Electroluminescent TPC Concept for Simultaneous Searches for Neutrino-less Double Beta Decay & WIMP Dark Matter

    NASA Astrophysics Data System (ADS)

    Nygren, David

    2013-04-01

    Xenon is an especially attractive candidate for both direct WIMP and 0- decay searches. Although the current trend has exploited the liquid phase, gas phase xenon offers some remarkable performance advantages for energy resolution, topology visualization, and discrimination between electron and nuclear recoils. The NEXT-100 experiment, now beginning construction in the Canfranc Underground Laboratory, Spain, will operate at 12 bars with 100 kg of ^136Xe for the 0- decay search. I will describe recent results with small prototypes, indicating that NEXT-100 can provide about 0.5% FWHM energy resolution at the decay 2457.83 keV Q-value, as well as rejection of -rays by topology. However, sensitivity goals for WIMP dark matter and 0- decay searches indicate the need for ton-scale active masses; NEXT-100 provides the springboard to reach this scale with xenon gas. I describe a scenario for performing both searches in a single high-pressure ton-scale xenon gas detector, without significant compromise to either. In addition, -- even in a single, ton-scale, high-pressure xenon gas TPC, an intrinsic sensitivity to the nuclear recoil direction may exist -- plausibly offering an advance of more than two orders of magnitude relative to current low-pressure TPC concepts. I argue that, in an era of deepening fiscal austerity, such a dual-purpose detector may be possible, at acceptable cost, within the time frame of interest, and deserves our collective attention.

  10. Dark matter sensitivity of multi-ton liquid xenon detectors

    NASA Astrophysics Data System (ADS)

    Schumann, Marc; Baudis, Laura; Bütikofer, Lukas; Kish, Alexander; Selvi, Marco

    2015-10-01

    We study the sensitivity of multi ton-scale time projection chambers using a liquid xenon target, e.g., the proposed DARWIN instrument, to spin-independent and spin-dependent WIMP-nucleon scattering interactions. Taking into account realistic backgrounds from the detector itself as well as from neutrinos, we examine the impact of exposure, energy threshold, background rejection efficiency and energy resolution on the dark matter sensitivity. With an exposure of 200 t × y and assuming detector parameters which have been already demonstrated experimentally, spin-independent cross sections as low as 2.5 × 10-49 cm2 can be probed for WIMP masses around 40 GeV/c2. Additional improvements in terms of background rejection and exposure will further increase the sensitivity, while the ultimate WIMP science reach will be limited by neutrinos scattering coherently off the xenon nuclei.

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

    PubMed Central

    Noeth, Nadine; 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 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. PMID:24366179

  12. Conformation-sensitive Raman lines of mononucleotides and their use in a structure analysis of polynucleotides: guanine and cytosine nucleotides

    NASA Astrophysics Data System (ADS)

    Nishimura, Yoshifumi; Tsuboi, Masamichi; Sato, Tomohiro; Aoki, Katsuyuki

    1986-08-01

    Raman spectra are presented for nine crystals containing the guanosine residue and ten crystals containing the cytidine residue whose conformations are known from their X-ray crystallographic analyses. A nearly complete set of assignments of all the observed Raman lines in the 1700150 cm -1 range is proposed on the basis of a previous normal coordinate treatment of guanine and cytosine with a set of force constants determined by an ab initio MO method, and on the basis of a mutual comparison of the observed spectra. A number of conformation sensitive Raman lines are found here, and several rules on the structurespectrum correlations are proposed. Raman spectral features in the 14001300 cm -1 and 700600 cm -1 ranges seem to reflect sensitively and regularly the conformation of the guanosine residue, namely its ribose-ring puckering state at the torsion angle around its glycosidic bond. A spectral feature in the 13001200 cm -1 range is found to be sensitive to the cytidine conformation. The position of a strong Raman line in the 900750 cm -1 region, on the other hand, seems to indicate a particular set of torsion angles along the P?O5'?C5'?C4'?C3'?O3' backbone. In the light of these proposed rules, the so-called B-form poly [d(G?C)]. poly[d(G?C)] in solution must have an O4' endo-anti guanosine, a C2' endo-anti cytidine, and an "alternating B" backbone as proposed by Klug [7] while its Z-form should have a C3' endo-syn guanosine, a form of cytidine in between C2' endo?C1' exo-anti cytidine, and a Z I form backbone, as defined by Wang [41].

  13. Optimizing line intercept sampling and estimation for feral swine damage levels in ecologically sensitive wetland plant communities.

    PubMed

    Thomas, Jacob F; Engeman, Richard M; Tillman, Eric A; Fischer, Justin W; Orzell, Steve L; Glueck, Deborah H; Felix, Rodney K; Avery, Michael L

    2013-03-01

    Ecological sampling can be labor intensive, and logistically impractical in certain environments. We optimize line intercept sampling and compare estimation methods for assessing feral swine damage within fragile wetland ecosystems in Florida. Sensitive wetland sites, and the swine damage within them, were mapped using GPS technology. Evenly spaced parallel transect lines were simulated across a digital map of each site. The length of each transect and total swine damage under each transect were measured and percent swine damage within each site was estimated by two methods. The total length method (TLM) combined all transects as a single long transect, dividing the sum of all damage lengths across all transects by the combined length of all transect lines. The equal weight method (EWM) calculated the damage proportion for each transect line and averaged these proportions across all transects. Estimation was evaluated using transect spacings of 1, 3, 5, 10, 15, and 20 m. Based on relative root mean squared error and relative bias measures, the TLM produced higher quality estimates than EWM at all transect spacings. Estimation quality decreased as transect spacing increased, especially for TLM. Estimation quality also increased as the true proportion of swine damage increased. Diminishing improvements in estimation quality as transect spacings decreased suggested 5 m as an optimal tradeoff between estimation quality and labor. An inter-transect spacing of 5 m with TLM estimation appeared an optimal starting point when designing a plan for estimating swine damage, with practical, logistical, economic considerations determining final design details. PMID:22707203

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

    PubMed Central

    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

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

    PubMed

    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

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

    PubMed Central

    Rossi, Alejandra; Parada, Francisco J.; Latinus, Marianne; Puce, Aina

    2015-01-01

    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. PMID:25914636

  17. Correlation between potassium channel expression and sensitivity to drug-induced cell death in tumor cell lines.

    PubMed

    Leanza, Luigi; O'Reilly, Paul; Doyle, Anne; Venturini, Elisa; Zoratti, Mario; Szegezdi, Eva; Szabo, Ildiko

    2014-01-01

    Plasma membrane (PM) and mitochondrial (mt) ion channels - particularly potassium channels - became oncological targets soon after the discovery that they are involved both in the regulation of proliferation and apoptosis. Some members of the Kv Shaker family, namely Kv1.1, Kv1.3, Kv1.5 and Kv11.1 (Herg), and the intermediate-conductance calcium-activated potassium KCa3.1 (IK) channels have been shown to contribute to apoptosis in various cell lines. Kv1.3, Kv1.5 and IK are located in the plasma membrane but also in the mitochondrial inner membrane, where they participate in apoptotic signalling. Interestingly, an altered protein expression of some of the channels mentioned above has been reported in neoplastic cell lines/tissues, but a systematic quantification addressing the protein expression of the above potassium channels in tumor cell lines of different origin has not been carried out yet. In the present study we investigated whether expression of specific potassium channels, at the mRNA and protein level, can be correlated with cell sensitivity to various apoptotic stimuli, including chemotherapeutic drugs, in a panel of cancer cell lines. The results show correlation between the protein expression of the Kv1.1 and Kv1.3 channels and susceptibility to death upon treatment with staurosporine, C2-ceramide and cisplatin. Furthermore, we investigated the correlation between Kv channel expression and sensitivity to three distinct membrane-permeant Kv1.3 inhibitors, since these drugs have recently been shown to be able to induce apoptosis and also reduce tumor volume in an in vivo model. Higher protein expression of Kv1.3 significantly correlated with lower cell survival upon treatment with clofazimine, one of the Kv1.3 inhibitors. These results suggest that expression of Kv1.1 and Kv1.3 sensitizes tumour cells of various origins to cytotoxins. Data reported in this work regarding potassium channel protein expression in different cancer cell lines may be exploited for pharmacological manipulation aiming to affect proliferation/apoptosis of cancer cells. PMID:23701546

  18. The sensitivity limitation by the recording ADC to Laser Fiducial Line and Precision Laser Inclinometer

    NASA Astrophysics Data System (ADS)

    Batusov, V.; Budagov, J.; Lyablin, M.; Shirkov, G.; Gayde, J.-Ch.; Mergelkuhl, D.

    2015-12-01

    For metrology set-ups using a laser beam (The Laser Fiducial Line, the Precision Laser Inclinometer) the recording noise has been determined. This noise is limiting the measurement precision of the beam displacement Δ x and consequently the precision Δψ of measurement of the beam inclination angle. For a 10 mm laser beam diameter the Δ x = ±2.9 × 10-9 m has been obtained. For a one-mode laser beam with a primary diameter of 10 mm and with subsequent focusing a value of Δψ = ±1.7 × 10-11 rad has been found.

  19. Identification and pharmacological characterization of sarcolemmal ATP-sensitive potassium channels in the murine atrial HL-1 cell line.

    PubMed

    Fox, Jocelyn E Manning; Jones, Lynn; Light, Peter E

    2005-01-01

    Activation of ATP-sensitive potassium (KATP) channels is known to have cardioprotective effects during periods of ischemia and reperfusion, making these channels important targets for clinical drug discovery. Using electrophysiological techniques we identify KATP channels in a mouse atrial cell line (HL-1). HL-1 KATP channels exhibited a concentration-dependent inhibition by ATP (IC50 = 23.3 +/- 3.2 microM), a unitary single-channel conductance of 55 pS, and sensitivity to the isoform-specific KATP channel opener P1075 and inhibitor HMR1098. Adenoviral infection of a dominant-negative Kir6.2 subunit significantly reduced the P1075-sensitive sarcKATP current. Taken together, the data indicate that HL-1 KATP channels are composed of sulfonylurea receptor isoform SUR2A coupled to the pore-forming Kir6.2 subunit--the molecular makeup of sarcKATP channels found in native cardiac myocytes. Pharmacological activation of HL-1 cell KATP channels also resulted in action potential shortening. Using the membrane potential-sensitive dye DiBac4(3), we demonstrated that the sarcKATP channel opener P1075 (20 microM) produced a concentration-dependent hyperpolarization of a monolayer of HL-1 cells that could be reversed by channel inhibition with HMR1098 (20 microM). We conclude that the HL-1 cells are an excellent cell line for studying cardiac sarcKATP channels, and these cells may also provide an important tool for the testing of novel pharmacological modulators of KATP channels in fluorescence-based assays. PMID:15613976

  20. Electron density-sensitive line ratios for Fe XII in the solar corona

    NASA Technical Reports Server (NTRS)

    Tayal, S. S.; Henry, Ronald J. W.

    1988-01-01

    The collision strengths for electron-impact excitation of fine-structure transitions from the ground 3s23p3 configuration to the excited 3s3p4 configuration in Fe XII are presented. These are calculated by transforming the K-matrices obtained in a nonrelativistic R-matrix method to K-matrices in intermediate coupling using term-coupling coefficients which take into account the effect of breakdown of target LS coupling. Extensive configuration-interaction wave functions are used to represent the target states. The effective collision strengths are determined assuming a Maxwellian distribution of electron energies. Rydberg series of resonances converging to the excited state thresholds are explicitly included in the calculation. The relative level populations and emission-line strengths for Fe XII are calculated using the new atomic data presented in this paper and that published by Tayal, Henry, and Pradhan (1987) and Tayal and Henry (1986) over a wide range of electron densities and temperatures (1-2 x 10 to the 6th K). Present results for collision strengths and emission-line strengths are compared with the previous calculation of Flower (1977). Some significant differences are noted.

  1. Simultaneous generation of WIMP miracle-like densities of baryons and dark matter

    NASA Astrophysics Data System (ADS)

    McDonald, John

    2011-11-01

    The observed density of dark matter is of the magnitude expected for a thermal relic weakly-interacting massive particle (WIMP). In addition, the observed baryon density is within an order of magnitude of the dark matter density. This suggests that the baryon density is physically related to a typical thermal relic WIMP dark matter density. We present a model which simultaneously generates thermal relic WIMP-like densities for both baryons and dark matter by modifying a large initial baryon asymmetry. Dark matter is due to O(100) GeV gauge singlet scalars produced in the annihilation of the O(TeV) colored scalars which are responsible for the final thermal WIMP-like baryon asymmetry. The requirement of no baryon washout implies that there are two gauge singlet scalars. The low-temperature transfer of the asymmetry to conventional baryons can be understood if the long-lived O(TeV) colored scalars have large hypercharge, |Y|>4/3. Production of such scalars at the LHC would be a clear signature of the model.

  2. The effects of QCD equation of state on the relic density of WIMP dark matter

    SciTech Connect

    Drees, Manuel; Hajkarim, Fazlollah; Schmitz, Ernany Rossi

    2015-06-12

    Weakly Interactive Massive Particles (WIMPs) are the most widely studied candidate particles forming the cold dark matter (CDM) whose existence can be inferred from a wealth of astrophysical and cosmological observations. In the framework of the minimal cosmological model detailed measurements on the cosmic microwave background by the PLANCK collaboration fix the scaled CDM relic density to Ω{sub c}h{sup 2}=0.1193±0.0014, with an error of less than 1.5%. In order to fully exploit this observational precision, theoretical calculations should have a comparable or smaller error. In this paper we use recent lattice QCD calculations to improve the description of the thermal plasma. This affects the predicted relic density of “thermal WIMPs”, which once were in chemical equilibrium with Standard Model particles. For WIMP masses between 3 and 15 GeV, where QCD effects are most important, our predictions differ from earlier results by up to 9% (12%) for pure S-wave (P-wave) annihilation. We use these results to compute the thermally averaged WIMP annihilation cross section that reproduces the correct CDM relic density, for WIMP masses between 0.1 GeV and 10 TeV.

  3. Towards Detection of Low Mass WIMPs (MWIMP<10 GeV/c2): Mini-Review

    NASA Astrophysics Data System (ADS)

    Drukier, A. K.; Nussinov, S.

    2013-10-01

    Weakly Interacting Massive Particles (WIMPs) may constitute most of the matter in the Universe. There are intriguing results from DAMA/LIBRA, CoGeNT and CRESST-II, and more recently CDMS-Si suggesting a relatively light dark matter candidate of mass <10 GeV/c2. At the same time, experiments using heavy nuclear targets such as CDMS-Ge and XENON detectors suggest that there is no DM candidates with MW>15 GeV/c2. We review the existing experiments and the problems associated with light mass WIMP detection. We find that all six experiments considered (DAMA, CoGeNT, CRESST, CDMS-Si, CDMS-Ge, XENON) are consistent if one assumes that the mass of WIMP is lower than expected: 3.4WIMPs.

  4. Prediction of skin sensitization potency of chemicals by human Cell Line Activation Test (h-CLAT) and an attempt at classifying skin sensitization potency.

    PubMed

    Nukada, Yuko; Ashikaga, Takao; Miyazawa, Masaaki; Hirota, Morihiko; Sakaguchi, Hitoshi; Sasa, Hitoshi; Nishiyama, Naohiro

    2012-10-01

    The human Cell Line Activation Test (h-CLAT), an in vitro skin sensitization test, is based on the augmentation of CD86 and CD54 expression in THP-1 cells following exposure to chemicals. The h-CLAT was found to be capable of determining the hazard of skin sensitization. In contrast, the local lymph node assay (LLNA), widely used as a stand-alone method in Europe and US, identifies the same hazard, but also classifies the potency by using the estimated concentration of SI=3 (EC3). In this study, several values calculated from the h-CLAT data were evaluated for its correlation to the LLNA EC3 determination. A statistically significant correlation was observed between h-CLAT concentration providing a cell viability of 75% (CV75), h-CLAT estimated concentration of RFI=150 for CD86 (EC150), and for CD54 (EC200) with LLNA's EC3. From EC150 and EC200, a minimum induction threshold (MIT) was determined as the smaller of either EC150 or EC200. MIT showed a correlation with EC3 (R=0.638). Also, MIT had an approximate 80% accuracy for sub-categories of the globally harmonized system (GHS) when a tentative threshold of 13 ?g/mL was used. From these data, the h-CLAT values may be one of the useful tools to predict the allergic potency of chemicals. PMID:22796097

  5. Generalization of the slip line field theory for temperature sensitive visco-plastic materials

    NASA Astrophysics Data System (ADS)

    Paesold, Martin; Peters, Max; Regenauer-Lieb, Klaus; Veveakis, Manolis; Bassom, Andrew

    2015-04-01

    Geological processes can be a combination of various effects such as heat production or consumption, chemical reactions or fluid flow. These individual effects are coupled to each other via feedbacks and the mathematical analysis becomes challenging due to these interdependencies. Here, we concentrate solely on thermo-mechanical coupling and a main result of this work is that the coupling can depend on material parameters and boundary conditions and the coupling is more or less pronounced depending on theses parameters. The transitions from weak to strong coupling can be studied in the context of a bifurcation analysis. classically, Material instabilities in solids are approached as material bifurcations of a rate-independent, isothermal, elasto-plastic solid. However, previous research has shown that temperature and deformation rate are important factors and are fully coupled with the mechanical deformation. Early experiments in steel revealed a distinct pattern of localized heat dissipation and plastic deformation known as heat lines. Further, earth materials, soils, rocks and ceramics are known to be greatly influenced by temperature with strain localization being strongly affected by thermal loading. In this work, we provide a theoretical framework for the evolution of plastic deformation for such coupled systems, with a two-pronged approach to the prediction of localized failure. First, slip line field theory is employed to predict the geometry of the failure patterns and second, failure criteria are derived from an energy bifurcation analysis. The bifurcation analysis is concerned with the local energy balance of a material and compares the effects of heat diffusion terms and heat production terms where the heat production is due to mechanical processes. Commonly, the heat is produced locally along the slip lines and if the heat production outweighs diffusion the material is locally weakened which eventually leads to failure. The effect of diffusion and heat production is captured by a dimensionless quantity, the Gruntfest number, and only if the Gruntfest number is larger than a critical value localized failure occurs. This critical Gruntfest number depends on boundary conditions such as temperature or pressure and hence this critical value gives rise to localization criteria. We find that the results of this approach agree with earlier contributions to the theory of plasticity but gives the advantage of a unified framework which might prove useful in numerical schemes for visco-plasticity.

  6. Combining solid-phase microextraction and on-line preconcentration-capillary electrophoresis for sensitive analysis of pesticides in foods.

    PubMed

    Hernández-Borges, Javier; Cifuentes, Alejandro; García-Montelongo, Francisco J; Rodríguez-Delgado, Miguel A

    2005-02-01

    The combined use of solid-phase microextraction (SPME) and different on-line preconcentration strategies for ultrasensitive capillary electrophoresis-ultraviolet (CE-UV) analysis of five pesticides in a single run is investigated. Normal stacking mode (NSM), field-enhanced sample injection (FESI), and stacking with matrix removal (SWMR) are explored to increase the sensitivity of the CE-UV analysis of a selected group of pesticides (cyprodinil, cyromazine, pyrifenox, pirimicarb, and pyrimethanil). It could be observed that reverse polarity-stacking with matrix removal (RP-SWMR) provided the best results in terms of sensitivity (enhancement was up to 272-fold compared with normal injection). The separation buffer consisted of 0.4 mM cetyltrimethylammonium chloride (CTAC), 0.4 M acetic acid at pH 4 containing 5% v / v 2-propanol. This approach was then combined with SPME to determine the pesticides in water, apple, and orange juice. The combination of both preconcentration procedures allowed the determination of these pesticides at concentrations down to 2.5 microg / L in water and 3.1 microg / L in juices (i.e., levels well below the maximum residue limits allowed for these compounds). To our knowledge, this is the first report showing the great possibilities of the combined use of SPME, on-line sample preconcentration, and CE for pesticide analysis. PMID:15714540

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

    PubMed

    Heidegger, Simon; Jarosch, Alexander; Schmickl, Martina; Endres, Stefan; Bourquin, Carole; Hotz, Christian

    2015-01-01

    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. PMID:26565413

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

    PubMed Central

    Heidegger, Simon; Jarosch, Alexander; Schmickl, Martina; Endres, Stefan; Bourquin, Carole; Hotz, Christian

    2015-01-01

    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. PMID:26565413

  9. Klotho Sensitizes Human Lung Cancer Cell Line to Cisplatin via PI3k/Akt Pathway

    PubMed Central

    Wang, Yan; Chen, Lei; Huang, Guochang; He, Dongmei; He, Juan; Xu, Wei; Zou, Chunying; Zong, Feng; Li, Yan; Chen, Bo; Wu, Shuanshuan; Zhao, Weihong; Wu, Jianqing

    2013-01-01

    Klotho was first identified in 1997 and has been considered as an anti-aging gene. Emerging evidence demonstrates that klotho has a close relationship with cancers, including lung cancer, breast cancer, etc, by inhibiting the proliferation and promoting apoptosis of cancer cells. Cisplatin has been the most widely used drug in the first-line chemotherapy. However, the increase in cisplatin-resistant cancer cells has become a major obstacle in clinical management of cancers. In our study, we for the first time demonstrated that klotho could attenuate the resistance of lung cancer to cisplatin based chemotherapy and the apoptosis of the resistant cells with klotho overexpression was markedly increased. However, klotho knockdown cells showed enhanced resistance to chemotherapy. Further analysis showed that inhibition of PI3K/Akt pathway with specific inhibitor (LY294002) attenuated the promotive effects on cancer growth following interfering with klotho shRNA. Moreover, we demonstrated that klotho modulated the resistance to cisplatin in a xenograft nude mice model. These observations suggested that klotho could improve the resistance of lung cancer cells to chemotherapy and may serve as a potential target for the gene therapy of lung cancers resistant to cisplatin based chemotherapy. PMID:23437382

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

    PubMed Central

    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 visual task as the EEG was recorded. A significantly larger visual Mismatch Negativity (vMMN) was observed for Chinese vs. 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 vs. 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. PMID:26074808

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

    PubMed Central

    Yang, Liming; Jiang, Tingbo; Fountain, Jake C.; Scully, Brian T.; Lee, Robert D.; Kemerait, Robert C.; Chen, Sixue; Guo, Baozhu

    2014-01-01

    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. PMID:25334062

  12. Metabolic characteristics of a human hepatoma cell line stably transfected with hormone-sensitive lipase.

    PubMed Central

    Pease, R J; Wiggins, D; Saggerson, E D; Tree, J; Gibbons, G F

    1999-01-01

    Clones of HepG2 cells were selected that stably express the cDNA for hormone-sensitive lipase (HSL). When cells were cultured in the presence of labelled extracellular oleate, accumulation of labelled fatty acid as cellular triacylglycerol (TAG) was significantly lower in the transfectants compared with the wild-type cells. There was no change in the net rate of phospholipid (PL) synthesis. Culture of cells containing isotopically prelabelled TAG resulted in a greater net loss of TAG from the transfected cells than from the wild-type cells. The excess loss of labelled TAG was primarily due to an increased TAG fatty acid oxidation. Free fatty acid release into the medium was not increased in the transfectants, nor was the very low rate of lipoprotein lipid secretion. Also, there was no increased net trafficking of fatty acids from TAG into PLs. Changes in the 3H:14C ratio of TAG prelabelled with [3H]glycerol and [14C]oleate suggested that none of excess TAG fatty acid released in the transfected cells underwent intracellular re-esterification to TAG prior to oxidation. The results suggest that fatty acids mobilized by HSL are directed immediately into the oxidative pathway and are not available for biosynthetic processes. It appears likely, therefore, that intracellular TAG-derived fatty acids which enter the oxidative pathway exist in a different compartment from those that are directed towards synthesis. PMID:10393105

  13. Inhibition of mTOR promotes hyperthermia sensitivity in SMMC-7721 human hepatocellular carcinoma cell line

    PubMed Central

    WANG, QING-LIANG; LIU, BO; LI, XIAO-JIE; HU, KUN-PENG; ZHAO, KUN; YE, XIAO-MING

    2016-01-01

    The mammalian target of rapamycin (mTOR) is a critical mediator of the phosphoinositide 3-kinase/protein kinase B/mTOR signaling pathway, and mTOR activity is induced following heat shock. Thermotherapy is used to treat hepatocellular carcinoma (HCC). However, the role of mTOR in modulating thermosensitivity in HCC has yet to be elucidated. In the present study, the antisense plasmid pEGFP-C1-mTOR was transfected into SMMC-7721 cells, and the expression levels of mTOR were analyzed by reverse transcription-polymerase chain reaction and western blot analysis. The thermal responses of the transfected cells were also examined. The results revealed that SMMC-7721 cells were sensitive to heat treatment, and cell viability was significantly inhibited following hyperthermia treatment (P<0.01). The mRNA and protein expression levels of mTOR decreased post-transfection. Cell proliferation, colony-forming ability and motility were all significantly decreased following hyperthermia treatment in the transfected cells. Flow cytometry analysis demonstrated that apoptosis was significantly increased following treatment (P<0.01). The number of cells in S phase was increased, and the cell cycle was arrested in S phase. In conclusion, inhibition of mTOR increased the thermosensitivity of SMMC-7721 cells by increasing cellular apoptosis and inducing S phase arrest. PMID:26998020

  14. Insecticide sensitivity of native chloride and sodium channels in a mosquito cell line.

    PubMed

    Jenson, Lacey J; Anderson, Troy D; Bloomquist, Jeffrey R

    2016-06-01

    The aim of this study was to investigate the utility of cultured Anopheles gambiae Sua1B cells for insecticide screening applications without genetic engineering or other treatments. Sua1B cells were exposed to the known insecticidal compounds lindane and DIDS, which inhibited cell growth at micromolar concentrations. In patch clamp studies, DIDS produced partial inhibition (69%) of chloride current amplitudes, and an IC50 of 5.1μM was determined for Sua1B cells. A sub-set of chloride currents showed no response to DIDS; however, inhibition (64%) of these currents was achieved using a low chloride saline solution, confirming their identity as chloride channels. In contrast, lindane increased chloride current amplitude (EC50=116nM), which was reversed when cells were bathed in calcium-free extracellular solution. Voltage-sensitive chloride channels were also inhibited by the presence of fenvalerate, a type 2 pyrethroid, but not significantly blocked by type 1 allethrin, an effect not previously shown in insects. Although no evidence of fast inward currents typical of sodium channels was observed, studies with fenvalerate in combination with veratridine, a sodium channel activator, revealed complete inhibition of cell growth that was best fit by a two-site binding model. The high potency effect was completely inhibited in the presence of tetrodotoxin, a specific sodium channel blocker, suggesting the presence of some type of sodium channel. Thus, Sua1B cells express native insect ion channels with potential utility for insecticide screening. PMID:27155485

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

    PubMed Central

    Hofmann, Ute; Priem, Melanie; Bartzsch, Christine; Winckler, Thomas; Feller, Karl-Heinz

    2014-01-01

    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. PMID:24967604

  16. A sensitive sensor cell line for the detection of oxidative stress responses in cultured human keratinocytes.

    PubMed

    Hofmann, Ute; Priem, Melanie; Bartzsch, Christine; Winckler, Thomas; Feller, Karl-Heinz

    2014-01-01

    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. PMID:24967604

  17. Relationships between Signaling Pathway Usage and Sensitivity to a Pathway Inhibitor: Examination of Trametinib Responses in Cultured Breast Cancer Lines

    PubMed Central

    Leung, Euphemia Y.; Kim, Ji Eun; Askarian-Amiri, Marjan; Rewcastle, Gordon W.; Finlay, Graeme J.; Baguley, Bruce C.

    2014-01-01

    Cellular signaling pathways involving mTOR, PI3K and ERK have dominated recent studies of breast cancer biology, and inhibitors of these pathways have formed a focus of numerous clinical trials. We have chosen trametinib, a drug targeting MEK in the ERK pathway, to address two questions. Firstly, does inhibition of a signaling pathway, as measured by protein phosphorylation, predict the antiproliferative activity of trametinib? Secondly, do inhibitors of the mTOR and PI3K pathways synergize with trametinib in their effects on cell proliferation? A panel of 30 human breast cancer cell lines was chosen to include lines that could be classified according to whether they were ER and PR positive, HER2 over-expressing, and “triple negative”. Everolimus (targeting mTOR), NVP-BEZ235 and GSK2126458 (both targeting PI3K/mTOR) were chosen for combination experiments. Inhibition of cell proliferation was measured by IC50 values and pathway utilization was measured by phosphorylation of signaling kinases. Overall, no correlation was found between trametinib IC50 values and inhibition of ERK signaling. Inhibition of ERK phosphorylation was observed at trametinib concentrations not affecting proliferation, and sensitivity of cell proliferation to trametinib was found in cell lines with low ERK phosphorylation. Evidence was found for synergy between trametinib and either everolimus, NVP-BEZ235 or GSK2126458, but this was cell line specific. The results have implications for the clinical application of PI3K/mTOR and MEK inhibitors. PMID:25170609

  18. A comparative study of glycoproteomes in androgen-sensitive and -independent prostate cancer cell lines.

    PubMed

    Drabik, Anna; Ciołczyk-Wierzbicka, Dorota; Dulińska-Litewka, Joanna; Bodzoń-Kułakowska, Anna; Suder, Piotr; Silberring, Jerzy; Laidler, Piotr

    2014-01-01

    Prostate cancer is one of the most common malignancies in men and is predicted to be the second leading cause of cancer-related deaths. After 6-18 months, hormone ablation treatment results in androgen-independent growth of cancer cells, metastasis and progression. The mechanism of androgen-independent growth of prostatic carcinoma cells is still unknown. Identification of factors that facilitate the transition from androgen-dependent to independent states is crucial in designing future diagnostics and medication strategies. To understand the biochemical meaning of hormone dependency deprivation, glycoproteins enriched profiles were compared between DU145 (hormone non-responding) and LNCaP (hormone responding) prostate cancer cells. These results allow for anticipation on the important role of glycosylation in malignant transformation. Both Tn antigen and complex antennary N-oligosaccharides were recognized. Their occurrence might be involved in the development and progression of tumor, and failure of hormone ablation therapy. Among identified proteins in androgen-sensitive cells nucleolin (P19338) was found that is widely described as apoptosis inhibitor, and also transporter of molecules from the membrane to the cytoplasm or nucleus. In addition, 14-3-3 protein family (P27348, P31946, P61981, P63104, P62258, Q04917, and P31947) was investigated across available databases as it forms stable complexes with glycoproteins. Our studies indicate that isoforms: sigma and eta were found in androgen-dependent prostate cancer cells, while other isoforms were present in androgen non-responding cells. 14-3-3 binding partners are involved in cancer pathogenesis. These findings may contribute to a better understanding of prostate cancer tumorigenesis and to a more efficient prognosis and individual therapy in a future. However, it still remains to be revealed how important those changes are for androgen dependency loss in prostate cancer patients carried out on clinically relevant populations. PMID:24104455

  19. Upregulation of microRNA-451 increases cisplatin sensitivity of non-small cell lung cancer cell line (A549)

    PubMed Central

    2011-01-01

    Background Recently, miR-451 as a tumor suppressor has been reported in other studies. However, whether miR-451 can affect the sensitivity of non-small cell lung cancer (NSCLC) cells to cisplatin (DDP) remains unclear. The aim of this study is to evaluate the roles of miR-451 in the sensitivity of NSCLC cells to DDP. Methods Quantitative RT-PCR assay was performed to detect the expression of miR-451 in 10 pairs of NSCLC and noncancerous tissue samples. pcDNA-GW/EmGFP-miR-451 was stably transfected into NSCLC cell line (A549). Then, the effects of miR-451 upregulation on growth, colony formation and apoptosis of A549 cells were investigated. Finally, the effects of miR-451 upregulation on in vitro and in vivo sensitivity of A549 cells of DDP were also determined. Results The level of miR-451 expression in NSCLC tissues was significantly higher than that in corresponding noncancerous tissues. Ectopic overexpression of miR-451 could significantly inhibit growth and induce apoptosis of A549 cells. Moreover, ectopic overexpression of miR-451 could sensitize A549 cells to DDP possibly by increasing DDP-induced apoptosis which might be associated with the inactivation of Akt signaling pathway. Conclusions This study demonstrated for the first time that combination of DDP application with miR-451 upregulation might be a potential strategy for the treatment of human NSCLC. PMID:21329503

  20. Integrating data on DNA copy number with gene expression levels and drug sensitivities in the NCI-60 cell line panel

    PubMed Central

    Bussey, Kimberly J.; Chin, Koei; Lababidi, Samir; Reimers, Mark; Reinhold, William C.; Kuo, Wen-Lin; Gwadry, Fuad; Ajay; Kouros-Mehr, Hosein; Fridlyand, Jane; Jain, Ajay; Collins, Colin; Nishizuka, Satoshi; Tonon, Giovanni; Roschke, Anna; Gehlhaus, Kristen; Kirsch, Ilan; Scudiero, Dominic A.; Gray, Joe W.; Weinstein, John N.

    2009-01-01

    Chromosome rearrangement, a hallmark of cancer, has profound effects on carcinogenesis and tumor phenotype. We used a panel of 60 human cancer cell lines (the NCI-60) as a model system to identify relationships among DNA copy number, mRNA expression level, and drug sensitivity. For each of 64 cancer-relevant genes, we calculated all 4,096 possible Pearson's correlation coefficients relating DNA copy number (assessed by comparative genomic hybridization using bacterial artificial chromosome microarrays) and mRNA expression level (determined using both cDNA and Affymetrix oligonucleotide microarrays). The analysis identified an association of ERBB2 overexpression with 3p copy number, a finding supported by data from human tumors and a mouse model of ERBB2-induced carcinogenesis. When we examined the correlation between DNA copy number for all 353 unique loci on the bacterial artificial chromosome microarray and drug sensitivity for 118 drugs with putatively known mechanisms of action, we found a striking negative correlation ( −0.983; 95% bootstrap confidence interval, −0.999 to −0.899) between activity of the enzyme drug L-asparaginase and DNA copy number of genes near asparagine synthetase in the ovarian cancer cells. Previous analysis of drug sensitivity and mRNA expression had suggested an inverse relationship between mRNA levels of asparagine synthetase and L-asparaginase sensitivity in the NCI-60. The concordance of pharmacogenomic findings at the DNA and mRNA levels strongly suggests further study of L-asparaginase for possible treatment of a low-synthetase subset of clinical ovarian cancers. The DNA copy number database presented here will enable other investigators to explore DNA transcript-drug relationships in their own domains of research focus. PMID:16648555

  1. Off-line simulation of the Amazon water balance: a sensitivity study with implications for GSWP

    NASA Astrophysics Data System (ADS)

    Chapelon, N.; Douville, H.; Kosuth, P.; Oki, T.

    2002-03-01

    As a first step of the international Global Soil Wetness Project (GSWP), several state-of-the-art land surface models were recently forced by 1° × 1° atmospheric analyses and observations to obtain global soil moisture climatologies over the 1987-1988 period. Besides the 6-hourly atmospheric forcing, the models also used common boundary conditions (soil and vegetation parameters), also drawn from the ISLSCP Initiative I dataset. While very few in situ observations are available to validate the soil moisture fields, the simulated runoff can be compared with river discharge measurements. This strategy is employed here to assess the quality of GSWP simulations based on the ISBA land surface model. The ISBA runoff is transformed into 1° × 1° gridded stream flows by using the TRIP river routing model. The focus is on the Amazon basin where all models participating in GSWP showed a strong underestimation in the annual runoff and a significant lag in the annual cycle of the runoff. A sample of 31 gauging stations is selected to validate the gridded runoff simulated by ISBA. Sensitivity tests have been performed, that suggest that deficiencies in both the precipitation forcing and the boundary conditions provided by ISLSCP contribute to the poor simulation of the Amazon water balance. The use of alternative precipitation, soil and vegetation datasets allows ISBA to produce a more realistic annual runoff, although the amplitude of the annual cycle remains exaggerated at the downstream gauging station of Obidos. Among these experiments, the simulation leading to the best annual runoff has been used as a reference to test simple modifications in the TRIP river routing model. Tuning the parameters of TRIP or increasing the resolution of the river channel network is not sufficient to improve the annual cycle of the simulated discharge. New developments are necessary to deal more explicitly with the floodplain inundation that occurs during the rainy season over the Amazon basin, and to derive a geographically variable and time-evolving stream flow velocity. In future, considerable efforts are needed to provide more reliable global land surface and forcing datasets in the continuation of GSWP, in order to validate more efficiently the land surface models and thereby to produce more realistic soil moisture climatologies.

  2. Enhanced sensitivity of Raman spectroscopy for tritium gas analysis using a metal-lined hollow glass fiber

    SciTech Connect

    Rupp, S.; Schloesser, M.; Bornschein, B.; James, T.M.; Telle, H.H.

    2015-03-15

    The precise compositional analysis of tritium-containing gases is of high interest for tritium accountancy in future fusion power plants. Raman spectroscopy provides a fast and contact-free gas analysis procedure with high precision, thus being an advantageous tool for the named purpose. In this paper, it is shown that the sensitivity achieved with conventional Raman systems (in 90 degrees or forward/backward configurations) can be enhanced by at least one order of magnitude by using a metal-lined hollow glass fiber as the Raman cell. This leads to the ability of detecting low partial pressures of tritium within short measurement intervals (< 0.5 mbar in < 0.5 s) opening the way for real-time applications.

  3. MultiNotch MS3 enables accurate, sensitive, and multiplexed detection of differential expression across cancer cell line proteomes.

    PubMed

    McAlister, Graeme C; Nusinow, David P; Jedrychowski, Mark P; Wühr, Martin; Huttlin, Edward L; Erickson, Brian K; Rad, Ramin; Haas, Wilhelm; Gygi, Steven P

    2014-07-15

    Multiplexed quantitation via isobaric chemical tags (e.g., tandem mass tags (TMT) and isobaric tags for relative and absolute quantitation (iTRAQ)) has the potential to revolutionize quantitative proteomics. However, until recently the utility of these tags was questionable due to reporter ion ratio distortion resulting from fragmentation of coisolated interfering species. These interfering signals can be negated through additional gas-phase manipulations (e.g., MS/MS/MS (MS3) and proton-transfer reactions (PTR)). These methods, however, have a significant sensitivity penalty. Using isolation waveforms with multiple frequency notches (i.e., synchronous precursor selection, SPS), we coisolated and cofragmented multiple MS2 fragment ions, thereby increasing the number of reporter ions in the MS3 spectrum 10-fold over the standard MS3 method (i.e., MultiNotch MS3). By increasing the reporter ion signals, this method improves the dynamic range of reporter ion quantitation, reduces reporter ion signal variance, and ultimately produces more high-quality quantitative measurements. To demonstrate utility, we analyzed biological triplicates of eight colon cancer cell lines using the MultiNotch MS3 method. Across all the replicates we quantified 8,378 proteins in union and 6,168 proteins in common. Taking into account that each of these quantified proteins contains eight distinct cell-line measurements, this data set encompasses 174,704 quantitative ratios each measured in triplicate across the biological replicates. Herein, we demonstrate that the MultiNotch MS3 method uniquely combines multiplexing capacity with quantitative sensitivity and accuracy, drastically increasing the informational value obtainable from proteomic experiments. PMID:24927332

  4. MultiNotch MS3 Enables Accurate, Sensitive, and Multiplexed Detection of Differential Expression across Cancer Cell Line Proteomes

    PubMed Central

    2015-01-01

    Multiplexed quantitation via isobaric chemical tags (e.g., tandem mass tags (TMT) and isobaric tags for relative and absolute quantitation (iTRAQ)) has the potential to revolutionize quantitative proteomics. However, until recently the utility of these tags was questionable due to reporter ion ratio distortion resulting from fragmentation of coisolated interfering species. These interfering signals can be negated through additional gas-phase manipulations (e.g., MS/MS/MS (MS3) and proton-transfer reactions (PTR)). These methods, however, have a significant sensitivity penalty. Using isolation waveforms with multiple frequency notches (i.e., synchronous precursor selection, SPS), we coisolated and cofragmented multiple MS2 fragment ions, thereby increasing the number of reporter ions in the MS3 spectrum 10-fold over the standard MS3 method (i.e., MultiNotch MS3). By increasing the reporter ion signals, this method improves the dynamic range of reporter ion quantitation, reduces reporter ion signal variance, and ultimately produces more high-quality quantitative measurements. To demonstrate utility, we analyzed biological triplicates of eight colon cancer cell lines using the MultiNotch MS3 method. Across all the replicates we quantified 8 378 proteins in union and 6 168 proteins in common. Taking into account that each of these quantified proteins contains eight distinct cell-line measurements, this data set encompasses 174 704 quantitative ratios each measured in triplicate across the biological replicates. Herein, we demonstrate that the MultiNotch MS3 method uniquely combines multiplexing capacity with quantitative sensitivity and accuracy, drastically increasing the informational value obtainable from proteomic experiments. PMID:24927332

  5. Reduced metabotropic glutamate receptor 5 in the Flinders Sensitive Line of rats, an animal model of depression: An autoradiographic study

    PubMed Central

    Kovačević, Tomislav; Skelin, Ivan; Minuzzi, Luciano; Rosa-Neto, Pedro; Diksic, Mirko

    2013-01-01

    Depression is a brain disorder and there is still only a partial understanding of its underlying pathophysiology. Antidepressant medications with a fast onset have not yet been developed. In addition to the monoaminergic systems, the brain glutaminergic system has been implicated in the etiology of depression. Animal studies of depression have gained importance because they permit a more invasive manipulation of the subjects than human studies. In the present study, we measured the densities of the brain regional metabotropic glutaminergic receptor 5 (mGluR5) in the Flinders Sensitive Line (FSL) rat model of depression and two groups of control rats, the Flinders Resistant Line (FRL) and Sprague Dawley (SPD), the parent strain for both the FSL and FRL rats. The FSL rats showed lower densities of mGluR5 in many brain regions compared to either the SPD and/or FRL rats. In addition, the densities in the FRL rats were larger than in the SPD rats, suggesting possible problems in using FRL rats as controls. The presented data suggest that mGluR5 is lower in animal models of depression which could be related to the cognitive and emotional dysfunctions in the FSL rat model of depression and could be relevant to a better understanding of depression in humans. PMID:22310150

  6. Sensitive simultaneous determination of three sulfanilamide artificial sweeters by capillary electrophoresis with on-line preconcentration and contactless conductivity detection.

    PubMed

    Yang, Lirong; Zhou, ShengJi; Xiao, Yuezhou; Tang, Yufeng; Xie, Tianyao

    2015-12-01

    A sensitive method followed by capillary electrophoresis with on-line perconcentration and capacitively coupled contactless conductivity detection (CE-C(4)D) was evaluated as a novel approach for the determination of three sulfanilamide artificial sweeteners (acesulfame-K, sodium saccharin and sodium cyclamate) in beverages. The on-line preconcentration technique, namely field-amplified sample injection, coupled with CE-C(4)D were successfully developed and optimized. The separation was achieved within 10 min under the following conditions: an uncoated fused-silica capillary (45 cm × 50 μm i.d., Leff=40 cm), 20 mmol L(-1) HAc as running buffer, separation voltage of -12 kV, electrokinetic injection of -11 kV × 8 s. The detection limits of acesulfame-K, sodium saccharin and sodium cyclamate were 4.4, 6.7 and 8.8 μg L(-1), respectively. The relative standard deviation varied in the range of 3.0-5.0%. Results of this study show a great potential method for the fast screening of these artificial sweeteners contents in commercial beverages. PMID:26041216

  7. Microwave-assisted on-line derivatization for sensitive flow injection fluorometric determination of formaldehyde in some foods.

    PubMed

    Zhao, Xiao-Qing; Zhang, Zhi-Qi

    2009-11-15

    A rapid and sensitive flow injection fluorometry has been developed for the determination of formaldehyde based on the microwave on-line accelerating its Hantzsch reaction with cyclohexane-1,3-dione. Under the optimized conditions, the fluorescent intensity is proportional to formaldehyde content in the range from 0.05 ng/mL to 2.000 microg/mL. The detection limit (S/N=3) is 0.02 ng/mL and the analytical frequency is 28 injections per hour. The relative standard deviations are 2.2% and 3.1% for eleven injections of 0.100 and 0.001 microg/mL of formaldehyde, respectively. With the assistance of microwave irradiation, a best sensitive fluorometry was established for the determination of formaldehyde at a high analytical frequency. This method was successfully applied to food analysis without requiring any sample pretreatment, and the determination results were correlated well with those obtained by the standard method with a sample pretreatment of steam distillation. PMID:19782221

  8. Mid- and far-infrared fine-structure-line sensitivities to hypothetical variability of the fine-structure constant

    NASA Astrophysics Data System (ADS)

    Kozlov, M. G.; Porsev, S. G.; Levshakov, S. A.; Reimers, D.; Molaro, P.

    2008-03-01

    Sensitivity coefficients to temporal variation of the fine-structure constant α for transitions between the fine-structure (FS) sublevels of the ground states of C I, Si I, S I, Ti I, Fe I, N II, Fe II, O III, S III, Ar III, Fe III, Mg V, Ca V, Na VI, Fe VI, Mg VII, Si VII, Ca VII, Fe VII, and Si IX are calculated. These transitions lie in the mid- and far-infrared regions and can be observed in spectra of high-redshift quasars and infrared bright galaxies with active galactic nuclei. Using FS transitions to study α variation over cosmological time scales allows one to improve the limit on Δα/α by several times as compared to contemporaneous optical observations (|Δα/α|<10-5) , and to suppress considerably systematic errors of the radial velocity measurements caused by the Doppler noise. Moreover, the far infrared lines can be observed at redshifts z≳10 , far beyond the range accessible to optical observations (z≲4) . We have derived a simple analytical expression which relates the FS intervals and the sensitivity of the FS transitions to the change of α .

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

    PubMed Central

    Delorenzi, Mauro; Jensen, Thomas; Jensen, Peter Buhl; Bosman, Fred; Tejpar, Sabine; Roth, Arnaud; Brunner, Nils; Hansen, Anker; Knudsen, Steen

    2016-01-01

    Purpose This study evaluates whether gene signatures for chemosensitivity for irinotecan and 5-fluorouracil (5-FU) derived from in vitro grown cancer cell lines can predict clinical sensitivity to these drugs. Methods To test if an irinotecan signature and a SN-38 signature could identify 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 significant association between the irinotecan or SN-38 profiles and benefit from irinotecan. The 5-FU sensitivity profile showed a statistically significant association with relapse free survival (RFS) (hazard ratio (HR) = 0.54 (0.41–0.71), p<1e-05) and overall survival (HR = 0.47 (0.34–0.63), p<1e-06) in the PETACC-3 subpopulation. The effect of the 5-FU profile remained significant in a multivariable Cox Proportional Hazards model, adjusting for several relevant clinicopathological parameters. No statistically significant effect of the 5-FU profile was observed in the untreated cohort of 359 patients (relapse free survival, p = 0.671). Conclusion The irinotecan predictor had no predictive value. The 5-FU predictor was prognostic in stage III patients in PETACC-3 but not in stage II patients with no adjuvant therapy. This suggests a potential predictive ability of the 5-FU sensitivity profile 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. PMID:27171152

  10. Tests on NaI(Tl) crystals for WIMP search at the Yangyang Underground Laboratory

    NASA Astrophysics Data System (ADS)

    Kim, K. W.; Kang, W. G.; Oh, S. Y.; Adhikari, P.; So, J. H.; Kim, N. Y.; Lee, H. S.; Choi, S.; Hahn, I. S.; Jeon, E. J.; Joo, H. W.; Kim, B. H.; Kim, H. J.; Kim, Y. D.; Kim, Y. H.; Lee, J. K.; Leonard, D. S.; Li, J.; Olsen, S. L.; Park, H. S.

    2015-03-01

    Among the direct searches for WIMP-type dark matter, the DAMA experiment is unique in that it has consistently reported a positive signal for an annual-modulation signal with a large (9.3σ) statistical significance. This result is controversial because if it is interpreted as a signature for WIMP interactions, it conflicts with other direct search experiments that report null signals in the regions of parameter space that are allowed by the DAMA observation. This necessitates an independent verification of the origin of the observed modulation signal using the same technique as that employed by the DAMA experiment, namely low-background NaI(Tl) crystal detectors. Here, we report first results of a program of NaI(Tl) crystal measurements at the Yangyang Underground Laboratory aimed at producing NaI(Tl) crystal detectors with lower background levels and higher light yields than those used for the DAMA measurements.

  11. Reevaluation of spin-dependent WIMP-proton interactions as an explanation of the DAMA data

    NASA Astrophysics Data System (ADS)

    Del Nobile, Eugenio; Gelmini, Graciela B.; Georgescu, Andreea; Huh, Ji-Haeng

    2015-08-01

    We reexamine the interpretation of the annual modulation signal observed by the DAMA experiment as due to WIMPs with a spin-dependent coupling mostly to protons. We consider both axial-vector and pseudo-scalar couplings, and elastic as well as endothermic and exothermic inelastic scattering. We conclude that the DAMA signal is in strong tension with null results of other direct detection experiments, particularly PICASSO and KIMS.

  12. Reevaluation of spin-dependent WIMP-proton interactions as an explanation of the DAMA data

    SciTech Connect

    Nobile, Eugenio Del; Gelmini, Graciela B.; Georgescu, Andreea; Huh, Ji-Haeng

    2015-08-25

    We reexamine the interpretation of the annual modulation signal observed by the DAMA experiment as due to WIMPs with a spin-dependent coupling mostly to protons. We consider both axial-vector and pseudo-scalar couplings, and elastic as well as endothermic and exothermic inelastic scattering. We conclude that the DAMA signal is in strong tension with null results of other direct detection experiments, particularly PICASSO and KIMS.

  13. Improvement of the antiproliferative effect of rapamycin on tumor cell lines by poly (monomethylitaconate)-based pH-sensitive, plasma stable liposomes.

    PubMed

    Ghanbarzadeh, Saeed; Arami, Sanam; Pourmoazzen, Zhaleh; Khorrami, Arash

    2014-03-01

    pH-responsive polymers produce liposomes with pH-sensitive property which can release their encapsulated drug under mild acidic conditions found inside the cellular endosomes, inflammatory tissues and cancerous cells. The aim of this study was preparing pH-sensitive and plasma stable liposomes in order to enhance the selectivity and antiproliferative effect of Rapamycin. In the present study we used PEG-poly (monomethylitaconate)-CholC6 (PEG-PMMI-CholC6) copolymer and Oleic acid (OA) to induce pH-sensitive property in Rapamycin liposomes. pH-sensitive liposomal formulations bearing copolymer PEG-PMMI-CholC6 and OA were characterized in regard to physicochemical stability, pH-responsiveness and stability in human plasma. The ability of pH-sensitive liposomes in enhancing the cytotoxicity of Rapamycin was evaluated in vitro by using colon cancer cell line (HT-29) and compared with its cytotoxicity on human umbilical vein endothelial cell (HUVEC) line. Both formulations were found to release their contents under mild acidic conditions rapidly. However, unlike OA-based liposomes, the PEG-PMMI-CholC6 bearing liposomes preserved their pH-sensitivity in plasma. Both types of pH-sensitive Rapamycin-loaded liposomes exhibited high physicochemical stability and could deliver antiproliferative agent into HT-29 cells much more efficiently in comparison with conventional liposomes. Conversely, the antiproliferative effect of pH-sensitive liposomes on HUVEC cell line was less than conventional liposomes. This study showed that both OA and PEG-PMMI-CholC6-based vesicles could submit pH-sensitive property, however, only PEG-PMMI-CholC6-based liposomes could preserve pH-sensitive property after incubation in plasma. As a result pH-sensitive PEG-PMMI-CholC6-based liposomal formulation can improve the selectivity, stability and antiproliferative effect of Rapamycin. PMID:24394948

  14. A data acquisition system for two-dimensional position sensitive micropattern gas detectors with delay-line readout

    NASA Astrophysics Data System (ADS)

    Hanu, A. R.; Prestwich, W. V.; Byun, S. H.

    2015-04-01

    We present a data acquisition (DAQ) system for two-dimensional position sensitive micropattern gas detectors using the delay-line method for readout. The DAQ system consists of a field programmable gate array (FPGA) as the main data processor and our time-to-digital (TDC) mezzanine card for making time measurements. We developed the TDC mezzanine card around the Acam TDC-GPX ASIC and it features four independent stop channels referenced to a common start, a typical timing resolution of ~81 ps, and a 17-bit measurement range, and is compliant with the VITA 57.1 standard. For our DAQ system, we have chosen the Xilinx SP601 development kit which features a single Spartan 6 FPGA, 128 MB of DDR2 memory, and a serial USB interface for communication. Output images consist of 1024×1024 square pixels, where each pixel has a 32-bit depth and corresponds to a time difference of 162 ps relative to its neighbours. When configured for a 250 ns acquisition window, the DAQ can resolve periodic event rates up to 1.8×106 Hz without any loses and will report a maximum event rate of 6.11×105 Hz for events whose arrival times follow Poisson statistics. The integral and differential non-linearities have also been measured and are better than 0.1% and 1.5%, respectively. Unlike commercial units, our DAQ system implements the delay-line image reconstruction algorithm entirely in hardware and is particularly attractive for its modularity, low cost, ease of integration, excellent linearity, and high throughput rate.

  15. MicroRNA-302b Enhances the Sensitivity of Hepatocellular Carcinoma Cell Lines to 5-FU via Targeting Mcl-1 and DPYD

    PubMed Central

    Cai, Donghui; He, Kang; Chang, Su’e; Tong, Dongdong; Huang, Chen

    2015-01-01

    MiR-302b is a member of miR-302-367 cluster. The miR-302-367 cluster played important roles in maintaining pluripotency in human embryonic stem cells (hESCs) and has been proved to be capable of suppressing cell growth in several types of cancer cell lines including Hepatocellular Carcinoma (HCC) Cell lines. However, the role that miR-302b plays in the 5-Fluorouracil (5-FU) sensitivity of HCC has not been known. This study showed that miR-302b could enhance the sensitivity to 5-FU in HCC cell lines and verified its two putative targeted genes responsible for its 5-FU sensitivity. PMID:26457704

  16. MicroRNA-302b Enhances the Sensitivity of Hepatocellular Carcinoma Cell Lines to 5-FU via Targeting Mcl-1 and DPYD.

    PubMed

    Cai, Donghui; He, Kang; Chang, Su'e; Tong, Dongdong; Huang, Chen

    2015-01-01

    MiR-302b is a member of miR-302-367 cluster. The miR-302-367 cluster played important roles in maintaining pluripotency in human embryonic stem cells (hESCs) and has been proved to be capable of suppressing cell growth in several types of cancer cell lines including Hepatocellular Carcinoma (HCC) Cell lines. However, the role that miR-302b plays in the 5-Fluorouracil (5-FU) sensitivity of HCC has not been known. This study showed that miR-302b could enhance the sensitivity to 5-FU in HCC cell lines and verified its two putative targeted genes responsible for its 5-FU sensitivity. PMID:26457704

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

    PubMed Central

    Spee, Bart; Jonkers, Martijn DB; Arends, Brigitte; Rutteman, Gerard R; Rothuizen, Jan; Penning, Louis C

    2006-01-01

    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. PMID:16953886

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

    PubMed Central

    Yan, Dong; Ge, Yang; Deng, Haiteng; Chen, Wenming; An, Guangyu

    2015-01-01

    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 rmhTRAIL synergistically interact to inhibit cell proliferation, and apoptosis assessment demonstrated that associations of drug increased the apoptotic index. rmhTRAIL when used alone downregulated DR5 and upregulated BAX, FLIP, and cleaved-caspase3 proteins expressions. However, results obtained in Western blot analyses demonstrated that the combined treatment-induced cell apoptosis was achieved involving upregulated DR5, cleaved-caspase3, and BAX proteins expression and downregulated FLIP protein expression. Moreover, quantitative polymerase chain reaction showed that gefitinib modulated the expression of targets related to rmhTRAIL activity. Conclusion These results indicate that epidermal growth factor receptor inhibitors enhance rmhTRAIL antitumor activity in the gefitinib-responsive PC9 cell line, and upregulated DR5 expression plays a critical role in activating caspase-signaling apoptotic pathway. PMID:26170696

  19. Growth and radiation sensitivity of the MLS human ovarian carcinoma cell line grown as multicellular spheroids and xenografted tumours.

    PubMed Central

    Rofstad, E. K.; Sutherland, R. M.

    1989-01-01

    The growth characteristics and the radiation sensitivity of multicellular spheroids of the MLS human ovarian carcinoma cell line grown in spinner culture in atmospheres of 5% CO2 in air or 5% CO2, 5% O2 and 90% N2 were studied and compared to that of MLS xenografted tumours. The spheroids grew exponentially with a volume-doubling time of approximately 24 h up to a diameter of approximately 580 microns and then the growth rate tapered off, more for spheroids grown at the low than at the high oxygen tension. Thirty days after initiation, the spheroid diameters were approximately 1,500 microns at the low and 2,100 microns at the high oxygen tension. The tumour volume-doubling times were approximately 8 days (V less than 200 mm3) and 17 days (V = 1,000-4,000 mm3). The histological appearance of the spheroids and the tumours was remarkably similar; both developed large central necrosis and both were composed of epithelial cells and showed pseudoglandular structures with lumen. The spheroids were slightly less differentiated than the tumours. The intrinsic, cellular radiation sensitivity was independent of whether the cells were grown in vitro as spheroids or in vivo as tumours, as revealed by irradiating single cells from dissociated spheroids and tumours under aerobic conditions and intact spheroids and tumours under hypoxic conditions. Studies of 1,600 microns spheroids grown in 5% CO2 in air showed that the intrinsic radiation sensitivity of the chronically hypoxic cells was the same as that of acutely hypoxic cells. The fraction of radiobiologically hypoxic cells under these conditions was approximately 15% and similar to those of 9% (V = 200 mm3) and 28% (V = 2,000 mm3) found for the tumours. Spheroids with diameter of 1,200 microns did not show survival curves parallel to those for acutely hypoxic cells, i.e. they did not contain a measurable fraction of clonogenic cells at complete radiobiological hypoxia. The final portion of their survival curves represented partially hypoxic cells; the OERs were 1.6 and 1.3 for spheroids grown at the high and the low oxygen tension, respectively. The considerable similarity between the spheroids and the tumours suggests that MLS spheroids constitute a valuable in vitro model for studies of human tumour radiation biology and related physiological processes. MLS spheroids may be particularly useful in studies of therapeutic consequences of partial radiobiological hypoxia since complete hypoxia and different levels of partial hypoxia can be studied separately by varying spheroid size and the oxygen tension in the culture medium. Images Figure 2 Figure 5 Figure 6 PMID:2757922

  20. Studies of variation in inherent sensitivities to radiation, 5-fluorouracil and methotrexate in a series of human and murine tumor cell lines in vitro

    SciTech Connect

    Bellamy, A.S.; Whelan, R.D.H.; Hill, B.T.

    1984-01-01

    Clinical studies have reported reduced response rates to subsequent chemotherapy in certain tumors recurring after radiotherapy. These authors have investigated whether there are any correlations between radiation and drug responses in vitro using a range of murine and human tumor cell lines. They have compared sensitivities to X-irradiation and to 24 hr exposures to two widely used antitumor drugs, methotrexate and 5-fluorouracil. The 4 murine lines selected showed a range of radiation responses with Do values of 0.48-0.76 Gy. Methotrexate sensitivities also exhibited an 800-fold difference which appeared to correlate inversely with radiation response. Sensitivity to 5-FU was less variable in these cells and was unrelated to radiation response. In contrast, in the human lines tested, no correlations were observed between drug sensitivities and radiation response. The six lines tested showed a range of radiation responses with Do values of 0.66-1.59 Gy. Methotrexate sensitivities ranged only over a 150-fold concentration but, contrasting with data from the murine cells, no correlation with radiation response was apparent. Similarly, no correlations between response to 5-fluorouracil and radiation or 5-fluorouracil and methotrexate were noted, which is inconsistent with results using murine cells.

  1. Comparative proteomic analysis of cisplatin sensitive IGROV1 ovarian carcinoma cell line and its resistant counterpart IGROV1-R10.

    PubMed

    Le Moguen, Karen; Lincet, Hubert; Deslandes, Edwige; Hubert-Roux, Marie; Lange, Catherine; Poulain, Laurent; Gauduchon, Pascal; Baudin, Bruno

    2006-10-01

    Ovarian cancer is one of the leading causes of mortality due to gynaecological cancer. Despite a good response to surgery and initial chemotherapy essentially based on cisplatin (cis-diamino-dichloro-platinum(II) (CDDP)) compounds, late tumour detection and frequent recurrences with chemoresistance acquisition are responsible for poor prognosis. Several mechanisms have been implicated in CDDP resistance but they are not sufficient to exhaustively explain this resistance emergence. We applied a proteomic approach based on 2-DE coupled with MS to identify proteins associated with the chemoresistance process. We first established a proteomic pattern of the CDDP sensitive ovarian cell line IGROV1 using MALDI-TOF-MS and PMF. We then compared this 2-D pattern with that of the CDDP-resistant counterpart IGROV1-R10. Among the 40 proteins identified, cytokeratins 8 and 18 and aldehyde dehydrogenase 1 were overexpressed in IGROV1-R10, whereas annexin IV was down-regulated. These observations have been confirmed by Western blotting. The characterization of such variations could lead to the development of new protein markers or to the establishment of new therapeutic strategies. Moreover, the identification of proteins involved in CDDP resistance in ovarian tumours would be useful in completing our understanding on this complex mechanism. PMID:16941573

  2. In vitro activities of native and designed peptide antibiotics against drug sensitive and resistant tumor cell lines.

    PubMed

    Kim, Sunkyu; Kim, Sukwon S; Bang, Yung Jue; Kim, Seong Jin; Lee, Byeong Jae

    2003-07-01

    In order to develop peptide agents with reduced length and enhanced tumoricidal activity, we have designed gaegurin 6 (GGN6) derivatives through deletions and/or substitutions of amino acids. The deletion of hydrophobic amino terminal region completely abolished antitumor activity whereas the deletion of carboxy terminal region had little influence on antitumor activity. Antitumor activity of the PTP peptides did not correlate with antibacterial activity. PTP7, the most potent derivative, was found to have comparable antitumor activity to GGN6 in spite of reduced number of amino acids which is about half the size of gaegurin 6; furthermore, it showed little cytotoxicity on PBMCs and RBCs. GGN6 and PTP7 also showed equivalent cytotoxicity against drug sensitive (MCF-7) and multidrug-resistant cell lines (MCF-7/DOX). Plasma membrane blebbing and DNA fragmentation of peptide-treated tumor cells indicated that the peptides could induce apoptosis in tumor cells. These results suggest that GGN6 and its derivatives can be developed as new anticancer agents and may provide a new strategy for overcoming MDR which is a major problem in cancer therapy. PMID:14499271

  3. 4NQO- or MNNG-resistant variants established from a human cell line, RSb, with high sensitivity to both agents.

    PubMed

    Suzuki, N

    1987-05-01

    From a human cell line, RSb, with high sensitivity to the killing effects of 4-nitroquinoline 1-oxide (4NQO), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 254-nm ultraviolet light, a 4NQO-resistant variant, Qr-10, and an MNNG-resistant one, Gr-10, were established using ethyl methanesulfonate as the mutagen. Cell proliferation studies and colony-formation assays revealed that Qr-10 and Gr-10 cells actively proliferated under conditions where RSb cell proliferation was greatly inhibited by 4NQO and MNNG, respectively. Total cellular DNA synthesis, as estimated by [Me-3H]thymidine uptake into acid-insoluble cell materials, was depressed in 4NQO-treated Qr-10 and MNNG-treated Gr-10 cells as it was in chemical-treated RSb cells, but recovered more markedly from such inhibition in the variants. 4NQO- and MNNG-induced DNA-repair replication synthesis was enhanced to a greater extent in Qr-10 and Gr-10 cells, respectively, than in RSb cells. The Qr-10 and Gr-10 cells showed the same respective susceptibility to the effects of MNNG and 4NQO, on cell growth and DNA synthesis and DNA-repair synthesis as did the parent cells. But, Qr-10 cells had more resistance to UV-killing and higher levels of UV-induced DNA-repair synthesis than did RSb cells, while UV-susceptibility of Gr-10 cells was the same as that of the latter. PMID:3106797

  4. New beam line for time-of-flight medium energy ion scattering with large area position sensitive detector

    SciTech Connect

    Linnarsson, M. K.; Hallen, A.; Astroem, J.; Primetzhofer, D.; Legendre, S.; Possnert, G.

    2012-09-15

    A new beam line for medium energy ion mass scattering (MEIS) has been designed and set up at the Angstroem laboratory, Uppsala University, Sweden. This MEIS system is based on a time-of-flight (ToF) concept and the electronics for beam chopping relies on a 4 MHz function generator. Repetition rates can be varied between 1 MHz and 63 kHz and pulse widths below 1 ns are typically obtained by including beam bunching. A 6-axis goniometer is used at the target station. Scattering angle and energy of backscattered ions are extracted from a time-resolved and position-sensitive detector. Examples of the performance are given for three kinds of probing ions, {sup 1}H{sup +}, {sup 4}He{sup +}, and {sup 11}B{sup +}. Depth resolution is in the nanometer range and 1 and 2 nm thick Pt layers can easily be resolved. Mass resolution between nearby isotopes can be obtained as illustrated by Ga isotopes in GaAs. Taking advantage of the large size detector, a direct imaging (blocking pattern) of crystal channels are shown for hexagonal, 4H-SiC. The ToF-MEIS system described in this paper is intended for use in semiconductor and thin film areas. For example, depth profiling in the sub nanometer range for device development of contacts and dielectric interfaces. In addition to applied projects, fundamental studies of stopping cross sections in this medium energy range will also be conducted.

  5. COUPP - a search for dark matter with a continuously sensitive bubble chamber

    SciTech Connect

    Collar, Juan,; Crum, Keith; Mishra, Smriti; Nakazawa, Dante; Odom, Brian; Rasmussen, Julia; Riley, Nathan; Szydagis, Matthew; Behnke, Ed; Levine, Ilan; Vander Werf, Nate; Cooper, Peter; Crisler, Mike; Hu, Martin; Ramberg, Erik; Sonnenschein, Andrew; Tschirhart, Robert; /Fermilab

    2007-01-01

    We propose to construct and operate a 60-kg room temperature CF{sub 3}I bubble chamber as a prototype dark matter (WIMP) detector. Operating in weakly-superheated mode, the chamber will be sensitive to WIMP induced nuclear recoils above 10 keV, while rejecting background electron recoils at a level approaching 10{sup 10}. We would first commission and operate this chamber in the MINOS near detector hall with the goal to demonstrate stable operation and measure internal contamination and any other backgrounds. This chamber, or an improved version, would then be relocated to an appropriate deep underground site such as the Soudan Mine. This detector will have unique sensitivity to spin-dependent WIMP-nucleon couplings, and even in this early stage of development will attain competitive sensitivity to spin-independent couplings.

  6. Applying the diode laser spectroscopy method for high sensitivity on-line control of 13С contained in the gaseous mixture with 12С

    NASA Astrophysics Data System (ADS)

    Kireev, S. V.; Kondrashov, A. A.; Shnyrev, S. L.

    2016-06-01

    This letter details the development of an on-line control method for carbon dioxide molecules of various isotopes contained in gaseous media on the basis of a tunable diode laser operating in the 4860–4880 cm‑1 range. It shows that the sensitivity of 13С registering may amount to ~1012 cm‑3.

  7. HSP90 inhibition downregulates thymidylate synthase and sensitizes colorectal cancer cell lines to the effect of 5FU-based chemotherapy.

    PubMed

    Nagaraju, Ganji Purnachandra; Alese, Olatunji B; Landry, Jerome; Diaz, Roberto; El-Rayes, Bassel F

    2014-10-30

    Cell cycle progression and DNA synthesis are essential steps in cancer cell growth. Thymidylate synthase (TS) is a therapeutic target for 5FU. We tested the hypothesis that HSP90 transcriptional and functional inhibition can inhibit cell cycle progression, downregulate TS levels and sensitize colorectal cancer (CRC) cell lines to the effects of 5FU. Treatment with ganetespib (50 nM) for 24 hours inhibited cyclin D1 and pRb at the transcriptional and translational levels and induced p21, leading to G0/G1 cell cycle arrest in both CRC cell lines (HCT-116 and HT-29). This was associated with downregulation of E2F1 and its target gene TS. In addition, ganetespib inhibited PI3K/Akt and ERK signalling pathways. Similar effects were observed with HSP90 knockdown in both cell lines. Ganetespib sensitized CRC cell lines to the effects of oxaliplatin and 5FU. Similar effects were also observed in tumors from animals treated with ganetespib, oxaliplatin and 5FU. In this study, we present in vitro and animal data supporting that the targeting of HSP90 decreases CRC cell survival and proliferation. Ganetespib sensitizes CRC cell lines to the effects of 5FU-based chemotherapy. Combining HSP90 inhibitors with chemotherapy is a rational approach for future drug development in CRC. PMID:25296971

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

    PubMed Central

    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; BCL2High) are exquisitely sensitive to navitoclax or the B-cell lymphoma protein-2 (BCL-2)-selective inhibitor venetoclax. Despite this, some BCL2High 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-XL-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 BCL2High NHL cell lines to a similar extent as A-1210477. A-1210477 also synergized with navitoclax in the majority of BCL2Low NHL cell lines. However, chemical segregation with venetoclax or A-1155463 revealed that synergy was driven by BCL-XL 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 (BCL2Low) that could benefit from BCL-XL (navitoclax)-driven combination therapy. PMID:26565405

  9. Cytotoxicity of 5-fluorouracil-loaded pH-sensitive liposomal nanoparticles in colorectal cancer cell lines

    PubMed Central

    Udofot, Ofonime; Affram, Kevin; Israel, Bridg'ette; Agyare, Edward

    2015-01-01

    5-Fluorouracil (5-FU) is widely used in cancer therapy, either alone or in combination with other anti-cancer drugs. However, poor membrane permeability and a short half-life (5-20 min) due to rapid metabolism in the body necessitate the continuous administration of high doses of 5-FU to maintain the minimum therapeutic serum concentration. This is associated with significant side effects and a possibility of severe toxic effects. This study aimed to formulate 5-FU-loaded pH-sensitive liposomal nanoparticles (pHLNps-5-FU) and evaluate 5-FU release characteristics and anti-cancer effect of pHLNps-5-FU. Particle size and zeta potential were determined using a particle size analyzer. The release patterns of pHLNps-5-FU formulations were evaluated at 37°C at pH 3, 5, 6.5, and 7.4, while drug release kinetics of 5-FU from a pHLNp3–5-FU formulation were determined at pH 3 and 7.4 at different time points (37°C). Cell viability and clonogenic studies were conducted to evaluate the effectiveness of pHLNps-5-FU against HCT-116 and HT-29 cell lines while cellular uptake of rhodamine-labeled pHLNps-5-FU was determined by flow cytometry and confocal imaging. The average sizes of the pHLNp1–5-FU, pHLNp2–5-FU and pHLNp3–5-FU liposomes were 200nm ± 9.8nm, 181.9 nm ± 9.1 nm, and 164.3 nm ± 8.4 nm respectively. In vitro drug release of 5-FU from different pHLNps-5-FU formulations was the highest at pH 3.8. Both cell lines treated with pHLNps-5-FU exhibited reduced viability, two- or three-fold lower than that of 5-FU-treated cells. Flow cytometry and confocal imaging confirmed high uptake of rhodamine-labeled pHLNps-5-FU in both cell lines. The drug release profile of the chosen pHLNp3-5-FU formulation was optimal at pH 3 and had the poorest release profile at pH 7.4. The release profile of pHLNp3-5-FU showed that 5-FU release was two-fold higher at pH 3 than that at pH 7.4. This study demonstrates that pHLNp3-5-FU may be a potential candidate for the treatment of colorectal cancer. PMID:26691592

  10. The Search for Milky Way Halo Substructure WIMP Annihilations Using the GLAST LAT

    SciTech Connect

    Wai, Larry; /SLAC

    2007-02-05

    The GLAST LAT Collaboration is one among several experimental groups, covering a wide range of approaches, pursuing the search for the nature of dark matter. The GLAST LAT has the unique ability to find new sources of high energy gamma radiation emanating directly from WIMP annihilations in situ in the universe. Using it's wide band spectral and full sky spatial capabilities, the GLAST LAT can form ''images'' in high energy gamma-rays of dark matter substructures in the gamma-ray sky. We describe a preliminary feasibility study for indirect detection of milky way dark matter satellites using the GLAST LAT.

  11. Mitsuyoshi Tanaka Dissertation Award in Experimental Particle Physics: Exclusion Limits on the WIMP-Nucleon Cross-Section from the Cryogenic Dark Matter Search

    NASA Astrophysics Data System (ADS)

    Golwala, Sunil

    2001-04-01

    It has long been suspected that nonbaryonic cold dark matter makes up a significant component of the energy density of the universe. Observations over the last few years have solidified this idea and make the fairly precise prediction that about 1/3 of the closure density is provided by this form of matter. Weakly Interacting Massive Particles (WIMPs) are an excellent candidate for nonbaryonic cold dark matter, motivated by both particle physics and cosmology. I present some of these arguments and discuss recent results from the Cryogenic Dark Matter Search (CDMS), an experiment that searches for scattering of WIMPs with normal matter using novel particle detectors that discriminate WIMP-induced nuclear recoils from background-induced electron recoils. CDMS data exclude new parameter space for WIMPs with masses above 10 GeV and appear to be inconsistent with a WIMP interpretation of the annual-modulation signal observed by the DAMA experiment.

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

    PubMed Central

    Sipos, Péter; Dér, Katalin; Csábi, József; Miklos, Walter; Berger, Walter; Zalatnai, Attila; Amaral, Leonard; Molnár, Joseph; Szabó-Révész, Piroska

    2015-01-01

    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. PMID:26075272

  13. Isolation and characterization of a Chinese hamster ovary mutant cell line with altered sensitivity to vaccinia virus killing.

    PubMed Central

    Bair, C H; Chung, C S; Vasilevskaya, I A; Chang, W

    1996-01-01

    The Chinese hamster ovary (CHO) cell line is nonpermissive for vaccinia virus, and translation of viral intermediate genes was reported to be blocked (A. Ramsey-Ewing and B. Moss, Virology 206:984-993, 1995). However, cells are readily killed by vaccinia virus. A vaccinia virus-resistant CHO mutant, VV5-4, was isolated by retroviral insertional mutagenesis. Parental CHO cells, upon infection with vaccinia virus, die within 2 to 3 days, whereas VV5-4 cells preferentially survive this cytotoxic effect. The survival phenotype of VV5-4 is partial and in inverse correlation with the multiplicity of infection used. In addition, viral infection fails to shut off host protein synthesis in VV5-4. VV5-4 was used to study the relationship of progression of the virus life cycle and cell fate. We found that in parental CHO cells, vaccinia virus proceeds through expression of viral early genes, uncoating, viral DNA replication, and expression of intermediate and late promoters. In contrast, we detect only expression of early genes and uncoating in VV5-4 cells, whereas viral DNA replication appears to be blocked. Consistent with the cascade regulation model of viral gene expression, we detect little intermediate- and late-gene expression in VV5-4 cells. Since vaccinia virus is known to be cytolytic, isolation of this mutant therefore demonstrates a new mode of the cellular microenvironment that affects progression of the virus life cycle, resulting in a different cell fate. This process appears to be mediated by a general mechanism, since VV5-4 is also resistant to Shope fibroma virus and myxoma virus killing. On the other hand, VV5-4 remains sensitive to cowpox virus killing. To examine the mechanism of VV5-4 survival, we investigated whether apoptosis is involved. DNA laddering and staining of apoptotic nuclei with Hoechst 33258 were observed in both CHO and VV5-4 cells infected with vaccinia virus. We concluded that the cellular pathway, which blocks viral DNA replication and allows VV5-4 to survive, is independent of apoptosis. This mutant also provides evidence that an inductive signal for apoptosis upon vaccinia virus infection occurs prior to viral DNA replication. PMID:8676492

  14. Gamma-ray lines and one-loop continuum from s-channel dark matter annihilations

    NASA Astrophysics Data System (ADS)

    Jackson, C. B.; Servant, Géraldine; Shaughnessy, Gabe; Tait, Tim M. P.; Taoso, Marco

    2013-07-01

    The era of indirect detection searches for dark matter has begun, with the sensitivities of gamma-ray detectors now approaching the parameter space relevant for weakly interacting massive particles. In particular, gamma ray lines would be smoking gun signatures of dark matter annihilation, although they are typically suppressed compared to the continuum. In this paper, we pay particular attention to the 1-loop continuum generated together with the gamma-ray lines and investigate under which conditions a dark matter model can naturally lead to a line signal that is relatively enhanced. We study generic classes of models in which DM is a fermion that annihilates through an s-channel mediator which is either a vector or scalar and identify the coupling and mass conditions under which large line signals occur. We focus on the ``forbidden channel mechanism" advocated a few years ago in the ``Higgs in space" scenario for which tree level annihilation is kinematically forbidden today. Detailed calculations of all 1-loop annihilation channels are provided. We single out very simple models with a large line over continuum ratio and present general predictions for a large range of WIMP masses that are relevant not only for Fermi and Hess II but also for the next generation of telescopes such as CTA and Gamma-400. Constraints from the relic abundance, direct detection and collider bounds are also discussed.

  15. Gamma-ray lines and one-loop continuum from s-channel dark matter annihilations

    SciTech Connect

    Jackson, C.B.; Servant, Géraldine; Shaughnessy, Gabe; Tait, Tim M.P.; Taoso, Marco E-mail: chris@uta.edu E-mail: ttait@uci.edu

    2013-07-01

    The era of indirect detection searches for dark matter has begun, with the sensitivities of gamma-ray detectors now approaching the parameter space relevant for weakly interacting massive particles. In particular, gamma ray lines would be smoking gun signatures of dark matter annihilation, although they are typically suppressed compared to the continuum. In this paper, we pay particular attention to the 1-loop continuum generated together with the gamma-ray lines and investigate under which conditions a dark matter model can naturally lead to a line signal that is relatively enhanced. We study generic classes of models in which DM is a fermion that annihilates through an s-channel mediator which is either a vector or scalar and identify the coupling and mass conditions under which large line signals occur. We focus on the ''forbidden channel mechanism'' advocated a few years ago in the ''Higgs in space'' scenario for which tree level annihilation is kinematically forbidden today. Detailed calculations of all 1-loop annihilation channels are provided. We single out very simple models with a large line over continuum ratio and present general predictions for a large range of WIMP masses that are relevant not only for Fermi and Hess II but also for the next generation of telescopes such as CTA and Gamma-400. Constraints from the relic abundance, direct detection and collider bounds are also discussed.

  16. GHB-C rats: the control line of GHB-sensitive (GHB-S) and GHB-resistant (GHB-R) rats.

    PubMed

    Lobina, Carla; Colombo, Giancarlo; Orrù, Alessandro; Maccioni, Paola; Gessa, Gian Luigi; Carai, Mauro A M

    2005-05-01

    Gamma-hydroxybutyric acid (GHB)-sensitive (GHB-S) and GHB-resistant (GHB-R) rats have been selectively bred for their opposite sensitivity to the sedative/hypnotic effect of GHB. This opposite sensitivity has been found to generalize to the GABA(B) receptor agonist, baclofen. A control line [named GHB-control (GHB-C)] has been derived from the foundation stock of GHB-S and GHB-R rats. GHB-C rats have been bred without any evaluation of their sensitivity to GHB. The experiments described here were designed to evaluate the sensitivity of GHB-C rats, from the 13th generation, to the sedative/hypnotic effect of GHB (1 g/kg, i.p.) and baclofen (20 mg/kg, i.p.). All measures (onset, sleep time and r = sleep time/onset) of sensitivity to GHB- and baclofen-induced sedation/hypnosis in GHB-C rats were significantly different from and intermediate to those recorded in GHB-S and GHB-R rats. Furthermore, these values were similar to those recorded in the foundation stock. These results suggest that GHB-C rats may constitute a valid control line for GHB-S and GHB-R rats, representing the "general population" from which GHB-S and GHB-R rats were derived. Furthermore, the relative equidistance of sensitivity to GHB- and baclofen-induced sedation/hypnosis of GHB-C rats from those of GHB-S and GHB-R rats suggests that genetic factors contributes to the development of both sensitivity in GHB-S rats and resistance in GHB-R rats. PMID:15878144

  17. Adaptation to persistent growth in the H9 cell line renders a primary isolate of human immunodeficiency virus type 1 sensitive to neutralization by vaccine sera.

    PubMed Central

    Wrin, T; Loh, T P; Vennari, J C; Schuitemaker, H; Nunberg, J H

    1995-01-01

    Seven diverse primary isolates of human immunodeficiency virus type 1 (HIV-1) were examined and found to be refractory to neutralization by antisera to recombinant gp120 (rgp120) protein from HIV-1 MN. This stands in marked contrast to the sensitivity exhibited by certain laboratory-adapted viruses. To understand the difference between primary and laboratory-adapted viruses, we adapted the primary virus ACH 168.10 to growth in the FDA/H9 cell line. ACH 168.10 was chosen because the V3 region of gp120 closely matches that of MN. After 4 weeks, infection became evident. The virus (168A) replicated in FDA/H9 cells with extensive cytopathic effect but was unchanged in sensitivity to antibody-mediated neutralization. Thus, growth in cell lines is not sufficient to render primary virus sensitive to neutralization. The 168A virus was, however, partially sensitive to CD4 immunoadhesin (CD4-Ig). Adaptation was continued to produce a persistently infected FDA/H9 culture that displayed minimal cytopathic effect. The virus (168C) was now sensitive to neutralization by MN rgp120 vaccine sera and by MN-specific monoclonal antibodies and showed increased sensitivity to HIVIG and CD4-Ig. 168C encoded three amino acid changes in gp120, including one within the V3 loop (I-166-->R, I-282-->N, G-318-->R). MN-specific monoclonal antibodies bound equally to the surface of cells infected with either neutralization-resistant or -sensitive virus. The coincidence of changes in neutralization sensitivity with changes in cell tropism and cytopathic effect suggests a common underlying mechanism(s) acting through the whole of the envelope protein complex. PMID:7983734

  18. Consequences of DM/antiDM oscillations for asymmetric WIMP dark matter

    SciTech Connect

    Cirelli, Marco; Panci, Paolo; Servant, Géraldine; Zaharijas, Gabrijela E-mail: panci@cp3-origins.net E-mail: gzaharij@ictp.it

    2012-03-01

    Assuming the existence of a primordial asymmetry in the dark sector, a scenario usually dubbed Asymmetric Dark Matter (aDM), we study the effect of oscillations between dark matter and its antiparticle on the re-equilibration of the initial asymmetry before freeze-out, which enable efficient annihilations to recouple. We calculate the evolution of the DM relic abundance and show how oscillations re-open the parameter space of aDM models, in particular in the direction of allowing large (WIMP-scale) DM masses. A typical WIMP with a mass at the EW scale ( ∼ 100 GeV – 1 TeV) presenting a primordial asymmetry of the same order as the baryon asymmetry naturally gets the correct relic abundance if the DM-number-violating Δ(DM) = 2 mass term is in the ∼ meV range. The re-establishment of annihilations implies that constraints from the accumulation of aDM in astrophysical bodies are evaded. On the other hand, the ordinary bounds from BBN, CMB and indirect detection signals on annihilating DM have to be considered.

  19. A novel way of constraining WIMPs annihilations in the Sun: MeV neutrinos

    SciTech Connect

    Bernal, Nicolás; Martín-Albo, Justo; Palomares-Ruiz, Sergio E-mail: justo.martin-albo@ific.uv.es

    2013-08-01

    Annihilation of dark matter particles accumulated in the Sun would produce a flux of high-energy neutrinos whose prospects of detection in neutrino telescopes and detectors have been extensively discussed in the literature. However, for annihilations into Standard Model particles, there would also be a flux of neutrinos in the MeV range from the decays at rest of muons and positively charged pions. These low-energy neutrinos have never been considered before and they open the possibility to also constrain dark matter annihilation in the Sun into e{sup +}e{sup −}, μ{sup +}μ{sup −} or light quarks. Here we perform a detailed analysis using the recent Super-Kamiokande data in the few tens of MeV range to set limits on the WIMP-nucleon scattering cross section for different annihilation channels and computing the evaporation rate of WIMPs from the Sun for all values of the scattering cross section in a consistent way.

  20. Correlation between the promoter methylation status of ATP-binding cassette sub-family G member 2 and drug sensitivity in colorectal cancer cell lines.

    PubMed

    Moon, Hyun-Hye; Kim, Sung-Hee; Ku, Ja-Lok

    2016-01-01

    Resistance to chemotherapeutic agents has been considered as a major reason for the high incidence rate of recurrence and metastasis suffered by colorectal cancer (CRC) patients. ATP?binding cassette sub?familyG member2 (ABCG2) is involved in drug resistance. DNA methylation of the ABCG2promoter site has a significant influence on the regulation of epigenetic gene expression. In the present study, we investigated whether the methylation status of the ABCG2 promoter is related to drug sensitivity in CRC cell lines. In order to examine the ABCG2 expression level and identify the methylation status, RT?PCR, qRT?PCR analysis, MS?PCR and bisulfite sequencing were conducted on 32CRC cell lines. SNU?C4, LS174T and NCI?H716 were selected as low ABCG2?expressing and high promoter methylated cell lines. The cell proliferation assay for 5?fluorouracil, oxaliplatin and irinotecan was performed after 5?aza?2'?deoxycytidine (5?aza) treatment in these cell lines. In the 32CRC cell lines, 25%of the cell lines expressed low or no ABCG2 expression. Of these cell lines, SNU?C4, LS174T and NCI?H716 were hypermethylated at the promoter region, ~20%. Demethylation of ABCG2 was induced by 5?aza, which enhanced the ABCG2expression level and influenced the cell proliferation similar to treatment with the anticancer agents. Our data suggest that the ABCG2expression level regulated by methylation is related to anticancer drug sensitivity. Based on these results, it can be applied to predict the anticancer drug response. PMID:26497773

  1. Modulators of Sensitivity and Resistance to Inhibition of PI3K Identified in a Pharmacogenomic Screen of the NCI-60 Human Tumor Cell Line Collection

    PubMed Central

    Kwei, Kevin A.; Baker, Joffre B.; Pelham, Robert J.

    2012-01-01

    The phosphoinositide 3-kinase (PI3K) signaling pathway is significantly altered in a wide variety of human cancers, driving cancer cell growth and survival. Consequently, a large number of PI3K inhibitors are now in clinical development. To begin to improve the selection of patients for treatment with PI3K inhibitors and to identify de novo determinants of patient response, we sought to identify and characterize candidate genomic and phosphoproteomic biomarkers predictive of response to the selective PI3K inhibitor, GDC-0941, using the NCI-60 human tumor cell line collection. In this study, sixty diverse tumor cell lines were exposed to GDC-0941 and classified by GI50 value as sensitive or resistant. The most sensitive and resistant cell lines were analyzed for their baseline levels of gene expression and phosphorylation of key signaling nodes. Phosphorylation or activation status of both the PI3K-Akt signaling axis and PARP were correlated with in vitro response to GDC-0941. A gene expression signature associated with in vitro sensitivity to GDC-0941 was also identified. Furthermore, in vitro siRNA-mediated silencing of two genes in this signature, OGT and DDN, validated their role in modulating sensitivity to GDC-0941 in numerous cell lines and begins to provide biological insights into their role as chemosensitizers. These candidate biomarkers will offer useful tools to begin a more thorough understanding of determinants of patient response to PI3K inhibitors and merit exploration in human cancer patients treated with PI3K inhibitors. PMID:23029544

  2. Calculations of H2O microwave line broadening in collisions with He atoms - Sensitivity to potential energy surfaces

    NASA Technical Reports Server (NTRS)

    Green, Sheldon; Defrees, D. J.; Mclean, A. D.

    1991-01-01

    Theoretical computations of broadening parameters are reported for three microwave lines of H2O in a bath of He atoms. The potential-energy surfaces employed are corrected for basis-set superposition error, and their reliability is checked by repeating the calculations with a different basis set for orbital expansion. The results are presented in extensive tables and discussed in detail. The corrections applied are shown to have a significant impact on the accuracy of the room-temperature broadenings determined: 8.9 sq A for the 22.2-GHz line, 11.8 sq A for the 183,3-GHz line, and 10.0 sq A for the 380.2-GHz line, in good agreement with published experimental data. The importance of collisional broadening for the atmospheric transmission of radiation and for remote-sensing applications is indicated.

  3. Suppression of a DNA base excision repair gene, hOGG1, increases bleomycin sensitivity of human lung cancer cell line

    SciTech Connect

    Wu Mei; Zhang Zunzhen Che Wangjun

    2008-05-01

    Bleomycin (BLM) has been found to induce 8-oxoguanine and DNA strand breaks through producing oxidative free radicals, thereby leading to cell cycle arrest, apoptosis and cell death. Cellular DNA damage repair mechanisms such as single strand DNA break repair/base excision repair (BER) are responsible for removing bleomycin-induced DNA damage, therefore confer chemotherapeutic resistance to bleomycin. In this study, we have investigated if down-regulation of human 8-oxoguanine DNA glycosylase (hOGG1), an important BER enzyme, could alter cellular sensitivity to bleomycin, thereby reducing chemotherapeutic resistance in human tumor cell. A human lung cancer cell line with hOGG1 deficiency (A549-R) was created by ribozyme gene knockdown technique. Bleomycin cellular sensitivity and DNA/chromosomal damages were examined using MTT, colony forming assay, comet assay as well as micronucleus assay. We demonstrated that hOGG1 gene knockdown enhanced bleomycin cytotoxicity and reduced the ability of colony formation of the lung cancer cell lines. We further demonstrated that bleomycin-induced DNA strand breaks resulted in an increase of micronucleus rate. hOGG1 deficiency significantly reduced DNA damage repair capacity of the lung cancer cell lines. Our results indicated that hOGG1 deficiency allowed the accumulation of bleomycin-induced DNA damage and chromosomal breaks by compromising DNA damage repair capacity, thereby increasing cellular sensitivity to bleomycin.

  4. PT -symmetry-induced evolution of sharp asymmetric line shapes and high-sensitivity refractive index sensors in a three-cavity array

    NASA Astrophysics Data System (ADS)

    Li, Jiahua; Yu, Rong; Ding, Chunling; Wu, Ying

    2016-02-01

    It is important to control and tune the Fano-resonance spectra to achieve a large slope with, in addition, a relatively high extinction ratio for low-power optical switching and high-sensitivity sensing. Here, we explore the evolution of sharp asymmetric Fano-like line shapes in a three-cavity array with local parity-time (PT ) symmetry. In this three-cavity configuration, a single cavity is coupled to a PT -symmetric combination of two cavities via a common waveguide. The influences of local PT symmetry on the asymmetric Fano-like line shapes are investigated by monitoring the output transmission spectra at various system parameters. It is found that both the slope and the extinction ratio within the sharp asymmetric line shapes can be significantly enhanced by introducing the PT -symmetric unit, compared with the configuration of two indirectly coupled cavities. Subsequently we discuss the application of such a PT -assisted configuration as a family of high-sensitivity refractive index sensors by numerical analysis. For practical parameters based on microring resonators, the best sensitivity of refractive index sensors is more than five orders of magnitude larger than two indirectly coupled lossy cavities. The proposed scheme can be implemented in current state-of-the-art experiments. This investigation can help us to understand the interplay between the Fano resonance and PT symmetry.

  5. Detection of replication-competent and pseudotyped human immunodeficiency virus with a sensitive cell line on the basis of activation of an integrated beta-galactosidase gene.

    PubMed Central

    Kimpton, J; Emerman, M

    1992-01-01

    We have constructed a HeLa cell line that both expresses high levels of CD4 and contains a single integrated copy of a beta-galactosidase gene that is under the control of a truncated human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR). This cell line, called CD4-LTR/beta-gal, can be used to determine quantitatively the titer of laboratory-adapted HIV strains, and the method used to do so is as sensitive as the determination of viral titers in a T-cell line by end point dilution. Using this cell line as a titer system, we calculated that HIV-1 stocks contain only one infectious particle per 3,500 to 12,000 virions. Virus derived from a molecular clone of a macrophagetropic provirus will not infect this cell line. We have also cocultivated peripheral blood lymphocyte cultures from HIV-infected individuals with the CD4-LTR/beta-gal indicator cells. In a majority of primary isolates (five of eight), including isolates from asymptomatic patients, rare virus-infected cells that can activate the beta-galactosidase gene are present. Images PMID:1548759

  6. Theoretical direct WIMP detection rates for transitions to the first excited state in 83Kr

    NASA Astrophysics Data System (ADS)

    Vergados, J. D.; Avignone, F. T.; Pirinen, P.; Srivastava, P. C.; Kortelainen, M.; Suhonen, J.

    2015-07-01

    The direct detection of dark matter constituents, in particular the weakly interacting massive particles (WIMPs), is central to particle physics and cosmology. In this paper we study transitions to the excited states, possible in some nuclei, which have sufficiently low lying excited states. Examples considered previously were the first excited states of 127I and 129Xe. We examine here 83Kr, which offers some kinematical advantages and is a possible target. We estimate appreciable rates for the inelastic scattering mediated by the spin cross sections, with an inelastic event rate of 4.4 ×10-4 kg-1 d-1 . So, the extra signature of the gamma ray following the de-excitation of these states can, in principle, be exploited experimentally. A brief discussion of the experimental feasibility is given.

  7. The Sensitivity of Tropical Squall Lines (GATE and TOGA COARE) to Surface Fluxes: Cloud Resolving Model Simulations

    NASA Technical Reports Server (NTRS)

    Wang, Yansen; Tao, Wei-Kuo; Simpson, Joanne; Lang, Stephen

    1999-01-01

    Two tropical squall lines from TOGA COARE and GATE were simulated using a two-dimensional cloud-resolving model to examine the impact of surface fluxes on tropical squall line development and associated precipitation processes. The important question of how CAPE in clear and cloudy areas is maintained in the tropics is also investigated. Although the cloud structure and precipitation intensity are different between the TOGA COARE and GATE squall line cases, the effects of the surface fluxes on the amount of rainfall and on the cloud development processes are quite similar. The simulated total surface rainfall amount in the runs without surface fluxes is about 67% of the rainfall simulated with surface fluxes. The area where surface fluxes originated was categorized into clear and cloudy regions according to whether there was cloud in the vertical column. The model results indicated that the surface fluxes from the large clear air environment are the dominant moisture source for tropical squall line development even though the surface fluxes in the cloud region display a large peak. The high-energy air from the boundary layer in the clear area is what feeds the convection while the CAPE is removed by the convection. The surface rainfall was only reduced 8 to 9% percent in the simulations without surface fluxes in the cloud region. Trajectory and water budget analysis also indicated that most moisture (92%) was from the boundary layer of the clear air environment.

  8. The translocator protein (TSPO) ligand PK11195 induces apoptosis and cell cycle arrest and sensitizes to chemotherapy treatment in pre- and post-relapse neuroblastoma cell lines

    PubMed Central

    Mendona-Torres, Maria C.; Roberts, Stephen S.

    2013-01-01

    High-risk neuroblastoma (NB) has a poor prognosis. Even with intensive myeloablative chemotherapy, relapse is common and almost uniformly fatal, and new treatments are needed. Translocator protein 18kDa (TSPO) ligands have been studied as potential new therapeutic agents in many cancers, but not in NB. We studied the effects of TSPO ligands on cell proliferation, cell cycle progression and apoptosis using paired cell lines derived from the same patient at the time of initial surgery and again after development of progressive disease or relapse post-chemotherapy. We found that TSPO expression was significantly increased 2- to 10-fold in post-relapse cell lines compared with pre-treatment lines derived from the same individual. Subsequently, these cell lines were treated with the specific TSPO ligand 1-(2-chlorophenyl-N-methylpropyl)-3-isoquinolinecarboxamide (PK11195) (0160M) as a single agent, with cytotoxic chemotherapy agents alone (carboplatin, etoposide or melphalan), or with combinations of PK11195 and chemotherapy drugs. We found that PK11195 inhibited proliferation in a dose-dependent manner, induced apoptosis and caused G1/S cell cycle arrest in all tested NB cell lines at micromolar concentrations. In addition, PK11195 significantly decreased mRNA expression of the chemotherapy resistance efflux pumps ABCA3, ABCB1 and ABCC1 in two post-relapse NB cell lines. We also found that pre-treatment with PK11195 sensitized these cell lines to treatment with cytotoxic chemotherapy agents. These results suggest that PK11195 alone or in combination with standard chemotherapeutic drugs warrants further study for the treatment of neuroblastoma. PMID:23358477

  9. Daptomycin cure after cefazolin treatment failure of Methicillin-sensitive Staphylococcus aureus (MSSA) tricuspid valve acute bacterial endocarditis from a peripherally inserted central catheter (PICC) line.

    PubMed

    Cunha, Burke A; Hamid, Naveed; Kessler, Heather; Parchuri, Subha

    2005-01-01

    Right-sided acute bacterial endocarditis (ABE) is an infrequent complication of central intravenous (IV) lines. We report a case of methicillin-sensitive Staphylococcus aureus tricuspid valve (TV) ABE related to a peripherally inserted central catheter line (PICC). Patients with right-sided ABE present with symptoms of fever and chills, and symptoms and signs of pulmonary emboli. In the patient presented, the PICC line was removed and high-dose cefazolin therapy, 2 g (IV) every 8 hours, was initiated. Although the patient's blood cultures became negative during the third week of cefazolin therapy, her erythrocyte sedimentation rate and teichoic acid antibody titers remained high. Pulmonary emboli developed. A large TV vegetation (1 x 2 cm) remained unchanged after 4 weeks of cefazolin therapy. For these reasons, cefazolin treatment was considered a treatment failure. Therapy with daptomycin was initiated at a dose of 6 mg/kg (IV) every 24 hours. During daptomycin therapy, the patient's erythrocyte sedimentation rate and teichoic acid antibody titers gradually returned to normal. Repeat transthoracic echocardiograph revealed the TV vegetation was gone and the methicillin-sensitive Staphylococcus aureus ABE was cured with daptomycin. We conclude daptomycin is a rapidly bactericidal antistaphylococcal antibiotic reliably effective even when other usually effective antistaphylococcal antibiotics have failed. PMID:16324966

  10. Differential expression of determinants of glucocorticoid sensitivity in androgen-dependent and androgen-independent human prostate cancer cell lines.

    PubMed

    Dovio, Andrea; Sartori, Maria Luisa; De Francia, Silvia; Mussino, Stefano; Perotti, Paola; Saba, Laura; Abbadessa, Giuliana; Racca, Silvia; Angeli, Alberto

    2009-08-01

    Glucocorticoids (GCs) are widely used for the treatment of hormone refractory prostate cancer. However, few data are available on the expression and regulation of glucocorticoid and mineralocorticoid receptors (GR and MR) and 11beta-hydroxysteroid dehydrogenase (11beta-HSD) 1 and -2 activities in prostate cancer cells. Here we show that GR is expressed in both the androgen-independent PC-3 cell line and, at very low levels, in the androgen-dependent LNCaP cells, and MR is expressed in both cell lines. IL-1beta increased GR expression in both cell lines. In LNCaP cells IL-1beta also increased MR expression. Significant 11beta-HSD oxidase activity and 11beta-HSD2 protein were found in LNCaP cells, but not in PC3 cells, and no ketoreductase activity was detected in either cell lines. GR function was assessed by measuring the inhibitory effect of dexamethasone on constitutive and IL-1beta-inducible IL-6 and osteoprotegerin (OPG) production. In PC-3 cells, IL-1beta stimulated IL-6 and OPG release, and dexamethasone dose-dependently inhibited IL-1beta-inducible IL-6 release, and constitutive and IL-1beta-inducible OPG release. In LNCaP cells, IL-1beta stimulated only OPG release. While dexamethasone was ineffective, cortisol dose-dependently inhibited IL-1beta-inducible OPG release. Eplerenone (Epl), a selective mineralocorticoid antagonist, reverted this effect. We conclude that different patterns of expression of receptors and 11beta-HSD activity were associated with different responsiveness to GCs in terms of regulated gene expression. GR and MR expression may vary as a function not only of the malignant phenotype, but also of local conditions such as the degree of inflammation. Inhibition of IL-6 and OPG release by GCs may contribute to the antitumor efficacy in prostate cancer. PMID:19406240

  11. Analysis of novel microRNA targets in drug-sensitive and -insensitive small cell lung cancer cell lines.

    PubMed

    Ma, Lijie; Li, Peipei; Wang, Ruixuan; Nan, Yandong; Liu, Xueying; Jin, Faguang

    2016-03-01

    Advances in chemotherapy have failed to improve the long-term survival rate of small cell lung cancer (SCLC) patients due to multidrug resistance (MDR). The mechanisms of MDR are complex involving multiple genes and a variety of mechanisms. MicroRNAs (miRNAs) are non-coding RNAs theoretically involved in gene regulation. The aim of the present study was to explore the role of miRNAs in SCLC occurrence and multidrug resistance. Expression levels of known miRNAs in SCLC cell line H446 and its multidrug-resistant cell line H446/CDDP were analyzed using the next generation high through-put Illumina Solexa sequencing technology, and expression of a group of specific miRNAs was validated by quantitative polymerase chain reaction (qPCR). Furthermore, novel miRNAs and their putative target genes in the two SCLC cell lines were predicted with the help of software developed by Beijing Genomics Institute and analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The results revealed a set of known miRNAs with altered expression in the H446 and H446/CDDP cells which may be associated with multidrug resistance of SCLC. Biological information analysis of the novel miRNAs and their putative target genes further elucidated the role of miRNAs in MDR. In addition, the pathway prediction by KEGG analysis may provide clues for further research on MDR of SCLC. PMID:26676926

  12. Macrolides sensitize EGFR-TKI-induced non-apoptotic cell death via blocking autophagy flux in pancreatic cancer cell lines

    PubMed Central

    MUKAI, SHUNTARO; MORIYA, SHOTA; HIRAMOTO, MASAKI; KAZAMA, HIROMI; KOKUBA, HIROKO; CHE, XIAO-FANG; YOKOYAMA, TOMOHISA; SAKAMOTO, SATOSHI; SUGAWARA, AKIHIRO; SUNAZUKA, TOSHIAKI; ŌMURA, SATOSHI; HANDA, HIROSHI; ITOI, TAKAO; MIYAZAWA, KEISUKE

    2016-01-01

    Pancreatic cancer is one of the most difficult types of cancer to treat because of its high mortality rate due to chemotherapy resistance. We previously reported that combined treatment with gefitinib (GEF) and clarithromycin (CAM) results in enhanced cytotoxicity of GEF along with endoplasmic reticulum (ER) stress loading in non-small cell lung cancer cell lines. An epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) such as GEF induces autophagy in a pro-survival role, whereas CAM inhibits autophagy flux in various cell lines. Pronounced GEF-induced cytotoxicity therefore appears to depend on the efficacy of autophagy inhibition. In the present study, we compared the effect on autophagy inhibition among such macrolides as CAM, azithromycin (AZM), and EM900, a novel 12-membered non-antibiotic macrolide. We then assessed the enhanced GEF-induced cytotoxic effect on pancreatic cancer cell lines BxPC-3 and PANC-1. Autophagy flux analysis indicated that AZM is the most effective autophagy inhibitor of the three macrolides. CAM exhibits an inhibitory effect but less than AZM and EM900. Notably, the enhancing effect of GEF-induced cytotoxicity by combining macrolides correlated well with their efficient autophagy inhibition. However, this pronounced cytotoxicity was not due to upregulation of apoptosis induction, but was at least partially mediated through necroptosis. Our data suggest the possibility of using macrolides as ‘chemosensitizers’ for EGFR-TKI therapy in pancreatic cancer patients to enhance non-apoptotic tumor cell death induction. PMID:26718641

  13. Macrolides sensitize EGFR-TKI-induced non-apoptotic cell death via blocking autophagy flux in pancreatic cancer cell lines.

    PubMed

    Mukai, Shuntaro; Moriya, Shota; Hiramoto, Masaki; Kazama, Hiromi; Kokuba, Hiroko; Che, Xiao-Fang; Yokoyama, Tomohisa; Sakamoto, Satoshi; Sugawara, Akihiro; Sunazuka, Toshiaki; Ōmura, Satoshi; Handa, Hiroshi; Itoi, Takao; Miyazawa, Keisuke

    2016-01-01

    Pancreatic cancer is one of the most difficult types of cancer to treat because of its high mortality rate due to chemotherapy resistance. We previously reported that combined treatment with gefitinib (GEF) and clarithromycin (CAM) results in enhanced cytotoxicity of GEF along with endoplasmic reticulum (ER) stress loading in non-small cell lung cancer cell lines. An epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) such as GEF induces autophagy in a pro-survival role, whereas CAM inhibits autophagy flux in various cell lines. Pronounced GEF-induced cytotoxicity therefore appears to depend on the efficacy of autophagy inhibition. In the present study, we compared the effect on autophagy inhibition among such macrolides as CAM, azithromycin (AZM), and EM900, a novel 12-membered non-antibiotic macrolide. We then assessed the enhanced GEF-induced cytotoxic effect on pancreatic cancer cell lines BxPC-3 and PANC-1. Autophagy flux analysis indicated that AZM is the most effective autophagy inhibitor of the three macrolides. CAM exhibits an inhibitory effect but less than AZM and EM900. Notably, the enhancing effect of GEF-induced cytotoxicity by combining macrolides correlated well with their efficient autophagy inhibition. However, this pronounced cytotoxicity was not due to upregulation of apoptosis induction, but was at least partially mediated through necroptosis. Our data suggest the possibility of using macrolides as 'chemosensitizers' for EGFR-TKI therapy in pancreatic cancer patients to enhance non-apoptotic tumor cell death induction. PMID:26718641

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

    NASA Astrophysics Data System (ADS)

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

    2015-02-01

    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/μɛ) are experimentally achieved using a droplet with a refractive index of ˜1.44.

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

    SciTech Connect

    Gao, Shecheng; Zhang, Weigang E-mail: haozhang@nankai.edu.cn; Zhang, Hao E-mail: haozhang@nankai.edu.cn; Zhang, Chonglei

    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.

  16. Neutrinos from WIMP annihilation in the Sun: Implications of a self-consistent model of the Milky Way's dark matter halo

    NASA Astrophysics Data System (ADS)

    Kundu, Susmita; Bhattacharjee, Pijushpani

    2012-06-01

    Upper limits on the spin-independent as well as spin-dependent elastic scattering cross sections of low mass (˜2-20GeV) weakly interacting massive particles (WIMPs ) with protons, imposed by the upper limit on the neutrino flux from WIMP annihilation in the Sun given by the Super-Kamiokande (S-K) experiment, and their compatibility with the “DAMA-compatible” regions of the WIMP parameter space—the regions of the WIMP mass versus cross-section parameter space within which the annual modulation signal observed by the DAMA/LIBRA experiment is compatible with the null results of other direct-detection experiments—are studied within the framework of a self-consistent model of the finite-size dark matter halo of the Galaxy. The halo model includes the gravitational influence of the observed visible matter of the Galaxy on the phase-space distribution function of the WIMPs constituting the Galaxy’s dark matter halo in a self-consistent manner. Unlike in the “standard halo model” used in earlier analyses, the velocity distribution of the WIMPs in our model is non-Maxwellian, with a high-velocity cutoff determined self-consistently by the model itself. The parameters of the model are determined from a fit to the rotation curve data of the Galaxy. We find that, for our best-fit halo model, for spin-independent interaction, while the S-K upper limits do not place additional restrictions on the DAMA-compatible region of the WIMP parameter space if the WIMPs annihilate dominantly to b¯b and/or c¯c, portions of the DAMA-compatible region can be excluded if WIMP annihilations to τ+τ- and νν¯ occur at larger than 35% and 0.4% levels, respectively. For spin-dependent interaction, on the other hand, the restrictions on the possible annihilation channels are much more stringent: they rule out the entire DAMA region if WIMPs annihilate to τ+τ- and νν¯ final states at greater than ˜0.05% and 0.0005% levels, respectively, and/or to b¯b and c¯c at greater than ˜0.5% levels. The very latest results from the S-K Collaboration [T. Tanaka , Astrophys. J. 742, 78 (2011)ASJOAB0004-637X10.1088/0004-637X/742/2/78] make the above constraints on the branching fractions of various WIMP annihilation channels even more stringent by roughly a factor of 3-4.

  17. Radiation survival parameters of antineoplastic drug-sensitive and -resistant human ovarian cancer cell lines and their modification by buthionine sulfoximine

    SciTech Connect

    Louie, K.G.; Behrens, B.C.; Kinsella, T.J.; Hamilton, T.C.; Grotzinger, K.R.; McKoy, W.M.; Winker, M.A.; Ozols, R.F.

    1985-05-01

    The optimum integration of chemotherapy and irradiation is of potential clinical significance in the treatment of ovarian cancer. A series of human ovarian cancer cell lines have been developed in which dose-response relationships to standard anticancer drugs have been determined, and the patterns of cross-resistance between these drugs and irradiation have been established. By stepwise incubation with drugs, sublines of A2780, a drug-sensitive cell line, have been made 100-fold, 10-fold, and 10-fold more resistant to Adriamycin (2780AD), melphalan (2780ME), and cisplatin (2780CP). Two additional cell lines, NIH:OVCAR-3nu(Ag+) and NIH:OVCAR-4(Ag+), were established from drug-refractory patients. 2780ME, 2780CP, OVCAR-3nu(Ag+), and OVCAR-4(Ag+) are all cross-resistant to irradiation, with DOS of 146, 187, 143, and 203, respectively. However, 2780AD remains sensitive to radiation, with a DO of 111, which is similar to that of A2780 (101). Glutathione (GSH) levels are elevated in 2780ME, 2780CP, OVCAR-3nu(Ag+), and OVCAR-4(Ag+) to 4.58, 6.13, 12.10, and 15.14 nmol/10(6) cells as compared to A2780, with 1.89 nmol/10(6) cells. However, the GSH level in 2780AD is only minimally higher than that in A2780 (2.94 nmol/10(6) cells). Buthionine sulfoximine, a specific inhibitor of GSH synthesis, significantly increases the radiation sensitivity of 2780ME (changing the DO from 143 to 95) and 2780CP to a lesser extent, suggesting that intracellular GSH levels may play an important role in the radiation response of certain neoplastic cells.

  18. 3-methyladenine-DNA-glycosylase and O6-alkyl guanine-DNA-alkyltransferase activities and sensitivity to alkylating agents in human cancer cell lines.

    PubMed Central

    Damia, G.; Imperatori, L.; Citti, L.; Mariani, L.; D'Incalci, M.

    1996-01-01

    The activities and the expression of 3-methyladenine glycosylase (3-meAde gly) and O6-alkylguanine-DNA-alkyltransferase (O6 ATase) were investigated in ten human cancer cell lines. Both 3-meAde gly and O6 ATase activities were variable among different cell lines. mRNA levels of the O6 ATase gene, appeared to be related to the content of O6 ATase in different cell lines, whereas no apparent correlation was found between mRNA of 3-meAde gly and the enzyme activity. No correlation was found between the activity of the two enzymes and the sensitivity to alkylating agents of different structures such as CC-1065, tallimustine, dimethylsulphate (DMSO), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), cis-diamminedichloroplatinum (cDDP) and melphalan (L-PAM). The most striking finding of this study is that a correlation exists between the activity of O6 ATase and 3-meAde gly in the various cell lines investigated (P<0.01), suggesting a common mechanism of regulation of two DNA repair enzymes. Images Figure 2 PMID:8611396

  19. Lymphoblastoid lines and skin fibroblasts from patients with tuberous sclerosis are abnormally sensitive to ionizing radiation and to a radiomimetic chemical

    SciTech Connect

    Scudiero, D.A.; Moshell, A.N.; Scarpinato, R.G.; Meyer, S.A.; Clatterbuck, B.E.; Tarone, R.E.; Robbins, J.H.

    1982-03-01

    Lymphoblastoid lines, derived by transforming peripheral blood lymphocytes with Epstein-Barr virus, and skin fibroblast lines were established from two patients with tuberous sclerosis. The number of viable lymphoblastoid cells was determined by their ability to exclude the vital dye trypan blue after their irradiation with x-rays or 254 nm ultraviolet light. The growth of fibroblasts was determined by their ability to form colonies after treatment with the radiomimetic, DNA-damaging chemical N-methyl-N'-nitro-N-nitrosoguanidine. The tuberous sclerosis lymphoblastoid lines were hypersensitive to x-rays but had normal sensitivity to the ultraviolet radiation. The tuberous sclerosis fibroblast lines were hypersensitive to the N-methyl-N'-nitro-N-nitrosoguanidine. The hypersensitivity of tuberous sclerosis cells to x-rays and to N-methyl-N'-nitro-N-nitrosoguanidine is believed to reflect defective repair of DNA damaged by these agents and may provide the basis for in vitro, including prenatal, diagnostic tests for tuberous sclerosis.

  20. Antrodia cinnamomea alleviates cisplatin-induced hepatotoxicity and enhances chemo-sensitivity of line-1 lung carcinoma xenografted in BALB/cByJ mice

    PubMed Central

    Huang, Tse-Hung; Chiu, Yi-Han; Chan, Yi-Lin; Wang, Hang; Li, Tsung-Lin; Liu, Chien-Yin; Yang, Cheng-Ta; Lee, Tzung-Yan; You, Jyh-Sheng; Hsu, Kuang-Hung; Wu, Chang-Jer

    2015-01-01

    Whereas cisplatin (cis-diamminedichloroplatinum II) is a first-line medicine to treat solid cancerous tumors, it often causes serious side effects. New medicines that have an equivalent or even better therapeutic effect but with free or less side effects than cisplatin are highly anticipated in cancer therapy. Recent reports revealed that Antrodia cinnamomea (AC) possesses hepatoprotective activity in addition to anticancer. In this study, we wanted to know whether AC enhances chemo-sensitivity of cisplatin and/or alleviates cisplatin-induced hepatotoxicity, as well as the underlying mechanisms thereof. Our results indicated that AC inhibited proliferation of line-1 lung carcinoma cells and rescued hepatic HepG2 cells from cisplatin-induced cell death in vitro. The fact is that AC and cisplatin synergized to constrain growth of line-1 lung carcinoma cells in BALB/cByJ mice. Quantitative real-time PCR further revealed that AC promoted expression of apoptosis-related genes, while it decreased expression of NF-κB and VEGF in tumor tissues. In liver, AC reduced cisplatin-induced liver dysfunctions, liver inflammation and hepatic apoptosis in addition to body weight restoration. In summary, AC is able to increase cisplatin efficacy by triggering expression of apoptosis-related genes in line-1 lung cancer cells as well as to protect liver from tissue damage by avoiding cisplatin-induced hepatic inflammation and cell death. PMID:26325335

  1. Antrodia cinnamomea alleviates cisplatin-induced hepatotoxicity and enhances chemo-sensitivity of line-1 lung carcinoma xenografted in BALB/cByJ mice.

    PubMed

    Huang, Tse-Hung; Chiu, Yi-Han; Chan, Yi-Lin; Wang, Hang; Li, Tsung-Lin; Liu, Chien-Yin; Yang, Cheng-Ta; Lee, Tzung-Yan; You, Jyh-Sheng; Hsu, Kuang-Hung; Wu, Chang-Jer

    2015-09-22

    Whereas cisplatin (cis-diamminedichloroplatinum II) is a first-line medicine to treat solid cancerous tumors, it often causes serious side effects. New medicines that have an equivalent or even better therapeutic effect but with free or less side effects than cisplatin are highly anticipated in cancer therapy. Recent reports revealed that Antrodia cinnamomea (AC) possesses hepatoprotective activity in addition to anticancer. In this study, we wanted to know whether AC enhances chemo-sensitivity of cisplatin and/or alleviates cisplatin-induced hepatotoxicity, as well as the underlying mechanisms thereof. Our results indicated that AC inhibited proliferation of line-1 lung carcinoma cells and rescued hepatic HepG2 cells from cisplatin-induced cell death in vitro. The fact is that AC and cisplatin synergized to constrain growth of line-1 lung carcinoma cells in BALB/cByJ mice. Quantitative real-time PCR further revealed that AC promoted expression of apoptosis-related genes, while it decreased expression of NF-?B and VEGF in tumor tissues. In liver, AC reduced cisplatin-induced liver dysfunctions, liver inflammation and hepatic apoptosis in addition to body weight restoration. In summary, AC is able to increase cisplatin efficacy by triggering expression of apoptosis-related genes in line-1 lung cancer cells as well as to protect liver from tissue damage by avoiding cisplatin-induced hepatic inflammation and cell death. PMID:26325335

  2. Genetic protein TmSm(T34A) enhances sensitivity of chemotherapy to breast cancer cell lines as a synergistic drug to doxorubicin.

    PubMed

    Xu, Yuxin; Zheng, Wenyun; Wang, Tianwen; Wang, Ping; Zhu, Ling; Ma, Xingyuan

    2012-07-01

    In order to eliminate common side effects to cancer patients and resistance from chemotherapy, a genetic protein TmSm(T34A) was investigated as a sensitizer to doxorubicin. The results indicated TmSm(T34A) enhanced the sensitivity of three breast cancer cell lines to doxorubicin with low dose, and reduced the dose of doxorubicin significantly in contrast to common effective dose. As a synergistic therapy, the TmSm(T34A) also caused strongest apoptotic activity in MCF-7, and the possible molecular mechanisms were explored primarily. The research showed the TmSm(T34A) is promising to be a potential drug in strengthening therapy effects of breast cancer chemotherapy. PMID:22560635

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

    SciTech Connect

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

    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.

  4. Medullary lateral line units of rudd, Scardinius erythrophthalmus, are sensitive to Kármán vortex streets.

    PubMed

    Klein, Adrian; Winkelnkemper, Jan; Dylda, Evelyn; Bleckmann, Horst

    2015-07-01

    We investigated the responses of medullary lateral line units of the rudd, Scardinius erythrophthalmus, to bulk water flow (7 cm s(-1)) and to water flow that contained vortices shed by an upstream half cylinder (diameter 1, 2, and 3 cm). Thirty-five percent of the medullary units either increased or decreased their discharge rate with the increasing cylinder diameter. In some units, the spike patterns revealed the vortex shedding frequency, i.e., in these units the amplitude of spike train frequency spectra was similar or identical to the vortex shedding frequency. PMID:26018072

  5. A subset of cancer cell lines is acutely sensitive to the Chk1 inhibitor MK-8776 as monotherapy due to CDK2 activation in S phase

    PubMed Central

    Sakurikar, Nandini; Thompson, Ruth; Montano, Ryan; Eastman, Alan

    2016-01-01

    DNA damage activates Checkpoint kinase 1 (Chk1) to halt cell cycle progression thereby preventing further DNA replication and mitosis until the damage has been repaired. Consequently, Chk1 inhibitors have emerged as promising anticancer therapeutics in combination with DNA damaging drugs, but their single agent activity also provides a novel approach that may be particularly effective in a subset of patients. From analysis of a large panel of cell lines, we demonstrate that 15% are very sensitive to the Chk1 inhibitor MK-8776. Upon inhibition of Chk1, sensitive cells rapidly accumulate DNA double-strand breaks in S phase in a CDK2- and cyclin A-dependent manner. In contrast, resistant cells can continue to grow for at least 7 days despite continued inhibition of Chk1. Resistance can be circumvented by inhibiting Wee1 kinase and thereby directly activating CDK2. Hence, sensitivity to Chk1 inhibition is regulated upstream of CDK2 and correlates with accumulation of CDC25A. We conclude that cells poorly tolerate CDK2 activity in S phase and that a major function of Chk1 is to ensure it remains inactive. Indeed, inhibitors of CDK1 and CDK2 arrest cells in G1 or G2, respectively, but do not prevent progression through S phase demonstrating that neither kinase is required for S phase progression. Inappropriate activation of CDK2 in S phase underlies the sensitivity of a subset of cell lines to Chk1 inhibitors, and this may provide a novel therapeutic opportunity for appropriately stratified patients. PMID:26595527

  6. A subset of cancer cell lines is acutely sensitive to the Chk1 inhibitor MK-8776 as monotherapy due to CDK2 activation in S phase.

    PubMed

    Sakurikar, Nandini; Thompson, Ruth; Montano, Ryan; Eastman, Alan

    2016-01-12

    DNA damage activates Checkpoint kinase 1 (Chk1) to halt cell cycle progression thereby preventing further DNA replication and mitosis until the damage has been repaired. Consequently, Chk1 inhibitors have emerged as promising anticancer therapeutics in combination with DNA damaging drugs, but their single agent activity also provides a novel approach that may be particularly effective in a subset of patients. From analysis of a large panel of cell lines, we demonstrate that 15% are very sensitive to the Chk1 inhibitor MK-8776. Upon inhibition of Chk1, sensitive cells rapidly accumulate DNA double-strand breaks in S phase in a CDK2- and cyclin A-dependent manner. In contrast, resistant cells can continue to grow for at least 7 days despite continued inhibition of Chk1. Resistance can be circumvented by inhibiting Wee1 kinase and thereby directly activating CDK2. Hence, sensitivity to Chk1 inhibition is regulated upstream of CDK2 and correlates with accumulation of CDC25A. We conclude that cells poorly tolerate CDK2 activity in S phase and that a major function of Chk1 is to ensure it remains inactive. Indeed, inhibitors of CDK1 and CDK2 arrest cells in G1 or G2, respectively, but do not prevent progression through S phase demonstrating that neither kinase is required for S phase progression. Inappropriate activation of CDK2 in S phase underlies the sensitivity of a subset of cell lines to Chk1 inhibitors, and this may provide a novel therapeutic opportunity for appropriately stratified patients. PMID:26595527

  7. Radio-sensitization of the murine osteosarcoma cell line LM8 with parthenolide, a natural inhibitor of NF-κB

    PubMed Central

    SUGIYASU, KENJIRO; NANNO, KATSUHIKO; TAMAI, NORIYUKI; HASHIMOTO, NOBUYUKI; KISHIDA, YUKI; YOSHIKAWA, HIDEKI; MYOUI, AKIRA

    2011-01-01

    Nuclear factor (NF)-κB has been shown to be associated with cancer resistance to radiotherapy (RT), and is constitutively active in the murine osteosarcoma cell line, LM8. Parthenolide has been reported to show antitumor activity through inhibition of the NF-κB pathway. In this study, we investigated the radio-sensitizing activity of parthenolide. We established Luc-LM8, a stable transfectant reporter construct of NF-κB transcriptional activity into LM8. Luc-LM8 maintained the malignancy observed with LM8. In vitro, Luc-LM8 cells were cultured with or without parthenolide treatment, irradiated, and subjected to cell viability and apoptosis assays. In vivo, to investigate whether parthenolide enhances radio-sensitivity of tumors, a tumor growth assay was conducted. Parthenolide enhanced the growth inhibitory effect of RT and induced the apoptosis of Luc-LM8 cells with RT in vitro. The in vivo tumor growth was significantly suppressed in the mice treated with parthenolide and RT. The present study suggests that parthenolide sensitizes Luc-LM8 cells to irradiation. Thus, parthenolide is a potential candidate for use as a potent radio-sensitizing drug for use in cancer RT. PMID:22866095

  8. Discovery of underground argon with low level of radioactive 39Ar and possible applications to WIMP dark matter detectors

    NASA Astrophysics Data System (ADS)

    Acosta-Kane, D.; Acciarri, R.; Amaize, O.; Antonello, M.; Baibussinov, B.; Baldo Ceolin, M.; Ballentine, C. J.; Bansal, R.; Basgall, L.; Bazarko, A.; Benetti, P.; Benziger, J.; Burgers, A.; Calaprice, F.; Calligarich, E.; Cambiaghi, M.; Canci, N.; Carbonara, F.; Cassidy, M.; Cavanna, F.; Centro, S.; Chavarria, A.; Cheng, D.; Cocco, A. G.; Collon, P.; Dalnoki-Veress, F.; de Haas, E.; Di Pompeo, F.; Fiorillo, G.; Fitch, F.; Gallo, V.; Galbiati, C.; Gaull, M.; Gazzana, S.; Grandi, L.; Goretti, A.; Highfill, R.; Highfill, T.; Hohman, T.; Ianni, Al.; Ianni, An.; LaCava, A.; Laubenstein, M.; Lee, H. Y.; Leung, M.; Loer, B.; Loosli, H. H.; Lyons, B.; Marks, D.; McCarty, K.; Meng, G.; Montanari, C.; Mukhopadhyay, S.; Nelson, A.; Palamara, O.; Pandola, L.; Pietropaolo, F.; Pivonka, T.; Pocar, A.; Purtschert, R.; Rappoldi, A.; Raselli, G.; Resnati, F.; Robertson, D.; Roncadelli, M.; Rossella, M.; Rubbia, C.; Ruderman, J.; Saldanha, R.; Schmitt, C.; Scott, R.; Segreto, E.; Shirley, A.; Szelc, A. M.; Tartaglia, R.; Tesileanu, T.; Ventura, S.; Vignoli, C.; Visnjic, C.; Vondrasek, R.; Yushkov, A.

    2008-03-01

    We report on the first measurement of 39Ar in argon from underground natural gas reservoirs. The gas stored in the US National Helium Reserve was found to contain a low level of 39Ar. The ratio of 39Ar to stable argon was measured to be ?410-17 (84% C.L.), less than 5% the value in atmospheric argon ( 39Ar/Ar=810-16). The total quantity of argon currently stored in the National Helium Reserve is estimated at 1000 tons. 39Ar represents one of the most important backgrounds in argon detectors for WIMP dark matter searches. The findings reported demonstrate the possibility of constructing large multi-ton argon detectors with low radioactivity suitable for WIMP dark matter searches.

  9. Discovery of underground argon with a low level of radioactive 39Ar and possible applications to WIMP dark matter detectors

    NASA Astrophysics Data System (ADS)

    Galbiati, C.; Acosta-Kane, D.; Acciarri, R.; Amaize, O.; Antonello, M.; Baibussinov, B.; Ceolin, M. B.; Ballentine, C. J.; Bansal, R.; Basgall, L.; Bazarko, A.; Benetti, P.; Benziger, J.; Burgers, A.; Calaprice, F.; Calligarich, E.; Cambiaghi, M.; Canci, N.; Carbonara, F.; Cassidy, M.; Cavanna, F.; Centro, S.; Chavarria, A.; Cheng, D.; Cocco, A. G.; Collon, P.; Dalnoki-Veress, F.; de Haas, E.; Di Pompeo, F.; Fiorillo, G.; Fitch, F.; Gallo, V.; Gaull, M.; Gazzana, S.; Grandi, L.; Goretti, A.; Highfill, R.; Highfill, T.; Hohman, T.; Ianni, A.; Ianni, A.; La Cava, A.; Laubenstein, M.; Lee, H. Y.; Leung, M.; Loer, B.; Loosli, H. H.; Lyons, B.; Marks, D.; McCarty, K.; Meng, G.; Montanari, C.; Mukhopadhyay, S.; Nelson, A.; Palamara, O.; Pandola, L.; Pietropaolo, F.; Pivonka, T.; Pocar, A.; Purtschert, R.; Rappoldi, A.; Raselli, G.; Resnati, F.; Robertson, D.; Roncadelli, M.; Rossella, M.; Rubbia, C.; Ruderman, J.; Saldanha, R.; Schmitt, C.; Scott, R.; Segreto, E.; Shirley, A.; Szelc, A. M.; Tartaglia, R.; Tesileanu, T.; Ventura, S.; Vignoli, C.; Visnjic, C.; Vondrasek, R.; Yushkov, A.

    2008-07-01

    We report on the first measurement of 39Ar in argon from underground natural gas reservoirs. The gas stored in the US National Helium Reserve was found to contain a low level of 39Ar. The ratio of 39Ar to stable argon was found to be <=410-17 (84% C.L.), less than 5% the value in atmospheric argon (39Ar/Ar=810-16). The total quantity of argon currently stored in the National Helium Reserve is estimated at 1000 tons. 39Ar represents one of the most important backgrounds in argon detectors for WIMP dark matter searches. The findings reported demonstrate the possibility of constructing large multi-ton argon detectors with low radioactivity suitable for WIMP dark matter searches.

  10. Discovery of underground argon with low level of radioactive 39Ar and possible applications to WIMP dark matter detectors.

    NASA Astrophysics Data System (ADS)

    Galbiati, Cristiano

    2008-04-01

    We report on the first measurement of 39Ar in argon from underground natural gas reservoirs. The gas stored in the US National Helium Reserve was found to contain a low level of 39Ar. The ratio of 39Ar to stable argon was found to be <4x10-17 (84% C.L.), less than 5% the value in atmospheric argon (39Ar/Ar=8x10-16). The total quantity of argon currently stored in the National Helium Reserve is estimated at 1000 tons. 39Ar represents one of the most important backgrounds in argon detectors for WIMP dark matter searches. The findings reported demonstrate the possibility of constructing large multi-ton argon detectors with low radioactivity suitable for WIMP dark matter searches.

  11. Limits on Spin-Independent Couplings of WIMP Dark Matter with a p-Type Point-Contact Germanium Detector

    NASA Astrophysics Data System (ADS)

    Li, H. B.; Liao, H. Y.; Lin, S. T.; Liu, S. K.; Singh, L.; Singh, M. K.; Soma, A. K.; Wong, H. T.; Wu, Y. C.; Zhao, W.; Asryan, G.; Chuang, Y. C.; Deniz, M.; Fang, J. M.; Hsu, C. L.; Huang, T. R.; Kiran Kumar, G.; Lee, S. C.; Li, J.; Li, J. M.; Li, Y. J.; Li, Y. L.; Lin, C. W.; Lin, F. K.; Liu, Y. F.; Ma, H.; Ruan, X. C.; Shen, Y. T.; Singh, V.; Tang, C. J.; Tseng, C. H.; Xu, Y.; Yang, S. W.; Yu, C. X.; Yue, Q.; Zeng, Z.; Zeyrek, M.; Zhou, Z. Y.

    2013-06-01

    We report new limits on a spin-independent weakly interacting massive particle (WIMP)-nucleon interaction cross section using 39.5 kg days of data taken with a p-type point-contact germanium detector of 840 g fiducial mass at the Kuo-Sheng Reactor Neutrino Laboratory. Crucial to this study is the understanding of the selection procedures and, in particular, the bulk-surface events differentiation at the sub-keV range. The signal-retaining and background-rejecting efficiencies were measured with calibration gamma sources and a novel n-type point-contact germanium detector. Part of the parameter space in the cross section versus WIMP-mass implied by various experiments is probed and excluded.

  12. Increased radiation sensitivity of an eosinophilic cell line following treatment with epigallocatechin-gallate, resveratrol and curcuma.

    PubMed

    Baatout, Sarah; Derradji, Hanane; Jacquet, Paul; Mergeay, Max

    2005-02-01

    Ionizing radiation is widely used in radiotherapy, in order to promote an apoptotic response in cancerous cells. Since the need to find new substances that would enhance the radiation-induced apoptosis in cancerous cells is great, we studied the effect of epigallocatechin-gallate (EGCG, a tea component), resveratrol (a wine component) and curcuma on cell proliferation and radiation-induced apoptosis in the human leukaemic cell line, EOL-1, derived from a patient with eosinophilic leukaemia. Cells were X-irradiated with 0, 2, 4, 6 or 8 Gy and cultured in the presence of EGCG, resveratrol or curcuma (concentrations ranging from 0 to 200 microM) for 1, 2 or 3 days of culture. Cell proliferation was measured using trypan blue exclusion. Apoptosis was evaluated using light microscopy (morphology study after May-Grunwald Giemsa staining) and flow cytometry (annexin-V staining). Irradiation alone induced a dose-related reduction in cell proliferation and the appearance of polyploid cells in EOL-1 cells. Additionally, EOL-1 cells underwent a dose-related increase of apoptosis which, from the second day on, was accompanied by a dose-related increase of necrosis. When cells were exposed to EGCG, resveratrol or curcuma alone, a decrease in cell proliferation was observed, beginning from 25 microM EGCG and 50 microM resveratrol and curcuma, while an increase in the percentage of apoptotic cells was noted from 50 microM EGCG, 100 microM resveratrol and curcuma in EOL-1 cells, after only one day of culture. Simultaneous exposure to X-irradiation and, EGCG, resveratrol or curcuma resulted in a synergistic decrease of cell proliferation as well as in a synergistic increase of apoptosis and necrosis. These results suggest that, depending on the concentration, EGCG, resveratrol and curcuma enhance radiation-induced apoptosis in the leukaemic cell line, EOL-1 (EGCG >resveratrol >curcuma). In order to further characterise the radiation-induced apoptosis of this leukaemic cell line, other flow cytometrical analyses are in progress. PMID:15647852

  13. Identification of death receptors DR4 and DR5 in HTB-12 astrocytoma cell lines and determination of TRAIL sensitivity

    PubMed Central

    Riddick, Elenia; Evans, Shavonda; Rousch, Jeffrey; Gwebu, Ephraim; Banerjee, Hirendra Nath

    2014-01-01

    Astrocytomas are tumors which arise from astrocytes, cells that form the blood-brain barrier. There are very few drugs that successfully treat brain tumors. In this study, the cytotoxic effects on the HTB-12 astrocytoma cell line by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were studied. The presence of the TRAIL receptors, Death receptor 4 (DR4) and Death receptor 5 (DR5), were detected in HTB-12 cells by Enzyme-Linked Immunosorbent Assay (ELISA). Cytotoxicity assay by Trypan Blue Exclusion Method showed effective cell killing by TRAIL treatment. Thus, the presence of death receptors and TRAIL efficacy raises the therapeutic potential for this type of brain tumor. PMID:25364476

  14. Reversal effect of arsenic sensitivity in human leukemia cell line K562 and K562/ADM using realgar transforming solution.

    PubMed

    Wang, Xin; Zhang, Xu; Xu, Zhiliang; Wang, Zhizeng; Yue, Xiaoxuan; Li, Hongyu

    2013-01-01

    The success of arsenic trioxide (ATO) in treatment of acute promyelocytic leukemia (APL) attracts a great deal of attention to researchers to explore its activity of anti-leukemia. However, ATO has unavailable effect on chronic myeloid leukemia (CML), especially multidrug resistant (MDR)-CML, unless using high concentration. Realgar (As(4)S(4)) has been employed in Chinese traditional medicine for 1500 years. Research evidences confirmed realgar has similar effect on treating with APL as ATO, but the problem of large dose and long period in the CML/MDR-CML treatment still exist. By using a microbial leaching process with Acidithiobacillus ferrooxidans, we obtained realgar transforming solution (RTS) which showed significantly higher extent in inhibiting CML cell line K562 and MDR-CML cell line K562/ADM, and then trigger apoptosis. Both K562 and K562/ADM showed arsenic-dose-dependent effect on RTS. Interestingly, the overexpression of MDR1 mRNA and P-glucoprotein (P-gp) in K562/ADM cells were down-regulated by RTS, where there are no obvious effects on ATO and realgar and arsenic can be subsequently accumulated in K562/ADM cells efficiently. The intracellular accumulation of arsenic in K562/ADM cells treated with RTS for 4 h was 2-fold and 16-folds higher than those treated with realgar or ATO. Meanwhile, Western blot analysis of AQP9, the main transporter of arsenic, was increased by RTS treatment particularly in K562/ADM. Thus, these results suggested that the effect from a certain arsenical or a variety of arsenicals in RTS might be a promising candidate both for treating CML/MDR-CML alone and as combinations with currently used anti-CML/MDR-CML drug, although arsenical forms in RTS are undefined. PMID:23358330

  15. 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

    SciTech Connect

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

    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.

  16. Estrogen Receptor ? Isoform 5 Confers Sensitivity of Breast Cancer Cell Lines to Chemotherapeutic Agent-Induced Apoptosis through Interaction with Bcl2L1212

    PubMed Central

    Lee, Ming-Tsung; Ho, Shuk-Mei; Tarapore, Pheruza; Chung, Irving; Leung, Yuet-Kin

    2013-01-01

    Alternative splicing of estrogen receptor ? (ER?) yields five isoforms, but their functions remain elusive. ER? isoform 5 (ER?5) has been positively correlated with better prognosis and longer survival of patients with breast cancer (BCa) in various clinical studies. In this study, we investigated the inhibitory role of ER?5 in BCa cells. Although ER?5 does not reduce proliferation of BCa cell lines MCF-7 and MDA-MB-231, its ectopic expression significantly decreases their survival by sensitizing them to doxorubicin- or cisplatin-induced apoptosis through the intrinsic apoptotic pathway. Moreover, we discovered Bcl2L12, which belongs to the Bcl-2 family regulating apoptosis, to be a specific interacting partner of ER?5, but not ER?1 or ER?, in an estradiol-independent manner. Knockdown of Bcl2L12 enhanced doxorubicin- or cisplatin-induced apoptosis, and this process was further promoted by ectopic expression of ER?5. Whereas Bcl2L12 was previously shown to inhibit apoptosis through binding to caspase 7, such interaction is reduced in the presence of ER?5, suggesting a mechanism by which ER?5 sensitizes cells to apoptosis. In conclusion, ER?5 interacts with Bcl2L12 and functions in a novel estrogen-independent molecular pathway that promotes chemotherapeutic Agent-Induced in vitro apoptosis of BCa cell lines. PMID:24339738

  17. Sensitivity to cisplatin in primary cell lines derived from human glioma correlates with levels of EGR-1 expression

    PubMed Central

    2011-01-01

    Background Less than 30% of malignant gliomas respond to adjuvant chemotherapy. Here, we have asked whether variations in the constitutive expression of early-growth response factor 1 (EGR-1) predicted acute cytotoxicity and clonogenic cell death in vitro, induced by six different chemotherapics. Materials and methods Cytotoxicity assays were performed on cells derived from fresh tumor explants of 18 human cases of malignant glioma. In addition to EGR-1, tumor cultures were investigated for genetic alterations and the expression of cancer regulating factors, related to the p53 pathway. Results We found that sensitivity to cisplatin correlates significantly with levels of EGR-1 expression in tumors with wild-type p53/INK4a/p16 status. Conclusion Increased knowledge of the mechanisms regulating EGR-1 expression in wild-type p53/INK4a/p16 cases of glioma may help in the design of new chemotherapeutic strategies for these tumors. PMID:21366897

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

    PubMed

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

    2015-07-01

    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. PMID:25963028

  19. Development and characterization of a cell line from Pacific herring, Clupea harengus pallasi, sensitive to both naphthalene cytotoxicity and infection by viral hemorrhagic septicemia virus.

    PubMed

    Ganassin, R C; Sanders, S M; Kennedy, C J; Joyce, E M; Bols, N C

    1999-01-01

    A cell line, PHL, has been successfully established from newly hatched herring larvae. The cells are maintained in growth medium consisting of Leibovitz's L-15 supplemented with 15% fetal bovine serum (FBS), and have been cryopreserved and maintain viability after thawing. These cells retain a diploid karotype after 65 population doublings. PHL are susceptible to infection by the North American strain of viral hemorrhagic septicemia (VHS) virus, and are sensitive to the cytotoxic effects of naphthalene, a common environmental contaminant. Naphthalene is a component of crude and refined oil, and may be found in the marine environment following acute events such as oil spills. In addition, chronic sources of naphthalene contamination include offshore drilling and petroleum contamination from areas such as docks and marinas that have creosote-treated docks and pilings and also receive constant small inputs of petroleum products. This cell line should be useful for investigations of the toxicity of naphthalene and other petroleum components to juvenile herring. In addition, studies of the VHS virus will be facilitated by the availability of a susceptible cell line from an alternative species. PMID:10813363

  20. A gallotannin-rich fraction from Caesalpinia spinosa (Molina) Kuntze displays cytotoxic activity and raises sensitivity to doxorubicin in a leukemia cell line

    PubMed Central

    2012-01-01

    Background Enhancement of tumor cell sensitivity may help facilitate a reduction in drug dosage using conventional chemotherapies. Consequently, it is worthwhile to search for adjuvants with the potential of increasing chemotherapeutic drug effectiveness and improving patient quality of life. Natural products are a very good source of such adjuvants. Methods The biological activity of a fraction enriched in hydrolysable polyphenols (P2Et) obtained from Caesalpinia spinosa was evaluated using the hematopoietic cell line K562. This fraction was tested alone or in combination with the conventional chemotherapeutic drugs doxorubicin, vincristine, etoposide, camptothecin and taxol. The parameters evaluated were mitochondrial depolarization, caspase 3 activation, chromatin condensation and clonogenic activity. Results We found that the P2Et fraction induced mitochondrial depolarization, activated caspase 3, induced chromatin condensation and decreased the clonogenic capacity of the K562 cell line. When the P2Et fraction was used in combination with chemotherapeutic drugs at sub-lethal concentrations, a fourfold reduction in doxorubicin inhibitory concentration 50 (IC50) was seen in the K562 cell line. This finding suggested that P2Et fraction activity is specific for the molecular target of doxorubicin. Conclusions Our results suggest that a natural fraction extracted from Caesalpinia spinosa in combination with conventional chemotherapy in combination with natural products on leukemia cells may increase therapeutic effectiveness in relation to leukemia. PMID:22490328

  1. Molecular Mechanism for the Thermo-Sensitive Phenotype of CHO-MT58 Cell Line Harbouring a Mutant CTP:Phosphocholine Cytidylyltransferase

    PubMed Central

    Marton, Lívia; Nagy, Gergely N.; Ozohanics, Olivér; Lábas, Anikó; Krámos, Balázs; Oláh, Julianna; Vékey, Károly; Vértessy, Beáta G.

    2015-01-01

    Control and elimination of malaria still represents a major public health challenge. Emerging parasite resistance to current therapies urges development of antimalarials with novel mechanism of action. Phospholipid biosynthesis of the Plasmodium parasite has been validated as promising candidate antimalarial target. The most prevalent de novo pathway for synthesis of phosphatidylcholine is the Kennedy pathway. Its regulatory and often also rate limiting step is catalyzed by CTP:phosphocholine cytidylyltransferase (CCT). The CHO-MT58 cell line expresses a mutant variant of CCT, and displays a thermo-sensitive phenotype. At non-permissive temperature (40°C), the endogenous CCT activity decreases dramatically, blocking membrane synthesis and ultimately leading to apoptosis. In the present study we investigated the impact of the analogous mutation in a catalytic domain construct of Plasmodium falciparum CCT in order to explore the underlying molecular mechanism that explains this phenotype. We used temperature dependent enzyme activity measurements and modeling to investigate the functionality of the mutant enzyme. Furthermore, MS measurements were performed to determine the oligomerization state of the protein, and MD simulations to assess the inter-subunit interactions in the dimer. Our results demonstrate that the R681H mutation does not directly influence enzyme catalytic activity. Instead, it provokes increased heat-sensitivity by destabilizing the CCT dimer. This can possibly explain the significance of the PfCCT pseudoheterodimer organization in ensuring proper enzymatic function. This also provide an explanation for the observed thermo-sensitive phenotype of CHO-MT58 cell line. PMID:26083347

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

    NASA Astrophysics Data System (ADS)

    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.

  3. Osmotic stress regulates mineralocorticoid receptor expression in a novel aldosterone-sensitive cortical collecting duct cell line

    PubMed Central

    Viengchareun, Say; Kamenicky, Peter; Teixeira, Marie; Butlen, Daniel; Meduri, Géri; Blanchard-Gutton, Nicolas; Kurschat, Christine; Lanel, Aurelie; Martinerie, Laetitia; Sztal-Mazer, Soshana; Blot-Chabaud, Marcel; Ferrary, Evelyne; Cherradi, Nadia; Lombès, Marc

    2009-01-01

    Aldosterone effects are mediated by the mineralocorticoid receptor (MR), a transcription factor highly expressed in the distal nephron. Given that MR expression level constitutes a key element controlling hormone responsiveness, there is much interest in elucidating the molecular mechanisms governing MR expression. To investigate whether hyper- or hypotonicity could affect MR abundance, we established by targeted oncogenesis a novel immortalized cortical collecting duct (CCD) cell line and examined the impact of osmotic stress on MR expression. KC3AC1 cells form domes, exhibit a high transepithelial resistance, express 11 β-hydroxysteroid dehydrogenase 2 and functional endogenous MR, which mediates aldosterone-stimulated Na+ reabsorption through the epithelial sodium channel activation. MR expression is tightly regulated by osmotic stress. Hypertonic conditions induce expression of TonEBP, an osmoregulatory transcription factor capable of binding TonE response elements located in MR regulatory sequences. Surprisingly, hypertonicity leads to a severe reduction in MR transcript and protein levels. This is accompanied by a concomitant tonicity-induced expression of Tis11b, a mRNA-destabilizing protein which, by binding to the AU-rich sequences of the 3′-UTR of MR mRNA, may favor hypertonicity-dependent degradation of labile MR transcripts. In sharp contrast, hypotonicity causes a strong increase in MR transcript and protein levels. Collectively, we demonstrate for the first time that optimal adaptation of CCD cells to changes in extracellular fluid composition is accompanied by drastic modification in MR abundance via transcriptional and post-transcriptional mechanisms. Osmotic stress-regulated MR expression may represent an important molecular determinant for cell-specific MR action, most notably in renal failure, hypertension, or mineralocorticoid resistance. PMID:19846540

  4. Differential modulation of nuclear texture, histone acetylation, and MDR1 gene expression in human drug-sensitive and -resistant OV1 cell lines.

    PubMed

    Yatouji, Sonia; El-Khoury, Victoria; Trentesaux, Chantal; Trussardi-Regnier, Aurelie; Benabid, Rym; Bontems, Franck; Dufer, Jean

    2007-04-01

    Image cytometric study of pathological specimens or cell lines has suggested that epigenetic mechanisms are likely to play a major role in determining chromatin patterns evaluable through nuclear texture analysis. We previously reported that nuclear textural changes observed in the OV1-VCR etoposide-resistant ovarian carcinoma cell line were associated with an increased acetylated histone H4 level. In this study we analyzed the effects of treatments with the HDAC inhibitor trichostatin A (TSA) or with nickel subsulfide on histone H4 acetylation, nuclear texture, and MDR1 gene expression in drug-sensitive IGROV1 and drug-resistant OV1-VCR cell lines. In IGROV1 cells, TSA induced an increase in acetylated H4 level associated with a chromatin textural decondensation and an increase in MDR1 gene expression. In OV1-VCR cells, a similar increase in H4 acetylation was observed, but nuclear texture or MDR1 gene expression remained unchanged. ChIP analysis revealed that MDR1 gene expression remained stable in TSA-treated OV1-VCR cells despite a localized increase in H4 acetylation at the promoter level. Analysis of the methylation status of MDR1 promoter showed an increase in DNA methylation at 3 specific sites in OV1-VCR cells, that could participate to TSA low responsiveness in these cells. Treatment with nickel subsulfide induced a decrease in H4 acetylation without any effect on nuclear texture characteristics in both cell lines. In OV1-VCR cells, nickel subsulfide induced a significant down-regulation of the MDR1 gene expression. These results indicate that modulation of histone H4 acetylation level can be associated with up- or down-regulation of the MDR1 gene in OV1 cells. However, this modulation does not always result in chromatin pattern alterations and these data emphasize the complexity of chromatin texture regulation in tumor cells. PMID:17332941

  5. RESTORATION OF ENDOGENOUS WILD-TYPE p53 ACTIVITY IN A GLIOBLASTOMA CELL LINE WITH INTRINSIC TEMPERATURE-SENSITIVE p53 INDUCES GROWTH ARREST BUT NOT APOPTOSIS

    PubMed Central

    Ikeda, Jun; Tada, Mitsuhiro; Ishii, Nobuaki; Saya, Hideyuki; Tsuchiya, Kazuhiko; Okaichi, Kumio; Mishima, Kazuhiko; Sawamura, Yutaka; Fulci, Giulia; Liu, Ta-Jen; Van Meir, Erwin G.

    2010-01-01

    p53 protein is a transcription factor involved in multiple tumor-suppressor activities including cell cycle control and apoptosis. TP53 gene is frequently mutated in glioblastoma, suggesting the importance of inactivation of this gene product in gliomagenesis. Restoration of p53 function in glioblastoma cell lines deficient for p53 has shown that p53 induces growth arrest or apoptosis depending on the cell line and vector used to transduce wild-type TP53 alleles. Considering that astrocytes grow and express p53, it is not clear whether these results reflect physiologic responses or the result of p53 overexpression in combination with cellular responses to viral vector infection. Here, we reassessed this issue using a glioblastoma cell line (LN382) that expresses an endogenous temperature-sensitive mutant p53. This cell line expresses TP53 alleles (100% as determined by a p53 transcriptional assay in yeast) mutated at codon 197 GTG (Val) > CTG (Leu). We found that the p53 protein in these cells acted as an inactive mutant at 37°C and as a functional wild-type p53 below 34°C as demonstrated by several lines of evidence, including (i) restoration of transactivating ability in yeast, (ii) induction of p53-modulated genes such as CDKN1p21 and transforming growth factor-α, (iii) disappearance of accumulated p53 protein in the nucleus and (iv) decrease in steady state p53 protein levels. This temperature switch allowed p53 levels, which were close to physiological levels to dramatically reduce LN382 cell proliferation by inducing a G1/S cell cycle block, but not to induce apoptosis. The lack of apoptosis was considered to be a result of the low level p53 expression, because increasing wild-type p53 levels by adenoviral-mediated gene transfer caused apoptosis in these cells. The LN382 cell line will be extremely useful for investigations into the roles of p53 in cellular responses to a variety of stimuli or damages. PMID:11668476

  6. Dependence of tumor cell lines and patient-derived tumors on the NAD salvage pathway renders them sensitive to NAMPT inhibition with GNE-618.

    PubMed

    Xiao, Yang; Elkins, Kristi; Durieux, Jenni K; Lee, Leslie; Oeh, Jason; Yang, Lulu X; Liang, Xiaorong; DelNagro, Chris; Tremayne, Jarrod; Kwong, Mandy; Liederer, Bianca M; Jackson, Peter K; Belmont, Lisa D; Sampath, Deepak; O'Brien, Thomas

    2013-10-01

    Nicotinamide adenine dinucleotide (NAD) is a critical metabolite that is required for a range of cellular reactions. A key enzyme in the NAD salvage pathway is nicotinamide phosphoribosyl transferase (NAMPT), and here, we describe GNE-618, an NAMPT inhibitor that depletes NAD and induces cell death in vitro and in vivo. While cells proficient for nicotinic acid phosphoribosyl transferase (NAPRT1) can be protected from NAMPT inhibition as they convert nicotinic acid (NA) to NAD independent of the salvage pathway, this protection only occurs if NA is added before NAD depletion. We also demonstrate that tumor cells are unable to generate NAD by de novo synthesis as they lack expression of key enzymes in this pathway, thus providing a mechanistic rationale for the reliance of tumor cells on the NAD salvage pathway. Identifying tumors that are sensitive to NAMPT inhibition is one potential way to enhance the therapeutic effectiveness of an NAMPT inhibitor, and here, we show that NAMPT, but not NAPRT1, mRNA and protein levels inversely correlate with sensitivity to GNE-618 across a panel of 53 non-small cell lung carcinoma cell lines. Finally, we demonstrate that GNE-618 reduced tumor growth in a patient-derived model, which is thought to more closely represent heterogeneous primary patient tumors. Thus, we show that dependence of tumor cells on the NAD salvage pathway renders them sensitive to GNE-618 in vitro and in vivo, and our data support further evaluation of the use of NAMPT mRNA and protein levels as predictors of overall sensitivity. PMID:24204194

  7. Dependence of Tumor Cell Lines and Patient-Derived Tumors on the NAD Salvage Pathway Renders Them Sensitive to NAMPT Inhibition with GNE-61812

    PubMed Central

    Xiao, Yang; Elkins, Kristi; Durieux, Jenni K; Lee, Leslie; Oeh, Jason; Yang, Lulu X; Liang, Xiaorong; DelNagro, Chris; Tremayne, Jarrod; Kwong, Mandy; Liederer, Bianca M; Jackson, Peter K; Belmont, Lisa D; Sampath, Deepak; O'Brien, Thomas

    2013-01-01

    Nicotinamide adenine dinucleotide (NAD) is a critical metabolite that is required for a range of cellular reactions. A key enzyme in the NAD salvage pathway is nicotinamide phosphoribosyl transferase (NAMPT), and here, we describe GNE-618, an NAMPT inhibitor that depletes NAD and induces cell death in vitro and in vivo. While cells proficient for nicotinic acid phosphoribosyl transferase (NAPRT1) can be protected from NAMPT inhibition as they convert nicotinic acid (NA) to NAD independent of the salvage pathway, this protection only occurs if NA is added before NAD depletion. We also demonstrate that tumor cells are unable to generate NAD by de novo synthesis as they lack expression of key enzymes in this pathway, thus providing a mechanistic rationale for the reliance of tumor cells on the NAD salvage pathway. Identifying tumors that are sensitive to NAMPT inhibition is one potential way to enhance the therapeutic effectiveness of an NAMPT inhibitor, and here, we show that NAMPT, but not NAPRT1, mRNA and protein levels inversely correlate with sensitivity to GNE-618 across a panel of 53 non-small cell lung carcinoma cell lines. Finally, we demonstrate that GNE-618 reduced tumor growth in a patient-derived model, which is thought to more closely represent heterogeneous primary patient tumors. Thus, we show that dependence of tumor cells on the NAD salvage pathway renders them sensitive to GNE-618 in vitro and in vivo, and our data support further evaluation of the use of NAMPT mRNA and protein levels as predictors of overall sensitivity. PMID:24204194

  8. Sensitive, high throughput HPLC-MS/MS method with on-line sample clean-up for everolimus measurement.

    PubMed

    Korecka, Magdalena; Solari, Sandra G; Shaw, Leslie M

    2006-08-01

    A new HPLC-MS/MS method for everolimus measurement was developed that includes the following features: small sample volume, short run time, fast, simple and cost-efficient sample preparation, assessment of performance of two internal standards (IS), SDZ RAD 223-756 and ascomycin and comparison of the method with an HPLC-MS/MS reference method. The authors established a multiple reaction monitoring positive ion HPLC-MS/MS method with on-line extraction and sample cleanup. This procedure includes: an API 2000 triple quadrupole mass spectrometer with turbo-ion spray, built-in Valco switching valve, an HPLC system; guard column; a Nova-Pak C18 analytical column; washing solution, methanol:30 mM ammonium acetate pH 5.1 (80:20); eluting solution, methanol:30 mM ammonium acetate pH 5.1 (97:3); flow rate 0.8 mL/min; and a run time of 2.8 minutes. The first and third quadrupoles were set to detect the ammonium adduct ion and a high mass fragment of everolimus (m/z 975.5-->908.5), and two ISs: SDZ RAD 223-756 (m/z 989.8-->922.8) and ascomycin (m/z 809.5-->756.5). The LLOQ was 1.0 microg/L for everolimus using either IS. Between day precision ranged from 3.1% to 5.7% for SDZ RAD 223-756 and 6.0% to 8.6% for ascomycin using spiked blood with everolimus concentrations 2.0 to 25.0 microg/L. Absolute recoveries using spiked samples over the range of 2.5 to 25 mug/L averaged 77.3% (SDZ RAD 223-756) and 76.8% (ascomycin). No matrix effect on everolimus was demonstrated based on the mean observed signal detection of 98.6% (SDZ RAD 223-756) and 105% (ascomycin). Comparison of everolimus concentrations obtained using this method with two internal standards with a reference laboratory demonstrated that the mean everolimus concentration obtained with ascomycin was statistically different (lower) than results with the reference method and the method that used SDZ RAD 223-756 as the internal standard gave equivalent results compared with the reference method. PMID:16885715

  9. Different Contribution of Redox-Sensitive Transient Receptor Potential Channels to Acetaminophen-Induced Death of Human Hepatoma Cell Line.

    PubMed

    Badr, Heba; Kozai, Daisuke; Sakaguchi, Reiko; Numata, Tomohiro; Mori, Yasuo

    2016-01-01

    Acetaminophen (APAP) is a safe analgesic antipyretic drug at prescribed doses. Its overdose, however, can cause life-threatening liver damage. Though, involvement of oxidative stress is widely acknowledged in APAP-induced hepatocellular death, the mechanism of this increased oxidative stress and the associated alterations in Ca(2+) homeostasis are still unclear. Among members of transient receptor potential (TRP) channels activated in response to oxidative stress, we here identify that redox-sensitive TRPV1, TRPC1, TRPM2, and TRPM7 channels underlie Ca(2+) entry and downstream cellular damages induced by APAP in human hepatoma (HepG2) cells. Our data indicate that APAP treatment of HepG2 cells resulted in increased reactive oxygen species (ROS) production, glutathione (GSH) depletion, and Ca(2+) entry leading to increased apoptotic cell death. These responses were significantly suppressed by pretreatment with the ROS scavengers N-acetyl-L-cysteine (NAC) and 4,5-dihydroxy-1,3-benzene disulfonic acid disodium salt monohydrate (Tiron), and also by preincubation of cells with the glutathione inducer Dimethylfumarate (DMF). TRP subtype-targeted pharmacological blockers and siRNAs strategy revealed that suppression of either TRPV1, TRPC1, TRPM2, or TRPM7 reduced APAP-induced ROS formation, Ca(2+) influx, and cell death; the effects of suppression of TRPV1 or TRPC1, known to be activated by oxidative cysteine modifications, were stronger than those of TRPM2 or TRPM7. Interestingly, TRPV1 and TRPC1 were labeled by the cysteine-selective modification reagent, 5,5'-dithiobis (2-nitrobenzoic acid)-2biotin (DTNB-2Bio), and this was attenuated by pretreatment with APAP, suggesting that APAP and/or its oxidized metabolites act directly on the modification target cysteine residues of TRPV1 and TRPC1 proteins. In human liver tissue, TRPV1, TRPC1, TRPM2, and TRPM7 channels transcripts were localized mainly to hepatocytes and Kupffer cells. Our findings strongly suggest that APAP-induced Ca(2+) entry and subsequent hepatocellular death are regulated by multiple redox-activated cation channels, among which TRPV1 and TRPC1 play a prominent role. PMID:26903865

  10. Different Contribution of Redox-Sensitive Transient Receptor Potential Channels to Acetaminophen-Induced Death of Human Hepatoma Cell Line

    PubMed Central

    Badr, Heba; Kozai, Daisuke; Sakaguchi, Reiko; Numata, Tomohiro; Mori, Yasuo

    2016-01-01

    Acetaminophen (APAP) is a safe analgesic antipyretic drug at prescribed doses. Its overdose, however, can cause life-threatening liver damage. Though, involvement of oxidative stress is widely acknowledged in APAP-induced hepatocellular death, the mechanism of this increased oxidative stress and the associated alterations in Ca2+ homeostasis are still unclear. Among members of transient receptor potential (TRP) channels activated in response to oxidative stress, we here identify that redox-sensitive TRPV1, TRPC1, TRPM2, and TRPM7 channels underlie Ca2+ entry and downstream cellular damages induced by APAP in human hepatoma (HepG2) cells. Our data indicate that APAP treatment of HepG2 cells resulted in increased reactive oxygen species (ROS) production, glutathione (GSH) depletion, and Ca2+ entry leading to increased apoptotic cell death. These responses were significantly suppressed by pretreatment with the ROS scavengers N-acetyl-L-cysteine (NAC) and 4,5-dihydroxy-1,3-benzene disulfonic acid disodium salt monohydrate (Tiron), and also by preincubation of cells with the glutathione inducer Dimethylfumarate (DMF). TRP subtype-targeted pharmacological blockers and siRNAs strategy revealed that suppression of either TRPV1, TRPC1, TRPM2, or TRPM7 reduced APAP-induced ROS formation, Ca2+ influx, and cell death; the effects of suppression of TRPV1 or TRPC1, known to be activated by oxidative cysteine modifications, were stronger than those of TRPM2 or TRPM7. Interestingly, TRPV1 and TRPC1 were labeled by the cysteine-selective modification reagent, 5,5′-dithiobis (2-nitrobenzoic acid)-2biotin (DTNB-2Bio), and this was attenuated by pretreatment with APAP, suggesting that APAP and/or its oxidized metabolites act directly on the modification target cysteine residues of TRPV1 and TRPC1 proteins. In human liver tissue, TRPV1, TRPC1, TRPM2, and TRPM7 channels transcripts were localized mainly to hepatocytes and Kupffer cells. Our findings strongly suggest that APAP-induced Ca2+ entry and subsequent hepatocellular death are regulated by multiple redox-activated cation channels, among which TRPV1 and TRPC1 play a prominent role. PMID:26903865

  11. Screening antitumor bioactive fraction from Sauromatum giganteum (Engl.) Cusimano & Hett and sensitive cell lines with the serum pharmacology method and identification by UPLC-TOF-MS.

    PubMed

    Gao, Shi-Yong; Gong, Yun-Fei; Sun, Qiu-Jia; Bai, Jing; Wang, Long; Fan, Zi-Quan; Sun, Yu; Su, Yi-Jun; Gang, Jian; Ji, Yu-Bin

    2015-01-01

    Sauromatum giganteum (Engl.) Cusimano & Hett Tuber are used in Chinese folklore medicine for treatment of neoplasms. However, the claim has not been scientifically validated. The aim of the study is to screen the antitumor bioactive fraction of Sauromatum giganteum (Engl.) Cusimano & Hett Tuber and sensitive tumor cell lines using a cytotoxicity assay in vitro and tumor transplantation method in vivo, to support its use in folk medicine. The petroleum ether fraction, chloroform fraction, ethyl acetate fraction, n-butanol fraction and water fraction were successively extracted by turn by the maceration under reflux assay. Screening of antitumor bioactive fraction and sensitive cell lines were measured by MTT assay and the serum pharmacology method, and in vivo the antitumor activities of the active fraction was evaluated by using S180 or H22 tumor-bearing mice model and Kunming mice. The active constituents of ethyl acetate fraction of Sauromatum giganteum (Engl.) Cusimano & Hett were characterized by UPLC-TOF-MS. Compared with control groups, mice serum containing ethyl acetate fraction had a inhibition effect on SMMC-7721 cell, SGC-7901 cell, MCF-7 cell, HeLa cell, A549 cell, HT-29, and MDA-MB-231, respectively, but mice serum containing other four fractions had no different with that of control group. The inhibition capabilities of mice serum containing ethyl acetate fraction on the seven cell lines in descending order is SGC-7901 > SMMC-7721 > MCF-7 > HT-29 > A549 > HeLa > MDA-MB-231. In vivo the inhibition rate of 106, 318, 954 mg/kgd ethyl acetate fraction dry extract to sarcoma S180 is 15.22%, 26.15% and 40.24%, respectively, and life prolonging rate to hepatoma H22 is 33.61%, 40.16% and 55.74%. A total of 14 compounds were identified in the ethyl acetate fraction of Sauromatum giganteum (Engl.) Cusimano & Hett. The results of the experimental studies proved the antitumor activity of Sauromatum giganteum (Engl.) Cusimano & Hett and supported the traditional use of this plant. These data indicate the potential for the use of ethyl acetate fraction of Sauromatum giganteum (Engl.) Cusimano & Hett Tuber in tumor therapy, anti-tumor activity on cancer cell line in descending order is SGC-7901 > SMMC-7721 > MCF-7 > HT-29 > A549 > HeLa > MDA-MB-231. PMID:25756649

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

    SciTech Connect

    Attota, Ravikiran Dixson, Ronald G.

    2014-07-28

    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.

  13. A Sensitive and Rapid Assay for Investigating Vertical Transmission of Hepatitis B Virus via Male Germ Line Using EGFP Vector as Reporter

    PubMed Central

    Ahmed, Mohamed Morsi M.; Huang, Tian-Hua; Xie, Qing-Dong

    2008-01-01

    Hepatitis B virus (HBV) constitutes a serious menace to man. DNA recombination and sequencing, interspecific in vitro fertilization, single-embryo PCR and RT-PCR were employed to establish a sensitive and rapid assay for exploring the vertical transmission of viruses via male germ line. Plasmid pIRES2-EGFP-HBs which expressed enhanced green fluorescent protein as reporter for the expression of hepatitis B virus S gene was successfully constructed and confirmed by PCR, EcoR I and Sal I digestion, and DNA sequencing. After exposure to the plasmid, human spermatozoa were used to fertilize with zona-free hamster ova. Two-cell embryos were collected and classified into group A with green fluorescence and group B without green fluorescence under fluorescence microscope. The results showed that HBs DNA positive bands were detected in the embryos with green fluorescence (PCR and RT-PCR) and positive control (PCR) indicating expression of pIRES2-EGFP-HBs, and not observed in the embryos without green fluorescence and negative controls (PCR and RT-PCR) indicating no pIRES2-EGFP-HBs in the cells. The advantages and application foreground of this assay for study on vertical transmission of viruses such as HCV, HIV, HPV, and SARS via germ line were discussed. PMID:18670607

  14. Sensitivity analysis and line edge roughness determination of 28-nm pitch silicon fins using Mueller matrix spectroscopic ellipsometry-based optical critical dimension metrology

    NASA Astrophysics Data System (ADS)

    Dixit, Dhairya; O'Mullane, Samuel; Sunkoju, Sravan; Gottipati, Abhishek; Hosler, Erik R.; Kamineni, Vimal; Preil, Moshe; Keller, Nick; Race, Joseph; Muthinti, Gangadhara Raja; Diebold, Alain C.

    2015-07-01

    Measurement and control of line edge roughness (LER) is one of the most challenging issues facing patterning technology. As the critical dimensions (CDs) of patterned structures decrease, an LER of only a few nanometers negatively impacts device performance. Here, Mueller matrix (MM) spectroscopic ellipsometry-based scatterometry is used to characterize LER in periodic line-space structures in 28-nm pitch Si fin samples fabricated by directed self-assembly patterning. The optical response of the MM elements is influenced by structural parameters like pitch, CDs, height, and side-wall angle, as well as the optical properties of the materials. Evaluation and decoupling MM element response to LER from other structural parameters requires sensitivity analysis using scatterometry models that include LER. Here, an approach is developed that can be used to characterize LER in Si fins by comparing the optical responses generated by systematically varying the grating shape and measurement conditions. Finally, the validity of this approach is established by comparing the results obtained from power spectral density analysis of top down scanning electron microscope images and cross-sectional transmission electron microscope image of the 28-nm pitch Si fins.

  15. DNA-protein crosslinking in normal and solar UV-sensitive ICR 2A frog cell lines exposed to solar UV-radiation.

    PubMed

    Rosenstein, B S; Lai, L W; Ducore, J M; Rosenstein, R B

    1989-05-01

    DNA-protein crosslinks (DPC) were measured following exposure to the solar UV wavelengths produced by a fluorescent sunlamp in ICR 2A frog cells and two solar UV-sensitive mutants derived from this cell line. Approx. 5-7 DPC per 10(10) dalton were induced in these cells by either 150 kJ/m2 of sunlamp UV greater than 315 nm plus photoreactivating light (PRL) or 10 kJ/m2 of sunlamp UV greater than 295 nm. The irradiated cells were then incubated for 0-24 h and the level of DPC measured using alkaline elution. It was found for the ICR 2A cells exposed to sunlamp UV greater than 315 nm that the level of DPC increased about 3-fold during a 2-h postirradiation incubation and then decreased. The mutant cell lines also showed an enhancement in the level of DPC following irradiation, although it was much less pronounced and the levels decreased much more rapidly. In a similar fashion, the level of DPC increased in ICR 2A cells exposed to sunlamp UV greater than 295 nm with more than a 5-fold enhancement after a 4-h incubation. Once again, the mutant cell lines showed an increase in the level of DPC that was smaller and more transient than the effect in the ICR 2A cells. These results suggests that this enhancement in DPC may be indicative of a process that plays a role in cellular survival following solar UV-irradiation. PMID:2716758

  16. Insulin-like Growth Factor 1 Differentially Affects Lithium Sensitivity of Lymphoblastoid Cell Lines from Lithium Responder and Non-responder Bipolar Disorder Patients.

    PubMed

    Milanesi, Elena; Hadar, Adva; Maffioletti, Elisabetta; Werner, Haim; Shomron, Noam; Gennarelli, Massimo; Schulze, Thomas G; Costa, Marta; Del Zompo, Maria; Squassina, Alessio; Gurwitz, David

    2015-07-01

    Bipolar disorder (BD) is a chronic psychiatric illness with an unknown etiology. Lithium is considered the cornerstone in the management of BD, though about 50-60 % of patients do not respond sufficiently to chronic treatment. Insulin-like growth factor 1 (IGF1) has been identified as a candidate gene for BD susceptibility, and its low expression has been suggested as a putative biomarker for lithium unresponsiveness. In this study, we examined the in vitro effects of insulin-like growth factor 1 (IGF-1) on lithium sensitivity in lymphoblastoid cell lines (LCLs) from lithium responder (R) and non-responder (NR) bipolar patients. Moreover, we evaluated levels of microRNA let-7c, a small RNA predicted to target IGF1. We found that exogenous IGF-1 added to serum-free media increased lithium sensitivity selectively in LCLs from NR BD patients. However, no significant differences were observed when comparing let-7c expression in LCLs from R vs. NR BD patients. Our data support a key role for IGF-1 in lithium resistance/response in the treatment of bipolar disorder. PMID:25740013

  17. Peroxyacetyl nitrate-induced oxidative and calcium signaling events leading to cell death in ozone-sensitive tobacco cell-line

    PubMed Central

    Yukihiro, Masaru; Hiramatsu, Takuya; Bouteau, Francois; Kadono, Takashi; Kawano, Tomonori

    2012-01-01

    It has long been concerned that some secondary air pollutants such as smog components, ozone (O3) and peroxyacetyl nitrate (PAN), are highly phytotoxic even at low concentrations. Compared with the biology of O3, we largely lack the information on the toxicity model for PAN at the cellular signaling levels. Here, we studied the cell-damaging impact of PAN using suspension culture of smog-sensitive tobacco variety (Bel-W3). The cells were exposed to freshly synthesized PAN and the induced cell death was assessed under microscope after staining with Evans blue. Involvement of reactive oxygen species (ROS) in PAN toxicity was suggested by PAN-dependently increased intracellular H2O2 and also by the cell-protective effects of ROS scavengers and related inhibitors. Calcium chelator also lowered the level of PAN-induced cell death, indicating that Ca2+ is also involved. Using a transgenic cell line expressing aequorin, an increase in cytosolic Ca2+ concentration responsive to the pulse of PAN, but sensitive to Ca2+ channel blockers, was recorded, indicating that Ca2+ channels are activated by PAN or PAN-derived signals. Above data show some similarity between the signaling mechanisms responsive to O3 and PAN. PMID:22301977

  18. Quantitative evaluation of cellular uptake, DNA incorporation and adduct formation in cisplatin sensitive and resistant cell lines: Comparison of different Pt-containing drugs.

    PubMed

    Corte-Rodríguez, M; Espina, M; Sierra, L M; Blanco, E; Ames, T; Montes-Bayón, M; Sanz-Medel, A

    2015-11-01

    The use of Pt-containing compounds as chemotherapeutic agents facilitates drug monitoring by using highly sensitive elemental techniques like inductively coupled plasma mass spectrometry (ICP-MS). However, methodological problems arise when trying to compare different experiments due to the high variability of biological parameters. In this work we have attempted to identify and correct such variations in order to compare the biological behavior of cisplatin, oxaliplatin and pyrodach-2 (a novel platinum-containing agent). A detailed study to address differential cellular uptake has been conducted in three different cell lines: lung adenocarcinoma (A549); cisplatin-sensitive ovarian carcinoma (A2780); and cisplatin-resistant ovarian carcinoma (A2780cis). The normalization of Pt results to cell mass, after freeze-drying, has been used to minimize the errors associated with cell counting. Similarly, Pt accumulation in DNA has been evaluated by referencing the Pt results to the DNA concentration, as measured by (31)P monitoring using flow-injection and ICP-MS detection. These strategies have permitted to address significantly lower Pt levels in the resistant cells when treated with cisplatin or oxaliplatin as well as an independent behaviour from the cell type (sensitive or resistant) for pyrodach-2. Similarly, different levels of incorporation in DNA have been found for the three drugs depending on the cell model revealing a different behavior regarding cell cisplatin resistance. Further speciation experiments (by using complementary HPLC-ICP-MS and HPLC-ESI-Q-TOF MS) have shown that the main target in DNA is still the N7 of the guanine but with different kinetics of the ligand exchange mechanism for each of the compounds under evaluation. PMID:26352094

  19. Intra- and inter-laboratory reproducibility and accuracy of the LuSens assay: A reporter gene-cell line to detect keratinocyte activation by skin sensitizers.

    PubMed

    Ramirez, Tzutzuy; Stein, Nadine; Aumann, Alexandra; Remus, Tina; Edwards, Amber; Norman, Kimberly G; Ryan, Cindy; Bader, Jackie E; Fehr, Markus; Burleson, Florence; Foertsch, Leslie; Wang, Xiaohong; Gerberick, Frank; Beilstein, Paul; Hoffmann, Sebastian; Mehling, Annette; van Ravenzwaay, Bennard; Landsiedel, Robert

    2016-04-01

    Several non-animal methods are now available to address the key events leading to skin sensitization as defined by the adverse outcome pathway. The KeratinoSens™ assay addresses the cellular event of keratinocyte activation and is a method accepted under OECD TG 442D. In this study, the results of an inter-laboratory evaluation of the "me-too" LuSens assay, a bioassay that uses a human keratinocyte cell line harboring a reporter gene construct composed of the rat antioxidant response element (ARE) of the NADPH:quinone oxidoreductase 1 gene and the luciferase gene, are described. Earlier in-house validation with 74 substances showed an accuracy of 82% in comparison to human data. When used in a battery of non-animal methods, even higher predictivity is achieved. To meet European validation criteria, a multicenter study was conducted in 5 laboratories. The study was divided into two phases, to assess 1) transferability of the method, and 2) reproducibility and accuracy. Phase I was performed by testing 8 non-coded test substances; the results showed a good transferability to naïve laboratories even without on-site training. Phase II was performed with 20 coded test substances (performance standards recommended by OECD, 2015). In this phase, the intra- and inter-laboratory reproducibility as well as accuracy of the method was evaluated. The data demonstrate a remarkable reproducibility of 100% and an accuracy of over 80% in identifying skin sensitizers, indicating a good concordance with in vivo data. These results demonstrate good transferability, reliability and accuracy of the method thereby achieving the standards necessary for use in a regulatory setting to detect skin sensitizers. PMID:26796489

  20. Line selection and sensitivity analysis for oxygen sensing in the 1.26-1.27 micron spectral band for the ASCENDS mission

    NASA Astrophysics Data System (ADS)

    Prasad, N.; Browell, E. V.; Zaccheo, T. S.; Karpowicz, B.

    2010-12-01

    The National Research Councils (NRC) Decadal Survey (DS) of Earth Science and Applications from Space has identified the Active Sensing of CO2 Emissions over Nights, Days, and Seasons (ASCENDS) as an important atmospheric science mission. The CO2 mixing ratio needs to be measured to a precision of 0.5 percent of background or better (slightly less than 2 ppm) at 100-km horizontal resolution overland and 200-km resolution over oceans. To meet this goal, the ASCENDS mission requires simultaneous laser remote sensing of CO2 and O2 in order to convert CO2 column number densities to average column CO2 mixing ratios (XCO2). As such, the CO2 column number density and the O2 column number density will be utilized to derive the average XCO2 column. NASA Langley Research Center, working with its partners, is developing O2 lidar technology in the 1.26-1.27-?m band for surface pressure measurements. To obtain XCO2 with LAS technique the simultaneous measurement of the CO2 column number density, the O2 column number density for converting the CO2 column number density to XCO2 and the total path length of the measurement are required. The O2 LAS operating at 1.26 ?m will be used to convert CO2 number density to mixing ratio. The 1.26-?m spectral band was chosen due to architectural advantage from wavelengths being close to 1.57-?m CO2 LAS column measurements and the favorable spectroscopic characteristics of the O2 absorption line parameters. Furthermore, the surface and atmospheric scattering characteristics from aerosols and thin clouds are nearly the same as for 1.26-?m O2 measurements and the 1.57-?m CO2 measurements. One or more "on-line" wavelengths in the 1.26-?m O2 absorption band have to be carefully chosen to eliminate ambient influences on them when used in conjunction with the integrated path differential absorption (IPDA) technique. The O2 model optical depth calculation is very sensitive to knowledge of the transmitted wavelengths and to the choice of Voigt input parameters. Uncertainties in atmospheric profiles of temperature, pressure and relative humidity can cause ~0.5 % errors in model optical depths. Uncertainties at line center and offset wavelengths of the candidate on-line wavelengths have to be precisely known to reduce uncertainties in O2 concentration measurements from airborne and space based platforms. In this paper, we evaluate systematic relative errors related to uncertainties in O2 absorption line pressure shifts and atmospheric temperature for selected O2 absorption lines suitable for making high precision O2 and XCO2 measurements based on HITRAN database and O2 absorption line measurements.

  1. Upregulated expression of BCL2, MCM7, and CCNE1 indicate cisplatin-resistance in the set of two human bladder cancer cell lines: T24 cisplatin sensitive and T24R2 cisplatin resistant bladder cancer cell lines

    PubMed Central

    Kim, Sung Han; Ho, Jin-Nyoung; Jin, Hyunjin; Lee, Sang Chul; Lee, Sang Eun; Hong, Sung-Kyu; Lee, Jeong Woo; Lee, Eun-Sik

    2016-01-01

    Purpose The mechanism of resistance to cisplatin during treatment of bladder cancer (BC) has been a subject of intense investigation in clinical research. This study aims to identify candidate genes associated with resistance to cisplatin, in order to understand the resistance mechanism of BC cells to the drug, by combining the use of microarray profiling, quantitative reverse transcription-polymerase chain reaction (RT-PCR), and Western blot analyses. Materials and Methods The cisplatin sensitive human BC cell line (T24) and the cisplatin resistant BC cell line, T24R2, were used for microarray analysis to determine the differential expression of genes that are significant in cisplatin resistance. Candidate upregulated genes belonging to three well-known cancer-related KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways (p53 tumor suppressor, apoptosis, and cell cycle) were selected from the microarray data. These candidate genes, differentially expressed in T24 and T24R2, were then confirmed by quantitative RT-PCR and western blot. A fold change ≥2 with a p-value <0.05 was considered significant. Results A total of 18 significantly upregulated genes were detected in the three selected cancer-related pathways in both microarray and RT-PCR analyses. These genes were PRKAR2A, PRKAR2B, CYCS, BCL2, BIRC3, DFFB, CASP6, CDK6, CCNE1, STEAP3, MCM7, ORC2, ORC5, ANAPC1, and ANAPC7, CDC7, CDC27, and SKP1. Western blot analyses also confirmed the upregulation of BCL2, MCM7, and CCNE1 at the protein level, indicating their crucial association with cisplatin resistance. Conclusions The BCL2, MCM7, and CCNE1 genes might play distinctive roles in cisplatin resistance in BC. PMID:26966728

  2. Exclusion limits on the WIMP-nucleon cross section from the first run of the Cryogenic Dark Matter Search in the Soudan Underground Laboratory

    SciTech Connect

    Armel-Funkhouser, M.S.; Attisha, M.J.; Bailey, C.N.; Baudis, L.; Bauer, Daniel A.; Brink, P.L.; Bunker, R.; Cabrera, B.; Caldwell, D.O.; Chang, C.L.; Crisler, M.B.; Cushman, P.; Daal, M.; Dixon, R.; Dragowsky, M.R.; Driscoll, D.D.; Duong, L.; Ferril, R.; Filippini, J.; Gaitskell, R.J.; Hennings-Yeomans, R.; /Case Western Reserve U. /Fermilab /Case Western Reserve U. /Denver U. /Case Western Reserve U. /UC, Berkeley /UC, Santa Barbara /UC, Berkeley /NIST, Boulder /UC, Berkeley /UC, Santa Barbara /Case Western Reserve U. /Case Western Reserve U. /UC, Berkeley /Fermilab /UC, Berkeley /Minnesota U. /UC, Berkeley /LBL, Berkeley /Case Western Reserve U. /UC, Berkeley /LBL, Berkeley /UC, Santa Barbara /Case Western Reserve U. /UC, Berkeley /Case Western Reserve U. /Case Western Reserve U. /Case Western Reserve U. /UC, Santa Barbara /Case Western Reserve U.

    2005-07-01

    The Cryogenic Dark Matter Search (CDMS-II) employs low-temperature Ge and Si detectors to seek Weakly Interacting Massive Particles (WIMPs) via their elastic scattering interactions with nuclei. Simultaneous measurements of both ionization and phonon energy provide discrimination against interactions of background particles. For recoil energies above 10 keV, events due to background photons are rejected with > 99.99% efficiency. Electromagnetic events very near the detector surface can mimic nuclear recoils because of reduced charge collection, but these surface events are rejected with > 96% efficiency by using additional information from the phonon pulse shape. Efficient use of active and passive shielding, combined with the 2090 m.w.e. overburden at the experimental site in the Soudan mine, makes the background from neutrons negligible for this first exposure. All cuts are determined in a blind manner from in situ calibrations with external radioactive sources without any prior knowledge of the event distribution in the signal region. Resulting efficiencies are known to {approx}10%. A single event with a recoil of 64 keV passes all of the cuts and is consistent with the expected misidentification rate of surface-electron recoils. Under the assumptions for a standard dark matter halo, these data exclude previously unexplored parameter space for both spin-independent and spin-dependent WIMP-nucleon elastic scattering. The resulting limit on the spin-independent WIMP-nucleon elastic-scattering cross-section has a minimum of 4 x 10{sup -43} cm{sup 2} at a WIMP mass of 60 GeV c{sup -2}. The minimum of the limit for the spin-dependent WIMP-neutron elastic-scattering cross-section is 2 x 10{sup -37} cm{sup 2} at a WIMP mass of 50 GeV c{sup -2}.

  3. Molecular basis for sensitivity and acquired resistance to gefitinib in HER2-overexpressing human gastric cancer cell lines derived from liver metastasis

    PubMed Central

    Yokoyama, H; Ikehara, Y; Kodera, Y; Ikehara, S; Yatabe, Y; Mochizuki, Y; Koike, M; Fujiwara, M; Nakao, A; Tatematsu, M; Nakanishi, H

    2006-01-01

    Gastric cancer metastasised to the liver was found to overexpress HER2 at a significantly higher incidence than primary gastric cancers. The purpose of the present study was to investigate the possibility of molecular therapy targeting HER2 overexpression in gastric cancer liver metastasis. We developed three new HER2-overexpressing gastric cancer cell lines (GLM-1, GLM-2, GLM-4) without epidermal growth factor receptor (EGFR) mutations derived from such liver metastasis, two of which had HER2 gene amplifications. All these GLM series of cell lines were highly sensitive to gefitinib in vitro, a specific inhibitor of EGFR tyrosine kinase (Iressa) rather than anti-HER2 antibody trastuzumab (Herceptin), whereas most of the HER2 low-expressing counterparts were not. In these HER2-overexpressing GLM series, protein kinase B (Akt), but not extracellular signal-regulated kinase 1/2 (ERK1/2), was constitutively phosphorylated, and gefitinib efficiently inhibited this Akt phosphorylation, induced strong apoptosis in vitro and exhibited antitumour activity in tumour xenografts in nude mice. This gefitinib-mediated antitumour effect in xenograft was significantly potentiated by trastuzumab treatment. On the other hand, gefitinib-resistant cells (GLM-1R) exhibited increased EGFR expression, followed by constitutive activation of mitogen-activated protein kinase (MAPK) pathway. These results suggest that the antitumour effect of gefitinib is due to the effective inhibition of HER2-driven constitutive activation of phosphatidylinositol-3-kinase (PI3K)/Akt pathway, and that the acquired resistance to gefitinib is due to the constitutive activation of Ras/MAPK pathway in compensation for PI3K/Akt pathway. Gastric cancer liver metastasis with HER2 overexpression would be a potential molecular target for gefitinib and trastuzumab. PMID:17088902

  4. Outcome of advanced NSCLC patients harboring sensitizing EGFR mutations randomized to EGFR tyrosine kinase inhibitors or chemotherapy as first-line treatment: a meta-analysis

    PubMed Central

    Bria, E.; Milella, M.; Cuppone, F.; Novello, S.; Ceribelli, A.; Vaccaro, V.; Sperduti, I.; Gelibter, A.; Scagliotti, G. V.; Cognetti, F.; Giannarelli, D.

    2011-01-01

    Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) are effective as first-line treatment of advanced non-small-cell lung cancer patients with EGFR mutations (EGFR-M+). Patients and methods: We conducted a literature-based meta-analysis to quantify the magnitude of benefit with upfront EGFR TKI in EGFR-M+ patients. Meta-regression and sensitivity analyses were also carried out to identify additional predictors of outcome and to assess the influence of trial design. Results: Five trials (805 patients) were identified (three trials prospectively enrolling EGFR-M+ patients and two retrospective analyses of EGFR-M+ patients). TKI significantly increased progression-free survival (PFS) [hazard ratio (HR) 0.45, 95% confidence interval (CI) 0.36–0.58, P < 0.0001] and overall response rate (ORR) (HR 2.08, 95% CI 1.75–2.46, P < 0.0001)] over chemotherapy, while significantly decreasing neutropenia. No significant difference was observed in overall survival. The rate of exon-19 mutations, female gender, and nonsmoking status were identified as additional predictors of outcome at meta-regression analysis. A significant interaction with trial design was found for both PFS (P = 0.028) and ORR (P = 0.008), suggesting a larger advantage for patients treated within prospective trials. Conclusions: In EGFR-M+ patients, first-line TKI increase both PFS and ORR by ∼25%, while significantly decreasing toxicity. The role of additional predictive factors and the influence of trial design on the magnitude of the observed benefit warrant further investigation. PMID:21325444

  5. Pseudomonas aeruginosa-mannose-sensitive hemagglutinin inhibits proliferation and induces apoptosis in a caspase-dependent manner in human bladder cancer cell lines

    PubMed Central

    ZHU, YI-PING; BIAN, XIAO-JIE; YE, DING-WEI; YAO, XU-DONG; ZHANG, SHI-LIN; DAI, BO; SHEN, YI-JUN

    2013-01-01

    The aim of the present study was to investigate the effects of Pseudomonas aeruginosa-mannose-sensitive hemagglutinin (PA-MSHA) on inhibiting the proliferation of bladder cancer cell lines and to further define its functional mechanisms. T24 and 5637 cells were treated with PA-MSHA at various concentrations and times. Cell proliferation was analyzed using Cell Counting Kit-8 (CCK-8) assays. The cell cycle distribution and apoptosis induced by PA-MSHA were measured by flow cytometry with propidium iodide (PI) and annexin V-fluorescein isothiocyanate (FITC) staining. Western blotting was used to evaluate the expression levels of the apoptosis-related molecules and PI3K-AKT-mTOR signaling pathway proteins. A time- and concentration-dependent cytotoxic effect of PA-MSHA was observed in the T24 and 5637 cells. Flow cytometry with PI and annexin V-FITC staining showed that the various concentrations of PA-MSHA were all able to induce the apoptosis and G0-G1 cell cycle arrest of the bladder cancer cells. Cleaved caspase-8 and -9 and Fas protein expression levels were markedly associated with an increase in the apoptosis of the bladder cancer cells. The cells stimulated with PA-MSHA also exhibited a downregulation of PI3K-AKT-mTOR signaling. PA-MSHA inhibits proliferation and induces apoptosis in the T24 and 5637 bladder cancer cell lines by modulating caspase family proteins and affecting the cell cycle regulation machinery. The PI3K-AKT-mTOR signaling pathway may be important in the direct anticancer cytotoxic effect of PA-MSHA. PMID:23599794

  6. Anion exchange chromatography for the determination of 5-methyl-2'-deoxycytidine: application to cisplatin-sensitive and cisplatin-resistant ovarian cancer cell lines.

    PubMed

    Iglesias, Tamara; Espina, Marta; Montes-Bayón, María; Sierra, Luisa María; Blanco-González, Elisa

    2015-03-01

    Epigenetic alterations are increasingly implicated in the initiation and progression of cancer. Genome-wide (global) hypomethylation seems to occur in early neoplasia and is a feature of genomic DNA derived from solid tumour tissues like ovarian cancer. Thus, analytical methods that provide sensitive and quantitative information about cytosine methylation in DNA are currently required. In this work, we compare two different anion-exchange columns for the separation of methylated cytosine from the other DNA nucleotides: a silica-based (Tracer Extrasil SAX) column and a polystyrene/divinyl benzene-based (Mono-Q™) column. Under the optimised conditions, linearity range, precision and detection limits of the developed high-performance liquid chromatography (HPLC) method were evaluated and compared using conventional ultraviolet (UV) absorbance detection at 270 nm. Good separation of the five target nucleotides, including 5-methyl-2'-deoxycytidine monophosphate (5mdCMP) and 2'-deoxycytidine monophosphate (dCMP) was achieved on the Mono-Q™ column with a gradient elution of ammonium acetate buffer (1 M, pH 6.9) at a flow rate of 1 mL min(-1). The coupling of this column to inductively coupled plasma mass spectrometry (ICP-MS) permitted also phosphorous ((31)P) specific detection of the nucleotides. Both detection systems offered adequate analytical performance characteristics, with detection limits of 30 and 40 μg L(-1) for 5mdCMP by HPLC-UV and HPLC-ICP-MS, respectively. However, the latter method allowed the determination of the global DNA methylation level (%) without the need for external calibration. Different genomic DNA samples were analysed including calf thymus DNA and DNA from two human cancer cell lines (adenocarcinoma epithelial A549 and ovarian carcinoma A2780) using the proposed strategy. In the line A2780, the cisplatin-sensitive and cisplatin-resistant variants were analysed, finding no significant differences in the methylation percentage after treatment with cisplatin. PMID:25142048

  7. PI3K/Akt inhibition and down-regulation of BCRP re-sensitize MCF7 breast cancer cell line to mitoxantrone chemotherapy

    PubMed Central

    Komeili-Movahhed, Tahereh; Fouladdel, Shamileh; Barzegar, Elmira; Atashpour, Shekoufeh; Hossein Ghahremani, Mohammad; Nasser Ostad, Seyed; Madjd, Zahra; Azizi, Ebrahim

    2015-01-01

    Objective(s): Multidrug resistance (MDR) of cancer cells is a major obstacle to successful chemotherapy. Overexpression of breast cancer resistance protein (BCRP) is one of the major causes of MDR. In addition, it has been shown that PI3K/Akt signaling pathway involves in drug resistance. Therefore, we evaluated the effects of novel approaches including siRNA directed against BCRP and targeted therapy against PI3K/Akt signaling pathway using LY294002 (LY) to re-sensitize breast cancer MCF7 cell line to mitoxantrone (MTX) chemotherapy. Materials and Methods: Anticancer effects of MTX, siRNA, and LY alone and in combination were evaluated in MCF7 cells using MTT cytotoxicity assay and flow cytometry analysis of cell cycle distribution and apoptosis induction. Results: MTT and apoptosis assays showed that both MTX and LY inhibited cell proliferation and induced apoptosis in MCF7 cells. Results indicated that inhibition of BCRP by siRNA or PI3K/Akt signaling pathway by LY significantly increased sensitivity of MCF7 cells to antiproliferation and apoptosis induction of MTX. Furthermore, MTX showed G2/M arrest, whereas LY induced G0/G1 arrest in cell cycle distribution of MCF7 cells. Combination of siRNA or LY with MTX chemotherapy significantly increased accumulation of MCF7 cells in the G2/M phase of cell cycle. Conclusion: Combination of MTX chemotherapy with BCRP siRNA and PI3K/Akt inhibition can overcome MDR in breast cancer cells. This study furthermore suggests that novel therapeutic approaches are needed to enhance anticancer effects of available drugs in breast cancer. PMID:26124933

  8. EGFR mutant lung adenocarcinomas treated first-line with the novel EGFR inhibitor, XL647, can subsequently retain moderate sensitivity to erlotinib

    PubMed Central

    Chmielecki, Juliann; Pietanza, M. Catherine; Aftab, Dana; Shen, Ronglai; Zhao, Zhiguo; Chen, Xi; Hutchinson, Katherine; Viale, Agnes; Kris, Mark G.; Stout, Thomas; Miller, Vincent; Rizvi, Naiyer; Pao, William

    2011-01-01

    Introduction EGFR mutant lung cancers are sensitive to EGFR tyrosine kinase inhibitors (TKIs). Unfortunately, they develop resistance, often due to acquisition of a second-site mutation (T790M). Current EGFR TKIs select for T790M in preclinical models of acquired resistance. We explored whether all EGFR TKIs similarly select for the T790M mutation using data from early clinical trials and established in vitro models of acquired resistance. Methods We analyzed the clinical characteristics of 8 patients with metastatic EGFR mutant lung adenocarcinoma who were treated first-line with XL647 and then progressed. XL647 is an ATP-competitive inhibitor of EGFR, HER2, KDR, and EPHB4. Additional molecular preclinical studies were performed to characterize resistance. Results Four patients displayed confirmed partial responses (PRs), three patients had unconfirmed PRs, and one patient displayed stable disease. Only one of five patients tumor samples available for analysis after disease progression harbored the T790M mutation. Eight patients subsequently received erlotinib, with (n=3) or without (n=5) chemotherapy. Three of five patients treated with single agent erlotinib derived additional benefit, staying on drug up to 9 months. EGFR mutant PC-9 cells with acquired resistance to XL647 did not harbor the T790M mutation, displayed a distinct mRNA profile from PC-9 cells with T790M-mediated resistance, and were moderately sensitive to erlotinib in growth inhibition assays. Crystal structure analyses of XL647/EGFR T790M did not reveal a different binding mode from that of erlotinib. Conclusions The findings of this exploratory study suggest different EGFR TKIs may select for distinct mechanisms of resistance. These results raise the possibility that different EGFR TKIs could be sequentially used to improve outcomes in patients with EGFR mutant lung cancer. Further work investigating this hypothesis is warranted. PMID:22173702

  9. Low Dose High Energy X-ray In-Line Phase Sensitive Imaging Prototype: Investigation of Optimal Geometric Conditions and Design Parameters

    PubMed Central

    Ghani, Muhammad. U.; Yan, Aimin; Wong, Molly. D.; Li, Yuhua; Ren, Liqiang; Wu, Xizeng; Liu, Hong

    2016-01-01

    The objective of this study was to investigate the optimization of a high energy in-line phase sensitive x-ray imaging prototype under different geometric and operating conditions for mammography application. A phase retrieval algorithm based on phase attenuation duality (PAD) was applied to the phase contrast images acquired by the prototype. Imaging performance was investigated at four magnification values of 1.67, 2, 2.5 and 3 using an acrylic edge, an American College of Radiology (ACR) mammography phantom and contrast detail (CD) phantom with tube potentials of 100, 120 and 140 kVp. The ACR and CD images were acquired at the same mean glandular dose (MGD) of 1.29 mGy with a computed radiography (CR) detector of 43.75 µm pixel pitch at a fixed source to image distance (SID) of 170 cm. The x-ray tube focal spot size was kept constant as 7 µm while a 2.5 mm thick aluminum (Al) filter was used for beam hardening. The performance of phase contrast and phase retrieved images were compared with computer simulations based on the relative phase contrast factor (RPF) at high x-ray energies. The imaging results showed that the x-ray tube operated at 100 kVp under the magnification of 2.5 exhibits superior imaging performance which is in accordance to the computer simulations. As compared to the phase contrast images, the phase retrieved images of the ACR and CD phantoms demonstrated improved imaging contrast and target discrimination. We compared the CD phantom images acquired in conventional contact mode with and without the anti-scatter grid using the same prototype at 1.295 mGy and 2.59 mGy using 40 kVp, a 25 µm rhodium (Rh) filter. At the same radiation dose, the phase sensitive images provided improved detection capabilities for both the large and small discs, while compared to the double dose image acquired in conventional mode, the observer study also indicated that the phase sensitive images provided improved detection capabilities for the large discs. This study therefore validates the potential of using high energy phase contrast x-ray imaging to improve lesion detection and reduce radiation dose for clinical applications such as mammography. PMID:26756405

  10. First limits on WIMP nuclear recoil signals in ZEPLIN-II: A two-phase xenon detector for dark matter detection

    NASA Astrophysics Data System (ADS)

    Alner, G. J.; Araújo, H. M.; Bewick, A.; Bungau, C.; Camanzi, B.; Carson, M. J.; Cashmore, R. J.; Chagani, H.; Chepel, V.; Cline, D.; Davidge, D.; Davies, J. C.; Daw, E.; Dawson, J.; Durkin, T.; Edwards, B.; Gamble, T.; Gao, J.; Ghag, C.; Howard, A. S.; Jones, W. G.; Joshi, M.; Korolkova, E. V.; Kudryavtsev, V. A.; Lawson, T.; Lebedenko, V. N.; Lewin, J. D.; Lightfoot, P.; Lindote, A.; Liubarsky, I.; Lopes, M. I.; Lüscher, R.; Majewski, P.; Mavrokoridis, K.; McMillan, J. E.; Morgan, B.; Muna, D.; Murphy, A. St. J.; Neves, F.; Nicklin, G. G.; Ooi, W.; Paling, S. M.; Pinto da Cunha, J.; Plank, S. J. S.; Preece, R. M.; Quenby, J. J.; Robinson, M.; Salinas, G.; Sergiampietri, F.; Silva, C.; Solovov, V. N.; Smith, N. J. T.; Smith, P. F.; Spooner, N. J. C.; Sumner, T. J.; Thorne, C.; Tovey, D. R.; Tziaferi, E.; Walker, R. J.; Wang, H.; White, J. T.; Wolfs, F. L. H.

    2007-11-01

    Results are presented from the first underground data run of ZEPLIN-II, a 31 kg two-phase xenon detector developed to observe nuclear recoils from hypothetical weakly interacting massive dark matter particles. Discrimination between nuclear recoils and background electron recoils is afforded by recording both the scintillation and ionisation signals generated within the liquid xenon, with the ratio of these signals being different for the two classes of event. This ratio is calibrated for different incident species using an AmBe neutron source and 60Co γ-ray sources. From our first 31 live days of running ZEPLIN-II, the total exposure following the application of fiducial and stability cuts was 225 kg × days. A background population of radon progeny events was observed in this run, arising from radon emission in the gas purification getters, due to radon daughter ion decays on the surfaces of the walls of the chamber. An acceptance window, defined by the neutron calibration data, of 50% nuclear recoil acceptance between 5 keV ee and 20 keV ee, had an observed count of 29 events, with a summed expectation of 28.6 ± 4.3 γ-ray and radon progeny induced background events. These figures provide a 90% c.l. upper limit to the number of nuclear recoils of 10.4 events in this acceptance window, which converts to a WIMP-nucleon spin-independent cross-section with a minimum of 6.6 × 10 -7 pb following the inclusion of an energy-dependent, calibrated, efficiency. A second run is currently underway in which the radon progeny will be eliminated, thereby removing the background population, with a projected sensitivity of 2 × 10 -7 pb for similar exposures as the first run.

  11. Switch of HLA-G alternative splicing in a melanoma cell line causes loss of HLA-G1 expression and sensitivity to NK lysis.

    PubMed

    Rouas-Freiss, Nathalie; Bruel, Sylvie; Menier, Catherine; Marcou, Céline; Moreau, Philippe; Carosella, Edgardo D

    2005-10-20

    Considerable information has been accumulated on HLA-G expression in tumor lesions in which HLA-G is viewed as a way to turn off anti-tumoral immunity. Nevertheless, there is little data concerning the mechanisms by which expression and function of HLA-G are regulated in malignant cells. Here, we have addressed these points by studying a melanoma cell line derived from a surgically-removed HLA-G-positive melanoma lesion. We show that HLA-G expression in melanoma cells can be regulated at the mRNA splicing level. Indeed, melanoma cells rapidly switched from cell-surface HLA-G1 to intra-cellular HLA-G2 expression. This mechanism restored tumor sensitivity to NK lysis. Moreover, switch from HLA-G1 to HLA-G2 was strong enough to prevent re-expression of immunoprotective HLA-G1 even following treatments with cytokines and DNA demethylating agent. Modulating HLA-G at the mRNA splicing level would be an efficient way of lifting in vivo HLA-G-mediated tumor immune escape. PMID:15880415

  12. A convenient and sensitive method for haloacetic acid analysis in tap water by on-line field-amplified sample-stacking CE-ESI-MS.

    PubMed

    Hung, Sih-Hua; Her, Guor-Rong

    2013-11-01

    In this study, we propose a simple strategy based on flow injection and field-amplified sample-stacking CE-ESI-MS/MS to analyze haloacetic acids (HAAs) in tap water. Tap water was passed through a desalination cartridge before field-amplified sample-stacking CE-ESI-MS/MS analysis to reduce sample salinity. With this treatment, the signals of the HAAs increased 300- to 1400-fold. The LODs for tap water analysis were in the range of 10 to 100 ng/L, except for the LOD of monochloroacetic acid (1 μg/L in selected-ion monitoring mode detection). The proposed method is fast, convenient, and sensitive enough to perform on-line analysis of five HAAs in the tap water of Taipei City. Four HAAs, including trichloroacetic acid, dichloroacetic acid, dibromoacetic acid, and monobromoacetic acid, were detected at concentrations of approximately 1.74, 1.15, 0.16, and 0.15 ppb, respectively. PMID:24019225

  13. [Genetic analysis and molecular mapping of stripe rust resistance gene in a restore line of Thermo-Photo sensitive hybrid wheat MR168].

    PubMed

    Ren, Yong; Li, Sheng-Rong; Li, Jun; Zhou, Qiang; DU, Xiao-Ying; Li, Tai-Jun; Yang, Wu-Yun; Zheng, You-Liang

    2011-11-01

    Stripe rust, caused by Puccinia striiformis f. sp. tritici, is an important limiting factor to popularize hybrid wheat. The objectives of this study were to map a stripe rust resistance gene in a Chinese thermo-photo-sensitive hybrid wheat restore line MR168 using gene postulation and SSR markers. MR168 was highly resistant to 23 Pst races including CYR29, CYR31, CYR32, and CYR33. The populations F1, BC1, F2, and F3 from the cross between MR168 and SY95-71 (a wheat cultivar susceptible to Pst races) were inoculated with the race of Pst CYR32 of China in greenhouse. MR168 carried a single dominant gene for resistance to CYR32, tentatively designated YrMR168. It originated from Liaochun 10, a spring wheat variety. A total of 183 F2 plants, the resistant and susceptible parents and resistant and susceptible bulks were used for resistance gene mapping with 329 pairs of wheat SSR markers.Five SSR markers on chromosome 1BS including Xgwm18, Xbarc187, Xwmc269, Xgwm273, and Xwmc406 were linked with YrMR168. The resistance gene was closely linked to Xgwm18 and Xbarc187 with the genetic distances of 1.9 and 2.4 cM, respectively. Xgwm18 and Xbarc187 could be used for molecular marker assisted selection of YrMR168 in hybrid wheat breeding program. PMID:22120084

  14. Limits on spin-independent wimp-nucleon interactions from the two-tower run of the cryogenic dark matter search

    SciTech Connect

    Akerib, D.S.; Attisha, M.J.; Bailey, C.N.; Baudis, L.; Bauer, Daniel A.; Brink, P.L.; Brusov, P.P.; Bunker, R.; Cabrera, B.; Caldwell, D.O.; Chang, C.L.; Cooley, J.; Crisler, M.B.; Cushman, P.; Daal, M.; Dixon, R.; Dragowsky, M.R.; Driscoll, D.D.; Duong, L.; Ferril, R.; Filippini, J.; /Brown U. /Case Western Reserve U. /Fermilab /LBL, Berkeley /Santa Clara U. /Minnesota U. /Stanford U., Phys. Dept. /UC, Berkeley /UC, Santa Barbara /Colorado U., Denver /Florida U. /Caltech

    2005-09-01

    We report new results from the Cryogenic Dark Matter Search (CDMS II) at the Soudan Underground Laboratory. Two towers, each consisting of six detectors, were operated for 74.5 live days, giving spectrum-weighted exposures of 34 kg-d for germanium and 12 kg-d for silicon targets after cuts, averaged over recoil energies 10-100 keV for a WIMP mass of 60GeV/c{sup 2}. A blind analysis was conducted, incorporating improved techniques for rejecting surface events. No WIMP signal exceeding expected backgrounds was observed. When combined with our previous results from Soudan, the 90% C.L. upper limit on the spin-independent WIMP-nucleon cross section is 1.6 x 10{sup -43} cm{sup 2} from Ge, and 3 x 10{sup -42} cm{sup 2} from Si, for a WIMP mass of 60GeV/c{sup 2}. The combined limit from Ge (Si) is a factor of 2.5 (10) lower than our previous results, and constrains predictions of supersymmetric models.

  15. Highly sensitive routine method for urinary 3-hydroxybenzo[a]pyrene quantitation using liquid chromatography-fluorescence detection and automated off-line solid phase extraction.

    PubMed

    Barbeau, Damien; Maître, Anne; Marques, Marie

    2011-03-21

    Many workers and also the general population are exposed to polycyclic aromatic hydrocarbons (PAHs), and benzo[a]pyrene (BaP) was recently classified as carcinogenic for humans (group 1) by the International Agency for Research on Cancer. Biomonitoring of PAHs exposure is usually performed by urinary 1-hydroxypyrene (1-OHP) analysis. 1-OHP is a metabolite of pyrene, a non-carcinogenic PAH. In this work, we developed a very simple but highly sensitive analytical method of quantifying one urinary metabolite of BaP, 3-hydroxybenzo[a]pyrene (3-OHBaP), to evaluate carcinogenic PAHs exposure. After hydrolysis of 10 mL urine for two hours and concentration by automated off-line solid phase extraction, the sample was injected in a column-switching high-performance liquid chromatography fluorescence detection system. The limit of quantification was 0.2 pmol L(-1) (0.05 ng L(-1)) and the limit of detection was estimated at 0.07 pmol L(-1) (0.02 ng L(-1)). Linearity was established for 3-OHBaP concentrations ranging from 0.4 to 74.5 pmol L(-1) (0.1 to 20 ng L(-1)). Relative within-day standard deviation was less than 3% and relative between-day standard deviation was less than 4%. In non-occupationally exposed subjects, median concentrations for smokers compared with non-smokers were 3.5 times higher for 1-OHP (p<0.001) and 2 times higher for 3-OHBaP (p<0.05). The two urinary biomarkers were correlated in smokers (ρ=0.636; p<0.05; n=10) but not in non-smokers (ρ=0.09; p>0.05; n=21). PMID:21264439

  16. In-Line Ozonation for Sensitive Air-Monitoring of a Mustard-Gas Simulant by Atmospheric Pressure Chemical Ionization Mass Spectrometry.

    PubMed

    Okumura, Akihiko

    2015-09-01

    A highly sensitive method for real-time air-monitoring of mustard gas (bis(2-chloroethyl) sulfide, HD), which is a lethal blister agent, is proposed. Humidified air containing a HD simulant, 2-chloroethyl ethyl sulfide (2CEES), was mixed with ozone and then analyzed by using an atmospheric pressure chemical ionization ion trap tandem mass spectrometer. Mass-spectral ion peaks attributable to protonated molecules of intact, monooxygenated, and dioxygenated 2CEES (MH(+), MOH(+), and MO(2)H(+), respectively) were observed. As ozone concentration was increased from zero to 30 ppm, the signal intensity of MH(+) sharply decreased, that of MOH(+) increased once and then decreased, and that of MO(2)H(+) sharply increased until reaching a plateau. The signal intensity of MO(2)H(+) at the plateau was 40 times higher than that of MH(+) and 100 times higher than that of MOH(+) in the case without in-line ozonation. Twenty-ppm ozone gas was adequate to give a linear calibration curve for 2CEES obtained by detecting the MO(2)H(+) signal in the concentration range up to 60 μg/m(3), which is high enough for hygiene management. In the low concentration range lower than 3 μg/m(3), which is equal to the short-term exposure limit for HD, calibration plots unexpectedly fell off the linear calibration curve, but 0.6-μg/m(3) vapor was actually detected with the signal-to-noise ratio of nine. Ozone was generated from instrumentation air by using a simple and inexpensive home-made generator. 2CEES was ozonated in 1-m extended sampling tube in only 1 s. PMID:26091887

  17. Long-term characterization of the Flinders Sensitive Line rodent model of human depression: Behavioral and PET evidence of a dysfunctional entorhinal cortex.

    PubMed

    Thiele, S; Spehl, T S; Frings, L; Braun, F; Ferch, M; Rezvani, A H; Furlanetti, L L; Meyer, P T; Coenen, V A; Döbrössy, M D

    2016-03-01

    The etiology of depression is unknown but has been associated with dysregulation of neuronal activity at numerous loci on the limbic-cortical circuitry. The Flinders Sensitive Line (FSL) is a validated rodent model of human depression with spontaneously emerging behavioral and physiological phenotype, however, the durability and robustness of the phenotypes have not been described. The objective of the current study was to evaluate longitudinal dynamics of the depressive-like symptoms in this animal model. FSL and control rats of both genders were assessed over 8 months, characterizing their performance at different time points on motor, sensorimotor and complex learning/memory based tasks. Changes over time in physiological parameters, such as corticosterone and blood glucose levels, were monitored. Regional glucose metabolism, used as a marker of neuronal activity, was assessed at different time points using F18-FDG Positron Emission Tomography (PET). Results show that certain deficits at 2-3 months - on tests such as the Elevated Plus Maze, Object Recognition, and the Forced Swim Test - were transitory and the phenotype was no longer present when re-testing at 6-7 months of age. However, a stable impairment was detected on a learning and memory task, particularly indicating dysfunction in retention of spatial information. Furthermore, at multiple time points, the PET scan indicated a significate bilateral, hypo-metabolism in the temporal lobes in the FSL rats compared to healthy controls. The data suggests possible alterations of entorhinal cortex metabolism concomitant with specific behavioral changes and supports the importance of understanding the dynamics and the time and gender dependence of the phenotypes present. PMID:26658515

  18. USE OF A MURINE EMBRYONIC STEM CELL LINE THAT IS SENSITIVE TO HIGH GLUCOSE ENVIRONMENT TO MODEL NEURAL TUBE DEVELOPMENT IN DIABETIC PREGNANCY

    PubMed Central

    Sanders, Kaitlyn; Jung, Jin Hyuk; Loeken, Mary R.

    2014-01-01

    Background Neural tube defects (NTDs) are significantly increased by maternal diabetes. Embryonic stem cells (ESC) that can differentiate into neuroepithelium and can sense supraphysiological glucose concentrations would be very valuable to simulate the effects of maternal diabetes on molecular and cellular processes during neural tube formation. Methods LG-ESC, a recently established ESC line that expresses the glucose transporter, Scl2a2, and is sensitive to elevated glucose concentrations, were grown for up to 8 days in a 3-dimensional culture to form neural cysts (NC). We tested whether high glucose media inhibits expression of Pax3, a gene that is required for neural tube closure and whose expression is inhibited in embryos of diabetic mice, and inhibits formation of NC. Results Pax3 expression was detected after 4 days of culture and increased with time. Pax3 expression was inhibited by high glucose media, but not if cells had been cultured in low glucose media for the first 4 days of culture. Pax7, which is also expressed in dorsal neural tube, was not detected. Pax6, which is expressed in the ventral neural tube, was detected only after 8 days of culture, but was not inhibited by high glucose. High glucose media did not inhibit formation of NC. Conclusions LG-ESC can be used as a model of embryonic exposure to a diabetic environment during neural tube development. While high glucose exposure inhibits expression of a gene required for neural tube closure, it may not inhibit all of the processes involved in formation of a neural tube-like structure. PMID:25124397

  19. In-Line Ozonation for Sensitive Air-Monitoring of a Mustard-Gas Simulant by Atmospheric Pressure Chemical Ionization Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Okumura, Akihiko

    2015-09-01

    A highly sensitive method for real-time air-monitoring of mustard gas (bis(2-chloroethyl) sulfide, HD), which is a lethal blister agent, is proposed. Humidified air containing a HD simulant, 2-chloroethyl ethyl sulfide (2CEES), was mixed with ozone and then analyzed by using an atmospheric pressure chemical ionization ion trap tandem mass spectrometer. Mass-spectral ion peaks attributable to protonated molecules of intact, monooxygenated, and dioxygenated 2CEES (MH+, MOH+, and MO2H+, respectively) were observed. As ozone concentration was increased from zero to 30 ppm, the signal intensity of MH+ sharply decreased, that of MOH+ increased once and then decreased, and that of MO2H+ sharply increased until reaching a plateau. The signal intensity of MO2H+ at the plateau was 40 times higher than that of MH+ and 100 times higher than that of MOH+ in the case without in-line ozonation. Twenty-ppm ozone gas was adequate to give a linear calibration curve for 2CEES obtained by detecting the MO2H+ signal in the concentration range up to 60 μg/m3, which is high enough for hygiene management. In the low concentration range lower than 3 μg/m3, which is equal to the short-term exposure limit for HD, calibration plots unexpectedly fell off the linear calibration curve, but 0.6-μg/m3 vapor was actually detected with the signal-to-noise ratio of nine. Ozone was generated from instrumentation air by using a simple and inexpensive home-made generator. 2CEES was ozonated in 1-m extended sampling tube in only 1 s.

  20. Theoretical study of fabrication of line-and-space patterns with 7 nm quarter-pitch (7 nm space width and 21 nm line width) using electron beam lithography with chemically amplified resist processes: I. Relationship between sensitivity and chemical gradient

    NASA Astrophysics Data System (ADS)

    Kozawa, Takahiro

    2015-05-01

    Electron beam (EB) lithography used for mask and mold fabrication is an indispensable technology in the lithography used for high-volume production of semiconductor devices. With the reduction in the critical dimensions of semiconductor devices, the requirement for EB lithography also becomes severe. In this study, the feasibility of single nano patterning using EB lithography with a chemically amplified resist process was investigated. The latent images of line-and-space patterns with a 7 nm quarter-pitch (7 nm space width and 21 nm line width) were calculated on the basis of sensitization and reaction mechanisms of chemically amplified EB resists. Simulations indicated that the line-and-space patterns with 7 nm quarter-pitch can be resolved with line edge roughness of 0.9-1.9 nm with a sensitivity of 270 µC cm-2 using a 3 nm electron beam.

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

    NASA Astrophysics Data System (ADS)

    Trummer, Brian J.

    A rapidly expanding understanding of molecular derangements in cancer cell function has led to the development of selective, targeted chemotherapeutic agents. Growth factor signal transduction networks are frequently activated in an aberrant fashion, particularly through the activity of receptor tyrosine kinases (RTK). This has spurred an intensive effort to develop receptor tyrosine kinase inhibitors (RTKI) that are targeted to specific receptors, or receptor subfamilies. Chapter 1 reviews the pharmacology, preclinical, and clinical aspects of RTKIs that target the epidermal growth factor receptor (EGFR). EGFR inhibitors demonstrate significant success at inhibiting phosphorylation-based signaling pathways that promote cancer cell proliferation. Additionally RTKIs have physicochemical and structural characteristics that enable them to function as inhibitors of multi-drug resistance transport proteins. Thus EGFR inhibitors and other RTKIs have both on-target and off-target activities that could be beneficial in cancer therapy. However, these agents exert a number of side effects, some of which arise from their hydrophobic nature and large in vivo volume of distribution. Side effects of the EGFR inhibitor gefitinib include skin rash, severe myelotoxicity when combined with certain chemotherapeutic agents, and impairment of the blood brain barrier to xenobiotics. Weighing the preclinical and clinical observations with the EGFR inhibitors, we developed the primary overall hypothesis of this research: that drug-carrier formulations of RTKIs such as the EGFR inhibitors could be developed based on nanoparticulate liposomal carriers. Theoretically, this carrier strategy would ameliorate toxicity and improve the biodistribution and tumor selectivity of these agents. We hypothesized specifically that liposomal formulations could shift the biodistribution of EGFR inhibitors such as gefitinib away from skin, bone marrow, and the blood brain barrier, and toward solid tumors, 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 MCF7S cell line, and MCF7R was 12-fold more resistant than MCF7S to doxorubicin. A concentration of 3 muM gefitinib, which had no discernible effect upon MCF7R cell proliferation, reduced resistance to paclitaxel to 6-fold, relative to the parental MCF7S cell line, and reduced resistance to doxorubicin to 8-fold, compared to MCF7S. The cytostatic effect of a wider range of gefitinib:paclitaxel ratios was evaluated in order to permit quantitative analysis of the mechanisms of drug interaction, using response surface models. LGEF in combination with paclitaxel was found to be synergistic in MCF7R multidrug-resistant cells, with a psi value of 0.29. Free GEF combined with paclitaxel was also synergistic, with a psi value of 0.40. The confidence intervals for both psi values were below 1, indicating statistical significance for synergy. The fluorescence of gefitinib and doxorubicin permitted visualization of cellular uptake and intracellular distribution of these drugs in multicellular spheroids of rat 9L gliosarcoma cells, which recapitulate some of the barrier functions to drug distribution within tumors. Gefitinib altered the intracellular distribution of doxorubicin, and overcame the nuclear exclusion of doxorubicin in these drug-resistant cells. Chapter 4 discusses the significance of the findings relating both to the formulations produced and to their pharmacology, and concludes that nanoparticulate formulations of gefitinib have the properties necessary to alter drug biodistribution and pharmacokinetics. Such formulations have the potential to provide an effective means to enhance EGFR-inhibitor efficacy in combination chemotherapy.

  2. Non-thermal dark matter production from the electroweak phase transition: multi-TeV WIMPs and "baby-zillas"

    NASA Astrophysics Data System (ADS)

    Falkowski, Adam; No, Jose M.

    2013-02-01

    Particle production at the end of a first-order electroweak phase transition may be rather generic in theories beyond the standard model. Dark matter may then be abundantly produced by this mechanism if it has a sizable coupling to the Higgs field. For an electroweak phase transition occuring at a temperature T EW 50-100 GeV, non- thermally generated dark matter with mass M X > TeV will survive thermalization after the phase transition, and could then potentially account for the observed dark matter relic density in scenarios where a thermal dark matter component is either too small or absent. Dark matter in these scenarios could then either be multi-TeV WIMPs whose relic abundace is mostly generated at the electroweak phase transition, or " Baby-Zillas" with mass M GUT ≫ M X ≫ {v_{EW}} that never reach thermal equilibrium in the early universe.

  3. Pre-launch Estimates for GLAST Sensitivity to Dark Matter Annihilation Signals

    SciTech Connect

    Baltz, E.A.; Berenji, B.; Bertone, G.; Bergstrom, L.; Bloom, E.; Bringmann, T.; Chiang, J.; Cohen-Tanugi, J.; Conrad, J.; Edmonds, Y.; Edsjo, J.; Godfrey, G.; Hughes, R.E.; Johnson, R.P.; Lionetto, A.; Moiseev, A.A.; Morselli, A.; Moskalenko, I.V.; Nuss, E.; Ormes, J.F.; Rando, R.; /INFN, Padua /Ohio State U. /Stockholm U. /Ohio State U. /Garching, Max Planck Inst., MPE /SLAC /KIPAC, Menlo Park /Ohio State U.

    2009-05-15

    We investigate the sensitivity of the Gamma-ray Large Area Space Telescope (GLAST) to indirectly detect weakly interacting massive particles (WIMPs) through the {gamma}-ray signal that their pair annihilation produces. WIMPs are among the favorite candidates to explain the compelling evidence that about 80% of the mass in the Universe is non-baryonic dark matter (DM). They are serendipitously motivated by various extensions of the standard model of particle physics such as Supersymmetry and Universal Extra Dimensions (UED). With its unprecedented sensitivity and its very large energy range (20 MeV to more than 300 GeV) the main instrument on board the GLAST satellite, the Large Area Telescope (LAT), will open a new window of discovery. As our estimates show, the LAT will be able to detect an indirect DM signature for a large class of WIMP models given a cuspy profile for the DM distribution. Using the current state of the art Monte Carlo and event reconstruction software developed within the LAT collaboration, we present preliminary sensitivity studies for several possible sources inside and outside the Galaxy. We also discuss the potential of the LAT to detect UED via the electron/positron channel. Diffuse background modeling and other background issues that will be important in setting limits or seeing a signal are presented.

  4. Constraints on WIMP annihilation for contracted dark matter in the inner Galaxy with the Fermi-LAT

    SciTech Connect

    Gómez-Vargas, Germán A.; Huh, Ji-Haeng; Peiró, Miguel; Cerdeño, David G.; Muñoz, Carlos; Sánchez-Conde, Miguel A.; Prada, Francisco; Morselli, Aldo; Klypin, Anatoly; Mambrini, Yann E-mail: masc@stanford.edu E-mail: miguel.peiro@uam.es E-mail: aldo.morselli@roma2.infn.it E-mail: davidg.cerdeno@uam.es E-mail: carlos.munnoz@uam.es

    2013-10-01

    We derive constraints on parameters of generic dark matter candidates by comparing theoretical predictions with the gamma-ray emission observed by the Fermi-LAT from the region around the Galactic Center. Our analysis is conservative since it simply requires that the expected dark matter signal does not exceed the observed emission. The constraints obtained in the likely case that the collapse of baryons to the Galactic Center is accompanied by the contraction of the dark matter are strong. In particular, we find that for b b-bar and τ{sup +}τ{sup −} or W{sup +}W{sup −} dark matter annihilation channels, the upper limits on the annihilation cross section imply that the thermal cross section is excluded for a Weakly Interacting Massive Particle (WIMP) mass smaller than about 700 and 500 GeV, respectively. For the μ{sup +}μ{sup −} channel, where the effect of the inverse Compton scattering is important, depending on models of the Galactic magnetic field the exclusion of the thermal cross-section is for a WIMP mass smaller than about 150 to 400 GeV. The upper limits on the annihilation cross section of dark matter particles obtained are two orders of magnitude stronger than without contraction. In the latter case our results are compatible with the upper limits from the Galactic halo analysis reported by the Fermi-LAT collaboration for the case in which the same conservative approach without modeling of the astrophysical background is employed.

  5. A Common Genetic Determinism for Sensitivities to Soil Water Deficit and Evaporative Demand: Meta-Analysis of Quantitative Trait Loci and Introgression Lines of Maize1[W][OA

    PubMed Central

    Welcker, Claude; Sadok, Walid; Dignat, Grégoire; Renault, Morgan; Salvi, Silvio; Charcosset, Alain; Tardieu, François

    2011-01-01

    Evaporative demand and soil water deficit equally contribute to water stress and to its effect on plant growth. We have compared the genetic architectures of the sensitivities of maize (Zea mays) leaf elongation rate with evaporative demand and soil water deficit. The former was measured via the response to leaf-to-air vapor pressure deficit in well-watered plants, the latter via the response to soil water potential in the absence of evaporative demand. Genetic analyses of each sensitivity were performed over 21 independent experiments with (1) three mapping populations, with temperate or tropical materials, (2) one population resulting from the introgression of a tropical drought-tolerant line in a temperate line, and (3) two introgression libraries genetically independent from mapping populations. A very large genetic variability was observed for both sensitivities. Some lines maintained leaf elongation at very high evaporative demand or water deficit, while others stopped elongation in mild conditions. A complex architecture arose from analyses of mapping populations, with 19 major meta-quantitative trait loci involving strong effects and/or more than one mapping population. A total of 68% of those quantitative trait loci affected sensitivities to both evaporative demand and soil water deficit. In introgressed lines, 73% of the tested genomic regions affected both sensitivities. To our knowledge, this study is the first genetic demonstration that hydraulic processes, which drive the response to evaporative demand, also have a large contribution to the genetic variability of plant growth under water deficit in a large range of genetic material. PMID:21795581

  6. 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 greater than 315 nm.

    PubMed

    Rosenstein, B S

    1989-08-01

    Cultures of the solar UV-sensitive cell lines, DRP 36 and DRP 153, and of the parental ICR 2A cell line, were exposed to 150 kJ/m2 of sunlamp UV greater than 315 nm plus photoreactivating light. This treatment resulted in the induction primarily of non-dimer DNA damage. Following either a 0, 3, 6, 12 or 24 h incubation, the cultures were pulse-labelled with [3H]thymidine, and the synthesis of different size classes of replicon intermediates measured using the alkaline step elution assay. For all three cell lines tested, an immediate depression of low molecular weight DNA synthesis was observed. This was followed by an inhibition of all size classes of replicon intermediates. Within 12 h following irradiation, recovery of DNA synthesis was observed, which was 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. However, a much smaller recovery of DNA synthesis was detected for the DRP 36 and DRP 153 cultures. This continued inhibition was primarily in the synthesis of full replicon size DNA, and was most pronounced for the DRP 36 cells. Hence, it appears that replicon chain elongation continues to be inhibited in these solar UV-sensitive cell lines long after irradiation. PMID:2569015

  7. IL-27 Promotes Proliferation of Human Leukemic Cell Lines Through the MAPK/ERK Signaling Pathway and Suppresses Sensitivity to Chemotherapeutic Drugs

    PubMed Central

    Dilger, Paula; Bird, Chris; Wadhwa, Meenu

    2016-01-01

    IL-27 is a pleiotropic cytokine of the IL-6/IL-12 family with diverse biological functions. Previous in vivo studies have suggested the antitumor activities of IL-27 in animal models, whereas clinical observations indicate the link of IL-27 in tumor progression. IL-27 has recently been shown to cause inhibition of proliferation on primary leukemic cells from pediatric patients, but information on its role in human leukemic cell lines is limited. In the present study, we investigated the ability of IL-27 to regulate cell growth and survival of various human leukemic cell lines. Our results showed that in human leukemic cell lines coexpressing both IL-27R chains, IL-27Rα and gp130, IL-27 did not inhibit cell growth, but caused dose-dependent proliferation of the acute myeloid leukemic cell line, OCI-AML5, and the erythroleukemic cell lines, TF-1, UT-7, and UT-7/EPO. Consistent with this, IL-27 promoted cell survival and reduced TNF-α-induced apoptosis of the leukemic cell lines. IL-27 also decreased the responsiveness of the leukemic cells to chemotherapeutic drugs, cytarabine and daunorubicin. We observed that IL-27 induced the activation of STAT1/3 and ERK1/2 in the leukemic cells. Growth stimulation by IL-27 was suppressed by the specific MEK inhibitor, U0126, indicating that IL-27-induced cell proliferation is mainly mediated through the activation of the MAPK/ERK signaling pathway. The present study is the first demonstration of the proliferative and antichemotherapeutic properties of IL-27 in human leukemic cell lines, suggesting that IL-27 can play an unfavorable role in tumor growth and can be an important determinant in the chemoresponsiveness of certain subtypes of human leukemia. PMID:27119567

  8. IL-27 Promotes Proliferation of Human Leukemic Cell Lines Through the MAPK/ERK Signaling Pathway and Suppresses Sensitivity to Chemotherapeutic Drugs.

    PubMed

    Jia, Haiyan; Dilger, Paula; Bird, Chris; Wadhwa, Meenu

    2016-05-01

    IL-27 is a pleiotropic cytokine of the IL-6/IL-12 family with diverse biological functions. Previous in vivo studies have suggested the antitumor activities of IL-27 in animal models, whereas clinical observations indicate the link of IL-27 in tumor progression. IL-27 has recently been shown to cause inhibition of proliferation on primary leukemic cells from pediatric patients, but information on its role in human leukemic cell lines is limited. In the present study, we investigated the ability of IL-27 to regulate cell growth and survival of various human leukemic cell lines. Our results showed that in human leukemic cell lines coexpressing both IL-27R chains, IL-27Rα and gp130, IL-27 did not inhibit cell growth, but caused dose-dependent proliferation of the acute myeloid leukemic cell line, OCI-AML5, and the erythroleukemic cell lines, TF-1, UT-7, and UT-7/EPO. Consistent with this, IL-27 promoted cell survival and reduced TNF-α-induced apoptosis of the leukemic cell lines. IL-27 also decreased the responsiveness of the leukemic cells to chemotherapeutic drugs, cytarabine and daunorubicin. We observed that IL-27 induced the activation of STAT1/3 and ERK1/2 in the leukemic cells. Growth stimulation by IL-27 was suppressed by the specific MEK inhibitor, U0126, indicating that IL-27-induced cell proliferation is mainly mediated through the activation of the MAPK/ERK signaling pathway. The present study is the first demonstration of the proliferative and antichemotherapeutic properties of IL-27 in human leukemic cell lines, suggesting that IL-27 can play an unfavorable role in tumor growth and can be an important determinant in the chemoresponsiveness of certain subtypes of human leukemia. PMID:27119567

  9. Stable expression of guinea pig NADPH-cytochrome P450 reductase and monkey P4501A1 cDNAs in Chinese hamster cells: establishment of cell lines highly sensitive to aflatoxin B [corrected].

    PubMed

    Sawada, M; Kitamura, R; Ohgiya, S; Kamataki, T

    1993-01-01

    To the cell line (A-15) expressing monkey P4501A1, which was developed from a Chinese hamster fibroblast cell line (CHL), a guinea pig [corrected] cDNA encoding NADPH-cytochrome P450 reductase was introduced and the transformants (designated AR-10, AR-13, and AR-18) stably expressing the reductase of increased level were established. The high-level expression of the reductase was confirmed by Northern and Western blot analyses and by measurement of the reductase activity in microsomes. The transfected clones showed 4- to 11-fold higher activity of the reductase than the parental cells. These cells showed about 9-fold higher sensitivity toward aflatoxin B1 (AFB1) cytotoxicity than A-15 cells and about 330-fold more than parental CHL cells. No difference in sensitivity was observed between CHL and the CHL-derived clones (CR-50, CR-52, and CR-68) expressing high levels of the reductase alone. Increased sensitivity of AR-10 cells was also observed with respect to sterigmatocystin cytotoxicity. Furthermore, in the assay for the induction of chromosomal aberrations, these clones were highly sensitive to AFB1. These results indicate that the level of the P450 reductase existing in parental CHL cells is not sufficient for maximal activity of monkey P4501A1. PMID:8424648

  10. The distribution and kinematics of ammonia in the Orion-KL nebula - high-sensitivity VLA maps of the NH sub 3 (3,2) line

    SciTech Connect

    Migenes, V.; Johnston, K.J.; Pauls, T.A.; Wilson, T.L. E. O. Hulburt Center for Space Research, Washington, DC Max-Planck-Institut fuer Radioastronomie, Bonn )

    1989-12-01

    VLA maps of the (J,K) = (3,2) rotation-inversion line of NH{sub 3} toward the Orion-KL nebula are presented which show that the emission is clumped on roughly 1 arcsec scales. There are 11 distinct fragments with peak intensities more than seven times the rms noise. The observations give a qualitatively different picture of the fragmentation process on scales of 10 to the 16th cm. Apparently, turbulent motions within the individual clumps are small, and most of the kinetic energy is contained in orbital motion. For VLA observations, it is found that the (3,2) line spectra agree better with spectra of other nonmetastable (J greater than K) lines than with metastable (J = K) lines. This confirms that the nonmetastable and metastable NH3 lines are formed in different regions of the hot core. The maps show that the structure in the hot core is consistent with a clumpy cylinder whose axis is inclined at about 40 deg east of north and expanding at 10 km/s. 24 refs.

  11. Comparative study of the sensitivity of lymphoblastoid and transformed monocytic cell lines to the cytotoxic effects of Viscum album extracts of different origin.

    PubMed

    Duong Van Huyen, Jean-Paul; Delignat, Sandrine; Kazatchkine, Michel D; Kaveri, Srini V

    2003-12-01

    Viscum album (VA) preparations consist of aqueous extracts of V. album, the European mistletoe. VA extracts contain mistletoe lectins, which are members of the ribosome-inactivating protein type II family. VA preparations have cytotoxic and immunomodulatory properties. Cytotoxicity induced by VA extracts may differ greatly according to the origin of the preparation (host tree, fermented extract) and the cell type. This work was performed to assess the cytotoxicity of various VA preparations, i.e. VA Qu FrF, Qu Spez, M Spez and VA P, in lymphoblastoid and monocytic cell lines. VA Qu FrF, Qu Spez and M Spez induced dose-dependent cell death and inhibition of cell proliferation in lymphoblastoid T cell lines and in transformed monocytic lines. In contrast, the majority of B cell lines tested were resistant to cytotoxicity induced by VA extracts. While VA Qu FrF, Qu Spez and M Spez were potent inducers of cell death, extracts of VA P, derived from mistletoe plants growing on pine trees, failed to induce any cell death in any of the cell lines examined. PMID:14671430

  12. Topoisomerase I Levels in the NCI-60 Cancer Cell line Panel Determined by Validated ELISA and Microarray Analysis and Correlation with Indenoisoquinoline Sensitivity

    PubMed Central

    Pfister, Thomas D.; Reinhold, William; Agama, Keli; Gupta, Shalu; Khin, Sonny A.; Kinders, Robert J.; Parchment, Ralph E.; Tomaszewski, Joseph E.; Doroshow, James H.; Pommier, Yves

    2009-01-01

    Topoisomerase I (Top1) is a proven target for cancer therapeutics, and the level of Top1 in tumors has been employed as a biomarker for chemotherapeutic efficacy. In this study, we report the development and validation of a two-site enzyme chemiluminescent immunoassay for Top1, which we used to measure Top1 levels in the NCI-60 cancer cell line panel. Top1 levels ranged from 0.9 to 9.8 ng/mL/μg protein extract in these cell lines. Levels varied both within and between cancer types but were generally highest in colon cancer and leukemia cell lines and lowest in central nervous system and renal cancer cell lines. Top1 mRNA levels in the NCI-60 cell lines were also measured by microarray; mRNA values generally demonstrated a good correlation with protein levels (Pearson correlation = 0.8). When these expression levels were compared with the activity of the indenoisoquinoline class of Top1 inhibitors across the NCI-60 cell panel, low levels of Top1 were associated with increased resistance to these drugs. The results of our studies indicate that our Top1 assay can be used to quantify Top1 levels in untreated cells as well as cells treated with Top1 inhibitors, and that the assay has the potential to be adapted for use in predicting clinical response to Top1-active antineoplastic agents. PMID:19584232

  13. Silicon photonic crystal microarrays for high throughput label-free detection of lung cancer cell line lysates with sensitivity and specificity

    NASA Astrophysics Data System (ADS)

    Chakravarty, Swapnajit; Lai, Wei-Cheng; Zou, Yi; Gemmill, Robert M.; Chen, Ray T.

    2013-03-01

    Detection of biomolecules on microarrays based on label-free on-chip optical biosensors is very attractive since this format avoids complex chemistries caused by steric hindrance of labels. Application areas include the detection of cancers and allergens, and food-borne pathogens to name a few. We have demonstrated photonic crystal microcavity biosensors with high sensitivity down to 1pM concentrations (67pg/ml). High sensitivities were achieved by slow light engineering which reduced the radiation loss and increased the stored energy in the photonic crystal microcavity resonance mode. Resonances with high quality factor Q~26,760 in liquid ambient, coupled with larger optical mode volumes allowed enhanced interaction with the analyte biomolecules which resulted in sensitivities down to 10 cells per micro-liter to lung cancer cell lysates. The specificity of detection was ensured by multiplexed detections from multiple photonic crystal microcavities arrayed on the arms of a multimode interference power splitter. Specific binding interactions and control experiments were performed simultaneously at the same instant of time with the same 60 microliter sample volume. Specificity is further ensured by sandwich assay methods in the multiplexed experiment. Sandwich assay based amplification increased the sensitivity further resulting in the detection of lung cancer cell lysates down to concentrations of 2 cells per micro-liter. The miniaturization enabled by photonic crystal biosensors coupled with waveguide interconnected layout thus offers the potential of high throughput proteomics with high sensitivity and specificity.

  14. Bacterial and fungal communities in bulk soil and rhizospheres of aluminum-tolerant and aluminum-sensitive maize (Zea mays L.) lines cultivated in unlimed and limed Cerrado soil.

    PubMed

    Da Mota, Fabio Faria; Gomes, Eliane Aparecida; Marriel, Ivanildo Evodio; Paiva, Edilson; Seldin, Lucy

    2008-05-01

    Liming of acidic soils can prevent aluminum toxicity and improve crop production. Some maize lines show aluminum (Al) tolerance, and exudation of organic acids by roots has been considered to represent an important mechanism involved in the tolerance. However, there is no information about the impact of liming on the structures of bacterial and fungal communities in Cerrado soil, nor if there are differences between the microbial communities from the rhizospheres of Al-tolerant and Al-sensitive maize lines. This study evaluated the effects of liming on the structure of bacterial and fungal communities in bulk soil and rhizospheres of Al-sensitive and Al-tolerant maize (Zea mays L.) lines cultivated in Cerrado soil by PCR-DGGE, 30 and 90 days after sowing. Bacterial fingerprints revealed that the bacterial communities from rhizospheres were more affected by aluminum stress in soil than by the maize line (Al-sensitive or Al-tolerant). Differences in bacterial communities were also observed over time (30 and 90 days after sowing), and these occurred mainly in the Actinobacteria. Conversely, fungal communities from the rhizosphere were weakly affected either by liming or by the rhizosphere, as observed from the DGGE profiles. Furthermore, only a few differences were observed in the DGGE profiles of the fungal populations during plant development when compared with bacterial communities. Cloning and sequencing of 16S rRNA gene fragments obtained from dominant DGGE bands detected in the bacterial profiles of the Cerrado bulk soil revealed that Actinomycetales and Rhizobiales were among the dominant ribotypes. PMID:18633275

  15. Optimal detectors for WIMP and 0 ν ββ searches: Identical high-pressure xenon gas TPCs?

    NASA Astrophysics Data System (ADS)

    Nygren, David

    2007-11-01

    A time projection chamber (TPC) filled with high-pressure gaseous xenon (HPXe)—instead of liquid xenon (LXe)—appears likely to offer both superior energy resolution for the 0-ν ββ decay search in 136Xe and superior γ-background rejection in the search for WIMPs. An augmentation to maximize the primary scintillation detection efficiency of the 0-ν ββ decay detector design will realize an optimum design for both purposes. In this scenario an attractive synergy exists: two identical HPXe TPCs differing only in isotopic content will provide significantly more robust evidence for the existence of either signal if present. A simple analysis of important factors that limit energy resolution leads to the conclusion that the optimal design for either next-generation search at the few hundred kg level is the same HPXe-based TPC. A careful measurement of the scintillation and ionization responses of HPXe to nuclear and electronic recoils is needed to test the claim of HPXe superiority to LXe for the combined goals.

  16. Dual regulation of skin sensitizer-induced HMOX1 expression by Bach1 and Nrf2: Comparison to regulation of the AKR1C2-ARE element in the KeratinoSens cell line.

    PubMed

    Emter, Roger; Natsch, Andreas

    2015-11-01

    Heme oxygenase (decycling) 1 (HMOX1) is the most consistently found genetic marker induced by skin sensitizers. HMOX1 is often referred to as typical gene regulated by nuclear factor erythroid 2-related factor 2 (Nrf2), however, it is also regulated by other DNA-binding factors, including BTB and CNC homolog 1 (Bach1). The KeratinoSens™ assay is the first validated in vitro assay for sensitizers that measures gene induction. It is based on luciferase expression regulated by the antioxidant response element (ARE) of the aldoketoreductase 1C2 (AKR1C2) gene. Luciferase upregulation is dependent on Nrf2, while HMOX1 upregulation is only partially Nrf2-dependent. Thus, sensitizer-dependent activation of HMOX1 may integrate multiple signals thereby providing additional information. We constructed reporter cell lines containing the full HMOX1 regulatory region or the HMOX1-ARE sequence and compared them with the construct containing the AKR1C2-ARE sequence. Induction of the AKR1C2-ARE depends on Nrf2, but not on the repressor Bach1. Results obtained with HMOX1-ARE and the full HMOX1 promoter indicate that, within the HMOX1 promoter, the HMOX1-ARE is sufficient to explain the induction by sensitizers and that (i) inhibiting Bach1 leads to strong basal expression, (ii) fold-induction by sensitizers above this level is reduced in the absence of Bach1 and (iii) these constructs are less dependent on Nrf2 as compared to the AKR1C2-ARE. Nevertheless, congruent dose response curves for luciferase activity were obtained with all constructs. Thus, while sensitizer-induced HMOX1 activation is dependent on Nrf2 and Bach1, all constructs give identical information for the in vitro prediction of the sensitization potential. PMID:26244607

  17. Improved calculations for the C III 1907,1909 and Si III 1883,1892 electron density sensitive emission-line ratios, and a comparison with IUE observations

    NASA Technical Reports Server (NTRS)

    Keenan, F. P.; Feibelman, W. A.; Berrington, K. A.

    1992-01-01

    Atomic data are used in conjunction with the statistical equilibrium code of Dufton (1977) to calculate relative C III and Si III level populations, and hence emission-line strengths for a range of electron temperatures and densities. It is assumed that photoexcitation and deexcitaton rates are negligible in comparison with the corresponding collisional rates, that ionization to and recombination from other ionic levels are slow compared with bound-bound rates, and that all transitions are optically thin. The observed values of R1 and R2 for several planetary nebulae and a symbiotic star, measured from high-resolution spectra obtained with the IUE satellite, lead to electron densities that are compatible, and are also in good agreement with those deduced from line ratios in other species.

  18. Development of an on-line temperature-assisted ionic liquid dispersive microextraction system for sensitive determination of vanadium in environmental and biological samples.

    PubMed

    Berton, Paula; Martinis, Estefanía M; Wuilloud, Rodolfo G

    2010-04-15

    An original flow injection (FI) system was developed for on-line microextraction of Vanadium (V) based on room temperature ionic liquid (RTIL). Vanadium was complexed with 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol (5-Br-PADAP) at pH 4.0. A 40 microL-volume of 1-butyl-3-methylimidazolium hexafluorophosphate ([C(4)mim][PF(6)]) RTIL was mixed with 5 mL of sample solution containing the V-5-Br-PADAP complex. Then, a fully on-line temperature-assisted dispersion procedure was developed, followed by, analyte microextraction; and final on-line separation of the RTIL phase with a florisil-containing microcolumn. Vanadium was removed from the microcolumn with a 10% (v/v) nitric acid (in acetone) solution, and finally measured by electrothermal atomic absorption spectrometry (ETAAS). The detection limit achieved after preconcentration of 5 mL of sample solution, was 4.8 ng L(-1). The relative standard deviation (RSD) for 10 replicate determinations at 5 microg L(-1) of vanadium level was 4.1%, calculated from the obtained peak heights. The calibration graph was linear, with a correlation coefficient of 0.9982 at levels from the detection limits up to 15 microg L(-1). The method was successfully applied for the determination of vanadium in environmental and biological samples. PMID:20006437

  19. Blockade of Hedgehog Signaling Synergistically Increases Sensitivity to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-Small-Cell Lung Cancer Cell Lines

    PubMed Central

    Bai, Xiao-Yan; Zhang, Xu-Chao; Yang, Su-Qing; An, She-Juan; Chen, Zhi-Hong; Su, Jian; Xie, Zhi; Gou, Lan-Ying; Wu, Yi-Long

    2016-01-01

    Aberrant activation of the hedgehog (Hh) signaling pathway has been implicated in the epithelial-to-mesenchymal transition (EMT) and cancer stem-like cell (CSC) maintenance; both processes can result in tumor progression and treatment resistance in several types of human cancer. Hh cooperates with the epidermal growth factor receptor (EGFR) signaling pathway in embryogenesis. We found that the Hh signaling pathway was silenced in EGFR-TKI-sensitive non-small-cell lung cancer (NSCLC) cells, while it was inappropriately activated in EGFR-TKI-resistant NSCLC cells, accompanied by EMT induction and ABCG2 overexpression. Upregulation of Hh signaling through extrinsic SHH exposure downregulated E-cadherin expression and elevated Snail and ABCG2 expression, resulting in gefitinib tolerance (P < 0.001) in EGFR-TKI-sensitive cells. Blockade of the Hh signaling pathway using the SMO antagonist SANT-1 restored E-cadherin expression and downregulate Snail and ABCG2 in EGFR-TKI-resistant cells. A combination of SANT-1 and gefitinib markedly inhibited tumorigenesis and proliferation in EGFR-TKI-resistant cells (P < 0.001). These findings indicate that hyperactivity of Hh signaling resulted in EGFR-TKI resistance, by EMT introduction and ABCG2 upregulation, and blockade of Hh signaling synergistically increased sensitivity to EGFR-TKIs in primary and secondary resistant NSCLC cells. E-cadherin expression may be a potential biomarker of the suitability of the combined application of an Hh inhibitor and EGFR-TKIs in EGFR-TKI-resistant NSCLCs. PMID:26943330

  20. Increased sensitivity of HPV-positive head and neck cancer cell lines to x-irradiation ± Cisplatin due to decreased expression of E6 and E7 oncoproteins and enhanced apoptosis

    PubMed Central

    Ziemann, Frank; Arenz, Andrea; Preising, Stefanie; Wittekindt, Claus; Klussmann, Jens P; Engenhart-Cabillic, Rita; Wittig, Andrea

    2015-01-01

    Squamous cell carcinoma of the head and neck region (HNSCC), which is related to an infection with human papilloma virus (HPV), responds better to simultaneous radio-chemotherapy with Cisplatin based regimens than HPV-negative tumors. The underlying molecular mechanisms for this clinical observation are not fully understood. Therefore, the response of four HPV-positive (HPV+) (UM-SCC-47, UM-SCC-104, 93-VU-147T, UPCI:SCC152) and four HPV-negative (HPV-) (UD-SCC-1, UM-SCC-6, UM-SCC-11b, UT-SCC-33) HNSCC cell lines to x-irradiation ± Cisplatin incubation in terms of clonogenic survival, cell cycle progression, protein expression (cyclin A2, cyclin E2, E6, E7, p53) and induction of apoptosis, was investigated. HPV+ cells were more radio- and chemosensitive and were more effectively sensitized to x-irradiation by simultaneous Cisplatin incubation than HPV- cell lines. HPV+ cell lines revealed an increased and prolonged G2/M arrest after irradiation, whereas Cisplatin induced a blockage of cells in S phase. In comparison to irradiation only, addition of Cisplatin significantly enhanced apoptosis especially in HPV+ cell lines. While irradiation alone increased the amount of HPV E6 and E7 proteins, both were down-regulated by Cisplatin incubation either alone or in combination with x-rays, which however did not increase the expression of endogenous p53. Our results demonstrate that cell cycle deregulation together with downregulation of HPV E6 and E7 proteins facilitating apoptosis after Cisplatin incubation promote the enhanced sensitivity of HPV+ HNSCC cells to simultaneous radio-chemotherapy. Combined effects of irradiation and Cisplatin appear to be relevant in mediating the enhanced therapeutic response of HPV-related HNSCC and are indicative of the benefit of combined modality approaches in future treatment optimization strategies. PMID:26045983

  1. Selective sensitivity to wasabi-derived 6-(methylsulfinyl)hexyl isothiocyanate of human breast cancer and melanoma cell lines studied in vitro.

    PubMed

    Nomura, Takahiro; Shinoda, Shoko; Yamori, Takao; Sawaki, Saeko; Nagata, Ikuko; Ryoyama, Kazuo; Fuke, Yoko

    2005-01-01

    Recently, attention has focused on the anticancer properties of an aromatic component 6-(methylsulfinyl)hexyl isothiocyanate (6-MITC) in a typical Japanese spice, wasabi. In this paper, anticancer activity of 6-MITC in vitro was studied by using a human cancer cell (HCC) panel. 6-MITC directly affected the cells in the HCC panel and inhibited their growth in culture. The mean concentration required to inhibit 50% of control cell growth was 3.9 microM, which is a sufficiently low dosage for practical use. The suppression influenced not only the cell growth, but also the survival of these cells. The mean concentration to suppress cells to a 50% survival was 43.7 microM. The reduction activity of 6-MITC was differential, and it suppressed specific cells. These severely suppressed cell lines included breast cancer and melanoma cell lines. For example, one melanoma line was seriously damaged at a concentration of 0.3 microM of 6-MITC. Compared with other MITCs (2-MITC, 4-MITC and 8-MITC), 6-MITC showed the most effective suppression and with the most specific manner of the cells mentioned above. A "COMPARE" analysis using a computerized algorithm, which was based on the HCC database, suggested that the suppression mechanism of 6-MITC is unique and may be different from that of other known chemicals. The actual mechanism may not a simple one but may involve multiple pathways. On account of its sufficiently small size, 6-MITC is a new possible candidate for controlling cancer cells. PMID:15829375

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

    PubMed Central

    2010-01-01

    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 identify small subpopulations of patients expected to predictably benefit from individualized treatment protocols using ICL-agents. PMID:20509860

  3. 6-Aryl and heterocycle quinazoline derivatives as potent EGFR inhibitors with improved activity toward gefitinib-sensitive and -resistant tumor cell lines.

    PubMed

    Hamed, Mostafa M; Abou El Ella, Dalal A; Keeton, Adam B; Piazza, Gary A; Abadi, Ashraf H; Hartmann, Rolf W; Engel, Matthias

    2013-09-01

    A group of novel anilinoquinazoline derivatives with variable aryl and heterocyclic substituents at position?6 were synthesized and tested for their EGFR-inhibitory activity. Aryl and heterocyclic rings were attached to the quinazoline scaffold through different linkages such as imine, amide, and thiourea. Most of the aryl and heterocyclic derivatives showed potent inhibition of wild-type EGFR with IC?? values in the low nanomolar range. Among these, thiourea derivatives 6?a, 6?b and compound 10?b also retained significant activity toward the gefitinib-insensitive EGFR(T790M/L858R) mutant, displaying up to 24-fold greater potency than gefitinib. In addition, cell growth inhibitory activity was tested against cancer cell lines with wild-type (KB cells) and mutant EGFR (H1975 cells). Several compounds including 6?a were found to be more potent than the reference compound gefitinib toward both cell lines, as was the case for compound 10?b against H1975 cells. Therefore, compounds 6?a and 10?b in particular may serve as new leads for the development of inhibitors effective against wild-type EGFR as well as gefitinib-resistant mutants. PMID:23847159

  4. Experimental Concept for a Precision Measurement of Nuclear Recoil Ionization Yields for Low Mass WIMP Searches

    NASA Astrophysics Data System (ADS)

    Saab, T.; Figueroa-Feliciano, E.

    2016-01-01

    Understanding the response of dark matter detectors at the lowest recoil energies is important for correctly interpreting data from current experiments or predicting the sensitivity of future experiments to low mass weakly interacting massive particles. In particular, the ionization yield is essential for determining the correct recoil energy of candidate nuclear recoil events; however, few measurements in cryogenic crystals exist below 1 keV. Using the voltage-assisted calorimetric ionization detection technique with a mono-energetic neutron source, we show that it is possible to determine the ionization yield in cryogenic crystals down to an energy to 100 eV. This measurement will also determine the statistics of ionization production at these low energies.

  5. Bosonic super-WIMPs as keV-scale dark matter

    SciTech Connect

    Pospelov, Maxim; Ritz, Adam; Voloshin, Mikhail

    2008-12-01

    We consider models of light superweakly interacting cold dark matter, with O(10-100) keV mass, focusing on bosonic candidates such as pseudoscalars and vectors. We analyze the cosmological abundance, the {gamma} background created by particle decays, the impact on stellar processes due to cooling, and the direct-detection capabilities in order to identify classes of models that pass all the constraints. In certain models, variants of photoelectric (or axioelectric) absorption of dark matter in direct-detection experiments can provide a sensitivity to the superweak couplings to the standard model which is superior to all existing indirect constraints. In all models studied, the annual modulation of the direct-detection signal is at the currently unobservable level of O(10{sup -5})

  6. VeroNectin-4 is a highly sensitive cell line that can be used for the isolation and titration of Peste des Petits Ruminants virus.

    PubMed

    Fakri, F; Elarkam, A; Daouam, S; Tadlaoui, K; Fassi-Fihri, O; Richardson, C D; Elharrak, M

    2016-02-01

    Peste des Petits Ruminants virus (PPRV) is a member of the Morbillivirus subgroup of the family Paramyxoviridae, and is one of the most contagious diseases of small ruminants throughout Africa and the rest of the world. Different cell lines have previously been used to isolate PPRV but with limited success. Thus, to improve the isolation of Morbilliviruses, human, canine, and goat homologues of the lymphocyte receptor signaling lymphocyte activation molecule (SLAM) have been introduced into cells that can support virus replication. However, the amino acid sequence of SLAM varies between species, and often requires adaptation of a particular virus to different versions of the receptor. The protein sequence of Nectin-4 is highly conserved between different mammals, which eliminate the need for receptor adaptation by the virus. Cell lines expressing Nectin-4 have previously been used to propagate measles and canine distemper viruses. In this study, we compared infections in Vero cells expressing canine SLAM (VeroDogSLAM) to those in Vero cells expressing Nectin-4 (VeroNectin-4), following inoculations with wild-type strains of PPRV. Virus isolation using VeroNectin-4 cells was successful with 23% of swabbed samples obtained from live infected animals, and was 89% effective using post-mortem tissues of infected sheep. By contrast, only 4.5% efficiency was observed from swab samples and 67% efficiency was obtained in virus isolation from post-mortem tissues using VeroDogSLAM cells. The average incubation period for virus recovery from post-mortem tissues was 3.4 days using VeroNectin-4 cells, compared with 5.5 days when using VeroDogSLAM cells. The virus titers of PPRV obtained from VeroNectin-4 cells were also higher than those derived from VeroDogSLAM cells. A comparison of the growth kinetics for PPRV in the two cell lines confirmed the superiority of VeroNectin-4 cells for PPR diagnostic purposes and vaccine virus titration. PMID:26615804

  7. Noscapine Increases the Sensitivity of Drug-Resistant Ovarian Cancer Cell Line SKOV3/DDP to Cisplatin by Regulating Cell Cycle and Activating Apoptotic Pathways.

    PubMed

    Shen, Wei; Liang, Bingfeng; Yin, Jie; Li, Xiurong; Cheng, Jianxin

    2015-05-01

    Cisplatin is a first-line chemotherapy drug against ovarian cancer. However, its strong toxic side effects and the development of cisplatin resistance in human cancer cells seriously influence the effects of chemotherapy and quality of life in patients. Noscapine (Nos), a non-toxic benzylisoquinoline alkaloid extracted from opium, has been recently reported to have anti-cancer activity, but the mechanism of that effect has not been clearly established. In the present study, we investigated cytotoxicity of Nos in combination with cisplatin (DDP) in drug-resistant human ovarian cancer cell line SKOV3/DDP in vitro and in vivo null mice xenograft model. Cell proliferation was measured by MTT assay, flow cytometry was used to analyze cell cycle and apoptosis, protein expression of several apoptotic factors was investigated by flow cytometry and immunohistochemical method, and their mRNA expression levels were determined by real-time PCR. In vitro experiments showed that Nos significantly inhibited proliferation of SKOV3/DDP cells. DDP/Nos-combined treatment notably enhanced DDP-induced inhibition of cell proliferation and increased the pro-apoptotic effect of DDP in SKOV3/DDP cells. DDP/Nos administration increased the proportion of G2/M cells, reduced both protein and mRNA expression of anti-apoptotic factors XIAP, surviving and NF-kB, and augmented protein and mRNA levels of pro-apoptotic caspase-3. In vivo experiments revealed that Nos/DDP treatment increased the apoptotic rate of xenograft tumors in null mice. Tumor volume decreased from 1.733 ± 0.155 g in mice treated with DDP alone to 1.191 ± 0.106 g in animals treated with Nos/DDP. These observations suggest that Nos increases the anti-cancer activity of DDP against the drug-resistant ovarian cancer cell line SKOV3/DDP by modulating the cell cycle and activating apoptotic pathways. The study provides a new chemotherapy strategy for the treatment of DDP-resistant human ovarian cancer. PMID:25510462

  8. Strong sensitivity of x-ray emission lines following charge exchange between highly charged ions and H (1 s ) in weakly screened media

    NASA Astrophysics Data System (ADS)

    Cariatore, N. D.; Otranto, S.

    2015-11-01

    We use the classical trajectory Monte Carlo method to analyze charge exchange processes between fully stripped projectiles with H (1 s ) in a screened environment at impact energies in the range 18 eV/amu to 10 keV/amu. For Fe+26 projectiles, (n ,l )-state selective charge exchange and line emission cross sections are presented for Debye screening lengths from 15 a.u. up to the unscreened case limit. At low-impact energies, a strong dependence of the hardness ratio on the Debye screening length is found. We show that such strong dependence also evidences itself for Ne+10,P+15,Ar+18, and Kr+36 projectiles. Clear indications of this dependence are noticeable in the photonic spectra even for large screening lengths (˜100 a.u.).

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

    PubMed

    Ortega, Claudia; Cerutti, Soledad; Olsina, Roberto A; Silva, Mara F; 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 degrees 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 microg L(-1). The precision for 10 replicate determinations at the 2.0 microg 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 microg L(-1). The method was successfully applied to the determination of dysprosium in urine. PMID:12560972

  10. In-Line Separation by Capillary Electrophoresis Prior to Analysis by Top-Down Mass Spectrometry Enables Sensitive Characterization of Protein Complexes

    PubMed Central

    2015-01-01

    Intact protein analysis via top-down mass spectrometry (MS) provides a bird’s eye view over the protein complexes and complex protein mixtures with the unique capability of characterizing protein variants, splice isoforms, and combinatorial post-translational modifications (PTMs). Here we applied capillary electrophoresis (CE) through a sheathless CE–electrospray ionization interface coupled to an LTQ Velos Orbitrap Elite mass spectrometer to analyze the Dam1 complex from Saccharomyces cerevisiae. We achieved a 100-fold increase in sensitivity compared to a reversed-phase liquid chromatography coupled MS analysis of recombinant Dam1 complex with a total loading of 2.5 ng (12 amol). N-terminal processing forms of individual subunits of the Dam1 complex were observed as well as their phosphorylation stoichiometry upon Mps1p kinase treatment. PMID:25382489

  11. In-line separation by capillary electrophoresis prior to analysis by top-down mass spectrometry enables sensitive characterization of protein complexes.

    PubMed

    Han, Xuemei; Wang, Yueju; Aslanian, Aaron; Fonslow, Bryan; Graczyk, Beth; Davis, Trisha N; Yates, John R

    2014-12-01

    Intact protein analysis via top-down mass spectrometry (MS) provides a bird's eye view over the protein complexes and complex protein mixtures with the unique capability of characterizing protein variants, splice isoforms, and combinatorial post-translational modifications (PTMs). Here we applied capillary electrophoresis (CE) through a sheathless CE-electrospray ionization interface coupled to an LTQ Velos Orbitrap Elite mass spectrometer to analyze the Dam1 complex from Saccharomyces cerevisiae. We achieved a 100-fold increase in sensitivity compared to a reversed-phase liquid chromatography coupled MS analysis of recombinant Dam1 complex with a total loading of 2.5 ng (12 amol). N-terminal processing forms of individual subunits of the Dam1 complex were observed as well as their phosphorylation stoichiometry upon Mps1p kinase treatment. PMID:25382489

  12. Sensitivity of grounding line dynamics to viscoelastic deformation of the solid Earth: Inferences from a fully coupled ice sheet - solid Earth model

    NASA Astrophysics Data System (ADS)

    Konrad, H.; Sasgen, I.; Thoma, M.; Klemann, V.; Grosfeld, K.; Martinec, Z.

    2013-12-01

    The interactions of ice sheets with the sea level and the solid Earth are important factors for the stability of the ice shelves and the tributary inland ice (e.g. Thomas and Bentley, 1978; Gomez et al, 2012). First, changes in ice extent and ice thickness induce viscoelastic deformation of the Earth surface and Earth's gravity field. In turn, global and local changes in sea level and bathymetry affect the grounding line and, subsequently, alter the ice dynamic behaviour. Here, we investigate these feedbacks for a synthetic ice sheet configuration as well as for the Antarctic ice sheet using a three-dimensional thermomechanical ice sheet and shelf model, coupled to a viscoelastic solid-Earth and gravitationally self-consistent sea-level model. The respective ice sheet undergoes a forcing from rising sea level, warming ocean, and/or changing surface mass balance. The coupling is realized by exchanging ice thickness, Earth surface deformation, and sea level periodically. We apply several sets of viscoelastic Earth parameters to our coupled model, e.g. simulating a low-viscous upper mantle present at the Antarctic Peninsula (Ivins et al., 2011). Special focus of our study lies on the evolution of Earth surface deformation and local sea level changes, as well as on the accompanying grounding line evolution. N. Gomez, D. Pollard, J. X. Mitrovica, P. Huybers, and P. U. Clark 2012. Evolution of a coupled marine ice sheet-sea level model, J. Geophys. Res., 117, F01013, doi:10.1029/2011JF002128. E. R. Ivins, M. M. Watkins, D.-N. Yuan, R. Dietrich, G. Casassa, and A. Rülke 2011. On-land ice loss and glacial isostatic adjustment at the Drake Passage: 2003-2009, J. Geophys. Res. 116, B02403, doi: 10.1029/2010JB007607 R. H. Thomas and C. R. Bentley 1978. A model for Holocene retreat of the West Antarctic Ice Sheet, Quaternary Research, 10 (2), pages 150-170, doi: 10.1016/0033-5894(78)90098-4.

  13. Case for a 700+GeV WIMP: Cosmic ray spectra from PAMELA, Fermi, and ATIC

    SciTech Connect

    Cholis, Ilias; Goodenough, Lisa; Weiner, Neal; Dobler, Gregory; Finkbeiner, Douglas P.

    2009-12-15

    Multiple lines of evidence indicate an anomalous injection of high-energy e{sup +}e{sup -} in the galactic halo. The recent e{sup +} fraction spectrum from the payload for antimatter matter exploration and light-nuclei astrophysics (PAMELA) shows a sharp rise up to 100 GeV. The Fermi gamma-ray space telescope has found a significant hardening of the e{sup +}e{sup -} cosmic-ray spectrum above 100 GeV, with a break, confirmed by HESS at around 1 TeV. The advanced thin ionization calorimeter (ATIC) has also detected a similar excess, falling back to the expected spectrum at 1 TeV and above. Excess microwaves towards the galactic center in the WMAP data are consistent with hard synchrotron radiation from a population of 10-100 GeV e{sup +}e{sup -} (the WMAP 'Haze'). We argue that dark matter annihilations can provide a consistent explanation of all of these data, focusing on dominantly leptonic modes, either directly or through a new light boson. Normalizing the signal to the highest energy evidence (Fermi and HESS), we find that similar cross sections provide good fits to PAMELA and the Haze, and that both the required cross section and annihilation modes are achievable in models with Sommerfeld-enhanced annihilation. These models naturally predict significant production of gamma rays in the galactic center via a variety of mechanisms. Most notably, there is a robust inverse-Compton scattered (ICS) gamma-ray signal arising from the energetic electrons and positrons, detectable at Fermi/GLAST energies, which should provide smoking gun evidence for this production.

  14. Case for a 700+GeV WIMP: Cosmic ray spectra from PAMELA, Fermi, and ATIC

    NASA Astrophysics Data System (ADS)

    Cholis, Ilias; Dobler, Gregory; Finkbeiner, Douglas P.; Goodenough, Lisa; Weiner, Neal

    2009-12-01

    Multiple lines of evidence indicate an anomalous injection of high-energy e+e- in the galactic halo. The recent e+ fraction spectrum from the payload for antimatter matter exploration and light-nuclei astrophysics (PAMELA) shows a sharp rise up to 100 GeV. The Fermi gamma-ray space telescope has found a significant hardening of the e+e- cosmic-ray spectrum above 100 GeV, with a break, confirmed by HESS at around 1 TeV. The advanced thin ionization calorimeter (ATIC) has also detected a similar excess, falling back to the expected spectrum at 1 TeV and above. Excess microwaves towards the galactic center in the WMAP data are consistent with hard synchrotron radiation from a population of 10-100 GeV e+e- (the WMAP “Haze”). We argue that dark matter annihilations can provide a consistent explanation of all of these data, focusing on dominantly leptonic modes, either directly or through a new light boson. Normalizing the signal to the highest energy evidence (Fermi and HESS), we find that similar cross sections provide good fits to PAMELA and the Haze, and that both the required cross section and annihilation modes are achievable in models with Sommerfeld-enhanced annihilation. These models naturally predict significant production of gamma rays in the galactic center via a variety of mechanisms. Most notably, there is a robust inverse-Compton scattered (ICS) gamma-ray signal arising from the energetic electrons and positrons, detectable at Fermi/GLAST energies, which should provide smoking gun evidence for this production.

  15. On-line coupling of ionic liquid-based single-drop microextraction with capillary electrophoresis for sensitive detection of phenols.

    PubMed

    Wang, Qing; Qiu, Hongdeng; Li, Jing; Liu, Xia; Jiang, Shengxiang

    2010-08-13

    An ionic liquid-based single-drop microextraction (IL-SDME) procedure using IL as an extractant on-line coupled to capillary electrophoresis (CE) is proposed. The method is capable of quantifying trace amounts of phenols in environmental water samples. For the SDME of three phenols, a 2.40 nL IL microdrop was exposed for 10 min to the aqueous sample and then was directly injected into the capillary column for analysis. Extraction parameters such as the extraction time, the IL single-drop volume, pH of the sample solution, ionic strength, volume of the sample solution and the extraction temperature were systematically investigated. Detection limits to three phenols were less than 0.05 microg mL(-1), and their calibration curves were all linear (R(2) > or = 0.9994) in the range from 0.05 to 50 microg mL(-1). And enrichment factors for three phenols were 156, 107 and 257 without agitation, respectively. This method was then utilized to analyze two real environmental samples from Yellow River and tap water, obtaining satisfactory results. Compared with the usual SDME for CE, IL-SDME-CE is a simple, low-cost, fast and environmentally friendly preconcentration technique. PMID:20621300

  16. High-sensitivity HLA class I peptidome analysis enables a precise definition of peptide motifs and the identification of peptides from cell lines and patients' sera.

    PubMed

    Ritz, Danilo; Gloger, Andreas; Weide, Benjamin; Garbe, Claus; Neri, Dario; Fugmann, Tim

    2016-05-01

    The characterization of peptides bound to human leukocyte antigen (HLA) class I is of fundamental importance for understanding CD8+ T cell-driven immunological processes and for the development of immunomodulatory therapeutic strategies. However, until now, the mass spectrometric analysis of HLA-bound peptides has typically required billions of cells, still resulting in relatively few high-confidence peptide identifications. Capitalizing on the recent developments in mass spectrometry and bioinformatics, we have implemented a methodology for the efficient recovery of acid-eluted HLA peptides after purification with the pan-reactive antibody W6/32 and have identified a total of 27 862 unique peptides with high confidence (1% false discovery rate) from five human cancer cell lines. More than 93% of the identified peptides were eight to 11 amino acids in length and contained signatures that were in excellent agreement with published HLA binding motifs. Furthermore, by purifying soluble HLA class I complexes (sHLA) from sera of melanoma patients, up to 972 high-confidence peptides could be identified, including melanoma-associated antigens already described in the literature. Knowledge of the HLA class I peptidome should facilitate multiplex tetramer technology-based characterization of T cells, and allow the development of patient selection, stratification and immunomodulatory therapeutic strategies. PMID:26992070

  17. The local dark matter phase-space density and impact on WIMP direct detection

    SciTech Connect

    Catena, Riccardo; Ullio, Piero E-mail: ullio@sissa.it

    2012-05-01

    We present a new determination of the local dark matter phase-space density. This result is obtained implementing, in the limit of isotropic velocity distribution and spherical symmetry, Eddington's inversion formula, which links univocally the dark matter distribution function to the density profile, and applying, within a Bayesian framework, a Markov Chain Monte Carlo algorithm to sample mass models for the Milky Way against a broad and variegated sample of dynamical constraints. We consider three possible choices for the dark matter density profile, namely the Einasto, NFW and Burkert profiles, finding that the velocity dispersion, which characterizes the width in the distribution, tends to be larger for the Burkert case, while the escape velocity depends very weakly on the profile, with the mean value we obtain being in very good agreement with estimates from stellar kinematics. The derived dark matter phase-space densities differ significantly — most dramatically in the high velocity tails — from the model usually taken as a reference in dark matter detection studies, a Maxwell-Boltzmann distribution with velocity dispersion fixed in terms of the local circular velocity and with a sharp truncation at a given value of the escape velocity. We discuss the impact of astrophysical uncertainties on dark matter scattering rates and direct detection exclusion limits, considering a few sample cases and showing that the most sensitive ones are those for light dark matter particles and for particles scattering inelastically. As a general trend, regardless of the assumed profile, when adopting a self-consistent phase-space density, we find that rates are larger, and hence exclusion limits stronger, than with the standard Maxwell-Boltzmann approximation. Tools for applying our result on the local dark matter phase-space density to other dark matter candidates or experimental setups are provided.

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

    PubMed

    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. PMID:26021708

  19. Suppression of telomere-binding protein TPP1 resulted in telomere dysfunction and enhanced radiation sensitivity in telomerase-negative osteosarcoma cell line

    SciTech Connect

    Qiang, Weiguang; Wu, Qinqin; Zhou, Fuxiang; Xie, Conghua; Wu, Changping; Zhou, Yunfeng

    2014-03-07

    Highlights: • Down-regulation of TPP1 shortened telomere length in telomerase-negative cells. • Down-regulation of TPP1 induced cell apoptosis in telomerase-negative cells. • Down-regulation of TPP1 increased radiosensitivity in telomerase-negative cells. - Abstract: Mammalian telomeres are protected by the shelterin complex that contains the six core proteins POT1, TPP1, TIN2, TRF1, TRF2 and RAP1. TPP1, formerly known as TINT1, PTOP, and PIP1, is a key factor that regulates telomerase recruitment and activity. In addition to this, TPP1 is required to mediate the shelterin assembly and stabilize telomere. Previous work has found that TPP1 expression was elevated in radioresistant cells and that overexpression of TPP1 led to radioresistance and telomere lengthening in telomerase-positive cells. However, the exact effects and mechanism of TPP1 on radiosensitivity are yet to be precisely defined in the ALT cells. Here we report on the phenotypes of the conditional deletion of TPP1 from the human osteosarcoma U2OS cells using ALT pathway to extend the telomeres.TPP1 deletion resulted in telomere shortening, increased apoptosis and radiation sensitivity enhancement. Together, our findings show that TPP1 plays a vital role in telomere maintenance and protection and establish an intimate relationship between TPP1, telomere and cellular response to ionizing radiation, but likely has the specific mechanism yet to be defined.

  20. The seminoma cell line TCam-2 is sensitive to HDAC inhibitor depsipeptide but tolerates various other chemotherapeutic drugs and loss of NANOG expression.

    PubMed

    Nettersheim, Daniel; Gillis, Ad; Biermann, Katharina; Looijenga, Leendert H J; Schorle, Hubert

    2011-12-01

    Seminomas and embryonal carcinomas (EC) are both type II germ cell tumor (GCT) entities and develop from the same precursor lesion (carcinoma-in situ, CIS). However, they show significant differences in growth behavior, differentiation potential, and gene expression. Although ECs are prone to differentiate into all three germ layers and give rise to the non-seminomatous GCT entities teratoma, choriocarcinoma, and yolk-sac tumor, differentiation of seminomas to these entities is only rarely observed. This might reflect the ability of seminomas to actively inhibit differentiation processes evoked by environmental cues. Also, it is not known why CIS gives rise to seminoma in some patients and to non-seminoma in the others. Here, we treated the seminoma-like cell line TCam-2 with the HDAC-inhibitor Depsipeptide, the global demethylating agent 5-aza-2'-deocycytidine, all-trans retinoic acid and the monaminooxidase inhibitor Tranylcipromine and also used knock down approaches to reduce expression of the pluripotency marker NANOG and/or the inhibitor of primordial germ cell differentiation TFAP2C. We found that TCam-2 cells induce apoptosis when treated with Depsipeptide (> 10 nM) but are resistant to treatments with 5-aza-2'-deocycytidine, all-trans retinoic acid and Tranylcipromine, highlighting Depsi as a treatment option for seminomas. We show that TCam-2 cells up-regulate endoderm- and throphectoderm-associated genes after down-regulation of NANOG expression; however, morphologically no indications of differentiation could be found. Instead, we observed up-regulation of OCT3/4 and SOX17 in TCam-2-NANOG knockdown and speculate that this compensates for the loss of the NANOG protein. Hence, NANOG is not a primary target gene responsible for the inhibition of differentiation in seminomas. PMID:21987446

  1. A sensitive emulsification liquid phase microextraction coupled with on-line phase separation followed by HPLC for trace determination of sulfonamides in water samples.

    PubMed

    Ebrahimpour, Behnam; Yamini, Yadollah; Rezazadeh, Maryam

    2015-01-01

    For the first time, ion-pair based emulsification liquid phase microextraction coupled with a novel approach for phase separation followed by high performace liquid chromatgraphy (HPLC) was utilized for trace determination of sulfonamides in water samples. After the formation of ion-pair complex with a cationic surfactant, sulfonamides were extracted into the drops of dispersed organic extracting solvent. Then, the cloudy solution was passed through an in-line filter located in a suitable holder and was separated based on emulsion filtration. By changing the HPLC valve position, the filter was laid in the mobile phase path, and the extraction phase was eluted by the mobile phase and introduced into the separation column for analysis. The effects of important parameters, such as type of extraction solvent, type of ion-pair agent and its concentration, pH of sample solution, ionic strength, and volume of extraction phase, on the extraction efficiency, were investigated and optimized. Under optimal conditions, the linear range, limits of detection, and precision (relative standard deviations) were 0.3-100, 0.1-0.3 μg L(-1), and 4.7-5.8%, respectively. Preconcentration factors (PFs) for the compounds studied were obtained in the range of 268-664. These PFs correspond to extraction recoveries in the range of 41-97%. The sample throughput of the method was 3 samples per hour, regarding 20 min analysis time for a single procedure. Finally, the method was successfully applied to determine the selected sulfonamides in some water samples. PMID:25427828

  2. The Sensitivity of Activated Cys Ret Mutants to Glial Cell Line-Derived Neurotrophic Factor Is Mandatory To Rescue Neuroectodermic Cells from Apoptosis

    PubMed Central

    Mograbi, Baharia; Bocciardi, Renata; Bourget, Isabelle; Juhel, Thierry; Farahi-Far, Dariush; Romeo, Giovanni; Ceccherini, Isabella; Rossi, Bernard

    2001-01-01

    Hirschsprung's disease (HSCR), a frequent developmental defect of the enteric nervous system is due to loss-of-function mutations of RET, a receptor tyrosine kinase essential for the mediation of glial cell-derived neurotrophic factor (GDNF)-induced cell survival. Instead, gain-of-function Cys mutations (e.g., Cys609, Cys620, and Cys634) of the same gene are responsible for thyroid carcinoma (MEN2A/familial medullary thyroid carcinoma) by causing a covalent Ret dimerization, leading to ligand-independent activation of its tyrosine kinase. In this context, the association of Cys609- or Cys620-activating mutations with HSCR is still an unresolved paradox. To address this issue, we have compared these two mutants with the Cys634 Ret variant, which has never been associated with HSCR, for their ability to rescue neuroectodermic cells (SK-N-MC cells) from apoptosis. We show here that despite their constitutively activated kinase, the mere expression of these three mutants does not allow cell rescue. Instead, we demonstrate that like the wild-type Ret, the Cys634 Ret variant can trigger antiapoptotic pathways only in response to GDNF. In contrast, Cys609 or Cys620 mutations, which impair the terminal Ret glycosylation required for its insertion at the plasma membrane, abrogate GDNF-induced cell rescue. Taken together, these data support the idea that sensitivity to GDNF is the mandatory condition, even for constitutively activated Ret mutants, to rescue neuroectodermic cells from apoptosis. These findings may help clarify how a gain-of-function mutation can be associated with a developmental defect. PMID:11564857

  3. Test battery with the human cell line activation test, direct peptide reactivity assay and DEREK based on a 139 chemical data set for predicting skin sensitizing potential and potency of chemicals.

    PubMed

    Takenouchi, Osamu; Fukui, Shiho; Okamoto, Kenji; Kurotani, Satoru; Imai, Noriyasu; Fujishiro, Miyuki; Kyotani, Daiki; Kato, Yoshinao; Kasahara, Toshihiko; Fujita, Masaharu; Toyoda, Akemi; Sekiya, Daisuke; Watanabe, Shinichi; Seto, Hirokazu; Hirota, Morihiko; Ashikaga, Takao; Miyazawa, Masaaki

    2015-11-01

    To develop a testing strategy incorporating the human cell line activation test (h-CLAT), direct peptide reactivity assay (DPRA) and DEREK, we created an expanded data set of 139 chemicals (102 sensitizers and 37 non-sensitizers) by combining the existing data set of 101 chemicals through the collaborative projects of Japan Cosmetic Industry Association. Of the additional 38 chemicals, 15 chemicals with relatively low water solubility (log Kow > 3.5) were selected to clarify the limitation of testing strategies regarding the lipophilic chemicals. Predictivities of the h-CLAT, DPRA and DEREK, and the combinations thereof were evaluated by comparison to results of the local lymph node assay. When evaluating 139 chemicals using combinations of three methods based on integrated testing strategy (ITS) concept (ITS-based test battery) and a sequential testing strategy (STS) weighing the predictive performance of the h-CLAT and DPRA, overall similar predictivities were found as before on the 101 chemical data set. An analysis of false negative chemicals suggested a major limitation of our strategies was the testing of low water-soluble chemicals. When excluded the negative results for chemicals with log Kow > 3.5, the sensitivity and accuracy of ITS improved to 97% (91 of 94 chemicals) and 89% (114 of 128). Likewise, the sensitivity and accuracy of STS to 98% (92 of 94) and 85% (111 of 129). Moreover, the ITS and STS also showed good correlation with local lymph node assay on three potency classifications, yielding accuracies of 74% (ITS) and 73% (STS). Thus, the inclusion of log Kow in analysis could give both strategies a higher predictive performance. PMID:25820183

  4. Cytotoxic, apoptotic, and sensitization properties of ent-kaurane-type diterpenoids from Croton tonkinensis Gagnep on human liver cancer HepG2 and Hep3b cell lines.

    PubMed

    Pham, Minh Quan; Iscache, Anne Laure; Pham, Quoc Long; Gairin, Jean Edouard

    2016-04-01

    Human hepatocellular carcinoma (HCC) is the most common type of liver cancer, the second most common cause of death from cancer worldwide. A very poor prognosis and a lack of effective treatments make liver cancer a major public health problem, notably in less developed regions, particularly in eastern Asia. This fully justifies the search of new molecules and therapeutic strategies against HCC. Ent-kaurane diterpenoids are natural compounds displaying a broad spectrum of potential therapeutic effects including anticancer activity. In this study, we analyzed the pharmacological properties of a family of ent-kaurane diterpenoids from Croton tonkinensis Gagnep in human HepG2 and Hep3b cell lines, used as cellular reference models for in vitro evaluation of new molecules active on HCC. A structure-related cytotoxicity was observed against both HCC cell lines, enlighting the role of the 16-en-15-one skeleton of ent-kaurane diterpenoids. Cytotoxicity was closely correlated to apoptosis, evidenced by concentration-dependent subG1 cell accumulation, and increased annexin V expression. In addition, subtoxic concentration of ent-kaurane diterpenoid dramatically enhanced the sensitivity of HCC cells to doxorubicin. All together, our data bring strong support to the potential interest of ent-kaurane diterpenoids, alone or in combination with a cytotoxic agent, in cancer and more precisely against HCC. PMID:26713517

  5. 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.

    PubMed

    Padilla-Sánchez, Juan Antonio; Haug, Line Småstuen

    2016-05-01

    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. PMID:27062722

  6. 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.

    PubMed

    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)). PMID:26593464

  7. Molecular changes associated with the development of resistance to imatinib in an imatinib-sensitive canine neoplastic mast cell line carrying a KIT c.1523A>T mutation.

    PubMed

    Kobayashi, Masato; Kuroki, Shiori; Tanaka, Yu; Moriya, Yukari; Kozutumi, Yukari; Uehara, Yuji; Ono, Kenichiro; Tamura, Kyoichi; Washizu, Tsukimi; Bonkobara, Makoto

    2015-12-01

    Although imatinib has therapeutic activity for certain subsets of patients with mastocytosis, it is not always curative. Here, molecular mechanisms that confer imatinib resistance to neoplastic mast cells were investigated using an imatinib-sensitive canine neoplastic mast cell line VI-MC carrying a KIT c.1523A>T activating mutation. Two imatinib-resistant sublines were established by culturing VI-MC cells in increasing concentrations of imatinib (1?M resistant, rVI-MC1; 10?M resistant, rVI-MC10). Both sublines had a second KIT mutation c.2443G>C. Recombinant KIT with the second mutation was insensitive to 1?M but sensitive to 10?M imatinib. The effect of imatinib on the phosphorylation of KIT and its downstream signalling proteins was then examined using these sublines. KIT and ERK were constitutively phosphorylated in both sublines, and their phosphorylation was suppressed by 10?M imatinib in rVI-MC1 cells. However, KIT but not ERK phosphorylation was suppressed in rVI-MC10 cells. The phosphorylation of ERK in rVI-MC10 cells was also not diminished by the Src family kinase (SFK) inhibitor dasatinib. This second mutation in KIT may play an important role in imatinib resistance in neoplastic mast cells. Furthermore, KIT/SFK-independent activation of ERK would be involved in imatinib resistance when the neoplastic cells are exposed to higher concentrations of imatinib. PMID:25684098

  8. Study of light detection and sensitivity for a ton-scale liquid xenon dark matter detector

    NASA Astrophysics Data System (ADS)

    Wei, Y.; Lin, Q.; Xiao, X.; Ni, K.

    2013-06-01

    Ton-scale liquid xenon detectors operated in two-phase mode are proposed and being constructed recently to explore the favored parameter space for the Weakly Interacting Massive Particles (WIMPs) dark matter. To achieve a better light collection efficiency while limiting the number of electronics channels compared to the previous generation detectors, large-size photo-multiplier tubes (PMTs) such as the 3-inch-diameter R11410 from Hamamatsu are suggested to replace the 1-inch-square R8520 PMTs. In a two-phase xenon dark matter detector, two PMT arrays on the top and bottom are usually used. In this study, we compare the performance of two different ton-scale liquid xenon detector configurations with the same number of either R11410 (config.1) or R8520 (config.2) for the top PMT array, while both using R11410 PMTs for the bottom array. The self-shielding of liquid xenon suppresses the background from the PMTs and the dominant background is from the pp solar neutrinos in the central fiducial volume. The light collection efficiency for the primary scintillation light is largely affected by the xenon purity and the reflectivity of the reflectors. In the optimistic situation with a 10 m light absorption length and a 95% reflectivity, the light collection efficiency is 43%(34%) for config.1(config.2). In the conservative situation with a 2.5 m light absorption length and a 85% reflectivity, the value is only 18%(13%) for config.1(config.2). The difference between the two configurations is due to the larger PMT coverage on the top for config.1. The slightly different position resolutions for the two configurations have a negligible effect on the sensitivity. Based on the above considerations, we estimate the sensitivity reach of the two detector configurations. Both configurations can reach a sensitivity of 2 ~ 3 × 10-47cm2 for spin-independent WIMP-nucleon cross section for 100 GeV/c2 WIMPs after two live-years of operation. The one with R8520 PMTs for the top PMT array is more cost-effective, while the one with R11410 PMTs on the top has a factor of two better sensitivity for light WIMPs at 10 GeV/c2.

  9. The physics of background discrimination in liquid xenon, and first results from Xenon10 in the hunt for WIMP dark matter

    NASA Astrophysics Data System (ADS)

    Dahl, Carl Eric

    2009-06-01

    The WIMP limit set by the Xenon10 experiment in 2007 signals a new era in direct detection of dark matter, with several large-scale liquid target detectors now under construction. A major challenge in these detectors will be to understand backgrounds at the level necessary to claim a positive WIMP signal. In liquid xenon, these backgrounds are dominated by electron recoils, which may be distinguished from the WIMP signal (nuclear recoils) by their higher charge-to-light ratio. During the construction and operation of Xenon10, the prototype detector Xed probed the physics of this discrimination. Particle interactions in liquid xenon both ionize and excite xenon atoms, giving charge and scintillation signals, respectively. Some fraction of ions recombine, reducing the charge signal and creating additional scintillation. The charge-to-light ratio, determined by the initial exciton-ion ratio and the ion recombination fraction, provides the basis for discrimination between electron and nuclear recoils. Intrinsic fluctuations in the recombination fraction limit discrimination. Changes in recombination induce an exact anti-correlation between charge and light, and when calibrated this anti-correlation distinguishes recombination fluctuations from uncorrelated fluctuations in the measured signals. We determine the mean recombination and recombination fluctuations as a function of energy and applied field for electron and nuclear recoils, finding that recombination fluctuations are already the limiting factor for discrimination above ~12 keVr (nuclear recoil energy). Below 12 keVr statistical fluctuations in the number of scintillation photons counted dominate, and we project a x6 improvement in background rejection with a x2 increase in light collection efficiency. We also build a simple recombination model that successfully reproduces the mean recombination in electron and nuclear recoils, including the surprising reversal of the expected trend for recombination with ionization density in low energy electron recoils. The model also reproduces the measured recombination fluctuations to within a factor of two at high energies. Surprisingly, the model suggests that recombination at low energies is independent of ionization density, and our observed discrimination is due not to the different stopping powers of electrons and nuclei as was thought, but rather to a different initial exciton-ion ratio. We suggest two possible physical models for this new result.

  10. NADPH-oxidase and a hydrogen peroxide-sensitive K+ channel may function as an oxygen sensor complex in airway chemoreceptors and small cell lung carcinoma cell lines

    PubMed Central

    Wang, Dashou; Youngson, Charlotte; Wong, Veronica; Yeger, Herman; Dinauer, Mary C.; de Miera, Eleazar Vega-Saenz; Rudy, Bernardo; Cutz, Ernest

    1996-01-01

    Pulmonary neuroepithelial bodies (NEB) are widely distributed throughout the airway mucosa of human and animal lungs. Based on the observation that NEB cells have a candidate oxygen sensor enzyme complex (NADPH oxidase) and an oxygen-sensitive K+ current, it has been suggested that NEB may function as airway chemoreceptors. Here we report that mRNAs for both the hydrogen peroxide sensitive voltage gated potassium channel subunit (KH2O2) KV3.3a and membrane components of NADPH oxidase (gp91phox and p22phox) are coexpressed in the NEB cells of fetal rabbit and neonatal human lungs. Using a microfluorometry and dihydrorhodamine 123 as a probe to assess H2O2 generation, NEB cells exhibited oxidase activity under basal conditions. The oxidase in NEB cells was significantly stimulated by exposure to phorbol esther (0.1 μM) and inhibited by diphenyliodonium (5 μM). Studies using whole-cell voltage clamp showed that the K+ current of cultured fetal rabbit NEB cells exhibited inactivating properties similar to KV3.3a transcripts expressed in Xenopus oocyte model. Exposure of NEB cells to hydrogen peroxide (H2O2, the dismuted by-product of the oxidase) under normoxia resulted in an increase of the outward K+ current indicating that H2O2 could be the transmitter modulating the O2-sensitive K+ channel. Expressed mRNAs or orresponding protein products for the NADPH oxidase membrane cytochrome b as well as mRNA encoding KV3.3a were identified in small cell lung carcinoma cell lines. The studies presented here provide strong evidence for an oxidase-O2 sensitive potassium channel molecular complex operating as an O2 sensor in NEB cells, which function as chemoreceptors in airways and in NEB related tumors. Such a complex may represent an evolutionary conserved biochemical link for a membrane bound O2-signaling mechanism proposed for other cells and life forms. PMID:8917565

  11. Endogenous gamma-aminobutyric acid (GABA)(A) receptor active neurosteroids and the sedative/hypnotic action of gamma-hydroxybutyric acid (GHB): a study in GHB-S (sensitive) and GHB-R (resistant) rat lines.

    PubMed

    Barbaccia, Maria Luisa; Carai, Mauro A M; Colombo, Giancarlo; Lobina, Carla; Purdy, Robert H; Gessa, Gian Luigi

    2005-07-01

    In the rat brain, gamma-hydroxybutyric-acid (GHB) increases the concentrations of 3alpha-hydroxy,5alpha-pregnan-20-one (allopregnanolone, 3alpha,5alpha-THP) and 3alpha,21-dihydroxy,5alpha-pregnan-20-one (allotetrahydrodeoxycorticosterone/3alpha,5alphaTHDOC), two neurosteroids acting as positive allosteric modulators of gamma-aminobutyric acid (GABA)(A) receptors. This study was aimed at assessing whether neurosteroids play a role in GHB-induced loss of righting reflex (LORR). Basal and GHB-stimulated brain concentrations of endogenous 3alpha,5alpha-THP and 3alpha,5alpha-THDOC were analyzed in two rat lines, GHB-sensitive (GHB-S) and GHB-resistant (GHB-R), selectively bred for opposite sensitivity to GHB-induced sedation/hypnosis. Basal neurosteroid concentrations were similar in brain cortex of the two rat lines. However, in male GHB-S rats, administration of GHB (1000 mg/kg, i.p., 30 min) increased brain cortical concentrations of 3alpha,5alpha-THP and 3alpha,5alpha-THDOC 7- and 2.5-fold, respectively, whilst male GHB-R animals displayed only a 4- and 2-fold increase, respectively. In GHB-S rats this increase lasted up to 90 min and declined 180 min following GHB administration, a time course that matches LORR onset and duration. In contrast, in GHB-R rats, which failed to show GHB-induced LORR, brain cortical 3alpha,5alpha-THP and 3alpha,5alpha-THDOC had returned to control values within 90 min. At onset of LORR, a similar increase in brain cortical levels of 3alpha,5alpha-THP and 3alpha,5alpha-THDOC (2-3-fold) was observed in GHB-S female rats and in the few female GHB-R rats that lost the righting reflex after GHB administration, but not in female GHB-R rats failing to show LORR. Sub-hypnotic doses (7.5 and 12.5 mg/kg, i.p.) of pregnanolone, administered 10 min before GHB, dose-dependently facilitated the expression of GHB-induced LORR in GHB-R male rats. These results suggest that the GHB-induced increases of brain 3alpha,5alpha-THP and 3alpha,5alpha-THDOC concentrations are implicated in the eliciting of the sedative/hypnotic action of GHB. PMID:15992580

  12. Characterization of Nuclear Recoils in High Pressure Xenon Gas: Towards a Simultaneous Search for WIMP Dark Matter and Neutrinoless Double Beta Decay

    NASA Astrophysics Data System (ADS)

    Renner, J.; Gehman, V. M.; Goldschmidt, A.; Oliveira, C. A. B.; Nygren, D.

    Xenon has recently been the medium of choice in several large scale detectors searching for WIMP dark matter and neutrinoless double beta decay. Though present-day large scale experiments use liquid xenon, the gas phase o_ers advantages favorable to both types of searches such as improved intrinsic energy resolution and fewer fluctuations in the partition of deposited energy between scintillation and ionization channels. We recently constructed a high pressure xenon gas TPC as a prototype for the NEXT (Neutrino Experiment with a Xenon TPC) neutrinoless double beta decay experiment and have demonstrated the feasibility of 0.5% FWHM energy resolution at the 136Xe double beta Q-value with 3-D tracking capabilities. We now present results from this prototype on the simultaneous observation of scintillation and ionization produced by nuclear recoils at approximately 14 bar pressure. The recoils were produced by neutrons of approximately 2-6 MeV emitted from a radioisotope plutonium-beryllium source, and primary scintillation (S1) and electroluminescent photons produced by ionization (S2) were observed. We discuss the potential of gaseous xenon to distinguish between electron and nuclear recoils through the ratio of these two signals S2/S1. From these results combined with the possibility of using columnar recombination to sense nuclear recoil directionality at high pressures we envision a dual-purpose, ton-scale gaseous xenon detector capable of a combined search for WIMP dark matter and neutrinoless double beta decay. This work has been performed within the context of the NEXT collaboration.

  13. Characterization of Nuclear Recoils in High Pressure Xenon Gas: Towards a Simultaneous Search for WIMP Dark Matter and Neutrinoless Double Beta Decay

    DOE PAGESBeta

    Renner, J.; Gehman, V. M.; Goldschmidt, A.; Oliveira, C. A.B.; Nygren, D.

    2015-03-24

    Xenon has recently been the medium of choice in several large scale detectors searching for WIMP dark matter and neutrinoless double beta decay. Though present-day large scale experiments use liquid xenon, the gas phase offers advantages favorable to both types of searches such as improved intrinsic energy resolution and fewer fluctuations in the partition of deposited energy between scintillation and ionization channels. We recently constructed a high pressure xenon gas TPC as a prototype for the NEXT (Neutrino Experiment with a Xenon TPC) neutrinoless double beta decay experiment and have demonstrated the feasibility of 0.5% FWHM energy resolution at themore » 136Xe double beta Q-value with 3-D tracking capabilities. We now present results from this prototype on the simultaneous observation of scintillation and ionization produced by nuclear recoils at approximately 14 bar pressure. The recoils were produced by neutrons of approximately 2-6 MeV emitted from a radioisotope plutonium-beryllium source, and primary scintillation (S1) and electroluminescent photons produced by ionization (S2) were observed. We discuss the potential of gaseous xenon to distinguish between electron and nuclear recoils through the ratio of these two signals S2/S1. From these results combined with the possibility of using columnar recombination to sense nuclear recoil directionality at high pressures we envision a dual-purpose, ton-scale gaseous xenon detector capable of a combined search for WIMP dark matter and neutrinoless double beta decay. This work has been performed within the context of the NEXT collaboration.« less

  14. Characterization of Nuclear Recoils in High Pressure Xenon Gas: Towards a Simultaneous Search for WIMP Dark Matter and Neutrinoless Double Beta Decay

    SciTech Connect

    Renner, J.; Gehman, V. M.; Goldschmidt, A.; Oliveira, C. A.B.; Nygren, D.

    2015-03-24

    Xenon has recently been the medium of choice in several large scale detectors searching for WIMP dark matter and neutrinoless double beta decay. Though present-day large scale experiments use liquid xenon, the gas phase offers advantages favorable to both types of searches such as improved intrinsic energy resolution and fewer fluctuations in the partition of deposited energy between scintillation and ionization channels. We recently constructed a high pressure xenon gas TPC as a prototype for the NEXT (Neutrino Experiment with a Xenon TPC) neutrinoless double beta decay experiment and have demonstrated the feasibility of 0.5% FWHM energy resolution at the 136Xe double beta Q-value with 3-D tracking capabilities. We now present results from this prototype on the simultaneous observation of scintillation and ionization produced by nuclear recoils at approximately 14 bar pressure. The recoils were produced by neutrons of approximately 2-6 MeV emitted from a radioisotope plutonium-beryllium source, and primary scintillation (S1) and electroluminescent photons produced by ionization (S2) were observed. We discuss the potential of gaseous xenon to distinguish between electron and nuclear recoils through the ratio of these two signals S2/S1. From these results combined with the possibility of using columnar recombination to sense nuclear recoil directionality at high pressures we envision a dual-purpose, ton-scale gaseous xenon detector capable of a combined search for WIMP dark matter and neutrinoless double beta decay. This work has been performed within the context of the NEXT collaboration.

  15. Lining up your service lines.

    PubMed

    Bilsky, Steven D; Aber, Jeffrey M

    2007-07-01

    Steps in implementing a service line approach include: Defining the service line. Allocating service line revenue and expense. Analyzing service line contribution margin and profitability. Determining the value of other factors. Creating standards for investment decisions, benchmarking, and ranking. PMID:17687972

  16. Reversal of the temperature-shift-induced growth restriction of a temperature-sensitive simian virus 40 T-antigen-transformed human fibroblast cell line by treatment with retinoic acid.

    PubMed Central

    Tsao, Y P; Li, S F; Kuo, S W; Liu, J C; Chen, S L

    1996-01-01

    We previously established a human fibroblast cell line, HFL 6-2, that contains a temperature sensitive simian virus 40 (SV40) T antigen, permitting cell growth at 35 degrees C but restricting growth at 39 degrees C. p21 (Waf1/Cip1) was significantly induced by temperature shifts in HFL 6-2 cells. Here we show that all-trans-retinoic acid (RA) treatment prevented the growth restriction of HFL 6-2 cells at 39 degrees C. In the presence of RA, HFL 6-2 cells proliferated into sizeable colonies even at 39 degrees C. [3H]Thymidine incorporation and flow cytometry analysis revealed that cells exposed to RA maintained DNA synthesis at 39 degrees C. Prevention of growth restriction by RA was correlated with a lack of induction of p21 at the transcription level. These observations suggest that RA may prevent the senescence process by repressing p21 gene expression, and perturb the growth regulation of somatic cells. PMID:8760353

  17. Measure Lines

    ERIC Educational Resources Information Center

    Crissman, Sally

    2011-01-01

    One tool for enhancing students' work with data in the science classroom is the measure line. As a coteacher and curriculum developer for The Inquiry Project, the author has seen how measure lines--a number line in which the numbers refer to units of measure--help students not only represent data but also analyze it in ways that generate…

  18. Circumstellar radio molecular lines

    NASA Technical Reports Server (NTRS)

    NGUYEN-QUANG-RIEU

    1987-01-01

    Radio molecular lines appear to be useful probes into the stellar environment. Silicon oxide masers provide information on the physical conditions in the immediate vicinity of the stellar photosphere. Valuable information on the physics operating in the envelope of IRC + 10216 was recently obtained by high sensitivity observations and detailed theoretical analyses. Infrared speckle interferometry in the molecular lines and in the continuum is helpful in the investigation of the inner region of the envelope. These techniques are discussed in terms of late-type star mass loss.

  19. Beau's Lines

    MedlinePlus

    ... run parallel to the shape of the white, moon-shaped portion of the nail bed (lunula) seen ... much time has elapsed since the line was formed. Because fingernails grow at a rate of approximately ...

  20. Sensitive skin.

    PubMed

    Misery, L; Loser, K; Ständer, S

    2016-02-01

    Sensitive skin is a clinical condition defined by the self-reported facial presence of different sensory perceptions, including tightness, stinging, burning, tingling, pain and pruritus. Sensitive skin may occur in individuals with normal skin, with skin barrier disturbance, or as a part of the symptoms associated with facial dermatoses such as rosacea, atopic dermatitis and psoriasis. Although experimental studies are still pending, the symptoms of sensitive skin suggest the involvement of cutaneous nerve fibres and neuronal, as well as epidermal, thermochannels. Many individuals with sensitive skin report worsening symptoms due to environmental factors. It is thought that this might be attributed to the thermochannel TRPV1, as it typically responds to exogenous, endogenous, physical and chemical stimuli. Barrier disruptions and immune mechanisms may also be involved. This review summarizes current knowledge on the epidemiology, potential mechanisms, clinics and therapy of sensitive skin. PMID:26805416

  1. Context Sensitive Modeling of Cancer Drug Sensitivity

    PubMed Central

    Chen, Bo-Juen; Litvin, Oren; Ungar, Lyle; Pe’er, Dana

    2015-01-01

    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. PMID:26274927

  2. Gluten Sensitivity

    MedlinePlus

    Gluten is a protein found in wheat, rye, and barley. It is found mainly in foods but ... products like medicines, vitamins, and supplements. People with gluten sensitivity have problems with gluten. It is different ...

  3. Climate Sensitivity

    NASA Astrophysics Data System (ADS)

    Hansen, J.

    2007-12-01

    Discussion of climate sensitivity requires careful definition of forcings, feedbacks and response times, indeed, foggy definitions have produced flawed assessments of climate sensitivity. The best information available on climate sensitivity comes from insightful interpretation of the Earth's history aided by quantitative information from climate models and understanding of climate processes. Climate sensitivity is a strong function of time scale, in part because of the nature of climate feedbacks. Unfortunately for humanity, the preponderance of feedbacks on the century time scale appears to be positive. The chief implication is the need for a sharp reversal in the trend of human-made climate forcing, if we are to avoid creating a planet that is dramatically different than the one on which civilization developed.

  4. Sensitivity analysis

    MedlinePlus

    The test shows which antibiotic drugs should be used to treat an infection. Many organisms are resistant to certain antibiotics. Sensitivity tests are important in helping find the right antibiotic for you. Your provider may start ...

  5. Gluten Sensitivity

    MedlinePlus

    ... Free Diet Celiac Disease in the Older Adult Flours, Grains, Thickening Agents, Starches GIG’s Gluten-Free Diet ... Disease Celiac Disease, Non-Celiac Gluten Sensitivity or Wheat Allergy: What is the Difference? Could Gluten be ...

  6. Sensitive Periods

    PubMed Central

    Zeanah, Charles H.; Gunnar, Megan R.; McCall, Robert B.; Kreppner, Jana M.; Fox, Nathan A.

    2010-01-01

    This chapter reviews sensitive periods in human brain development based on the literature on children raised in institutions. Sensitive experiences occur when experiences are uniquely influential for the development of neural circuitry. Because in humans, we make inferences about sensitive periods from evaluations of complex behaviors, we underestimate the occurrence of sensitive periods at the level of neural circuitry. Although we are most interested in complex behaviors, such as IQ or attachment or externalizing problems, many different sensitive periods at the level of circuits probably underlie these complex behaviors. Results from a number of studies suggest that across most, but not all, domains of development, institutional rearing limited to the first 4–6 months of life is associated with no significant increase risk for long-term adverse effects relative to non-institutionalized children. Beyond that, evidence for sensitive periods is less compelling, meaning that “the earlier the better” rule for enhanced caregiving is a reasonable conclusion at the current state of the science. PMID:25125708

  7. Salt Sensitivity in Wheat 1

    PubMed Central

    Kingsbury, Ralph W.; Epstein, Emanuel

    1986-01-01

    Two selected lines of bread wheat, Triticum aestivum L., differing in their relative salt resistance, were grown in isosmotic solutions of different ionic compositions to investigate sensitivity to specific ions. Growth rates and ion accumulation were determined. The salt composition of the various solutions had little effect on the growth of the salt-resistant line, but significantly affected that of the salt-sensitive line. Specifically, solutions containing high Na+ concentrations were more toxic than those containing high Cl− concentrations or high concentrations of nutrient ions. There were few differences in ion accumulation between lines in a given treatment, although the sensitive line tended to accumulate more Na+ than the tolerant line in the salt treatments with high Na+ concentrations. The overall results provide evidence that there is a definite specific ion effect which is related to salt sensitivity in wheat. It is suggested that superior compartmentation of toxic ions, principally Na+, may be a mechanism of salt resistance in this case. PMID:16664679

  8. Diatomic predissociation line widths

    NASA Technical Reports Server (NTRS)

    Child, M. S.

    1973-01-01

    Predissociation by rotation and curve crossing in diatomic molecules is discussed. The pattern of predissociation line widths is seen as providing a highly sensitive yardstick for the determination of unknown potential curves. In addition, the computation of such a pattern for given potential curves is considered a matter of routine, unless the predissociation happens to occur from an adiabatic potential curve. Analytic formulas are used to provide physical insight into the details of the predissociation pattern, to the extent that a direct inversion procedure is developed for determination of the repulsive potential curves for Type 1 predissociations.

  9. Evaluation of TPGS-modified thermo-sensitive Pluronic PF127 hydrogel as a potential carrier to reverse the resistance of P-gp-overexpressing SMMC-7721 cell lines.

    PubMed

    Gao, Lei; Wang, Xiaoqing; Ma, Jianli; Hao, Daifeng; Wei, Pei; Zhou, Liang; Liu, Guiyang

    2016-04-01

    In the present studies locally injectable docetaxel nanocrystals loaded d-alpha tocopheryl polyethylene glycol 1000 succinate-modified Pluronic F127 (DOC-NCs-TPGS-PF127) thermo-sensitive hydrogels were prepared to reverse drug resistance of P-glycoprotein (P-gp)-overexpressing human liver cancer SMMC-7721 tumors. Firstly, DOC nanosuspensions with mean particle size of 196nm were prepared and dispersed into series of mixed solutions containing PF127 and TPGS of different ratios to obtain DOC-NCs-TPGS-PF127 hydrogels. DOC NCs, exhibiting a uniform distribution and very good physical stability during three sol-gel cycles in the hydrogel network, did not influence the gelation temperature. Swelling-dependent release pattern was found for DOC NCs from hydrogels and release profiles could be well fitted by the Peppas equation. MTT test showed that hydrogels containing 0% or 0.1% TPGS had no cytotoxicity against L929 fibroblasts. Both DOC solution and DOC-NCs-TPGS-PF127 hydrogels exhibited obvious cytotoxicity against sensitive SMMC-7721 cells. When resistant SMMC7721 cells were treated, DOC-NCs-TPGS-PF127 hydrogels showed significantly higher cytotoxicity compared with DOC solution and hydrogels containing no TPGS (DOC-NCs-PF127), with markedly lower IC50 and resistant index (RI). After intratumoral injection in SMMC-7721/RT tumor xenograft Balb/c mice model, DOC-NCs-TPGS-PF127 hydrogels exhibited about 5-fold increase and 1.8-fold increase in the inhibition rate of tumor growth compared with intravenous and intratumoral injection of DOC solution, respectively. It could be concluded that TPGS-modified PF127 thermo-sensitive hydrogel was an excellent locally injectable carrier to reverse P-gp overexpression associated multi-drug resistance. PMID:26764117

  10. High Voltage Lines: Hazard at a Distance.

    ERIC Educational Resources Information Center

    Marino, Andrew A.; Becker, Robert O.

    1978-01-01

    It appears that a variety of biological organisms, including man, are sensitive to both long and short-term exposure to the extra low frequency electric and magnetic fields produced by high voltage lines. (BB)

  11. Differential Gene Expression Profiles of Radioresistant Non-Small-Cell Lung Cancer Cell Lines Established by Fractionated Irradiation: Tumor Protein p53-Inducible Protein 3 Confers Sensitivity to Ionizing Radiation

    SciTech Connect

    Lee, Young Sook; Oh, Jung-Hwa; Yoon, Seokjoo; Kwon, Myung-Sang

    2010-07-01

    Purpose: Despite the widespread use of radiotherapy as a local and regional modality for the treatment of cancer, some non-small-cell lung cancers commonly develop resistance to radiation. We thus sought to clarify the molecular mechanisms underlying resistance to radiation. Methods and Materials: We established the radioresistant cell line H460R from radiosensitive parental H460 cells. To identify the radioresistance-related genes, we performed microarray analysis and selected several candidate genes. Results: Clonogenic and MTT assays showed that H460R was 10-fold more resistant to radiation than H460. Microarray analysis indicated that the expression levels of 1,463 genes were altered more than 1.5-fold in H460R compared with parental H460. To evaluate the putative functional role, we selected one interesting gene tumor protein p53-inducible protein 3 (TP53I3), because that this gene was significantly downregulated in radioresistant H460R cells and that it was predicted to link p53-dependent cell death signaling. Interestingly, messenger ribonucleic acid expression of TP53I3 differed in X-ray-irradiated H460 and H460R cells, and overexpression of TP53I3 significantly affected the cellular radiosensitivity of H460R cells. Conclusions: These results show that H460R may be useful in searching for candidate genes that are responsible for radioresistance and elucidating the molecular mechanism of radioresistance.

  12. Absolute line strengths for carbon and sulfur

    NASA Technical Reports Server (NTRS)

    Miller, M. H.; Wilkerson, T. D.; Roig, R. A.; Bengtson, R. D.

    1974-01-01

    Work has been conducted to reduce substantially uncertainties concerning the line strengths for carbon and sulfur. Two or more independent methods were used to measure thermodynamic variables and to calibrate detectors for absolute sensitivity and spectral response. The absolute transition probabilities of 124 visible and infrared lines of C I, S I, and S II were measured in a consistent way.

  13. Gluten Sensitivity.

    PubMed

    Catassi, Carlo

    2015-01-01

    Non-celiac gluten sensitivity (NCGS) is a syndrome characterized by intestinal and extraintestinal symptoms related to the ingestion of gluten-containing food in subjects who are not affected by either celiac disease (CD) or wheat allergy (WA). The prevalence of NCGS is not clearly defined yet. Indirect evidence suggests that NCGS is slightly more common than CD, the latter affecting around 1% of the general population. NCGS has been mostly described in adults, particularly in females in the age group of 30-50 years; however, pediatric case series have also been reported. Since NCGS may be transient, gluten tolerance needs to be reassessed over time in patients with NCGS. NCGS is characterized by symptoms that usually occur soon after gluten ingestion, disappear with gluten withdrawal, and relapse following gluten challenge within hours/days. The 'classical' presentation of NCGS is a combination of irritable bowel syndrome-like symptoms, including abdominal pain, bloating, bowel habit abnormalities (either diarrhea or constipation), and systemic manifestations such as 'foggy mind', headache, fatigue, joint and muscle pain, leg or arm numbness, dermatitis (eczema or skin rash), depression, and anemia. In recent years, several studies explored the relationship between the ingestion of gluten-containing food and the appearance of neurological and psychiatric disorders/symptoms like ataxia, peripheral neuropathy, schizophrenia, autism, depression, anxiety, and hallucinations (so-called gluten psychosis). The diagnosis of NCGS should be considered in patients with persistent intestinal and/or extraintestinal complaints showing a normal result of the CD and WA serological markers on a gluten-containing diet, usually reporting worsening of symptoms after eating gluten-rich food. NCGS should not be an exclusion diagnosis only. Unfortunately, no biomarker is sensitive and specific enough for diagnostic purposes; therefore, the diagnosis of NCGS is currently based on establishing a clear-cut cause-effect relationship between the ingestion of gluten and the appearance of symptoms by a standardized double-blind, placebo-controlled gluten challenge. PMID:26605537

  14. Stochastic resonance in visual sensitivity.

    PubMed

    Kundu, Ajanta; Sarkar, Sandip

    2015-04-01

    It is well known from psychophysical studies that stochastic resonance, in its simplest threshold paradigm, can be used as a tool to measure the detection sensitivity to fine details in noise contaminated stimuli. In the present manuscript, we report simulation studies conducted in the similar threshold paradigm of stochastic resonance. We have estimated the contrast sensitivity in detecting noisy sine-wave stimuli, with varying area and spatial frequency, as a function of noise strength. In all the cases, the measured sensitivity attained a peak at intermediate noise strength, which indicate the occurrence of stochastic resonance. The peak sensitivity exhibited a strong dependence on area and spatial frequency of the stimulus. We show that the peak contrast sensitivity varies with spatial frequency in a nonmonotonic fashion and the qualitative nature of the sensitivity variation is in good agreement with human contrast sensitivity function. We also demonstrate that the peak sensitivity first increases and then saturates with increasing area, and this result is in line with the results of psychophysical experiments. Additionally, we also show that critical area, denoting the saturation of contrast sensitivity, decreases with spatial frequency and the associated maximum contrast sensitivity varies with spatial frequency in a manner that is consistent with the results of psychophysical experiments. In all the studies, the sensitivities were elevated via a nonlinear filtering operation called stochastic resonance. Because of this nonlinear effect, it was not guaranteed that the sensitivities, estimated at each frequency, would be in agreement with the corresponding results of psychophysical experiments; on the contrary, close agreements were observed between our results and the findings of psychophysical investigations. These observations indicate the utility of stochastic resonance in human vision and suggest that this paradigm can be useful in psychophysical studies. PMID:25398687

  15. Multivariate Ensemble Sensitivity with Localization

    NASA Astrophysics Data System (ADS)

    Hacker, Joshua; Lei, Lili

    2014-05-01

    So far in the literature, covariance localization (tapering) has not been applied when performing ensemble sensitivity analysis. Sampling error in computing the sensitivities via lagged covariances leads to an over-estimation of the impact of a perturbation. Most commonly when computing sensitivities, the analysis covariance is approximated with the corresponding diagonal matrix. Two consequences follow: (1) the multi-variate sensitivity is approximated by a univariate sensitivity, and (2) sampling error in off-diagonal elements are obviated. It is unknown, however, how much information is lost by ignoring the off-diagonal elements in the full covariance. When forecasts depend on many details of the previous analysis, it is reasonable to expect that the diagonal approximation is too severe. The purpose of this presentation is to clarify the effects of the diagonal approximation, and investigate the need for localization when off-diagonal elements are considered. Motivated by examples arising from sensitivities estimated within a cycling mesoscale ensemble data assimilation system, for easier interpretation we turn to the two-scale model first presented by Lorenz in 2005. We show that for most problems, an efficient matrix inversion is possible by finding a minimum-norm solution, and employing appropriate matrix factorization. Comparing the full inversion with off-diagonal elements, the fine-scale sensitivity estimates can be substantially different from those arising when the diagonal approximation is used. Localization on the sensitivity can be handled by an off-line empirical or Bayesian estimation technique. Because the sensitivity estimated from the full inversion is subject to sampling error, it is sensitive to the localization. The results show that compared to typical practices, more complete ensemble sensitivity formulations may be needed to draw robust inferences in general.

  16. Improved Sensitivity SBC Prisms

    NASA Astrophysics Data System (ADS)

    Walsh, Jeremy

    2006-07-01

    The flux calibration of the SBC {PR110L and PR130L} will be improved by observing for each prism white dwarf standards {WD1657+343 and LTT9491}. The blue standard star WD1657+343 has previously been observed with ACS/SBC and will serve as a reference point to track time dependent variations. LTT9491 is much redder and thus will be used to investigate the sensitivity curve of ?red? targets to check for a potential red leak of the SBC. Additionally, LTT9491 shows various strong absorption lines which can be used to confirm the wavelength calibration of the PR110L and PR130L prisms. The standard stars are observed at a variety of pointings across the SBC detector in order to map spatial variations. LTT9491 will also be observed with ACS/HRC PR200L to obtain an improved flux calibration from about 1800 A to 4000 A.

  17. Veterans Crisis Line

    MedlinePlus

    ... Enter ZIP code here Enter ZIP code here Suicide Prevention Veterans Crisis Line Warning Signs Resources Educational ... at www.VeteransCrisisLine.net , or text 838255 today. Suicide Prevention Resources Veterans Chat - Veterans Crisis Line : Veterans ...

  18. Gravitational-wave sensitivity curves

    NASA Astrophysics Data System (ADS)

    Moore, C. J.; Cole, R. H.; Berry, C. P. L.

    2015-01-01

    There are several common conventions in use by the gravitational-wave community to describe the amplitude of sources and the sensitivity of detectors. These are frequently confused. We outline the merits of and differences between the various quantities used for parameterizing noise curves and characterizing gravitational-wave amplitudes. We conclude by producing plots that consistently compare different detectors. Similar figures can be generated on-line for general use at http://rhcole.com/apps/GWplotter.

  19. Dark Matter Searches With GLAST

    SciTech Connect

    Wai, Lawrence; Nuss, E.

    2007-02-05

    Indirect detection of particle dark matter relies upon pair annihilation of Weakly Interaction Massive Particles (WIMPs), which is complementary to the well known techniques of direct detection (WIMP-nucleus scattering) and collider production (WIMP pair production). Pair annihilation of WIMPs results in the production of gamma-rays, neutrinos, and anti-matter. Of the various experiments sensitive to indirect detection of dark matter, the Gamma-ray Large Area Space Telescope (GLAST) may play the most crucial role in the next few years. After launch in late 2007, The GLAST Large Area Telescope (LAT) will survey the gamma-ray sky in the energy range of 20MeV-300GeV. By eliminating charged particle background above 100 MeV, GLAST may be sensitive to as yet to be observed Milky Way dark matter subhalos, as well as WIMP pair annihilation spectral lines from the Milky Way halo. Discovery of gamma-ray signals from dark matter in the Milky Way would not only demonstrate the particle nature of dark matter; it would also open a new observational window on galactic dark matter substructure. Location of new dark matter sources by GLAST would dramatically alter the experimental landscape; ground based gamma ray telescopes could follow up on the new GLAST sources with precision measurements of the WIMP pair annihilation spectrum.

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

    ERIC Educational Resources Information Center

    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)

  1. Dynamic Line-by-line Pulse Shaping

    NASA Astrophysics Data System (ADS)

    Willits, John Thomas

    In pursuit of optical arbitrary waveform generation (OAWG), line-by-line pulse shapers use dynamic masks that can be modulated at the repetition rate of an input pulse train. The pulse-to-pulse control of the output pulse train with the waveform fidelity provided by line-by-line pulse shaping creates the most arbitrary waveform output possible, OAWG. This thesis studies the theoretical dynamic effects of such a pulse shaper and presents efforts towards realization of OAWG. Pulse shaping theory is extended to include rapid waveform update for line-by-line pulse shaping. The fundamental tradeoff between response speed and waveform fidelity is illustrated by several examples. Line-by-line pulse shaping is demonstrated at a repetition rate of 890 MHz on a mode-locked titanium sapphire laser. This pulse shaper relies on a virtual imaged phased array (VIPA) to obtain the necessary high spectral resolution. The details of the VIPA's ideal and nonideal performance are analyzed, simulated and tested. Individual frequency modes from the mode-locked titanium sapphire laser are also resolved using the same VIPA paired with a diffraction grating creating a 2-D spectral brush with a resolution of 357 MHz. The advantages and nonideal effects of VIPA-based pulse shaping are investigated. Analysis of several high speed modulation techniques are explored. The optical system required to separate adjacent comb lines into different single mode (SM) fibers necessary for several modulation techniques is designed and tested.

  2. Sensitivity analysis of hydrodynamic stability operators

    NASA Technical Reports Server (NTRS)

    Schmid, Peter J.; Henningson, Dan S.; Khorrami, Mehdi R.; Malik, Mujeeb R.

    1992-01-01

    The eigenvalue sensitivity for hydrodynamic stability operators is investigated. Classical matrix perturbation techniques as well as the concept of epsilon-pseudoeigenvalues are applied to show that parts of the spectrum are highly sensitive to small perturbations. Applications are drawn from incompressible plane Couette, trailing line vortex flow and compressible Blasius boundary layer flow. Parametric studies indicate a monotonically increasing effect of the Reynolds number on the sensitivity. The phenomenon of eigenvalue sensitivity is due to the non-normality of the operators and their discrete matrix analogs and may be associated with large transient growth of the corresponding initial value problem.

  3. Familial melanoma associated with dominant ultraviolet radiation sensitivity

    SciTech Connect

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

    1982-07-01

    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.

  4. Abstract Line Designs

    ERIC Educational Resources Information Center

    Nevinskas, Nancy

    2011-01-01

    In this article, the author describes a unit on the exploration of line. The unit was composed of two individual line lessons. In the first lesson, students were introduced to line as an element of design. They were asked to describe different types of lines, and look for them in art reproductions. The second lesson in the unit involved painting

  5. The Language of Lines.

    ERIC Educational Resources Information Center

    Breig-Allen, Cheryl; Hill, Janet; Geismar-Ryan, Lori; Cadwell, Louise Boyd

    1998-01-01

    Describes a project about lines in the environment used with 2- and 3-year olds and based on the Reggio Emilia approach. Activities included making tracks with riding toys, drawing lines on papers, seeing cloud lines, and making lines with yarn and Cuisenaire rods. Shows how young children's observations and ongoing discoveries can uncover their…

  6. Abstract Line Designs

    ERIC Educational Resources Information Center

    Nevinskas, Nancy

    2011-01-01

    In this article, the author describes a unit on the exploration of line. The unit was composed of two individual line lessons. In the first lesson, students were introduced to line as an element of design. They were asked to describe different types of lines, and look for them in art reproductions. The second lesson in the unit involved painting…

  7. Sensitivity Analysis in Engineering

    NASA Technical Reports Server (NTRS)

    Adelman, Howard M. (Compiler); Haftka, Raphael T. (Compiler)

    1987-01-01

    The symposium proceedings presented focused primarily on sensitivity analysis of structural response. However, the first session, entitled, General and Multidisciplinary Sensitivity, focused on areas such as physics, chemistry, controls, and aerodynamics. The other four sessions were concerned with the sensitivity of structural systems modeled by finite elements. Session 2 dealt with Static Sensitivity Analysis and Applications; Session 3 with Eigenproblem Sensitivity Methods; Session 4 with Transient Sensitivity Analysis; and Session 5 with Shape Sensitivity Analysis.

  8. Ringberg15: Earth's Climate Sensitivities

    NASA Technical Reports Server (NTRS)

    Stevens, Bjorn; Abe-Ouchi, Ayako; Bony, Sandrine; Hegerl, Gabi; Schmidt, Gavin; Sherwood, Steven; Webb, Mark

    2015-01-01

    To assess gaps in understanding of Earth's climate sensitivities a workshop was organised under the auspices of the WCRP (World Climate Research Programme) Grand Science Challenge on Clouds, Circulation and Climate Sensitivity (Ringberg15). The workshop took place in March 2015 and gathered together over thirty experts from around the world for one week. Attendees each gave short presentations and participated in moderated discussions of specific questions related to understanding Earth's climate sensitivities. Most of the time was focused on understanding of the equilibrium climate sensitivity, defined as the equilibrium near-surface warming associated with a doubling of atmospheric carbon dioxide. The workshop produced nine recommendations, many of them focusing on specific research avenues that could be exploited to advance understanding of climate sensitivity. Many of these dealt, in one fashion or another, with the need to more sharply focus research on identifying and testing story lines for a high (larger than 4 degrees Kelvin) or low (less than 2 degrees Kelvin) equilibrium climate sensitivity. Additionally, a subset of model intercomparison projects (CFMIP (Cloud Feedback Model Intercomparison Project), PMIP (Palaeoclimate Modelling Intercomparison Project), PDRMIP (Precipitation Driver and Response Model Intercomparison Project), RFMIP (Radiative Forcing Model Intercomparison Project) and VolMIP (Volcanic Forcings Model Intercomparison Project)) that have been proposed for inclusion within CMIP were identified as being central to resolving important issues raised at the workshop; for this reason modelling groups were strongly encouraged to participate in these projects. Finally the workshop participants encouraged the WCRP to initiate and support an assessment process lead by the Grand Science Challenge on Clouds, Circulation and Climate Sensitivity on the topic of Earth's Climate Sensitivities, culminating in a report that will be published in 2019, forty years after the seminal report by Charney and co-authors.

  9. Light sensitivity in a vertebrate mechanoreceptor?

    PubMed Central

    Baker, Gary E.; de Grip, Willem J.; Turton, Michael; Wagner, Hans-Joachim; Foster, Russell G.; Douglas, Ron H.

    2015-01-01

    ABSTRACT Using immunohistochemistry and western blot analysis, we demonstrate that melanopsin is localised in cells around the central pore of lateral line neuromasts in the African clawed frog, Xenopus laevis. Since melanopsin is a known photoreceptor pigment with diverse functions in vertebrates, we suggest that the lateral line of Xenopus laevis, which is primarily a mechanoreceptor, might also be light sensitive. Potential functions of such photosensitivity are discussed, including its role in mediating locomotor responses following dermal illumination. PMID:26206352

  10. Peripheral arterial line - infants

    MedlinePlus

    PAL - infants; Art line - infants ... an "art line." This article addresses PALs in babies. Why is a PAL used? Doctors and nurses use a PAL to watch your baby's blood pressure. A PAL can also be use ...

  11. Peripheral intravenous line - infants

    MedlinePlus

    PIV - infants; Peripheral IV - infants; Peripheral line - infants ... A peripheral intravenous line (PIV) is a small, short, plastic tube, called a catheter. A health care provider puts the PIV through the ...

  12. Peripheral arterial line (image)

    MedlinePlus

    A peripheral arterial line is a small, short plastic catheter placed through the skin into an artery of the arm or leg. The purpose of a peripheral arterial line is to allow continuous monitoring of blood pressure ...

  13. A plan for directional dark matter sensitivity in high-pressure xenon detectors through the addition of wavelength shifting gaseous molecules

    NASA Astrophysics Data System (ADS)

    Gehman, V. M.; Goldschmidt, A.; Nygren, D.; Oliveira, C. A. B.; Renner, J.

    2013-10-01

    Xenon is an especially attractive candidate for both direct WIMP and 0νββ decay searches. Although the current trend has exploited the liquid phase, the gas phase xenon offers remarkable performance advantages for: energy resolution, topology visualization, and discrimination between electron and nuclear recoils. The NEXT-100 experiment, now under construction in the Canfranc Underground Laboratory, Spain, will operate at ~ 15 bars with 100 kg of 136Xe for the 0νββ decay search. We will describe recent results with small prototypes, indicating that NEXT-100 can provide about 0.5% FWHM energy resolution at the decay's Q value (2457.83 keV), as well as rejection of γ-rays with topological cuts. However, sensitivity goals for WIMP dark matter and 0νββ decay searches indicate the probable need for ton-scale active masses. NEXT-100 provides the springboard to reach this scale with xenon gas. We describe a scenario for performing both searches in a single, high-pressure, ton-scale xenon gas detector, without significant compromise to either. In addition, even in a single ton-scale, high-pressure xenon gas TPC, an intrinsic sensitivity to the nuclear recoil direction may exist. This plausibly offers an advance of more than two orders of magnitude relative to current low-pressure TPC concepts. We argue that, in an era of deepening fiscal austerity, such a dual-purpose detector may be possible at acceptable cost, within the time frame of interest, and deserves our collective attention.

  14. Easy Observation of Infrared Spectral Lines

    ERIC Educational Resources Information Center

    Cortel, Adolf

    2012-01-01

    The spectra of some chemical elements display intense infrared (IR) lines that can be used more effectively than the ones in the visible region for identification purposes. A simple setup, based on the IR sensitivity of a handycam in nightshot mode, is described to record the visible as well as the IR spectra from decorative bulbs or salts on the

  15. Easy Observation of Infrared Spectral Lines

    ERIC Educational Resources Information Center

    Cortel, Adolf

    2012-01-01

    The spectra of some chemical elements display intense infrared (IR) lines that can be used more effectively than the ones in the visible region for identification purposes. A simple setup, based on the IR sensitivity of a handycam in nightshot mode, is described to record the visible as well as the IR spectra from decorative bulbs or salts on the…

  16. Near infrared hydrogen emission line ratios as diagnostics of the broad emission line region

    NASA Astrophysics Data System (ADS)

    Ruff, Andrea J.; Floyd, David J. E.; Korista, Kirk T.; Webster, Rachel L.; Porter, Ryan L.; Ferland, Gary J.

    2012-07-01

    Broad emission line flux ratios are a powerful diagnostic of the physical conditions of the broad-line region gas in Active Galactic Nuclei. With recent advances in infrared spectroscopy, previously unstudied emission lines provide a new means to investigate the physical nature of the BELR gas. The hydrogen emission lines are particularly sensitive to the upper limits of both the radius from the central ionising source and the number density of the gas. Using an existing subset of near-infrared quasar spectra from the Glikman et al. (2006) sample [1] together with Cloudy photoionization simulations, we confirm the Locally Optimally emitting Cloud (LOC) model's ability to reproduce observed emission line flux ratios. The model is then used to constrain physical conditions for individual sources. The photoionization models show that high number density, low incident flux gas is required to reproduce observed near-infrared hydrogen emission line ratios. We also find that comparison to individual sources, rather than composites, is vital.

  17. How Sensitively Timed Are Sensitive Periods?

    ERIC Educational Resources Information Center

    Zener, Rita Schaefer

    2003-01-01

    Reviews Maria Montessori's view of sensitive periods and examines the kinds of help needed from adults: an open mind, specific help from a prepared learning environment, and challenges presented at the right time. Stresses the universality of sensitive periods and their connection to brain development. Focuses on the unconscious nature and…

  18. Gamma ray line astronomy

    NASA Technical Reports Server (NTRS)

    Ramaty, R.

    1984-01-01

    The interpretations and implications of the astrophysical observations of gamma-ray lines are reviewed. At the Galactic Center e(+)-e(-) pairs from a compact object produce an annihilation line that shows no redshift, indicating an annihilation site far removed from this object. In the jets of SS433, gamma-ray lines are produced by inelastic excitations, probably in dust grains, although line emission from fusion reactions has also been considered. Observations of diffuse galactic line emission reveal recently synthesized radioactive aluminum in the interstellar medium. In gamma-ray bursts, redshifted pair annihilation lines are consistent with a neutron star origin for the bursts. In solar flares, gamma-ray line emission reveals the prompt acceleration of protons and nuclei, in close association with the flare energy release mechanism.

  19. Unveiling the nature of dark matter with high redshift 21 cm line experiments

    SciTech Connect

    Evoli, C.; Mesinger, A.; Ferrara, A. E-mail: andrei.mesinger@sns.it

    2014-11-01

    Observations of the redshifted 21 cm line from neutral hydrogen will open a new window on the early Universe. By influencing the thermal and ionization history of the intergalactic medium (IGM), annihilating dark matter (DM) can leave a detectable imprint in the 21 cm signal. Building on the publicly available 21cmFAST code, we compute the 21 cm signal for a 10 GeV WIMP DM candidate. The most pronounced role of DM annihilations is in heating the IGM earlier and more uniformly than astrophysical sources of X-rays. This leaves several unambiguous, qualitative signatures in the redshift evolution of the large-scale (k ≅ 0.1 Mpc{sup -1}) 21 cm power amplitude: (i) the local maximum (peak) associated with IGM heating can be lower than the other maxima; (ii) the heating peak can occur while the IGM is in emission against the cosmic microwave background (CMB); (iii) there can be a dramatic drop in power (a global minimum) corresponding to the epoch when the IGM temperature is comparable to the CMB temperature. These signatures are robust to astrophysical uncertainties, and will be easily detectable with second generation interferometers. We also briefly show that decaying warm dark matter has a negligible role in heating the IGM.

  20. Pharmacogenomic agreement between two cancer cell line data sets.

    PubMed

    2015-12-01

    Large cancer cell line collections broadly capture the genomic diversity of human cancers and provide valuable insight into anti-cancer drug response. Here we show substantial agreement and biological consilience between drug sensitivity measurements and their associated genomic predictors from two publicly available large-scale pharmacogenomics resources: The Cancer Cell Line Encyclopedia and the Genomics of Drug Sensitivity in Cancer databases. PMID:26570998

  1. High energy beam lines

    NASA Astrophysics Data System (ADS)

    Marchetto, M.; Laxdal, R. E.

    2014-01-01

    The ISAC post accelerator comprises an RFQ, DTL and SC-linac. The high energy beam lines connect the linear accelerators as well as deliver the accelerated beams to two different experimental areas. The medium energy beam transport (MEBT) line connects the RFQ to the DTL. The high energy beam transport (HEBT) line connects the DTL to the ISAC-I experimental stations (DRAGON, TUDA-I, GPS). The DTL to superconducting beam (DSB) transport line connects the ISAC-I and ISAC-II linacs. The superconducting energy beam transport (SEBT) line connects the SC linac to the ISAC-II experimental station (TUDA-II, HERACLES, TIGRESS, EMMA and GPS). All these lines have the function of transporting and matching the beams to the downstream sections by manipulating the transverse and longitudinal phase space. They also contain diagnostic devices to measure the beam properties.

  2. Series Transmission Line Transformer

    DOEpatents

    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.

  3. Computing overhead line parameters

    SciTech Connect

    Chan, S.M.

    1993-01-01

    The resistance, reactance, and capacitance of overhead transmission lines (line constants) are functions of the conductors' physical characteristics and other parameters. Power engineers are familiar with the handbook formulas for computing the line constants, but few realize that the handbook formulas are simplifications of Carson's method, which has been available since the 1930s. Computer implementation of Carson's method and other methods for computing line constants began in the 1960s. Computer line-constants programs are widely available today from a variety of sources, and they run on mainframes as well as on personal computers. At least one line-constants program is in the public domain. This article focuses on the computation of line constants at the power-line frequencies of 50 and 60 Hz. At this frequency range, computer methods and handbook formulas give virtually identical positive-sequence impedances, with the exception of overhead lines with ground wires. A study by H. Dommel confirmed that the positive-sequence impedance given by the two methods are usually within a small fraction of 1%, a difference that is negligible compared to the uncertainties in the physical parameters. But in cases where ground wires are present, the study showed a substantial difference between the results of handbook formulas and those of computer programs.

  4. Dynamical compactness and sensitivity

    NASA Astrophysics Data System (ADS)

    Huang, Wen; Khilko, Danylo; Kolyada, Sergiĭ; Zhang, Guohua

    2016-05-01

    To link the Auslander point dynamics property with topological transitivity, in this paper we introduce dynamically compact systems as a new concept of a chaotic dynamical system (X , T) given by a compact metric space X and a continuous surjective self-map T : X → X. Observe that each weakly mixing system is transitive compact, and we show that any transitive compact M-system is weakly mixing. Then we discuss the relationships between it and other several stronger forms of sensitivity. We prove that any transitive compact system is Li-Yorke sensitive and furthermore multi-sensitive if it is not proximal, and that any multi-sensitive system has positive topological sequence entropy. Moreover, we show that multi-sensitivity is equivalent to both thick sensitivity and thickly syndetic sensitivity for M-systems. We also give a quantitative analysis for multi-sensitivity of a dynamical system.

  5. Pressure Sensitive Paints

    NASA Technical Reports Server (NTRS)

    Liu, Tianshu; Bencic, T.; Sullivan, J. P.

    1999-01-01

    This article reviews new advances and applications of pressure sensitive paints in aerodynamic testing. Emphasis is placed on important technical aspects of pressure sensitive paint including instrumentation, data processing, and uncertainty analysis.

  6. Line Shapes and Opacity Studies in Divertor Plasmas

    SciTech Connect

    Rosato, J.

    2008-10-22

    Large or dense divertor plasmas of magnetic fusion devices can be optically thick to the resonance lines of the hydrogen isotopes. In this work we examine the sensitivity of the line radiation transport to the detailed structure of the spectral profiles.

  7. Literature and Social Sensitivity.

    ERIC Educational Resources Information Center

    Loban, Walter

    Focusing on the responses of adolescents to literature "involving values based on the concept of human dignity," this study examined two groups of adolescents (60 students each) in grades 8-12. The two groups represented extremes of social sensitivity: highly sensitive and least sensitive to the feelings of others. Teachers read aloud 10 short…

  8. Tangent Lines without Calculus

    ERIC Educational Resources Information Center

    Rabin, Jeffrey M.

    2008-01-01

    This article presents a problem that can help high school students develop the concept of instantaneous velocity and connect it with the slope of a tangent line to the graph of position versus time. It also gives a method for determining the tangent line to the graph of a polynomial function at any point without using calculus. (Contains 1 figure.)

  9. Transmission Line Security Monitor

    SciTech Connect

    2011-01-01

    The Transmission Line Security Monitor is a multi-sensor monitor that mounts directly on high-voltage transmission lines to detect, characterize and communicate terrorist activity, human tampering and threatening conditions around support towers. For more information about INL's critical infrastructure protection research, visit http://www.facebook.com/idahonationallaboratory.

  10. Structuring a service line.

    PubMed

    Zablocki, E

    1997-05-01

    In 1993, Community Hospitals Indianapolis created 10 service lines--each unique to the needs of the patients it serves. Two service line leaders talk about the factors critical to successful restructuring, the working relationships established, and the importance of clear communication to ensure understanding and get buy-in to the process. PMID:10167712

  11. Airborne Fraunhofer Line Discriminator

    NASA Technical Reports Server (NTRS)

    Gabriel, F. C.; Markle, D. A.

    1969-01-01

    Airborne Fraunhofer Line Discriminator enables prospecting for fluorescent materials, hydrography with fluorescent dyes, and plant studies based on fluorescence of chlorophyll. Optical unit design is the coincidence of Fraunhofer lines in the solar spectrum occurring at the characteristic wavelengths of some fluorescent materials.

  12. Attachment Line Blockage Models

    NASA Technical Reports Server (NTRS)

    1995-01-01

    Photographs shows the attachment-line experiment model with fairing and fence for supersonic attachment-line experiments. The fairing is intended to eliminate the wing/fuselage juncture shock and align the flow for the streamlined fence. The streamlined fence traps the turbulent fuselage boundary layer to prevent turbulent contamination of the leading edge flow.

  13. Transmission Line Security Monitor

    ScienceCinema

    None

    2013-05-28

    The Transmission Line Security Monitor is a multi-sensor monitor that mounts directly on high-voltage transmission lines to detect, characterize and communicate terrorist activity, human tampering and threatening conditions around support towers. For more information about INL's critical infrastructure protection research, visit http://www.facebook.com/idahonationallaboratory.

  14. Microstructural lines involving luminescence

    NASA Astrophysics Data System (ADS)

    Shimada, Kazuhiko

    2004-06-01

    Japanese National Printing Bureau has been focused upon the development of anti-copy lines for many years. The basic concept with regard to security measure lies in the merge of art and technology. On this basis, our originally developed anti-copy lines show flexibility to various security designs. Our newest anti-copy lines comprising from the Tri-Branched and Divided Lines shows clearer latent image effect compared to that of our other developed anti-copy lines. However, the anti-copy effect of security printing lines with microstructure is deteriorating due to the emergence of digital image techniques with higher resolution. In this situation, this paper introduces a new security measure comprising from luminescence and security printing lines with microstructure. It gives rise to a latent image effect under UV light due to the characteristic microstructure while visually same density. The principle advantage is that the combination of the anti-copy and luminescent feature strongly enhances its secure effect in documents. There is no necessity of two kinds of inks and any specially designed equipment to produce security documents with microstructural lines involving luminescence.

  15. Zebrafish Sensitivity to Botulinum Neurotoxins.

    PubMed

    Chatla, Kamalakar; Gaunt, Patricia S; Petrie-Hanson, Lora; Ford, Lorelei; Hanson, Larry A

    2016-01-01

    Botulinum neurotoxins (BoNT) are the most potent known toxins. The mouse LD50 assay is the gold standard for testing BoNT potency, but is not sensitive enough to detect the extremely low levels of neurotoxin that may be present in the serum of sensitive animal species that are showing the effects of BoNT toxicity, such as channel catfish affected by visceral toxicosis of catfish. Since zebrafish are an important animal model for diverse biomedical and basic research, they are readily available and have defined genetic lines that facilitate reproducibility. This makes them attractive for use as an alternative bioassay organism. The utility of zebrafish as a bioassay model organism for BoNT was investigated. The 96 h median immobilizing doses of BoNT/A, BoNT/C, BoNT/E, and BoNT/F for adult male Tübingen strain zebrafish (0.32 g mean weight) at 25 °C were 16.31, 124.6, 4.7, and 0.61 picograms (pg)/fish, respectively. These findings support the use of the zebrafish-based bioassays for evaluating the presence of BoNT/A, BoNT/E, and BoNT/F. Evaluating the basis of the relatively high resistance of zebrafish to BoNT/C and the extreme sensitivity to BoNT/F may reveal unique functional patterns to the action of these neurotoxins. PMID:27153088

  16. Zebrafish Sensitivity to Botulinum Neurotoxins

    PubMed Central

    Chatla, Kamalakar; Gaunt, Patricia S.; Petrie-Hanson, Lora; Ford, Lorelei; Hanson, Larry A.

    2016-01-01

    Botulinum neurotoxins (BoNT) are the most potent known toxins. The mouse LD50 assay is the gold standard for testing BoNT potency, but is not sensitive enough to detect the extremely low levels of neurotoxin that may be present in the serum of sensitive animal species that are showing the effects of BoNT toxicity, such as channel catfish affected by visceral toxicosis of catfish. Since zebrafish are an important animal model for diverse biomedical and basic research, they are readily available and have defined genetic lines that facilitate reproducibility. This makes them attractive for use as an alternative bioassay organism. The utility of zebrafish as a bioassay model organism for BoNT was investigated. The 96 h median immobilizing doses of BoNT/A, BoNT/C, BoNT/E, and BoNT/F for adult male Tübingen strain zebrafish (0.32 g mean weight) at 25 °C were 16.31, 124.6, 4.7, and 0.61 picograms (pg)/fish, respectively. These findings support the use of the zebrafish-based bioassays for evaluating the presence of BoNT/A, BoNT/E, and BoNT/F. Evaluating the basis of the relatively high resistance of zebrafish to BoNT/C and the extreme sensitivity to BoNT/F may reveal unique functional patterns to the action of these neurotoxins. PMID:27153088

  17. Sensitivity Test Analysis

    Energy Science and Technology Software Center (ESTSC)

    1992-02-20

    SENSIT,MUSIG,COMSEN is a set of three related programs for sensitivity test analysis. SENSIT conducts sensitivity tests. These tests are also known as threshold tests, LD50 tests, gap tests, drop weight tests, etc. SENSIT interactively instructs the experimenter on the proper level at which to stress the next specimen, based on the results of previous responses. MUSIG analyzes the results of a sensitivity test to determine the mean and standard deviation of the underlying population bymore » computing maximum likelihood estimates of these parameters. MUSIG also computes likelihood ratio joint confidence regions and individual confidence intervals. COMSEN compares the results of two sensitivity tests to see if the underlying populations are significantly different. COMSEN provides an unbiased method of distinguishing between statistical variation of the estimates of the parameters of the population and true population difference.« less

  18. CRIRES spectroscopy and empirical line-by-line identification of FeH molecular absorption in an M dwarf

    NASA Astrophysics Data System (ADS)

    Wende, S.; Reiners, A.; Seifahrt, A.; Bernath, P. F.

    2010-11-01

    Molecular FeH provides a large number of sharp and isolated absorption lines that can be used to measure radial velocity, rotation, or magnetic field strength with high accuracy. Our aim is to provide an FeH atlas for M-type stars in the spectral region from 986 nm to 1077 nm (Wing-Ford band). To identify these lines in CRIRES spectra of the magnetically inactive, slowly rotating, M5.5 dwarf GJ1002, we calculated model spectra for the selected spectral region with theoretical FeH line data. In general this line list agrees with the observed data, but several individual lines differ significantly in position or in line strength. After identification of as many as possible FeH lines, we corrected the line data for position and line strength to provide an accurate atlas of FeH absorption lines for use in high precision spectroscopy of low mass stars. For all lines, we used a Voigt function to obtain their positions and equivalent widths. Identification with theoretical lines was done by hand. For confirmation of the identified lines, we used statistical methods, cross-correlation techniques, and line intensities. Eventually, we were able to identify FeH lines from the (0,0), (1,0), (1,1), (2,1), (2,2), (3,2), and (4,3) vibrational bands in the observed spectra and correct the positions of the lines if necessary. The deviations between theoretical and observed positions follow a normal distribution approximately around zero. In order to empirically correct the line strength, we determined Teff, instrumental broadening (rotational broadening) and a van der Waals enhancement factor for the FeH lines in GJ1002. We also give the scaling factors for the Einstein A values to correct the line strengths. With the identified lines, we derived rotational temperatures from the line intensities for GJ1002. We conclude that FeH lines can be used for a wide variety of applications in astrophysics. With the identified lines it will be possible for example to characterize magnetically sensitive or very temperature sensitive lines, which can be used to investigate M-type stars. Data were taken at ESO Telescopes under the program 79.D-0357(A).Full Table 4 and FeH atlas are only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/viz-bin/qcat?J/A+A/523/A58

  19. Linear Polarization Measurements of Chromospheric Emission Lines

    NASA Technical Reports Server (NTRS)

    Sheeley, N. R., Jr.; Keller, C. U.

    2003-01-01

    We have used the Zurich Imaging Stokes Polarimeter (ZIMPOL I) with the McMath-Pierce 1.5 m main telescope on Kitt Peak to obtain linear polarization measurements of the off-limb chromosphere with a sensitivity better than 1 x 10(exp -5). We found that the off-disk observations require a combination of good seeing (to show the emission lines) and a clean heliostat (to avoid contamination by scattered light from the Sun's disk). When these conditions were met, we obtained the following principal results: 1. Sometimes self-reversed emission lines of neutral and singly ionized metals showed linear polarization caused by the transverse Zeeman effect or by instrumental cross talk from the longitudinal Zeeman effect in chromospheric magnetic fields. Otherwise, these lines tended to depolarize the scattered continuum radiation by amounts that ranged up to 0.2%. 2. Lines previously known to show scattering polarization just inside the limb (such as the Na I lambda5889 D2 and the He I lambda5876 D3 lines) showed even more polarization above the Sun's limb, with values approaching 0.7%. 3. The O I triplet at lambda7772, lambda7774, and lambda7775 showed a range of polarizations. The lambda7775 line, whose maximum intrinsic polarizability, P(sub max), is less than 1%, revealed mainly Zeeman contributions from chromospheric magnetic fields. However, the more sensitive lambda7772 (P(sub max) = 19%) and lambda7774 (P(sub max) = 29%) lines had relatively strong scattering polarizations of approximately 0.3% in addition to their Zeeman polarizations. At times of good seeing, the polarization spectra resolve into fine structures that seem to be chromospheric spicules.

  20. Flow line sampler

    DOEpatents

    Nicholls, Colin I.

    1992-07-14

    An on-line product sampling apparatus and method for measuring product samples from a product stream (12) in a flow line (14) having a sampling aperture (11), includes a sampling tube (18) for containing product samples removed from flow line (14). A piston (22) removes product samples from the product stream (12) through the sampling aperture (11) and returns samples to product stream (12). A sensor (20) communicates with sample tube (18), and senses physical properties of samples while the samples are within sample tube (18). In one embodiment, sensor (20) comprises a hydrogen transient nuclear magnetic resonance sensor for measuring physical properties of hydrogen molecules.

  1. Coherent soliton communication lines

    SciTech Connect

    Yushko, O. V. Redyuk, A. A.; Fedoruk, M. P.; Turitsyn, S. K.

    2014-11-15

    The data transmission in coherent fiber-optical communication lines using solitons with a variable phase is studied. It is shown that nonlinear coherent structures (solitons) can be applied for effective signal transmission over a long distance using amplitude and optical-phase keying of information. The optimum ratio of the pulse width to the bit slot at which the spectral efficiency (transmitted bits per second and hertz) is maximal is determined. It is shown that soliton fiber-optical communication lines can ensure data transmission at a higher spectral efficiency as compared to traditional communication lines and at a high signal-to-noise ratio.

  2. Neutral line chaos and phase space structure

    NASA Technical Reports Server (NTRS)

    Burkhart, Grant R.; Speiser, Theodore W.; Martin, Richard F., Jr.; Dusenbery, Paul B.

    1991-01-01

    Phase space structure and chaos near a neutral line are studied with numerical surface-of-section (SOS) techniques and analytic methods. Results are presented for a linear neutral line model with zero crosstail electric field. It was found that particle motion can be divided into three regimes dependening on the value of the conserved canonical momentum, Py, and the conserved Hamiltonian, h. The phase space structure, using Poincare SOS plots, is highly sensitive to bn = Bn/B0 variations, but not to h variations. It is verified that the slow motion preserves the action, Jz, as evaluated by Sonnerup (1971), when the period of the fast motion is smaller than the time scale of the slow motion. Results show that the phase space structure and particle chaos depend sensitively upon Py and bn, but are independent of h.

  3. Emission line spectropolarimetry and circumstellar structures

    NASA Astrophysics Data System (ADS)

    Vink, Jorick S.

    2015-10-01

    We discuss the role of linear emission-line polarimetry in a wide set of stellar environments, involving the accretion disks around young pre-main sequence stars, to the aspherical outflows from O stars, luminous blue variables and Wolf-Rayet stars, just prior to explosion as a supernova or a gamma-ray burst. We predict subtle QU line signatures, such as single/double QU loops for un/disrupted disks. Whilst there is plenty of evidence for single QU loops, suggesting the presence of disrupted disks around young stars, current sensitivity (with S/N of order 1000) is typically not sufficient to allow for quantitative 3D Monte Carlo modeling. However, the detection of our predicted signatures is expected to become feasible with the massive improvement in sensitivity of extremely large mirrors.

  4. Central line infections - hospitals

    MedlinePlus

    ... risk is higher if you: Are in the intensive care unit (ICU) Have a weakened immune system or serious ... unless you have washed your hands. Tell your nurse if your central line: Gets dirty Is coming ...

  5. Folly Island Tidal Lines

    Lines of debris from tidal action on Folly Island. Folly Island, a preserve owned by the Maine Coast Heritage Trust, is about 7 acres. It is located in Bartlett Narrows, along the western coast of Mount Desert Island....

  6. Folly Island Tidal Lines

    Lines of debris from tidal action on Folly Island. Folly Island, a preserve owned by the Maine Coast Heritage Trust, is about 7 acres. It is located in Bartlett Narrows, along the western coast of Mount Desert Island....

  7. Line, Shape, Color.

    ERIC Educational Resources Information Center

    Greenman, Geri

    2002-01-01

    Describes an art project used with beginning high school art students that teaches them about continuous line drawing. Explains that the students create portraits of themselves, or another student, using glue, black construction paper, and chalk. (CMK)

  8. Power line detection system

    DOEpatents

    Latorre, Victor R.; Watwood, Donald B.

    1994-01-01

    A short-range, radio frequency (RF) transmitting-receiving system that provides both visual and audio warnings to the pilot of a helicopter or light aircraft of an up-coming power transmission line complex. Small, milliwatt-level narrowband transmitters, powered by the transmission line itself, are installed on top of selected transmission line support towers or within existing warning balls, and provide a continuous RF signal to approaching aircraft. The on-board receiver can be either a separate unit or a portion of the existing avionics, and can also share an existing antenna with another airborne system. Upon receipt of a warning signal, the receiver will trigger a visual and an audio alarm to alert the pilot to the potential power line hazard.

  9. Power line detection system

    DOEpatents

    Latorre, V.R.; Watwood, D.B.

    1994-09-27

    A short-range, radio frequency (RF) transmitting-receiving system that provides both visual and audio warnings to the pilot of a helicopter or light aircraft of an up-coming power transmission line complex. Small, milliwatt-level narrowband transmitters, powered by the transmission line itself, are installed on top of selected transmission line support towers or within existing warning balls, and provide a continuous RF signal to approaching aircraft. The on-board receiver can be either a separate unit or a portion of the existing avionics, and can also share an existing antenna with another airborne system. Upon receipt of a warning signal, the receiver will trigger a visual and an audio alarm to alert the pilot to the potential power line hazard. 4 figs.

  10. Working with Wilson Lines

    NASA Astrophysics Data System (ADS)

    van der Veken, Frederik F.

    2016-02-01

    We present an algorithm to express Wilson lines that are defined on piecewise linear paths in function of their individual segments, reducing the number of diagrams needed to be calculated. The important step lies in the observation that different linear path topologies can be related to each other using their color structure. This framework allows one to easily switch results between different Wilson line topologies, which is helpful when testing different structures against each other.

  11. A behavior-genetic approach to multiple chemical sensitivity.

    PubMed Central

    Newlin, D B

    1997-01-01

    This report emphasizes the application of behavior-genetic designs to the study of sensitivity to toxic chemicals, and features of multiple chemical sensitivity and substance abuse that are polar opposites. The implications of these issues for future research are discussed in relation to twin, adoption, and sibling pair studies, as well as in relation to the degree to which genetically selected lines of rodents that have been developed in the alcoholism field are applicable to multiple chemical sensitivity. PMID:9167987

  12. Strain monitoring averts line failure in Rockies

    SciTech Connect

    Miller, B.; Bukovansky, M.

    1987-08-10

    The case history of a landslide in the U.S. Rocky Mountains shows that the potential for pipeline monitoring in geologically sensitive areas, those subject to landslides and subsidence, for example. A properly installed monitoring system monitored by the pipeline operator, Western Gas Supply Co. (West Gas), Denver, provided an early warning of increasing line strains. The problem was complicated by rugged topography which is described here. Stability analysis was the key technique utilized in the process.

  13. Easy observation of infrared spectral lines

    NASA Astrophysics Data System (ADS)

    Cortel, Adolf

    2012-05-01

    The spectra of some chemical elements display intense infrared (IR) lines that can be used more effectively than the ones in the visible region for identification purposes. A simple setup, based on the IR sensitivity of a handycam in nightshot mode, is described to record the visible as well as the IR spectra from decorative bulbs or salts on the flame of a Bunsen burner.

  14. Measurement of Deflection Line on Bridges

    NASA Astrophysics Data System (ADS)

    Urban, Rudolf; Štroner, Martin

    2013-12-01

    Prestressed concrete bridges are very sensitive to the increase in long-term deflections. Reliable forecasts of deflections of bridge structures during construction and durability are crucial for achieving good durability. The main results of measurements are the changes of the deflection line of the bridge structures, which places special demands on the measurement procedure. Results from measurements are very useful for the improvement of mathematical prediction methods of behaviour of long span prestressed concrete structures.

  15. On-Line and Off-Line Assessment of Metacognition

    ERIC Educational Resources Information Center

    Saraç, Seda; Karakelle, Sema

    2012-01-01

    The study investigates the interrelationships between different on-line and off-line measures for assessing metacognition. The participants were 47 fifth grade elementary students. Metacognition was assessed through two off-line and two on-line measures. The off-line measures consisted of a teacher rating scale and a self-report questionnaire. The…

  16. PORTION OF A LINE (AT LEFT) AND B LINE (AT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    PORTION OF A LINE (AT LEFT) AND B LINE (AT RIGHT) ON GENTLE TERRACE SLOPE. A LINE POLE 75A (LEFT FOREGROUND) HAS ORIGINAL GLASS PIN-TYPE INSULATORS AND INTACT COMMUNICATION LINE CROSS ARM. VIEW TO WEST-SOUTHWEST. - Mystic Lake Hydroelectric Facility, Electric Transmission A Line, Along West Rosebud Creek, Fishtail, Stillwater County, MT

  17. Nasca Lines, Peru

    NASA Technical Reports Server (NTRS)

    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.

  18. Flash Mob Project Creates Awareness of Environmental Sensitivities: Making "Multiple Chemical Sensitivity" a Household Name

    ERIC Educational Resources Information Center

    Smith, Melva Gail

    2011-01-01

    Having severe Asthma and trying to maintain a social life isn't easy, but when one adds the disability of Multiple Chemical Sensitivity (MCS) to the combination, the challenges become even tougher. As a dancer with both Asthma and MCS, the author was forced to give up the sport for 15 years before finding a group of line dancers that were

  19. Flash Mob Project Creates Awareness of Environmental Sensitivities: Making "Multiple Chemical Sensitivity" a Household Name

    ERIC Educational Resources Information Center

    Smith, Melva Gail

    2011-01-01

    Having severe Asthma and trying to maintain a social life isn't easy, but when one adds the disability of Multiple Chemical Sensitivity (MCS) to the combination, the challenges become even tougher. As a dancer with both Asthma and MCS, the author was forced to give up the sport for 15 years before finding a group of line dancers that were…

  20. Fabrics Protect Sensitive Skin from UV Rays

    NASA Technical Reports Server (NTRS)

    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.

  1. Monochromatic neutrino lines from sneutrino dark matter

    NASA Astrophysics Data System (ADS)

    Arina, Chiara; Kulkarni, Suchita; Silk, Joseph

    2015-10-01

    We investigate the possibility of observing monochromatic neutrino lines originating from annihilation of dark matter. We analyze several astrophysical sources with overdensities of dark matter that can amplify the signal. As a case study, we consider mixed left- and right-handed sneutrino dark matter. We demonstrate that in the physically viable region of the model, one can obtain a prominent monochromatic neutrino line. We propose a search strategy to observe these neutrino lines in future generations of neutrino telescopes that is especially sensitive to dwarf spheroidal galaxies. We demonstrate that the presence of massive black holes in the cores of dwarfs as well as of more massive galaxies substantially boosts any putative signal. In particular, dark matter in dwarf galaxies spiked by an intermediate massive black hole provides a powerful means of probing low-annihilation cross sections well below 10-26 cm3 s-1 that are otherwise inaccessible by any future direct detection or collider experiment.

  2. Optical interstellar absorption lines toward 29 stars

    NASA Technical Reports Server (NTRS)

    Hobbs, L. M.

    1984-01-01

    Observations of optical interstellar absorption lines of Ti II, Ca II, and/or Na I acquired at an instrumental resolution typically of 5.6 km/s are reported for 29 stars. The data were recorded primarily with a Digicon detector and achieve 2 sigma detection limits generally near an equivalent width of 1 mA. The primary purpose of the observations is, in combination with previously published data, to provide a comprehensive, high-sensitivity survey of Ti II, Ca II, and Na I absorption at all velocities, toward 41 stars for which a correspondingly complete survey of certain ultraviolet interstellar lines also is available. New high-velocity optical interstellar lines at /v(LSR)/ greater than about 25 km/s are found toward four of the 29 stars.

  3. Transmission line capital costs

    SciTech Connect

    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.

  4. Line Lengths and Starch Scores.

    ERIC Educational Resources Information Center

    Moriarty, Sandra E.

    1986-01-01

    Investigates readability of different line lengths in advertising body copy, hypothesizing a normal curve with lower scores for shorter and longer lines, and scores above the mean for lines in the middle of the distribution. Finds support for lower scores for short lines and some evidence of two optimum line lengths rather than one. (SKC)

  5. Mentoring Emotionally Sensitive Individuals.

    ERIC Educational Resources Information Center

    Shaughnessy, Michael F.; Self, Elizabeth

    Mentoring individuals who are gifted, talented, and creative, but somewhat emotionally sensitive is a challenging and provocative arena. Several reasons individuals experience heightened sensitivity include: lack of nurturing, abuse, alcoholism in the family, low self-esteem, unrealistic parental expectations, and parental pressure to achieve.…

  6. Are Psychopaths Morally Sensitive?

    ERIC Educational Resources Information Center

    Maxwell, Bruce; Le Sage, Leonie

    2009-01-01

    Philosophical and psychological opinion is divided over whether moral sensitivity, understood as the ability to pick out a situation's morally salient features, necessarily involves emotional engagement. This paper seeks to offer insight into this question. It reasons that if moral sensitivity does draw significantly on affective capacities of…

  7. Tuned cavity magnetometer sensitivity.

    SciTech Connect

    Okandan, Murat; Schwindt, Peter

    2009-09-01

    We have developed a high sensitivity (sensitivity levels.

  8. Straight-line stabilization

    PubMed

    Mao; Zengrong; Ling

    2000-10-01

    For finite-dimensional maps, an unstable orbit in a neighborhood of an unstable fixed point can be stabilized by adjusting parameters so that the orbit goes to the fixed point along the straight line connecting the orbit (at a given time) and the fixed point [Yang Ling, Liu Zengrong and Jian-min Mao, Phys. Rev. Lett. 84, 67 (2000)]. This is called straight-line stabilization. In this paper, we derive the expression for the region of stabilization, i.e., the region within which the straight-line stabilization method is valid. For two-dimensional maps, the parameter adjustments needed by the stabilization method are explicitly given for nine cases. Stabilization of unstable flows, with or without introducing a Poincare map, is also investigated. PMID:11089028

  9. Product line management.

    PubMed

    Moye, C E

    1991-01-01

    The application of Product Line Management to the health care industry in the United States is an effort to use a management approach from the business world that aims at implementing, maintaining, and enhancing productivity without compromising quality patient care. Product Line Management is an opportunity for the nurse in management to develop a business acumen that will directly influence patient outcomes. Under this concept the product, is defined, priced, marketed and sold. The result is the ability to secure a competitive edge in the health care marketplace that not only allows us to survive, but to thrive. PMID:1996218

  10. Pipe Line Control

    NASA Technical Reports Server (NTRS)

    1978-01-01

    The array of tanks, pipes and valves in the photo below is a petroleum tank farm in Georgia, part of a petrochemical pipe line system that moves refined petroleum products from Texas and Louisiana to the mid-Eastern seaboard. The same pipes handle a number of different products, such as gasoline, kerosene, jet fuel or fuel oil. The fluids are temporarily stored in tanks, pumped into the pipes in turn and routed to other way stations along the pipe line. The complex job of controlling, measuring and monitoring fuel flow is accomplished automatically by a computerized control and communications system which incorporates multiple space technologies.

  11. Maize sensitivity to drought stress is associated with differential responses to reactive oxygen species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aflatoxin contamination of crops is exacerbated by preharvest drought stress. Previously, we identified maize drought responsive proteins in lines with differing drought sensitivities, and proposed a model for drought responses. The sensitive line, B73, exhibited a vigorous induced response to stres...

  12. Quantile Sensitivity Estimation

    NASA Astrophysics Data System (ADS)

    Heidergott, Bernd; Volk-Makarewicz, Warren

    Quantiles are important performance characteristics that have been adopted in many areas for measuring the quality of service. Recently, sensitivity analysis of quantiles has attracted quite some attention. Sensitivity analysis of quantiles is particularly challenging as quantiles cannot be expressed as the expected value of some sample performance function, and it is therefore not evident how standard gradient estimation methods can be applied. In this paper we present a straightforward quantile sensitivity estimator based on measure-valued differentiation (MVD). We compare our new estimator with the known infinitesimal perturbation analysis (IPA) estimator and discuss implementation issues. Numerical examples will illustrate our results.

  13. The potential effectiveness of nanoparticles as radio sensitizers for radiotherapy

    PubMed Central

    Babaei, Mohammad; Ganjalikhani, Maryam

    2014-01-01

    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. PMID:24790894

  14. The Front Line.

    ERIC Educational Resources Information Center

    Unks, Gerald

    1979-01-01

    The author draws an analogy between today's school system and an assembly line, deploring the notion that all children are taught the same thing at the same time, ending in humiliation, disgrace, and failure for some, and nonchallenging academic activities for others. (KC)

  15. Introduction to Line Designs.

    ERIC Educational Resources Information Center

    Seymour, Dale

    Pattern manifests itself in many ways through properties such as symmetry, repetition, translation, and illusion. This guide, appropriate for use with grades 6-12, presents patterns that are formed entirely by straight lines, yet appear to contain or be formed by curves. Exploring these geometrical shapes offers an opportunity to discover various…

  16. Microwave spectral line listing

    NASA Technical Reports Server (NTRS)

    White, W. F., Jr.

    1975-01-01

    The frequency, intensity, and identification of 9615 spectral lines belonging to 75 molecules are tabulated in order of increasing frequency. Measurements for all 75 molecules were made in the frequency range from 26500 to 40000 MHz by a computer controlled spectrometer. Measurements were also made in the 18000 to 26500 MHz range for some of the molecules.

  17. On-Line Nutrition.

    ERIC Educational Resources Information Center

    Kongshem, Lars

    1995-01-01

    Several sources of nutrition information are available on the Internet. Good online sources include the U.S. Department of Agriculture Food and Consumer Service bulletin board, the Food and Drug Administration's Center for Food Safety and Applied Nutrition, and the IFIC (International Food Information Council) Foundation On-Line. E-mail addresses…

  18. Glue-Line Insects.

    ERIC Educational Resources Information Center

    Dugas, Christine

    2001-01-01

    Presents an activity for fourth- and fifth-grade students in which they create a realistic or imaginative insect of their choice following a brief slide presentation on insects. Explains that the activity combines the use of line, shape, and color and takes two 40-minute class periods. (CMK)

  19. Building with a Line

    ERIC Educational Resources Information Center

    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…

  20. Straight Line Graphs

    ERIC Educational Resources Information Center

    Krueger, Tom

    2010-01-01

    In this article, the author shares one effective lesson idea on straight line graphs that he applied in his lower ability Y9 class. The author wanted something interesting for his class to do, something that was fun and engaging with direct feedback, and something that worked because someone else had tried it before. In a word, the author admits…

  1. Building with a Line

    ERIC Educational Resources Information Center

    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

  2. Method for rapid isolation of sensitive mutants

    DOEpatents

    Freyer, J.P.

    1997-07-29

    Sensitive mammalian cell mutants are rapidly isolated using flow cytometry. A first population of clonal spheroids is established to contain both normal and mutant cells. The population may be naturally occurring or may arise from mutagenized cells. The first population is then flow sorted by size to obtain a second population of clonal spheroids of a first uniform size. The second population is then exposed to a DNA-damaging agent that is being investigated. The exposed second population is placed in a growth medium to form a third population of clonal spheroids comprising spheroids of increased size from the mammalian cells that are resistant to the DNA-damaging agent and spheroids of substantially the first uniform size formed from the mammalian cells that are sensitive to the DNA-damaging agent. The third population is not flow sorted to differentiate the spheroids formed from resistant mammalian cells from spheroids formed from sensitive mammalian cells. The spheroids formed from sensitive mammalian cells are now treated to recover viable sensitive cells from which a sensitive cell line can be cloned. 15 figs.

  3. Method for rapid isolation of sensitive mutants

    DOEpatents

    Freyer, James P.

    1997-01-01

    Sensitive mammalian cell mutants are rapidly isolated using flow cytometry. A first population of clonal spheroids is established to contain both normal and mutant cells. The population may be naturally occurring or may arise from mutagenized cells. The first population is then flow sorted by size to obtain a second population of clonal spheroids of a first uniform size. The second population is then exposed to a DNA-damaging agent that is being investigated. The exposed second population is placed in a growth medium to form a third population of clonal spheroids comprising spheroids of increased size from the mammalian cells that are resistant to the DNA-damaging agent and spheroids of substantially the first uniform size formed from the mammalian cells that are sensitive to the DNA-damaging agent. The third population is not flow sorted to differentiate the spheroids formed from resistant mammalian cells from spheroids formed from sensitive mammalian cells. The spheroids formed from sensitive mammalian cells are now treated to recover viable sensitive cells from which a sensitive cell line can be cloned.

  4. Sensitivity of photoacoustic microscopy

    PubMed Central

    Yao, Junjie; Wang, Lihong V.

    2014-01-01

    Building on its high spatial resolution, deep penetration depth and excellent image contrast, 3D photoacoustic microscopy (PAM) has grown tremendously since its first publication in 2005. Integrating optical excitation and acoustic detection, PAM has broken through both the optical diffusion and optical diffraction limits. PAM has 100% relative sensitivity to optical absorption (i.e., a given percentage change in the optical absorption coefficient yields the same percentage change in the photoacoustic amplitude), and its ultimate detection sensitivity is limited only by thermal noise. Focusing on the engineering aspects of PAM, this Review discusses the detection sensitivity of PAM, compares the detection efficiency of different PAM designs, and summarizes the imaging performance of various endogenous and exogenous contrast agents. It then describes representative PAM applications with high detection sensitivity, and outlines paths to further improvement. PMID:25302158

  5. Personalized chemotherapy profiling using cancer cell lines from selectable mice

    PubMed Central

    Kamiyama, Hirohiko; Rauenzahn, Sherri; Shim, Joong Sup; Karikari, Collins A.; Feldmann, Georg; Hua, Li; Kamiyama, Mihoko; Schuler, F. William; Lin, Ming-Tseh; Beaty, Robert M.; Karanam, Balasubramanyam; Liang, Hong; Mullendore, Michael E.; Mo, Guanglan; Hidalgo, Manuel; Jaffee, Elizabeth; Hruban, Ralph H.; Jinnah, H. A.; Roden, Richard B. S.; Jimeno, Antonio; Liu, Jun O.; Maitra, Anirban; Eshleman, James R.

    2013-01-01

    Purpose High-throughput chemosensitivity testing of low-passage cancer cell lines can be used to prioritize agents for personalized chemotherapy. However, generating cell lines from primary cancers is difficult, because contaminating stromal cells overgrow the malignant cells. Experimental Design We produced a series of hypoxanthine phosphoribosyl transferase (hprt)-null immunodeficient mice. During growth of human cancers in these mice, hprt-null murine stromal cells replace their human counterparts. Results Pancreatic and ovarian cancers explanted from these mice were grown in selection media to produce pure human cancer cell lines. We screened one cell line with a 3,131-drug panel and identified seventy-seven FDA approved drugs with activity, including two novel drugs to which the cell line was uniquely sensitive. Xenografts of this carcinoma were selectively responsive to both drugs. Conclusion Chemotherapy can be personalized using patient-specific cell lines derived in biochemically selectable mice. PMID:23340293

  6. LISA Telescope Sensitivity Analysis

    NASA Technical Reports Server (NTRS)

    Waluschka, Eugene; Krebs, Carolyn (Technical Monitor)

    2001-01-01

    The results of a LISA telescope sensitivity analysis will be presented, The emphasis will be on the outgoing beam of the Dall-Kirkham' telescope and its far field phase patterns. The computed sensitivity analysis will include motions of the secondary with respect to the primary, changes in shape of the primary and secondary, effect of aberrations of the input laser beam and the effect the telescope thin film coatings on polarization. An end-to-end optical model will also be discussed.

  7. Wideband sensitivity analysis of plasmonic structures

    NASA Astrophysics Data System (ADS)

    Ahmed, Osman S.; Bakr, Mohamed H.; Li, Xun; Nomura, Tsuyoshi

    2013-03-01

    We propose an adjoint variable method (AVM) for efficient wideband sensitivity analysis of the dispersive plasmonic structures. Transmission Line Modeling (TLM) is exploited for calculation of the structure sensitivities. The theory is developed for general dispersive materials modeled by Drude or Lorentz model. Utilizing the dispersive AVM, sensitivities are calculated with respect to all the designable parameters regardless of their number using at most one extra simulation. This is significantly more efficient than the regular finite difference approaches whose computational overhead scales linearly with the number of design parameters. A Z-domain formulation is utilized to allow for the extension of the theory to a general material model. The theory has been successfully applied to a structure with teethshaped plasmonic resonator. The design variables are the shape parameters (widths and thicknesses) of these teeth. The results are compared to the accurate yet expensive finite difference approach and good agreement is achieved.

  8. Absolute sensitivity calibration of extreme ultraviolet photoresists.

    PubMed

    Naulleau, Patrick P; Gullikson, Eric M; Aquila, Andrew; George, Simi; Niakoula, Dimitra

    2008-07-21

    One of the major challenges facing the commercialization of extreme ultraviolet (EUV) lithography remains simultaneously achieving resist sensitivity, line-edge roughness, and resolution requirement. Sensitivity is of particular concern owing to its direct impact on source power requirements. Most current EUV exposure tools have been calibrated against a resist standard with the actual calibration of the standard resist dating back to EUV exposures at Sandia National Laboratories in the mid 1990s. Here we report on an independent sensitivity calibration of two baseline resists from the SEMATECH Berkeley MET tool performed at the Advanced Light Source Calibrations and Standards beamline. The results show the baseline resists to be approximately 1.9 times faster than previously thought based on calibration against the long standing resist standard. PMID:18648473

  9. Absolute sensitivity calibration of extreme ultraviolet photoresists

    SciTech Connect

    Jones, Juanita; Naulleau, Patrick P.; Gullikson, Eric M.; Aquila, Andrew; George, Simi; Niakoula, Dimitra

    2008-05-16

    One of the major challenges facing the commercialization of extreme ultraviolet (EUV) lithography remains simultaneously achieving resist sensitivity, line-edge roughness, and resolution requirement. Sensitivity is of particular concern owing to its direct impact on source power requirements. Most current EUV exposure tools have been calibrated against a resist standard with the actual calibration of the standard resist dating back to EUV exposures at Sandia National Laboratories in the mid 1990s. Here they report on an independent sensitivity calibration of two baseline resists from the SEMATECH Berkeley MET tool performed at the Advanced Light Source Calibrations and Standards beamline. The results show the baseline resists to be approximately 1.9 times faster than previously thought based on calibration against the long standing resist standard.

  10. A study of eigenvalue sensitivity for hydrodynamic stability operators

    NASA Technical Reports Server (NTRS)

    Schmid, Peter J.; Henningson, Dan S.; Khorrami, Mehdi R.; Malik, Mujeeb R.

    1993-01-01

    The eigenvalue sensitivity for hydrodynamic stability operators is investigated. Classical matrix perturbation techniques as well as the concept of epsilon-pseudospectra are applied to show that parts of the spectrum are highly sensitive to small perturbations. Applications are drawn from incompressible plane Couette flow, trailing line vortex flow, and compressible Blasius boundary-layer flow. Parameter studies indicate a monotonically increasing effect of the Reynolds number on the sensitivity. The phenomenon of eigenvalue sensitivity is due to the nonnormality of the operators and their discrete matrix analogs and may be associated with large transient growth of the corresponding initial value problem.

  11. The Bicycle Assembly Line Game

    ERIC Educational Resources Information Center

    Klotz, Dorothy

    2011-01-01

    "The Bicycle Assembly Line Game" is a team-based, in-class activity that helps students develop a basic understanding of continuously operating processes. Each team of 7-10 students selects one of seven prefigured bicycle assembly lines to operate. The lines are run in real-time, and the team that operates the line that yields the…

  12. The Bicycle Assembly Line Game

    ERIC Educational Resources Information Center

    Klotz, Dorothy

    2011-01-01

    "The Bicycle Assembly Line Game" is a team-based, in-class activity that helps students develop a basic understanding of continuously operating processes. Each team of 7-10 students selects one of seven prefigured bicycle assembly lines to operate. The lines are run in real-time, and the team that operates the line that yields the

  13. A Quantitative Transmission Line Experiment

    ERIC Educational Resources Information Center

    Johnston, D. C.; Silbernagel, B. G.

    1969-01-01

    Describes modifications of a commercially available strip-type transmission line, which makes possible reproducible measurements of standing waves on the line. Experimental data yield values for the characteristic impedance, phase velocity and line wavelength of radiation in the transmission line, and the dielectric constant of material in the…

  14. Temperature diagnostic line ratios of Fe XVII. [of Sun

    NASA Technical Reports Server (NTRS)

    Raymond, J. C.; Smith, B. W.

    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.

  15. Printed circuit dispersive transmission line

    DOEpatents

    Ikezi, H.; Lin-Liu, Y.R.; DeGrassie, J.S.

    1991-08-27

    A printed circuit dispersive transmission line structure is disclosed comprising an insulator, a ground plane formed on one surface of the insulator, a first transmission line formed on a second surface of the insulator, and a second transmission line also formed on the second surface of the insulator and of longer length than the first transmission line and periodically intersecting the first transmission line. In a preferred embodiment, the transmission line structure exhibits highly dispersive characteristics by designing the length of one of the transmission line between two adjacent periodic intersections to be longer than the other. 5 figures.

  16. Printed circuit dispersive transmission line

    DOEpatents

    Ikezi, Hiroyuki; Lin-Liu, Yuh-Ren; DeGrassie, John S.

    1991-01-01

    A printed circuit dispersive transmission line structure is disclosed comprising an insulator, a ground plane formed on one surface of the insulator, a first transmission line formed on a second surface of the insulator, and a second transmission line also formed on the second surface of the insulator and of longer length than the first transmission line and periodically intersecting the first transmission line. In a preferred embodiment, the transmission line structure exhibits highly dispersive characteristics by designing the length of one of the transmission line between two adjacent periodic intersections to be longer than the other.

  17. Coolant line hydrometer

    SciTech Connect

    Barber, M.D.; Kipp, W.G.

    1987-03-17

    This patent describes a hydrometer unit for connection in an automobile coolant flow line comprising: a tubular fitting adapted to be connected to the coolant flow line; a coolant receiving chamber means connected to the tubular fitting for receiving coolant from the tubular fitting; and indicating float elements contained within the coolant receiving chamber means and adapted to rise therein individually as a function of the specific gravity of the coolant. The coolant receiving chamber means includes a closure cap which when connected to the tubular fitting forms a coolant receiving chamber, retaining means for retaining the indicating float elements within the coolant receiving chamber, a viewing window member of a substantially clear material through which the float elements can be visually observed within the coolant receiving chamber means, and air venturi means located within the coolant receiving chamber means for automatically removing air which may collect within the coolant chamber means.

  18. Transmission line: design manual

    SciTech Connect

    Farr, H.H.

    1980-01-01

    The purpose of this manual is to outline the various requirements for, and the procedures to be followed in the design of power transmission lines by the Bureau of Reclamation, US Department of the Interior. Numerous design studies, which have been made on specific aspects of transmission line design, are included with explanations of their applications. Information is presented concerning such aspects as selection of type of construction, conductor sags and tensions, insulation, lightning protection, clearance patterns, galloping conductors, structure limitation and guying charts, and structure spotting. Structure design examples are limited to wood-pole construction. Interpretations of the National Electrical Safety Code and other codes are made as required. Some of the example problems were developed when the sixth edition of NESC was current, and are so noted; however, most examples use the 1977 edition of NESC.

  19. CRUCIBLE LINING METHOD

    DOEpatents

    Bone, W.H.; Schmidt, W.W.

    1958-11-01

    A method is presented for forming refractory liners in cylindrical reaction vessels used for the reductlon of uranium tetrafluoride to metallic uranium. A preliminary form, having positioning lugs attached thereto, is inserted into the reaction vessel and the refractory powder, usually CaO, is put in the annular space between the form and the inner wall of the reaction vessel. A jolting table is used to compact this charge of liner material ln place, and after thls has been done, the preliminary form is removed and the flnal form or plug is lnserted without disturbing the partially completed lining. The remainder of the lining charge is then introduced and compacted by jolting, after which the form is removed.

  20. Cryoresistive gas insulated line

    NASA Astrophysics Data System (ADS)

    Hidaka, K.; Matsumoto, S.; Kouno, T.

    An insulation strength of more than 16 kV mm -1 has been realized using nitrogen gas at 133 K and 0.4 MPa with the application of a.c. and impulse voltages. A cryoresistive gas insulated line (CRGIL) using nitrogen gas is proposed on the basis of the measured insulation strength. An efficient method for use of the cooling heat of liquefied natural gas is also proposed so that no refrigerator is required and the cost of cooling is reduced. The CRGIL has the advantages of having a large current carrying capacity, small power loss and small capacitance. Moreover, a given transmission capacity is achieved by a CRGIL whose rated voltage is about half that in a conventional gas insulated line.