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Sample records for wimp line sensitivity

  1. Development of bubble chambers with sensitivity to WIMPs

    NASA Astrophysics Data System (ADS)

    Bond, L.; Collar, J. I.; Ely, J.; Flake, M.; Hall, J.; Jordan, D.; Nakazawa, D.; Raskin, A.; Sonnenschein, A.; O'Sullivan, K.

    2005-01-01

    We constructed a small bubble chamber, with special features needed to search for WIMPs: long sensitive time periods, intrinsic insensitivity to minimum ionizing particles and target liquids with high sensitivity to both spin-dependent and -independent couplings. Stereo photography of bubbles allows rejection of events occuring at the chamber walls and discrimination of neutron backgrounds. The chamber can be operated with a variety of liquids, including CF 3Br, CF 3I, C 3F 8 and liquid xenon. A >60% live time fraction has been achieved and sensitivity to nuclear recoils demonstrated. Detectors of this type may be scalable to very large size at modest cost.

  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; 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.

  3. 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.

  4. Development of bubble chambers with sensitivity to WIMPs

    NASA Astrophysics Data System (ADS)

    Bond, L.; Collar, J. I.; Ely, J.; Flake, M.; Hall, J.; Jordan, D.; Nakazawa, D.; Raskin, A.; Sonnenschein, A.; Sullivan, K. 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 CF 3Br, CF 3I, and C 3F 8. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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 ? =8 GeV/c2 and ?=1.810-42 cm2 (with significant sensitivity for M ? >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 ? =8 GeV/c2 and ?=3.310-41 cm2.

  10. 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.

  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

    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.

  15. 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.

  16. Direct Detection Searches for WIMPs

    NASA Astrophysics Data System (ADS)

    Cabrera, Blas

    2014-03-01

    We have seen remarkable progress in direct detection searches for dark matter in the form of weakly interacting particles or WIMPs. Existing experiments using diverse technologies have set convincing limits for WIMPs under the spin independent interaction framework and have ruled out much of the phase space suggested by supersymmetric models. Liquid xenon experiments have provided the best limits for masses above 6 GeV/c2, with cryogenic detectors and bubble chambers setting the best limits for lighter mass WIMPs. In tension with the liquid xenon experiments are hints of signals and a claimed detection in the light WIMP mass sector. A number of theoretical ideas are consistent with light mass WIMPs, and a general approach, which probes all possible interactions between WIMPs and nucleons, stresses the need for a variety of target nuclei with the lowest possible thresholds to broadly cover the possibilities. As discussed extensively in P5 meetings, the down selection process for the second generation experiments (G2) will determine the progress over the next decade. As a community, we have asked the agencies for significant additional funds to be identified so that several G2 experiments can move forward and R&D on others continue. We need to continue this important search aggressively until we find WIMPs or reach the natural floor where the solar and atmospheric neutrinos become an irreducible background.

  17. 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.

  18. 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.

  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. COUPP, A Heavy-Liquid Bubble Chamber for WIMP Detection

    NASA Astrophysics Data System (ADS)

    Bolte, J.; Collar, J. I.; Crisler, M.; Holmgren, D.; Nakazawa, D.; Odom, B.; O'Sullivan, K.; Plunkett, R.; Ramberg, E.; Raskin, A.; Sonnenschein, A.; Vieira, J.

    2005-04-01

    The capabilities and reach of the first phase of COUPP (the Chicago Observatory for Underground Particle Physics) are described. During this first phase of the experiment a 2 kg CF3I bubble chamber sensitive to WIMPs will be operated at the ~300 m.w.e. of the Minos-near gallery at FNAL. Prospects for larger devices are briefly discussed.

  4. 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.

  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. 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.

  7. Dark Matter: Looking for WIMPs in the Galactic Halo

    NASA Astrophysics Data System (ADS)

    Akerib, Daniel S.

    2006-07-01

    Overwhelming observational evidence indicates that most of the matter in the Universe consists of non-baryonic dark matter. One possibility is that the dark matter is Weakly-Interacting Massive Particles (WIMPs) that were produced in the early Universe. These relics could comprise the Milky Way's dark halo and provide evidence for new particle physics, such as Supersymmetry. After reviewing some of the evidence for dark matter and the WIMP hypothesis, I will describe the strategy for searching for WIMPs, along with a survey of the current status and outlook. In particular, dark matter searches have begun to explore the region of parameter space where SUSY particles could provide dark matter candidates. I will also mention some of the recent theoretical work on dark matter candidates which is being done in anticipation of the turn-on of the LHC and as part of the active R&D on the ILC. Finally, a vigorous detector development program promises significant advances in WIMP sensitivity in the coming years.

  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. Improved Detection Sensitivity of Line-Scanning Optical Coherence Microscopy

    PubMed Central

    Chen, Yu; Huang, Shu-Wei; Zhou, Chao; Potsaid, Benjamin; Fujimoto, James G.

    2012-01-01

    Optical coherence microscopy (OCM) is a promising technology for high-resolution cellular-level imaging in human tissues. Line-scanning OCM is a new form of OCM that utilizes line-field illumination for parallel detection. In this study, we demonstrate improved detection sensitivity by using an achromatic design for line-field generation. This system operates at 830-nm wavelength with 82-nm bandwidth. The measured axial resolution is 3.9 ?m in air (corresponding to ~2.9 ?m in tissue), and the transverse resolutions are 2.1 ?m along the line-field illumination direction and 1.7 ?m perpendicular to line illumination direction. The measured sensitivity is 98 dB with 25 line averages, resulting in an imaging speed of ~2 frames/s (516 lines/s). Real-time, cellular-level imaging of scattering tissues is demonstrated using human-colon specimens. PMID:22685379

  10. A sensitive line search in circumstellar envelopes

    NASA Astrophysics Data System (ADS)

    Nguyen-Q-Rieu; Deguchi, S.; Izumiura, H.; Kaifu, N.; Ohishi, M.; Suzuki, H.; Ukita, N.

    A molecular line search in the range between 85 and 89 GHz has been performed in the circumstellar envelopes of 11 evolved stars. Emissions of 29SiO J=2-1,28SiO J=2-1, HCN J=1-0, H13CN J=1-0, HC5 N J=33-32, HCO+ J=1-0 transitions and other transitions of C2 H, C4 H, and C3 N have been observed in 11 stars. We have detected the ground state 29SiO J=2-1 maser in several stars. We have also detected HCN emission in VY CMa. A narrow H13CN spike feature near the central velocity has been found in the spectrum of CRL 2688.

  11. 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.

  12. 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...

  13. Investigation of Magnetically Sensitive FeH Lines

    NASA Astrophysics Data System (ADS)

    Wende, S.; Reiners, A.; Seifahrt, A.; Shulyak, D.; Kochukhov, O.

    2011-12-01

    M-type stars exhibit strong magnetic fields towards decreasing effective temperatures. The measurement of these fields is complicated due to missing indicators. Molecular FeH lines provide an excellent means to determine magnetic field strengths from the Zeeman broadening of magnetically sensitive lines. Our aim is the investigation of possible dependencies of the amount of sensitivity to magnetic fields from rotational quantum number, branch, and the projection of the total angular momentum onto the internuclear axis (?). We also compare results from computations with those from observations. We use high resolution CRIRES spectra of the two M dwarfs GJ1002 (M5.5 inactive) and GJ1224 (M4.5 active). Individual lines are fitted by Gaussians and the obtained line depths and widths from the active and inactive star can be compared with each other. In this way, magnetically sensitive lines can be detected. For test purposes, we do the same with computed spectra of FeH. One with zero magnetic field and the other with a 2 kG magnetic field vector used in the disc integration (i.e. pure radial at the disc center). We found, in agreement with theory, that lines with high ? show strong sensitivity to magnetic fields. No obvious correlation with branch or J was found, which was also expected for lines formed in intermediate Hund's case. The computations agreed in general well with the observations, but in many cases the individual splitting of certain lines can be very different to observations.

  14. 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

  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¯), 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.

  16. 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 m? lesssim 165 GeV. These are to be compared to previous fits that concluded only much lighter dark matter annihilating into b, ?, 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.

  17. WIMPs at the galactic center

    DOE PAGESBeta

    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,moreZZ, 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 ? m? ? 165 GeV. These are to be compared to previous fits that concluded only much lighter dark matter annihilating into b, ?, 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

  18. WIMPs at the galactic center

    SciTech Connect

    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, 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 ? m? ? 165 GeV. These are to be compared to previous fits that concluded only much lighter dark matter annihilating into b, ?, 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.

  19. 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.

  20. Precise relic WIMP abundance and its impact on searches for dark matter annihilation

    NASA Astrophysics Data System (ADS)

    Steigman, Gary; Dasgupta, Basudeb; Beacom, John F.

    2012-07-01

    If dark matter (DM) is a weakly interacting massive particle (WIMP) that is a thermal relic of the early Universe, then its total self-annihilation cross section is revealed by its present-day mass density. This result for a generic WIMP is usually stated as ??v??310-26cm3s-1, with unspecified uncertainty, and taken to be independent of WIMP mass. Recent searches for annihilation products of DM annihilation have just reached the sensitivity to exclude this canonical cross section for 100% branching ratio to certain final states and small WIMP masses. The ultimate goal is to probe all kinematically allowed final states as a function of mass and, if all states are adequately excluded, set a lower limit to the WIMP mass. Probing the low-mass region is further motivated due to recent hints for a light WIMP in direct and indirect searches. We revisit the thermal relic abundance calculation for a generic WIMP and show that the required cross section can be calculated precisely. It varies significantly with mass at masses below 10 GeV, reaching a maximum of 5.210-26cm3s-1 at m?0.3GeV, and is 2.210-26cm3s-1 with feeble mass dependence for masses above 10 GeV. These results, which differ significantly from the canonical value and have not been taken into account in searches for annihilation products from generic WIMPs, have a noticeable impact on the interpretation of present limits from Fermi-LAT and WMAP+ACT.

  1. 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 ~ ? log(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 ofmorethis 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 ? ~ 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. 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

  2. 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 ~ ? log(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. 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 ? ~ 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. 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.

  3. 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.

  4. 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.

  5. 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)

  6. Lines of Fe XII sensitive to coronal electron density

    SciTech Connect

    Feldman, U.; Cohen, L.; Doschek, G.A.

    1983-10-15

    Lines of Fe XII sensitive to coronal electron density are discussed. The lines appear in solar spectra obtained by the Naval Research Laboratory (NRL) slit spectrograph flown on Skylab. These lines are due to transitions between levels of the 3s/sup 2/3p/sup 3/ configuration and fall at the wavelengths 1242.03 A, 1349.38 A, 2169.71 A,2405.71 A, and 2565.99 A. We show that the line at 2169.03 A is severely blended by a line of Ni II at heights less than 12'' outside the solar limb. Above 12'' the lines at 2169.03 and 2405.71 A are apparently unblended and can be used to derive electron densities. We obtain an average coronal electron pressure of approx.6 x 10/sup 14/ cm/sup -3/ K. However, the emitting path lengths of the Fe XII lines, deduced using the electron densities and absolute intensities, are unrealistically large. The reason for this difficulty is unclear.

  7. In-line phase sensitive amplifier based on PPLN waveguides.

    PubMed

    Umeki, Takeshi; Asobe, Masaki; Takenouchi, Hirokazu

    2013-05-20

    We demonstrate a ?(2)-based in-line PSA with a carrier-recovery and phase-locking system for a phase shift keying (PSK) signal. By doubling the signal phase using a wavelength conversion technique, the carrier was recovered from a PSK signal. The carrier phase was synchronized to a local oscillator using optical injection locking. Phase sensitive amplification with a wide phase sensitive dynamic range of 20 dB was achieved using degenerate parametric amplification in a periodically poled LiNbO(3) (PPLN) waveguide. The phase regeneration effect was examined for a degraded signal by means of constellation analyses and bit-error rate measurements. The in-line PSA also operated successfully as a repeater amplifier in a 160 km fiber link without a power penalty. Finally, we demonstrate the regeneration of non-linear impairments induced by fiber non-linearity. PMID:23736428

  8. 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.

  9. 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

  10. 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.; Cerdeo, 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.

  11. 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.

  12. 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 1.81044 and 1.181041 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.

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

    SciTech Connect

    Profumo, Stefano; Ubaldi, Lorenzo; Sigurdson, Kris E-mail: krs@physics.ubc.ca

    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.

  14. 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.

  15. Low-Background Detector Development at EFI: WIMPs, Axions, Neutrinos, and Other Sneaky Beasts

    SciTech Connect

    Collar, Juan

    2003-12-03

    I will review the status of several experimental efforts at University of Chicago aiming at the detection of astrophysical exotica: a bubble chamber using CF3I and CF3Br dedicated to WIMP searches, the CAST experiment at CERN (looking for solar axions) and R&D towards a detector sensitive to very low-energy nuclear recoils from coherent neutrino scattering.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. Alignment Sensitivity Study of the St. ANA Beam Line

    NASA Astrophysics Data System (ADS)

    Gervais, Michelle; Couder, Manoel; Jung, Hyo Soon; Setoodehnia, Kiana

    2014-09-01

    The St. ANA (STable Accelerator for Nuclear Astrophysics) accelerator is being prepared for use with the St. George recoil mass separator. The accelerator is in working condition for use in direct kinematic experiments but the St. George separator works with inverse kinematics and requires a highly controlled beam restricted by severe position and divergence parameters that are not achieved at the present time. A systematic sensitivity study was conducted using a simulation of the beam line in order to assess the impact of a misalignment in each optical element or in the beam itself. Tests were done with the beam to analyze how the beam behaves at various points in the line and to compare this data with simulation results to determine possible causes of misalignment. The results of these tests and simulations are that the beam characteristics are now better understood and the possible causes of the limitations have been narrowed down. The St. ANA (STable Accelerator for Nuclear Astrophysics) accelerator is being prepared for use with the St. George recoil mass separator. The accelerator is in working condition for use in direct kinematic experiments but the St. George separator works with inverse kinematics and requires a highly controlled beam restricted by severe position and divergence parameters that are not achieved at the present time. A systematic sensitivity study was conducted using a simulation of the beam line in order to assess the impact of a misalignment in each optical element or in the beam itself. Tests were done with the beam to analyze how the beam behaves at various points in the line and to compare this data with simulation results to determine possible causes of misalignment. The results of these tests and simulations are that the beam characteristics are now better understood and the possible causes of the limitations have been narrowed down. Project advisor

  1. 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.

  2. Tracking differential interference contrast diffraction line images with nanometre sensitivity.

    PubMed

    Danuser, G; Tran, P T; Salmon, E D

    2000-04-01

    This paper presents a computer vision framework for detecting and tracking diffraction images of linear structures in differential interference contrast (DIC) microscopy. The tracker can resolve image displacements of 1/10 of a pixel despite the weak and orientation-dependent contrast in DIC, as well as the variable blur in such image data caused by vertical specimen movement. In our high numerical aperture, high magnification microscope set-up, this resolution corresponds to 5 nm in object space. In video DIC similar resolution has been reported hitherto only for rotationally symmetric targets such as bead images. The tracker was developed for measuring deflections of clamped microtubules with a freely moving second end. By analysing the thermal fluctuations of such microtubules it was possible to derive their elasticity. The paper describes a filtering scheme for the detection and localization of DIC diffraction line images which represent loci of microtubules. For tracking the movements of the extracted lines we adopted the sum of squared (brightness) differences algorithm from computer vision. The analysis of the fluctuation measurements demonstrates the high sensitivity of this tracking technique in quantifying positional and orientational changes. We derived that the theoretical limit in tracking displacements of such diffraction line images is 1.25 nm, four times below the experimentally verified sensitivity. This indicates that the proposed tracker is still suboptimal. Nevertheless, the tracking precision was sufficient to reveal subtle deviations in the distribution of microtubule deflection from free diffusion. They were induced by pivotal points and multiple positions of relaxation. Also, the results suggest that there were defects in the polymer structure which caused very small but significant bends in the microtubule axis. PMID:10781207

  3. 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.

  4. New limits on spin-independent and spin-dependent couplings of low-mass WIMP dark matter with a germanium detector at a threshold of 220 eV

    SciTech Connect

    Lin, S. T.; Li, H. B.; Lin, S. K.; Wong, H. T.; Lin, C. W.; Lin, F. K.; Wang, J. J.; Wang, Y. R.; Wu, S. C.; Li, X.; Fang, B. B.; He, D.; Yue, Q.; Deniz, M.; Li, J.; Ruan, X. C.; Zhou, Z. Y.; Singh, V.; Soma, A. K.

    2009-03-15

    An energy threshold of (220{+-}10) eV was achieved at an efficiency of 50% with a four-channel ultralow-energy germanium detector, each with an active mass of 5 g. This provides a unique probe to weakly interacting massive particles (WIMP) dark matter with mass below 10 GeV. With a data acquisition live time of 0.338 kg-day at the Kuo-Sheng Laboratory, constraints on WIMPs in the galactic halo were derived. The limits improve over previous results on both spin-independent WIMP-nucleon and spin-dependent WIMP-neutron cross-sections for WIMP mass between 3 and 6 GeV. Sensitivities for full-scale experiments are projected. This detector technique makes the unexplored sub-keV energy window accessible for new neutrino and dark matter experiments.

  5. 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.

  6. 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.

  7. 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.; Cebrin, S.; Dafni, T.; Garca, J. A.; Gmez, H.; Gonzlez-Diaz, D.; Irastorza, I. G.; Lagraba, A.; Luzn, G.; Peir, A.; Rodrguez, 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.

  8. 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.

  9. 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.

  10. 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.

  11. Gefitinib (IRESSA) sensitive lung cancer cell lines show phosphorylation of Akt without ligand stimulation

    PubMed Central

    Noro, Rintaro; Gemma, Akihiko; Kosaihira, Seiji; Kokubo, Yutaka; Chen, Mingwei; Seike, Masahiro; Kataoka, Kiyoko; Matsuda, Kuniko; Okano, Tetsuya; Minegishi, Yuji; Yoshimura, Akinobu; Kudoh, Shoji

    2006-01-01

    Background Phase III trials evaluating the efficacy of gefitinib (IRESSA) in non-small cell lung cancer (NSCLC) lend support to the need for improved patient selection in terms of gefitinib use. Mutation of the epidermal growth factor receptor (EGFR) gene is reported to be associated with clinical responsiveness to gefitinib. However, gefitinib-sensitive and prolonged stable-disease-defined tumors without EGFR gene mutation have also been reported. Methods To identify other key factors involved in gefitinib sensitivity, we analyzed the protein expression of molecules within the EGFR family, PI3K-Akt and Ras/MEK/Erk pathways and examined the sensitivity to gefitinib using the MTT cell proliferation assay in 23 lung cancer cell lines. Results We identified one highly sensitive cell line (PC9), eight cell lines displaying intermediate-sensitivity, and 14 resistant cell lines. Only PC9 and PC14 (intermediate-sensitivity) displayed an EGFR gene mutation including amplification. Eight out of the nine cell lines showing sensitivity had Akt phosphorylation without ligand stimulation, while only three out of the 14 resistant lines displayed this characteristic (P = 0.0059). Furthermore, the ratio of phosphor-Akt/total Akt in sensitive cells was higher than that observed in resistant cells (P = 0.0016). Akt phosphorylation was partially inhibited by gefitinib in all sensitive cell lines. Conclusion These results suggest that Akt phosphorylation without ligand stimulation may play a key signaling role in gefitinib sensitivity, especially intermediate-sensitivity. In addition, expression analyses of the EGFR family, EGFR gene mutation, and FISH (fluorescence in situ hybridization) analyses showed that the phosphorylated state of EGFR and Akt might be a useful clinical marker of Akt activation without ligand stimulation, in addition to EGFR gene mutation and amplification, particularly in adenocarcinomas. PMID:17150102

  12. Directional recoil rate for direct detection of WIMPs

    NASA Astrophysics Data System (ADS)

    Alenazi, Moqbil; Gondolo, Paolo

    2007-10-01

    The problem of directional direct detection of weakly interacting massive particles (WIMPs) dark matter (DM) is investigated. We compute, analytically and numerically, the directional differential recoil rate dRd? of recoiled target nuclei hit by WIMPs in direct detection experiments in terms of the angle ?, which is the angle between the reference direction and the recoil direction. While the analytic method is for fixed reference direction and Gaussian distribution of WIMPs, the numeric method is a general method. The two methods give the same results. We apply the numeric method to various Maxwellian distributions including; a stream of WIMPs, the standard dark halo, streams of WIMPs from Sikivie's late-infall (SLI) halo model, and streams with anisotropic velocity distributions. We show the results as distributions of the nuclei's directional differential recoil rate dRd? as a function of ?. We introduce a `folded' directional differential recoil rate dRd|?| to overcome the difficulty of head-tail discrimination in some WIMP's direct detectors. We conclude that dRd|?| can be helpful in recognizing cases of anisotropic streams and isotropic standard dark halo but not in the case of SLI streams.

  13. 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

  14. 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...

  15. 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.

  16. 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.

  17. Hapten-specific T cell lines mediating delayed hypersensitivity to contact-sensitizing agents

    PubMed Central

    1982-01-01

    Continuous cultures of T cells from the lymph nodes of mice sensitized to the contact sensitizers 4-ethoxymethylene-2-phenyl oxazolone or picryl chloride have been established. For continuous proliferation, the lines required specific antigen, syngeneic antigen-presenting cells, and growth factors from the supernatant of concanavalin-A- stimulated lymphoid cultures. Cells from the lines showed antigen specificity and major histocompatibility complex restriction in proliferation assays and in delayed hypersensitivity. They could mediate delayed hypersensitivity to the sensitizer presented as a reactive hapten or coupled to keyhold limpet hemocyanin. PMID:6177826

  18. Hapten-specific T cell lines mediating delayed hypersensitivity to contact-sensitizing agents.

    PubMed

    Thomas, W R; Mottram, P L; Miller, J F

    1982-07-01

    Continuous cultures of T cells from the lymph nodes of mice sensitized to the contact sensitizers 4-ethoxymethylene-2-phenyl oxazolone or picryl chloride have been established. For continuous proliferation, the lines required specific antigen, syngeneic antigen-presenting cells, and growth factors from the supernatant of concanavalin-A-stimulated lymphoid cultures. Cells from the lines showed antigen specificity and major histocompatibility complex restriction in proliferation assays and in delayed hypersensitivity. They could mediate delayed hypersensitivity to the sensitizer presented as a reactive hapten or coupled to keyhold limpet hemocyanin. PMID:6177826

  19. 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.

  20. 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.

  1. Status of CDMS search for dark matter WIMPs

    NASA Astrophysics Data System (ADS)

    Cabrera, B.; Abusaidi, R.; Akerib, D. S.; Barnes, P. D.; Bauer, D. A.; Bolozdynya, A.; Brink, P. L.; Bunker, R.; Caldwell, D. O.; Castle, J. P.; Chang, C.; Clarke, R. M.; Colling, P.; Cristler, M. B.; Cummings, A.; da Silva, A.; Davies, A. K.; Dixon, R.; Dougherty, B. L.; Driscoll, D.; Eichblatt, S.; Emes, J.; Gaitskell, R. J.; Golwala, S. R.; Hale, D.; Haller, E. E.; Holmgren, D.; Hellmig, J.; Huber, M. E.; Irwin, K. D.; Jochum, J.; Lipschultz, F. P.; Lu, A.; Maloney, C.; Mandic, V.; Martinis, J. M.; Meunier, P.; Nam, S. W.; Nelson, H.; Neuhauser, B.; Penn, M. J.; Perera, T. A.; Perillo Isaac, M. C.; Pritychenko, B.; Ross, R. R.; Saab, T.; Sadoulet, B.; Sander, J.; Seitz, D. N.; Shestople, P.; Shutt, T.; Smith, A.; Smith, G. W.; Schnee, R. W.; Sonnenschein, A. H.; Spadafora, A. L.; Stockwell, W.; Taylor, J. D.; White, S.; Yellin, S.; Young, B. A.

    2001-10-01

    We report on the latest results from the CDMS (cryogenic dark matter search) experiment. The experiment uses superconducting particle detectors, operated below 100 mK, to search for dark matter in the form of weakly interacting massive elementary particles or WIMPs. These detectors are either Si or Ge crystals, where the electron-hole production and the phonon production are measured for each event, allowing the discrimination of electron recoils (most backgrounds due to gammas and betas) from nuclear recoils (due to WIMPs and neutrons). We have recently reported new limits from the Stanford shallow site experiment (CDMS-I) which explore supersymmetric models where the lightest supersymmetric particle is often an excellent WIMP candidate. We will also report on the Soudan deep site facility for the CDMS-II experiment which is under construction, and on the status of the CDMS-II detector fabrication. .

  2. 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}.

  3. Increased sensitivity of a xeroderma pigmentosum lymphoblastoid cell line to serum deprivation in vitro.

    PubMed

    Lambert, W C; Lambert, M W

    1983-08-01

    Two human lymphoblastoid cell lines, GM 1989, from a normal individual, and GM 2345, from a patient with xeroderma pigmentosum, complementation group A, were selected for comparative biochemical studies because they both grow rapidly and at virtually identical rates in sealed flasks in RPMI 1640 medium buffered to physiological pH with HEPES buffer, supplemented with 12% heat-inactivated fetal bovine serum. Although the two cell lines showed no difference in growth parameters assayed by standard methods, further studies showed that the GM 2345 cell line was markedly more sensitive to diminution of the serum concentration of the culture medium than was the normal cell line. These results indicate that lymphoblastoid cell lines, particularly those from individuals with certain genetic or metabolic diseases, may be growing under marginal or limiting circumstances, different from those of control cell lines, which are not detected by standard techniques used to monitor mammalian cell cultures. PMID:6885101

  4. Dark matter spin-dependent limits for WIMP interactions on 19F by PICASSO

    NASA Astrophysics Data System (ADS)

    Beltran, Berta; Picasso Collaboration

    2010-01-01

    The PICASSO experiment at SNOLAB uses super-heated C4F10 droplets suspended in a gel as a target sensitive to WIMP-proton spin-dependent elastic scattering. The phase II setup has been improved substantially in sensitivity by using an array of 32 detectors with an active mass of ~65 g each and largely reduced background. First results are presented for a subset of two detectors with target masses of 19F of 65 g and 69 g respectively and a total exposure of 13.75 0.48 kgd. No dark matter signal was found and for WIMP masses around 24 GeV/c2 new limits have been obtained on the spin-dependent cross section on 19F of ?F = 13.9 pb (90% C.L.) which can be converted into cross section limits on protons and neutrons of ?p = 0.15 pb and ?n = 2.45 pb respectively (90% C.L). The obtained limits on protons restrict recent interpretations of the DAMA/LIBRA annual modulations in terms of spin-dependent interactions.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. Magnetic fluid hyperthermia enhances cytotoxicity of bortezomib in sensitive and resistant cancer cell lines.

    PubMed

    Alvarez-Berros, Merlis P; Castillo, Amalchi; Rinaldi, Carlos; Torres-Lugo, Madeline

    2014-01-01

    The proteasome inhibitor bortezomib (BZ) has shown promising results in some types of cancer, but in others it has had minimal activity. Recent studies have reported enhanced efficacy of BZ when combined with hyperthermia. However, the use of magnetic nanoparticles to induce hyperthermia in combination with BZ has not been reported. This novel hyperthermia modality has shown better potentiation of chemotherapeutics over other types of hyperthermia. We hypothesized that inducing hyperthermia via magnetic nanoparticles (MFH) would enhance the cytotoxicity of BZ in BZ-sensitive and BZ-resistant cancer cells more effectively than hyperthermia using a hot water bath (HWH). Studies were conducted using BZ in combination with MFH in two BZ-sensitive cell lines (MDA-MB-468, Caco-2), and one BZ-resistant cell line (A2780) at two different conditions, ie, 43C for 30 minutes and 45C for 30 minutes. These experiments were compared with combined application of HWH and BZ. The results indicate enhanced potentiation between hyperthermic treatment and BZ. MFH combined with BZ induced cytotoxicity in sensitive and resistant cell lines to a greater extent than HWH under the same treatment conditions. The observation that MFH sensitizes BZ-resistant cell lines makes this approach a potentially effective anticancer therapy platform. PMID:24379665

  11. Detection of residual krypton in xenon gas for WIMP dark matter searches

    NASA Astrophysics Data System (ADS)

    Dobi, Attila

    2011-04-01

    The next generation of WIMP dark matter searches using liquid xenon as a target medium will require unprecedented rejection of residual krypton contamination. Krypton contains the beta emitting isotope 85 Kr, with a relative abundance of about 10-11 (85 Kr /nat Kr), and this beta decay can be an important source of background for these experiments. Krypton is typically present in commercially produced xenon at the level of tens of parts-per-billion, about four orders of magnitude too large for present day dark matter experiments such as XENON, LUX, and XMASS. Additional processing via gas chromatography and distillation are used to separate krypton from xenon, but measuring the remaining krypton level at the part-per-trillion (ppt) level is challenging. Recently we have developed a highly sensitive and simple technique to measure residual krypton contamination in xenon gas using an RGA mass spectrometer and a liquid nitrogen cold trap. We describe here the results of our calibration experiments to determine the ultimate limit of detection of the method, and we discuss the implications for the next generation of WIMP dark matter experiments. Supported by the National Science Foundation.

  12. DarkSide-50: A WIMP Search with a Two-phase Argon TPC

    NASA Astrophysics Data System (ADS)

    Meyers, P. D.; Agnes, P.; Alton, D.; Arisaka, K.; Back, H. O.; Baldin, B.; Biery, K.; Bonfini, G.; Bossa, M.; Brigatti, A.; Brodsky, J.; Budano, F.; Cadonati, L.; Calaprice, F.; Canci, N.; Candela, A.; Cao, H.; Cariello, M.; Cavalcante, P.; Chavarria, A.; Chepurnov, A.; Cocco, A. G.; Crippa, L.; DAngelo, D.; D'Incecco, M.; Davini, S.; De Deo, M.; Derbin, A.; Di Eusanio, F.; Di Pietro, G.; Edkins, E.; Empl, A.; Fan, A.; Fiorillo, G.; Fomenko, K.; Forster, G.; Franco, D.; Gabriele, F.; Galbiati, C.; Goretti, A.; Grandi, L.; Gromov, M.; Guan, M.; Guardincerri, Y.; Hackett, B.; Herner, K.; Humble, P.; Hungerford, E. V.; Ianni, Al.; Ianni, An.; Joliet, C.; Keeter, K.; Kendziora, C.; Kidner, S.; Kobychev, V.; Koh, G.; Korablev, D.; Korga, G.; Kurlej, A.; Li, P.; Loer, B.; Lombardi, P.; Love, C.; Ludhova, L.; Luitz, S.; Ma, Y.; Machulin, I.; Mandarano, A.; Mari, S.; Maricic, J.; Martoff, C. J.; Meregaglia, A.; Meroni, E.; Meyers, P. D.; Milincic, R.; Montanari, D.; Montuschi, M.; Monzani, M. E.; Mosteiro, P.; Mount, B.; Muratova, V.; Musico, P.; Nelson, A.; Okounkova, M.; Orsini, M.; Ortica, F.; Pagani, L.; Pallavicini, M.; Pantic, E.; Papp, L.; Parmeggiano, S.; Parsells, R.; Pelczar, K.; Pelliccia, N.; Perasso, S.; Perfetto, F.; Pocar, A.; Pordes, S.; Qian, H.; Randle, K.; Ranucci, G.; Razeto, A.; Reinhold, B.; Romani, A.; Rossi, B.; Rossi, N.; Rountree, S. D.; Sablone, D.; Saggese, P.; Saldanha, R.; Sands, W.; Segreto, E.; Semenov, D.; Shields, E.; Skorokhvatov, M.; Smirnov, O.; Sotnikov, A.; Suvarov, Y.; Tartaglia, R.; Tatarowicz, J.; Testera, G.; Tonazzo, A.; Unzhakov, E.; Vogelaar, R. B.; Wada, M.; Wang, H.; Wang, Y.; Watson, A.; Westerdale, R.; Wojcik, M.; Wright, A.; Xu, J.; Yang, C.; Yoo, J.; Zavatarelli, S.; Zuzel, G.

    DarkSide-50 is a two phase argon TPC for direct dark matter detection which is installed at the Gran Sasso underground laboratory, Italy. DarkSide-50 has a 50-kg active volume and will make use of underground argon low in 39Ar. The TPC is installed inside an active neutron veto made with boron-loaded high radiopurity liquid scintillator. The neutron veto is installed inside a 1000 m3 water Cherenkov muon veto. The DarkSide-50 TPC and cryostat are assembled in two radon-free clean rooms to reduce radioactive contaminants. The overall design aims for a background free exposure after selection cuts are applied. The expected sensitivity for WIMP-nucleon cross section is of the order of 10-45 cm2 for WIMP masses around 100 GeV/c2. The commissioning and performance of the detector are described. Details of the low-radioactivity underground argon and other unique features of the projects are reported.

  13. 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.; Lafrenire, 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 ?pSD=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 ?pSI=1.4110-4 pb (90% C.L.) are excluded.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Intoxicating effects of lorazepam and barbital in rat lines selected for differential sensitivity to ethanol.

    PubMed

    Hellevuo, K; Kiianmaa, K; Juhakoski, A; Kim, C

    1987-01-01

    The motor impairing effects and plasma concentrations of barbital and lorazepam were studied in the alcohol tolerant (AT) and alcohol non-tolerant (ANT) rat lines developed for low and high sensitivity to motor impairment from ethanol. The mixed (M) line, from which the AT and ANT rats were derived, was also included in the study. Like ethanol, barbital and lorazepam impaired the performance of the ANT rats more than that of the AT rats. The motor performance of the M rats was relatively more impaired after barbital than after lorazepam administration at the same dose used in the AT and ANT rats. At the two latter time points (2.5 and 3.5 h) the sensitive ANT rats had significantly higher serum barbital concentrations than the AT rats. The serum barbital concentrations of the AT and ANT rats did not differ, however, at the two first time points (0.5 and 1.5 h) of the tilting plane tests, although the ANT rats were significantly more intoxicated. The concentrations of lorazepam in plasma do not explain the differential motor impairment either, since the sensitive ANT rats had lower plasma concentrations than the insensitive AT rats. The results, thus, suggest that the selection involved in the development of the AT and ANT lines has not been specific for ethanol. The results also support the idea that ethanol, barbiturates and benzodiazepines have some modes of action in common. PMID:3104948

  1. 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

  2. [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

  3. Isolation and preliminary characterization of u. v. -sensitive mutants from the human cell line EUE

    SciTech Connect

    Fiorio, R.; Frosina, G.; Abbondandolo, A.

    1983-01-01

    Five u.v. light-sensitive clones were isolated in the EUE cell line by means of a modified form of the original 5-bromodeoxyuridine (BUdR)-light method worked out by Puck and Kao for the isolation of nutritional mutants. A cell population was mutagenized with ethylmethanesulfonate. After the expression time, cells were u.v.-irradiated and incubated with BUdR to label excision patches in repair proficient cells. A subsequent irradiation with black light caused DNA strand breakage in BUdR-substituted cells. During BUdR treatment, hydroxyurea and a fluorochrome (Hoechst 33258) were added to possibly enhance the analogue incorporation into DNA and to increase the photolability of BUdR containing sequences, respectively. Out of 192 colonies selected with this method, 38 were isolated and tested for their u.v.-sensitivity. Five of them showed significant, reproducible differences with respect to the parental line. As a partial characterization, the five u.v.-sensitive clones were assayed for unscheduled (/sup 3/H)thymidine incorporation after exposure to u.v. light, by means of liquid scintillation spectrometry and autoradiography. In all clones. DNA repair synthesis was significantly decreased with respect to the parental line.

  4. 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

  5. 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.

  6. 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

  7. 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

  8. Comparative sensitivity of four different cell lines for the isolation of Coxiella burnetii.

    PubMed

    Lockhart, Michelle G; Islam, Aminul; Fenwick, Stan G; Graves, Stephen R; Stenos, John

    2012-09-01

    Coxiella burnetii is an obligate intracellular bacterium that causes the disease Q-fever. This is usually diagnosed by serology (immunofluorescence assay) and/or PCR detection of C.burnetii DNA. However, neither of these methods can determine the viability of the bacterium. Four different cell lines were compared for their ability to amplify very low numbers of viable C.burnetii. Two different isolates of C.burnetii were used. For the Henzerling isolate, DH82 (dog macrophage) cells were the most sensitive with an ID (50) (dose required to infect 50% of cell cultures) of 14.6 bacterial copies. For the Arandale isolate, Vero (monkey epithelial) cells were the most sensitive with an ID (50) of less than one bacterium in a 100-?L inoculum. The Vero cell line appeared highly useful as vacuoles could be seen microscopically in unstained infected cells. The findings of this study favour the use of Vero and DH82 tissue culture cell lines for isolation and growth of C.burnetii in vitro. The other cell lines, XTC-2 and L929, were less suitable. PMID:22681323

  9. Heat shock protein expression in testis and bladder cancer cell lines exhibiting differential sensitivity to heat.

    PubMed Central

    Richards, E. H.; Hickman, J. A.; Masters, J. R.

    1995-01-01

    Testis cancer cells are more sensitive than bladder and most other cancer cells to chemotherapeutic drugs both in the clinic and in vitro. In this study we show that they are also more sensitive than bladder cancer cells to heat. Since heat and drug sensitivity may be related to the ability of a cell to mount a stress response, constitutive and induced levels of heat shock proteins (HSPs) in three testis and three bladder human cancer cell lines were measured using Western blotting and scanning densitometry. No correlation between constitutive levels of HSP 90 or HSP 73/72 and cellular heat sensitivity was found. However, HSP 27 levels were much lower in the testis tumour cells, suggesting that low HSP 27 expression might contribute to heat sensitivity. Protein synthesis studies using [35S]methionine indicated that, for the same heat shocks, the kinetics of synthesis and decay of HSP 90 and HSP 73/72 in 833K (the most heat sensitive testis cells) was similar to or greater than that in HT1376 (the most heat-resistant bladder cells). Both 833K and HT1376 developed thermotolerance, and this followed an increase in synthesis of HSPs. These results indicate that, although there are differences in the constitutive levels of HSPs between testis and bladder cancer cells, both cell types are capable of mounting an induced heat shock response and can develop a similar degree of thermotolerance. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:7669571

  10. 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

  11. Differential sensitivity of ovarian carcinoma cell lines to apoptosis induced by the IMPDH inhibitor benzamide riboside.

    PubMed

    Hunkov, L; Bies, J; Sedlk, J; Duraj, J; Jakubkov, J; Takcsov, X; Novotn, L; Chorvth, B

    2000-01-01

    The differential sensitivity of examined human ovarian carcinoma cell lines (CH1, A-2780 and SKOV-3) to the IMPDH inhibitor, benzamide riboside (BR), was demonstrated with the aid of MTT assay. Present data show that all three examined ovarian carcinoma cell lines were sensitive to the cytotoxic effects of BR in the order of sensitivity CH1, SKOV-3, A-2780, (IC50 = 2.8, 4.0 and 7.4 microM, respectively). Although the IC50 of SKOV-3 cells was similar to that previously determined by others, more than 20% of SKOV-3 cells remained viable in a plateau up to 40 microM BR concentration. This relative resistance of SKOV-3 cells to BR corresponded to the absence ofBR-induced apoptosis in SKOV-3 cells, which together with clearly demonstrated sensitivity of CH1 cells to BR-induced apoptosis, established by flow cytometry (presence of nuclei with sub-G0 DNA content, Annexin V binding) and western blotting (poly-ADP-ribosyl-polymerase (PARP) cleavage), further stressed the role of drug-induced apoptosis in the over-all drug-induced cytotoxicity. PMID:11130242

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. Exclusion limits on the WIMP-nucleon cross section from the cryogenic dark matter search.

    PubMed

    Abusaidi, R; Akerib, D S; Barnes, P D; Bauer, D A; Bolozdynya, A; Brink, P L; Bunker, R; Cabrera, B; Caldwell, D O; Castle, J P; Clarke, R M; Colling, P; Crisler, M B; Cummings, A; Da Silva, A; Davies, A K; Dixon, R; Dougherty, B L; Driscoll, D; Eichblatt, S; Emes, J; Gaitskell, R J; Golwala, S R; Hale, D; Haller, E E; Hellmig, J; Huber, M E; Irwin, K D; Jochum, J; Lipschultz, F P; Lu, A; Mandic, V; Martinis, J M; Nam, S W; Nelson, H; Neuhauser, B; Penn, M J; Perera, T A; Perillo Isaac, M C; Pritychenko, B; Ross, R R; Saab, T; Sadoulet, B; Schnee, R W; Seitz, D N; Shestople, P; Shutt, T; Smith, A; Smith, G W; Sonnenschein, A H; Spadafora, A L; Stockwell, W; Taylor, J D; White, S; Yellin, S; Young, B A

    2000-06-19

    The Cryogenic Dark Matter Search (CDMS) employs Ge and Si detectors to search for weakly interacting massive particles (WIMPs) via their elastic-scattering interactions with nuclei while discriminating against interactions of background particles. CDMS data, accounting for the neutron background, give limits on the spin-independent WIMP-nucleon elastic-scattering cross section that exclude unexplored parameter space above 10 GeV/c2 WIMP mass and, at >75% C.L., the entire 3sigma allowed region for the WIMP signal reported by the DAMA experiment. PMID:10991035

  17. 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, {?_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 ({?N_?}). These BBN results are compared to those derived independently from the Planck CMB data. In the absence of a light WIMP ({m_?} ? 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 {?N_?} = 0.400.17, disfavoring standard big bang nucleosynthesis (SBBN) ({?N_?} = 0) at 2.4 sigma , as well as a sterile neutrino ({?N_?} = 1) at 3.5 sigma . In the presence of a light WIMP ({m_?} ? 20 MeV), the relation between {N_eff and {?N_&nu}; depends on the WIMP mass, leading to degeneracies among {N_eff, {?N_?}, and {m_?}. 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_?} in the range 0.5 - 5 MeV (mchi /me ? 1 - 10) and, they identify best fit values for {m_?} in the range 5 - 10 MeV. The joint BBN + CMB analyses find a best fit value for the number of equivalent neutrinos, {?N_?} ? 0.65, nearly independent of the nature of the WIMP. The best fit still disfavors the absence of dark radiation ({?N_?} = 0 at 95% confidence), while allowing for the presence of a sterile neutrino ({?N_?} = 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}.

  18. Sensitivities of the equilibrium line altitude to temperature and precipitation changes along the Andes

    NASA Astrophysics Data System (ADS)

    Sagredo, Esteban A.; Rupper, Summer; Lowell, Thomas V.

    2014-03-01

    Equilibrium line altitudes (ELAs) of alpine glaciers are sensitive indicators of climate change and have been commonly used to reconstruct paleoclimates at different temporal and spatial scales. However, accurate interpretations of ELA fluctuations rely on a quantitative understanding of the sensitivity of ELAs to changes in climate. We applied a full surface energy- and mass-balance model to quantify ELA sensitivity to temperature and precipitation changes across the range of climate conditions found in the Andes. Model results show that ELA response has a strong spatial variability across the glaciated regions of South America. This spatial variability correlates with the distribution of the present-day mean climate conditions observed along the Andes. We find that ELAs respond linearly to changes in temperature, with the magnitude of the response being prescribed by the local lapse rates. ELA sensitivities to precipitation changes are nearly linear and are inversely correlated with the emissivity of the atmosphere. Temperature sensitivities are greatest in the inner tropics; precipitation becomes more important in the subtropics and northernmost mid-latitudes. These results can be considered an important step towards developing a framework for understanding past episodes of glacial fluctuations and ultimately for predicting glacier response to future climate changes.

  19. Characterization of paclitaxel (Taxol) sensitivity in human glioma- and medulloblastoma-derived cell lines.

    PubMed Central

    Tseng, S. H.; Bobola, M. S.; Berger, M. S.; Silber, J. R.

    1999-01-01

    Paclitaxel (Taxol), a cytotoxic natural product that disrupts microtubule integrity, is being clinically evaluated for use against gliomas. We examined paclitaxel-induced killing in seven cell lines derived from human malignant astrocytic gliomas and medulloblastomas with the goal of characterizing range of sensitivity, contribution of P-glycoprotein 170-mediated drug efflux to resistance, and cross-resistance with alkylating agents. Exposure to paclitaxel for 8 h or less produced biphasic survival curves for all lines, with 40-75% of cells comprising a subpopulation that was 9-26 times more resistant to paclitaxel than the more sensitive fraction. Increasing exposure to 24 h eliminated the resistant subpopulation, increasing sensitivity 50- to 400-fold. The dose producing one log of kill (LD10) after a 24-h exposure ranged from 4 to 18 nM, comparable to concentrations in the cerebrospinal fluid of brain tumor patients given a 3-h infusion of paclitaxel. Concurrent exposure to paclitaxel and either nimodipine or verapamil, inhibitors of P-glycoprotein activity, did not increase sensitivity, demonstrating that the fivefold range in sensitivity was not due to P-glycoprotein-mediated drug efflux. Importantly, there was no correlation between LD10 for paclitaxel and LD10 for 1,3-bis(2-chloroethyl)-1-nitrosourea, streptozotocin, and temozolomide, indicating no expression of cross-resistance to these different classes of tumoricidal agents. Our results suggest that greater clinical efficacy of paclitaxel against malignant brain tumors may be obtained by infusion for 24 h or longer and support the use of paclitaxel in combination with alkylating agents. PMID:11550305

  20. miRNAs associated with chemo-sensitivity in cell lines and in advanced bladder cancer

    PubMed Central

    2012-01-01

    Background MicroRNA is a naturally occurring class of non-coding RNA molecules that mediate posttranscriptional gene regulation and are strongly implicated in cellular processes such as cell proliferation, carcinogenesis, cell survival and apoptosis. Consequently there is increasing focus on miRNA expression as prognostic factors for outcome and chemotherapy response. Only approximately 50% of patients with bladder cancer respond to chemotherapy. Therefore, predictive markers, such as miRNAs, that can identify subgroups of patients who will benefit from chemotherapy will have great value for treatment guidance. Methods We profiled the expression of 671 miRNAs in formalin fixed paraffin embedded tumors from patients with advanced bladder cancer treated with cisplatin based chemotherapy. We delineated differentially expressed miRNAs in tumors from patients with complete response vs. patients with progressive disease and in tumors form patients with short and long overall survival time. Furthermore, we studied the effect of up- and down regulation of key miRNAs on the cisplatin sensitivity in eight bladder cancer cell lines with different sensitivities to cisplatin. Results miRNA expression profiling identified 15 miRNAs that correlated with response to chemotherapy and 5 miRNAs that correlated with survival time. Three miRNAs were associated with both response and survival (886-3p, 923, 944). By changing the cellular level of the response-identified miRNAs in eight bladder cell lines with different cisplatin sensitivity we found that down-regulation of miR-27a, miR296-5p and miR-642 generally reduced the cell viability, whereas up-regulation of miR-138 and miR-886-3p reduced the viability of more than half of the cell lines. Decreasing miR-138 increased the cisplatin sensitivity in half of the cell lines and increasing miR-27a and miR-642 generally increased cisplatin sensitivity. Conclusions MiRNAs seem to be involved in cisplatin based chemo response and may form a new target for therapy and serve as biomarkers for treatment response. PMID:22954303

  1. 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

  2. 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.; Kndlseder, 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.; Rain, S.; Rando, R.; Razzano, M.; Razzaque, S.; Reimer, A.; Reimer, O.; Romani, R. W.; Snchez-Conde, M.; Schulz, A.; Sgr, 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 ? rays detectable by the Fermi Large Area Telescope (LAT) against the astrophysical ?-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.

  3. Direct WIMP detection with cryogenic detectors.

    PubMed

    Kraus, Hans

    2003-11-15

    Cryogenic detectors have been developed since the mid 1980s and have been applied successfully to dark-matter searches since the mid 1990s. Among the advantages of cryogenic detectors are their high sensitivity to nuclear recoil, their low detection thresholds, the wide choice of target materials and the possibility of implementing event type recognition on an event-by-event basis. I explain the basics of cryogenic detectors, review various implementations, discuss advantages and drawbacks and give an overview of current dark-matter-search experiments based upon cryogenic detectors. PMID:14667319

  4. Position- and time-sensitive single photon detector with delay-line readout

    NASA Astrophysics Data System (ADS)

    Czasch, A.; Milnes, J.; Hay, N.; Wicking, W.; Jagutzki, O.

    2007-10-01

    We have developed an image intensifier tube with delay-line anode for time- and position-sensitive detection of single photons. By combining two well-approved techniques, the helical-wire delay-line readout for single particle detection and the production capability for large-format sealed photo-multiplier tubes with microchannel-plates, it is possible to build single photon sensors with 40 and 75 mm diameter. Applications are found wherever precise time tagging (< 1 ns) in combination with high position resolution (10001000 pixel) for single photon detection is of equal importance. Due to the low background this technique is especially suited for imaging at very low light intensity or for "3d" imaging and timing applications such as fluorescence microscopy or coincident photon detection experiments. We present the performance of prototype detectors with 75 mm low-noise S-20 and 40 mm S-20 red-enhanced photo-cathodes.

  5. 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.

  6. 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.

  7. 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.

  8. [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

  9. 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

  10. Establishment of three cell lines from Chinese giant salamander and their sensitivities to the wild-type and recombinant ranavirus.

    PubMed

    Yuan, Jiang-Di; Chen, Zhong-Yuan; Huang, Xing; Gao, Xiao-Chan; Zhang, Qi-Ya

    2015-01-01

    Known as lethal pathogens, Ranaviruses have been identified in diseased fish, amphibians (including Chinese giant salamander Andrias davidianus, the world's largest amphibian) and reptiles, causing organ necrosis and systemic hemorrhage. Here, three Chinese giant salamander cell lines, thymus cell line (GSTC), spleen cell line (GSSC) and kidney cell line (GSKC) were initially established. Their sensitivities to ranaviruses, wild-type Andrias davidianus ranavirus (ADRV) and recombinant Rana grylio virus carrying EGFP gene (rRGV-EGFP) were tested. Temporal transcription pattern of ranavirus major capsid protein (MCP), fluorescence and electron microscopy observations showed that both the wild-type and recombinant ranavirus could replicate in the cell lines. PMID:26070783

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

    NASA Astrophysics Data System (ADS)

    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.

  12. 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.

  13. Silicon fin line edge roughness determination and sensitivity analysis by Mueller matrix spectroscopic ellipsometry based scatterometry

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

    Measurement and control of line edge roughness (LER) is one of the most challenging issues facing patterning technology. As the critical dimensions (CD) of patterned structures decrease, LER of only a few nanometers can negatively impact device performance. Here, Mueller matrix spectroscopic ellipsometry (MMSE) based scatterometry is used to determine LER in periodic line-space structures in 28 nm pitch Si fin samples fabricated by directed selfassembly (DSA) patterning. The optical response of the Mueller matrix (MM) elements is influenced by structural parameters like pitch, CD, height, and side-wall angle (SWA), 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 simulations of optical models that include LER. Here, an approach is developed that quantifies Si fin LER 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 top down scanning electron microscope (SEM) images and cross-sectional TEM image of the 28 nm pitch Si fins.

  14. 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.

  15. 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.

  16. Genome-wide association for methamphetamine sensitivity in an advanced intercross mouse line

    PubMed Central

    Parker, Clarissa C.; Cheng, Riyan; Sokoloff, Greta; Palmer, Abraham A.

    2012-01-01

    Sensitivity to the locomotor stimulant effects of methamphetamine is a heritable trait that utilizes neurocircuitry also associated with the rewarding effects of drugs. We used the power of a C57BL/6J x DBA/2J F2 intercross (n = 676) and the precision of a C57BL/6J x DBA/2J F8 advanced intercross line (Aap: B6, D2 G8; or F8 AIL; n = 552) to identify and narrow quantitative trait loci (QTL) associated with sensitivity to the locomotor stimulant effects of methamphetamine. We used the program QTLRel to simultaneously map QTL in the F2 and F8 AIL mice. We identified six genome-wide significant QTLs associated with locomotor activity at baseline and seven genome-wide significant QTLs associated with methamphetamine induced locomotor activation. The average percent decrease in QTL width between the F2 and the integrated analysis was 65%. Additionally, these QTLs showed a distinct temporal specificity within each session that allowed us to further refine their locations, and identify one QTL with a 1.8-LOD support interval = 1.47 Mb. Next, we utilized publicly available bioinformatics resources to exploit strain-specific sequence data and strain- and region-specific expression data to identify candidate genes. These results illustrate the power of AILs in conjunction with sequence and gene expression data to investigate the genetic underpinnings of behavioral and other traits. PMID:22032291

  17. 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

  18. Prodigiosin down-regulates survivin to facilitate paclitaxel sensitization in human breast carcinoma cell lines

    SciTech Connect

    Ho, T.-F.; Peng, Y.-T.; Chuang, S.-M.; Lin, S.-C.; Feng, B.-L.; Lu, C.-H.; Yu, W.-J.; Chang, J.-S. Chang, C.-C.

    2009-03-01

    Prodigiosin is a bacterial metabolite with potent anticancer activity, which is attributed to its proapoptotic effect selectively active in malignant cells. Still, the molecular mechanisms whereby prodigiosin induces apoptosis remain largely unknown. In particular, the role of survivin, a vital inhibitor of apoptosis, in prodigiosin-induced apoptosis has never been addressed before and hence was the primary goal of this study. Our results showed that prodigiosin dose-dependently induced down-regulation of survivin in multiple breast carcinoma cell lines, including MCF-7, T-47D and MDA-MB-231. This down-regulation is mainly regulated at the level of transcription, as prodigiosin reduced the levels of both survivin mRNA and survivin promoter activity but failed to rescue survivin expression when proteasome-mediated degradation is abolished. Importantly, overexpression of survivin rendered cells more resistant to prodigiosin, indicating an essential role of survivin down-regulation in prodigiosin-induced apoptosis. In addition, we found that prodigiosin synergistically enhanced cell death induced by paclitaxel, a chemotherapy drug known to up-regulate survivin that in turn confers its own resistance. This paclitaxel sensitization effect of prodigiosin is ascribed to the lowering of survivin expression, because prodigiosin was shown to counteract survivin induction by paclitaxel and, notably, the sensitization effect was severely abrogated in cells that overexpress survivin. Taken together, our results argue that down-regulation of survivin is an integral component mediating prodigiosin-induced apoptosis in human breast cancer cells, and further suggest the potential of prodigiosin to sensitize anticancer drugs, including paclitaxel, in the treatment of breast cancer.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. KRAS G13D Mutation and Sensitivity to Cetuximab or Panitumumab in a Colorectal Cancer Cell Line Model

    PubMed Central

    Kumar, Shalini Sree; Price, Timothy J.; Mohyieldin, Omar; Borg, Matthew; Townsend, Amanda

    2014-01-01

    ABSTRACT BACKGROUND: The treatment of metastatic colorectal cancer (mCRC) includes drugs targeting the epidermal growth factor receptor (EGFR). Mutation in codon 12 or 13 in the Kirsten rat sarcoma viral oncogene homolog (KRAS) gene, downstream of the EGFR, evokes constitutive activation of the RAS/RAF/MAPK signaling pathway and correlates with resistance to anti-EGFR monoclonal antibody (mAb) therapies. However, a retrospective study reported that a proportion of patients with the KRAS G13D mutation may respond to cetuximab. A similar analysis for panitumumab was not as conclusive. We sought to determine the sensitivity of CRC cell lines to cetuximab or panitumumab treatment and to investigate the correlation of the KRAS mutational status of the CRC cell lines to the responsiveness to cetuximab or panitumumab. METHODS: To determine the responsiveness of CRC cell lines to cetuximab or panitumumab, cell lines were treated with an optimized concentration of each mAb, and proliferation assays were conducted. RESULTS: After treatment with cetuximab or panitumumab, at the optimum concentration of 8 ?g/well, the KRAS G13D mutant cell lines HCT-116, LoVo, and T84 showed intermediate sensitivity to both treatments, between the resistant KRAS G12V mutant cell line SW480 and the sensitive KRAS wild-type cell line LIM1215. One of the G13D cell lines was significantly more sensitive to panitumumab than to cetuximab (P = .02). CONCLUSION: The specific KRAS mutation determines the responsiveness to anti-EGFR monoclonal antibody treatment, corresponding to reported clinical observations. PMID:24558511

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. Vasohibin 2 Decreases the Cisplatin Sensitivity of Hepatocarcinoma Cell Line by Downregulating p53

    PubMed Central

    Han, Bei; Gu, Yuqing; Xue, Xiaofeng; Sun, Jie; Ge, Qianqian; Miao, Yi; Qian, Zhuyin

    2014-01-01

    Hepatocellular carcinoma (HCC) is a prevalent problem worldwide. Chemotherapy, especially cisplatin (CDDP)-based systemic chemotherapy, is the best option for advanced liver cancer. However, CDDP resistance is becoming common and hindering the clinical application of CDDP. Meanwhile, no consensus has been reached regarding the chemotherapeutic use of vasohibin 2 (VASH2), which promotes the angiogenesis and proliferation of cancer cells. In this work, a tissue microarray was used to observe VASH2 and its possible role in cancer treatment. Results showed that VASH2 was highly expressed in HCC tissues and was significantly correlated with cancer differentiation. To further investigate the efficacy and mechanism of the combination of VASH2 with anti-cancer drugs in liver cancer cells, we stably built VASH2 overexpression and knockdown cell lines. We found that VASH2 can influence the CDDP sensitivity and that the cell overexpression of VASH2 had a higher cell viability and lower apoptosis rate after CDDP exposure. We also observed that VASH2 overexpression downregulated wild-type p53, as well as suppressed the expression of the pro-apoptotic protein BCL2-associated X protein (Bax) and cleaved caspase-3 (CC-3) after treatment by CDDP. Conversely, the knockdown of VASH2 significantly inhibited these effects. In an in vivo chemosensitivity study, nude mice were subcutaneously injected with tumor cells and received CDDP treatment through intraperitoneal administration every 3 days. We found that VASH2 knockdown markedly limited the tumor growth and enhanced the CDDP toxicity and apoptosis of tumor cells. Western blot analysis revealed that tumor cells with downregulated VASH2 had a higher expression of wild-type p53, Bax, and CC-3 than control cells. Overall, our results indicated the novel roles of VASH2 in the chemoresistance of hepatocarcinoma cells to CDDP and suggested that VASH2 may be a promising anticancer target. PMID:24595063

  12. 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.

  13. 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,...

  14. Antitumor activity of D-mannosamine in vitro: different sensitivities among human leukemia cell lines possessing T-cell properties.

    PubMed

    Onoda, T; Morikawa, S; Harada, T; Suzuki, Y; Inoue, K; Nishigami, K

    1982-07-01

    D-Mannosamine is toxic to human malignant T-lymphoid cell lines derived from patients with T-cell leukemia. We observed heterogeneity of mannosamine susceptibility among those cell lines. The leukemic T-cell lines, subgrouped according to the degree of mannosamine inhibition on nucleic acid biosyntheses, were: Subgroup 1, HPB-MLT cells; Subgroup 2, CCRF-HSB-2 and HPB-ALL cells; and Subgroup 3, MOLT-4 cells. The most sensitive line, HPB-MLT, originated from the patient with adult T-cell leukemia. The cytotoxicity of mannosamine was potentiated by a fatty acid, sodium oleate, at concentrations that were noncytolytic, and the interaction between the two drugs was synergistic. These results would suggest that mannosamine induces changes in the membrane structure of the leukemia cells. Thus, the primary target of the tumoricidal activity of mannosamine may also be the cellular membranes. PMID:6979385

  15. Effects of a novel porphyrin-based photosensitizer on sensitive and multidrug-resistant human gastric cancer cell lines.

    PubMed

    Chen, Jingjing; Mao, Lina; Liu, Shuping; Liang, Yanling; Wang, Sicheng; Wang, Yeyu; Zhao, Qiang; Zhang, Xiaojing; Che, Yanjun; Gao, Lijing; Liu, Tianjun

    2015-10-01

    Photodynamic therapy (PDT) has been considered to be a possible candidate approach in combating multidrug resistance (MDR) phenomenon during the treatment of cancer. To investigate the photocytotoxicity of a novel porphyrin-based photosensitizer, meso-5-[?-DTPA-aminophenyl]-10, 15, 20-triphenyl-porhyrin (DTP) (Fig. 1A), on MDR cells, the intracellular DTP uptake, phototoxicity and subcellular DTP localization were studied by using a human gastric cancer MGC803 cell line and its paclitaxel selected subline MGC803/PA expressing MDR phenotype. No significant difference was observed in intracellular DTP accumulation between sensitive and resistant cell lines after exposure to 1.56 ?M concentration for 6h. DTP-PDT induced significant photocytotoxicity on both MGC803 and MGC803/PA cell lines and the photokilling was greater in MGC803 cell line in comparison to MGC803/PA. The fluence that caused 50% cell death was 4.42 and 6.29 J/cm(2) in MGC803 and MGC803/PA cell lines, respectively. The presence of Pgp inhibitors verapamil and cyclosporin A could not modify the intracellular DTP level in MGC803/PA cell line and the phototoxic effects. DTP was localized at lysosomes of MGC803 cell line but at lysosomes and mitochondria of MGC803/PA. Our results indicated that DTP-mediated PDT could eradicate gastric cancer cells whether or not they express MDR although the efficacy is slightly reduced in the MDR cells. The photokilling in MDR cells could not be altered by MDR inhibitor verapamil. The slightly different photocytotoxicity between sensitive and resistant cell lines could not explained by classical Pgp MDR and might be attributed to the differential intracellular DTP localization sites. PMID:26302181

  16. 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.

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

    SciTech Connect

    Labadi, Karim; Saggadi, Samira; Amodeo, Lionel

    2009-03-05

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

  18. Phenotypic characterization of second generation offspring of alcohol-sensitive ANT and alcohol-insensitive AT rat lines.

    PubMed

    Tuominen, K; Sarviharju, M; Honkanen, A; Korpi, E R

    1994-01-01

    The alcohol-sensitive ANT and the alcohol-insensitive AT rat lines developed by selective breeding for differential sensitivity to motor impairment on the tilting plane by a moderate ethanol dose (2 g/kg, IP), were cross-bred to produce second generation (F2) offspring to study phenotypic correlations between various behavioral and biochemical properties and the degree of initial alcohol sensitivity in the tilting plane test. The F2 population (n = 75) was subjected to alcohol sensitivity tests using a tilting plane test and a sleep time test, and to the elevated plus-maze test of sober activity and anxiety. Finally, the animals were sacrificed and the concentrations of dopamine and its acidic metabolites were analyzed in their striatal tissues. Serum corticosterone was determined to obtain information about the stress responses of the animals after the tilting plane test. The behaviors studied had no significant correlations with each other, suggesting that the various genetic and environmental factors affecting these behavioral phenotypes are different for each behavior. The biochemical measures yielded some correlations with the tilting plane test results that were contrary to the differences between the parent rat lines (dopaminergic indices) or that were confounded by the correlations with the body weight of the animals (corticosterone). Body-weight independent correlational tendency between the alcohol-induced impairment in motor performance and serum corticosterone concentration, however, fitted the differences between the parent lines, suggesting that stress mechanisms cannot be fully excluded as factors contributing to the differential alcohol sensitivity between the ANT and AT rat lines. PMID:7818795

  19. The sensitivity of lateral line receptors and their role in the behavior of Mexican blind cavefish (Astyanax mexicanus)

    PubMed Central

    Yoshizawa, Masato; Jeffery, William R.; van Netten, Sietse M.; McHenry, Matthew J.

    2014-01-01

    The characid fish species Astyanax mexicanus offers a classic comparative model for the evolution of sensory systems. Populations of this species evolved in caves and became blind while others remained in streams (i.e. surface fish) and retained a functional visual system. The flow-sensitive lateral line receptors, called superficial neuromasts, are more numerous in cavefish than in surface fish, but it is unclear whether individual neuromasts differ in sensitivity between these populations. The aims of this study were to determine whether the neuromasts in cavefish impart enhanced sensitivity relative to surface fish and to test whether this aids their ability to sense flow in the absence of visual input. Sensitivity was assessed by modeling the mechanics and hydrodynamics of a flow stimulus. This model required that we measure the dimensions of the transparent cupula of a neuromast, which was visualized with fluorescent microspheres. We found that neuromasts within the eye orbit and in the suborbital region were larger and consequently about twice as sensitive in small adult cavefish as in surface fish. Behavioral experiments found that these cavefish, but not surface fish, were attracted to a 35 Hz flow stimulus. These results support the hypothesis that the large superficial neuromasts of small cavefish aid in flow sensing. We conclude that the morphology of the lateral line could have evolved in cavefish to permit foraging in a cave environment. PMID:24265419

  20. Increased Sensitivity to Cisplatin in Non-Small Cell Lung Cancer Cell Lines after FHIT Gene Transfer1

    PubMed Central

    Andriani, F; Perego, P; Carenini, N; Sozzi, G; Roz, L

    2006-01-01

    Abstract To evaluate the relevance of fragile histidine triad (FHIT) status in relation to drug treatment, we analyzed the sensitivity of the Fhit-negative non-small cell lung cancer (NSCLC) cell line NCI-H460 to different drugs, after treatment with an adenoviral vector expressing the FHIT transgene. Expression of Fhit resulted in reduced sensitivity to etoposide, doxorubicin, and topotecan. This feature was associated with Fhit-induced downregulation of DNA topoisomerases I and II. In contrast, expression of Fhit did not modulate sensitivity to Taxol, but produced a slight increase in sensitivity to cisplatin, as shown by colony-forming assays. Analysis of apoptosis revealed that, after cisplatin exposure, the number of apoptotic cells was two-fold higher in Fhit-expressing H460 cells. Moreover, it appeared that wild-type p53 was required for sensitization to cisplatin because the effect was marginal in A549 and Calu-1 cells, where the p53 pathway is altered and simultaneous restoration of p53 and Fhit in Calu-1 cells increased cisplatin sensitivity. Fhit could also partially restore sensitivity to cisplatin in Bcl-2- and Bcl-xL-overexpressing H460 cells that are normally resistant to this drug. Our results support the possible relevance of FHIT in cisplatin-based chemotherapy as well as in the reversal of drug resistance in NSCLC. PMID:16533421

  1. 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,...

  2. Dark matter production in the early Universe: Beyond the thermal WIMP paradigm

    NASA Astrophysics Data System (ADS)

    Baer, Howard; Choi, Ki-Young; Kim, Jihn E.; Roszkowski, Leszek

    2015-02-01

    Increasingly stringent limits from LHC searches for new physics, coupled with lack of convincing signals of weakly interacting massive particle (WIMP) in dark matter searches, have tightly constrained many realizations of the standard paradigm of thermally produced WIMPs as cold dark matter. In this article, we review more generally both thermally and non-thermally produced dark matter (DM). One may classify DM models into two broad categories: one involving bosonic coherent motion (BCM) and the other involving WIMPs. BCM and WIMP candidates need, respectively, some approximate global symmetries and almost exact discrete symmetries. Supersymmetric axion models are highly motivated since they emerge from compelling and elegant solutions to the two fine-tuning problems of the Standard Model: the strong CP problem and the gauge hierarchy problem. We review here non-thermal relics in a general setup, but we also pay particular attention to the rich cosmological properties of various aspects of mixed SUSY/axion dark matter candidates which can involve both WIMPs and BCM in an interwoven manner. We also review briefly a panoply of alternative thermal and non-thermal DM candidates.

  3. LUX likelihood and limits on spin-independent and spin-dependent WIMP couplings with LUXCalc

    NASA Astrophysics Data System (ADS)

    Savage, Christopher; Scaffidi, Andre; White, Martin; Williams, Anthony G.

    2015-11-01

    We present LUXCalc, a new utility for calculating likelihoods and deriving weakly interacting massive particle (WIMP)-nucleon coupling limits from the recent results of the LUX direct search dark matter experiment. After a brief review of WIMP-nucleon scattering, we derive LUX limits on the spin-dependent WIMP-nucleon couplings over a broad range of WIMP masses, under standard assumptions on the relevant astrophysical parameters. We find that, under these and other common assumptions, LUX excludes the entire spin-dependent parameter space consistent with a dark matter interpretation of DAMA's anomalous signal, the first time a single experiment has been able to do so. We also revisit the case of spin-independent couplings, and demonstrate good agreement between our results and the published LUX results. Finally, we derive constraints on the parameters of an effective dark matter theory in which a spin-1 mediator interacts with a fermionic WIMP and Standard Model fermions via axial-vector couplings. A detailed appendix describes the use of LUXCalc with standard codes to place constraints on generic dark matter theories.

  4. 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.

  5. 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

  6. A Novel Line Immunoassay Based on Recombinant Virulence Factors Enables Highly Specific and Sensitive Serologic Diagnosis of Helicobacter pylori Infection

    PubMed Central

    Formichella, Luca; Romberg, Laura; Bolz, Christian; Vieth, Michael; Geppert, Michael; Gttner, Gereon; Nlting, Christina; Walter, Dirk; Schepp, Wolfgang; Schneider, Arne; Ulm, Kurt; Wolf, Petra; Busch, Dirk H.; Soutschek, Erwin

    2013-01-01

    Helicobacter pylori colonizes half of the world's population, and infection can lead to ulcers, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. Serology is the only test applicable for large-scale, population-based screening, but current tests are hampered by a lack of sensitivity and/or specificity. Also, no serologic test allows the differentiation of type I and type II strains, which is important for predicting the clinical outcome. H. pylori virulence factors have been associated with disease, but direct assessment of virulence factors requires invasive methods to obtain gastric biopsy specimens. Our work aimed at the development of a highly sensitive and specific, noninvasive serologic test to detect immune responses to important H. pylori virulence factors. This line immunoassay system (recomLine) is based on recombinant proteins. For this assay, six highly immunogenic virulence factors (CagA, VacA, GroEL, gGT, HcpC, and UreA) were expressed in Escherichia coli, purified, and immobilized to nitrocellulose membranes to detect serological immune responses in patient's sera. For the validation of the line assay, a cohort of 500 patients was screened, of which 290 (58.0%) were H. pylori negative and 210 (42.0%) were positive by histology. The assay showed sensitivity and specificity of 97.6% and 96.2%, respectively, compared to histology. In direct comparison to lysate blotting and enzyme-linked immunosorbent assay (ELISA), the recomLine assay had increased discriminatory power. For the assessment of individual risk for gastrointestinal disease, the test must be validated in a larger and defined patient cohort. Taking the data together, the recomLine assay provides a valuable tool for the diagnosis of H. pylori infection. PMID:24006137

  7. A novel line immunoassay based on recombinant virulence factors enables highly specific and sensitive serologic diagnosis of Helicobacter pylori infection.

    PubMed

    Formichella, Luca; Romberg, Laura; Bolz, Christian; Vieth, Michael; Geppert, Michael; Gttner, Gereon; Nlting, Christina; Walter, Dirk; Schepp, Wolfgang; Schneider, Arne; Ulm, Kurt; Wolf, Petra; Busch, Dirk H; Soutschek, Erwin; Gerhard, Markus

    2013-11-01

    Helicobacter pylori colonizes half of the world's population, and infection can lead to ulcers, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. Serology is the only test applicable for large-scale, population-based screening, but current tests are hampered by a lack of sensitivity and/or specificity. Also, no serologic test allows the differentiation of type I and type II strains, which is important for predicting the clinical outcome. H. pylori virulence factors have been associated with disease, but direct assessment of virulence factors requires invasive methods to obtain gastric biopsy specimens. Our work aimed at the development of a highly sensitive and specific, noninvasive serologic test to detect immune responses to important H. pylori virulence factors. This line immunoassay system (recomLine) is based on recombinant proteins. For this assay, six highly immunogenic virulence factors (CagA, VacA, GroEL, gGT, HcpC, and UreA) were expressed in Escherichia coli, purified, and immobilized to nitrocellulose membranes to detect serological immune responses in patient's sera. For the validation of the line assay, a cohort of 500 patients was screened, of which 290 (58.0%) were H. pylori negative and 210 (42.0%) were positive by histology. The assay showed sensitivity and specificity of 97.6% and 96.2%, respectively, compared to histology. In direct comparison to lysate blotting and enzyme-linked immunosorbent assay (ELISA), the recomLine assay had increased discriminatory power. For the assessment of individual risk for gastrointestinal disease, the test must be validated in a larger and defined patient cohort. Taking the data together, the recomLine assay provides a valuable tool for the diagnosis of H. pylori infection. PMID:24006137

  8. 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

  9. 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).

  10. 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}

  11. 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.

  12. Constraints on WIMP Dark Matter from the High Energy PAMELA p/p Data

    SciTech Connect

    Donato, F.; Maurin, D.; Brun, P.; Delahaye, T.; Salati, P.

    2009-02-20

    A new calculation of the p/p ratio in cosmic rays is compared to the recent PAMELA data. The good match up to 100 GeV allows us to set constraints on exotic contributions from thermal weakly interacting massive particle (WIMP) dark matter candidates. We derive stringent limits on possible enhancements of the WIMP p flux: a m{sub WIMP}=100 GeV (1 TeV) signal cannot be increased by more than a factor of 6 (40) without overrunning PAMELA data. Annihilation through the W{sup +}W{sup -} channel is also inspected and cross-checked with e{sup +}/(e{sup -}+e{sup +}) data. This scenario is strongly disfavored as it fails to simultaneously reproduce positron and antiproton measurements.

  13. 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...

  14. 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.

  15. 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.

  16. 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

  17. 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.

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

    NASA Astrophysics Data System (ADS)

    Schumann, Marc; Baudis, Laura; Btikofer, 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.

  19. 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

  20. 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].

  1. 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

  2. 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

  3. 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

  4. 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

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

    PubMed

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

    2014-12-01

    The apoptosis pathway of programmed cell death is frequently deregulated in cancer. An intact apoptosis pathway is required for proper response to anti-cancer treatment. We investigated the chromatin status of key apoptosis genes in the apoptosis pathway in colorectal cancer cell lines in relation to apoptosis induced by chemo-, immune- or radiation therapy. Using chromatin immunoprecipitation (ChIP), we measured the presence of transcription-activating histone modifications H3Ac and H3K4me3 and silencing modifications H3K9me3 and H3K27me3 at the gene promoter regions of key apoptosis genes Bax, Bcl2, Caspase-9, Fas (CD95) and p53. Cell lines DLD1, SW620, Colo320, Caco2, Lovo and HT29 were treated with cisplatin, anti-Fas or radiation. The apoptotic response was measured by flow cytometry using propidium iodide and annexin V-FITC. The chromatin status of the apoptosis genes reflected the activation status of the intrinsic (Bax, Bcl2, Caspase-9 and p53) and extrinsic (Fas) pathways. An active intrinsic apoptotic pathway corresponded to sensitivity to cisplatin and radiation treatment of cell lines DLD1, SW620 and Colo320. An active Fas promoter corresponded to an active extrinsic apoptotic pathway in cell line DLD1. mRNA expression data correlated with the chromatin status of the apoptosis genes as measured by ChIP. In conclusion, the results presented in this study indicate that the balance between activating and silencing histone modifications, reflecting the chromatin status of apoptosis genes, can be used to predict the response of tumor cells to different anti-cancer therapies and could provide a novel target to sensitize tumors to obtain adequate treatment responses. PMID:25292014

  6. 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 150350 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

  7. 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.

  8. Medullary lateral line units of rudd, Scardinius erythrophthalmus, are sensitive to Krmn 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 (7cms(-1)) and to water flow that contained vortices shed by an upstream half cylinder (diameter 1, 2, and 3cm). 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

  9. 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

  10. 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

  11. Everolimus restores gefitinib sensitivity in resistant non-small cell lung cancer cell lines.

    PubMed

    La Monica, Silvia; Galetti, Maricla; Alfieri, Roberta R; Cavazzoni, Andrea; Ardizzoni, Andrea; Tiseo, Marcello; Capelletti, Marzia; Goldoni, Matteo; Tagliaferri, Sara; Mutti, Antonio; Fumarola, Claudia; Bonelli, Mara; Generali, Daniele; Petronini, Pier Giorgio

    2009-09-01

    The epidermal growth factor receptor (EGFR) is a validated target for therapy in non-small cell lung cancer (NSCLC). Most patients, however, either do not benefit or develop resistance to specific inhibitors of the EGFR tyrosine kinase activity, such as gefitinib or erlotinib. The mammalian target of rapamycin (mTOR) is a key intracellular kinase integrating proliferation and survival pathways and has been associated with resistance to EGFR tyrosine kinase inhibitors. In this study, we assessed the effects of combining the mTOR inhibitor everolimus (RAD001) with gefitinib on a panel of NSCLC cell lines characterized by gefitinib resistance and able to maintain S6K phosphorylation after gefitinib treatment. Everolimus plus gefitinib induced a significant decrease in the activation of MAPK and mTOR signaling pathways downstream of EGFR and resulted in a growth-inhibitory effect rather than in an enhancement of cell death. A synergistic effect was observed in those cell lines characterized by high proliferative index and low doubling time. These data suggest that treatment with everolimus and gefitinib might be of value in the treatment of selected NSCLC patients that exhibit high tumor proliferative activity. PMID:19427302

  12. 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

  13. 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.

  14. 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.

  15. Search for WIMPs with NaI(Tl) detectors at Oto Cosmo Observatory

    NASA Astrophysics Data System (ADS)

    Yoshida, S.; Ejiri, H.; Fushimi, K.; Hayashi, K.; Kishimoto, T.; Kudomi, N.; Kume, K.; Kuramoto, H.; Matsuoka, K.; Ohsumi, H.; Takahisa, K.; Tsujimoto, Y.; Umehara, S.

    2003-06-01

    The cold dark matter search has been carried out at Oto Cosmo Observatory with the large volume NaI(Tl) scintillators of ELEGANT V(ELE-V). The new limits on WIMPs could be obtained by the analysis of the annual modulation. Recently, the performance of NaI(Tl) detector in ELE-V was successfully improved. these are also discussed.

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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

  1. Increased sensitivity to gemcitabine of P-glycoprotein and multidrug resistance-associated protein-overexpressing human cancer cell lines.

    PubMed

    Bergman, A M; Pinedo, H M; Talianidis, I; Veerman, G; Loves, W J P; van der Wilt, C L; Peters, G J

    2003-06-16

    Gemcitabine (2',2'-difluorodeoxycytidine) is a deoxycytidine analogue that is activated by deoxycytidine kinase (dCK) to its monophosphate and subsequently to its triphosphate dFdCTP, which is incorporated into both RNA and DNA, leading to DNA damage. Multidrug resistance (MDR) is characterised by an overexpression of the membrane efflux pumps P-glycoprotein (P-gP) or multidrug resistance-associated protein (MRP). Gemcitabine was tested against human melanoma, non-small-cell lung cancer, small-cell lung cancer, epidermoid carcinoma and ovarian cancer cells with an MDR phenotype as a result of selection by drug exposure or by transfection with the mdr1 gene. These cell lines were nine- to 72-fold more sensitive to gemcitabine than their parental cell lines. The doxorubicin-resistant cells 2R120 (MRP1) and 2R160 (P-gP) were nine- and 28-fold more sensitive to gemcitabine than their parental SW1573 cells, respectively (P<0.01), which was completely reverted by 25 micro M verapamil. In 2R120 and 2R160 cells, dCK activities were seven- and four-fold higher than in SW1573, respectively, which was associated with an increased dCK mRNA and dCK protein. Inactivation by deoxycytidine deaminase was 2.9- and 2.2-fold decreased in 2R120 and 2R160, respectively. dFdCTP accumulation was similar in SW1573 and its MDR variants after 24 h exposure to 0.1 micro M gemcitabine, but dFdCTP was retained longer in 2R120 (P<0.001) and 2R160 (P<0.003) cells. 2R120 and 2R160 cells also incorporated four- and six-fold more [(3)H]gemcitabine into DNA (P<0.05), respectively. P-glycoprotein and MRP1 overexpression possibly caused a cellular stress resulting in increased gemcitabine metabolism and sensitivity, while reversal of collateral gemcitabine sensitivity by verapamil also suggests a direct relation between the presence of membrane efflux pumps and gemcitabine sensitivity. PMID:12799644

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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

  7. Ambient temperature influences core body temperature response in rat lines bred for differences in sensitivity to 8-hydroxy-dipropylaminotetralin.

    PubMed

    Nicholas, Andrea C; Seiden, Lewis S

    2003-04-01

    Agonist-induced decrease in core body temperature has commonly been used as a measure of serotonin1A (5-HT(1A)) receptor sensitivity in mood disorder. The thermoregulatory basis for 5-HT(1A) receptor agonist-induced temperature responses in humans and rats remains unclear. Therefore, the influence of ambient temperature on 5-HT(1A) receptor-mediated decreases in core body temperature were measured in rat lines bred for high (HDS) or low (LDS) sensitivity to the selective 5-HT(1A) receptor agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT). HDS and LDS rats were injected with either saline, 0.25 or 0.50 mg/kg 8-OH-DPAT at ambient temperatures of 10.5, 24, 30, or 37.5 degrees C, and core temperature was measured by radiotelemetry. For both lines, the thermic response to acute 8-OH-DPAT was greatest at 10.5 degrees C and decreased in magnitude as ambient temperature increased to 30 degrees C, consistent with hypothermia. HDS rats displayed a greater hypothermic response than LDS rats at 10.5, 24, and 30 degrees C. At 37.5 degrees C, LDS rats showed a lethal elevation of temperature in response to 0.50 mg/kg 8-OH-DPAT. All thermic responses to 8-OH-DPAT, including the lethality, were effectively blocked by pretreatment with the 5-HT(1A) receptor antagonist WAY100635, suggesting line differences in thermoregulatory circuits that are influenced by 5-HT(1A) receptor activation. Following repeated injection of 8-OH-DPAT, the magnitude of the hypothermic response decreased in both lines at 10.5 degrees C, but increased in HDS rats treated with 0.50 mg/kg 8-OH-DPAT at 30 and 37.5 degrees C. This pattern was reversed in HDS rats following 8-OH-DPAT challenge at 24 degrees C, suggesting that a compensatory thermoregulatory response accounts for changes in the hypothermic response to chronic 8-OH-DPAT. PMID:12649391

  8. Cadmium has contrasting effects on polyethylene glycol-sensitive and resistant cell lines in the Mediterranean halophyte species Atriplex halimus L.

    PubMed

    Lefvre, Isabelle; Marchal, Geoffrey; Edmond Ghanem, Michel; Correal, Enrique; Lutts, Stanley

    2010-03-15

    Beside a direct toxicity, cadmium impact on plants involves both a secondary-induced water stress and an oxidative stress. Proliferating cell lines of Atriplex halimus were selected for their sensitivity or resistance to polyethylene glycol (PEG 10,000, 20%) and then exposed to 100 microM CdCl2 in the simultaneous presence or absence of PEG 20% or 150 mM NaCl. The PEG resistant cell line exhibited a higher growth in the presence of Cd than the sensitive line, although Cd acccumulation was higher in the former than in the latter. Exogenous PEG induced an increase in Cd concentration in the sensitive but not in the resistant cell line while NaCl induced a decrease in Cd accumulation in both cell lines. In the presence of Cd alone, the water content (WC) was higher and the osmotic potential was lower in PEG-sensitive than in PEG resistant line. The presence of PEG in the Cd-containing medium increased the WC and decreased the osmotic potential in PEG-resistant line comparatively to Cd stress alone, while an inverse trend was observed for the sensitive line. The PEG-resistant cell line displayed a higher ability to cope with oxidative stress in relation to an increase of endogenous antioxidants (glutathione and ascorbic acid), a high constitutive superoxide dismutase (EC 1.15.1.1) activity and an efficient Cd-induced increase in glutathione reductase (GR) (EC 1.6.4.1) and ascorbate peroxidase (APX) (EC 1.11.1.11). Cadmium tolerance in PEG-resistant line is thus not related to any strategy of Cd exclusion or osmotic adjustment but to tolerance mechanisms allowing the tissue to restrict the deleterious impact of accumulated Cd. PMID:20031255

  9. Exceptional sensitivity of testicular germ cell tumour cell lines to the new anti-cancer agent, temozolomide.

    PubMed Central

    Pera, M. F.; Kberle, B.; Masters, J. R.

    1995-01-01

    Metastatic testicular germ cell tumours are cured in approximately 85% of patients using cisplatin-based combination chemotherapy. Patients who fail to respond have a poor prognosis, and there is a need for more effective treatments for cisplatin-resistant disease. In this study, it is shown that two of four cell lines derived from human non-seminomatous testicular germ cell tumours are exceptionally sensitive to temozolomide, a new imidazotetrazine which can cross the blood-brain barrier in mice. In addition, three pairs of cisplatin-resistant sublines show little cross-resistance to temozolomide. These data suggest that temozolomide might have activity against non-seminomatous testicular germ cell tumours which have relapsed following cisplatin-containing chemotherapy, and could have a role in the treatment of patients with metastatic lesions in the brain. PMID:7734313

  10. 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.

  11. 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

  12. 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

  13. A Meta-Analysis Approach for Characterizing Pan-Cancer Mechanisms of Drug Sensitivity in Cell Lines

    PubMed Central

    Wang, Kendric; Shrestha, Raunak; Wyatt, Alexander W.; Reddy, Anupama; Lehr, Joseph; Wang, Yuzhou

    2014-01-01

    Understanding the heterogeneous drug response of cancer patients is essential to precision oncology. Pioneering genomic analyses of individual cancer subtypes have begun to identify key determinants of resistance, including up-regulation of multi-drug resistance (MDR) genes and mutational alterations of drug targets. However, these alterations are sufficient to explain only a minority of the population, and additional mechanisms of drug resistance or sensitivity are required to explain the remaining spectrum of patient responses to ultimately achieve the goal of precision oncology. We hypothesized that a pan-cancer analysis of in vitro drug sensitivities across numerous cancer lineages will improve the detection of statistical associations and yield more robust and, importantly, recurrent determinants of response. In this study, we developed a statistical framework based on the meta-analysis of expression profiles to identify pan-cancer markers and mechanisms of drug response. Using the Cancer Cell Line Encyclopaedia (CCLE), a large panel of several hundred cancer cell lines from numerous distinct lineages, we characterized both known and novel mechanisms of response to cytotoxic drugs including inhibitors of Topoisomerase 1 (TOP1; Topotecan, Irinotecan) and targeted therapies including inhibitors of histone deacetylases (HDAC; Panobinostat) and MAP/ERK kinases (MEK; PD-0325901, AZD6244). Notably, our analysis implicated reduced replication and transcriptional rates, as well as deficiency in DNA damage repair genes in resistance to TOP1 inhibitors. The constitutive activation of several signaling pathways including the interferon/STAT-1 pathway was implicated in resistance to the pan-HDAC inhibitor. Finally, a number of dysregulations upstream of MEK were identified as compensatory mechanisms of resistance to the MEK inhibitors. In comparison to alternative pan-cancer analysis strategies, our approach can better elucidate relevant drug response mechanisms. Moreover, the compendium of putative markers and mechanisms identified through our analysis can serve as a foundation for future studies into these drugs. PMID:25036042

  14. 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

  15. Targeting DNA-PKcs increased anticancer drug sensitivity by suppressing DNA damage repair in osteosarcoma cell line MG63.

    PubMed

    Li, Xin; Tian, Jiguang; Bo, Qiyu; Li, Ka; Wang, Hongliang; Liu, Ting; Li, Jianmin

    2015-12-01

    Many chemotherapy drugs exert anticancer effects through causing DNA damage, such as DNA topoisomerase inhibitor and platinum-containing drugs. DNA damage repair is an important mechanism of drug resistance which is responsible for metastasis and recurrence after chemotherapy. DNA-dependent protein kinase (DNA-PK) plays an important role in non-homology end joining (NHEJ) pathway. In this study, we aimed to determine whether DNA-PK catalytic subunit (DNA-PKcs) is expressed in osteosarcoma MG63 cell line and involved in drug resistance induced by DNA repair. We found that DNA-PKcs was expressed in osteosarcoma cell line MG63. The pDNA-PKcs(T2609) was more expressed in cells treated with cisplatin (DDP) and etoposide (VP16). Down-regulation of DNA-PKcs produced higher sensitivity of MG63 cells to DDP or VP16 through increasing apoptosis and causing cell cycle arrest in the G1 phase. Our study supported that DNA-PKcs was involved in drug-induced DNA damage repair and related to chemosensitivity of osteosarcoma MG63 cells. PMID:26108997

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

    NASA Astrophysics Data System (ADS)

    Golubnitchaya-Labudov, O.; Portele, A.; Vaata, V.; Lubec, G.; Rink, H.; Hfer, M.

    1997-10-01

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

  17. 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

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

    PubMed

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

    2012-11-01

    Rapeseed (Brassica napus L.), which is the third leading source of vegetable oil, is sensitive to drought stress during the early vegetative growth stage. To investigate the initial response of rapeseed to drought stress, changes in the protein expression profiles of drought-sensitive (RGS-003) and drought-tolerant lines (SLM-003), and their F1 hybrid, were analyzed using a proteomics approach. Seven-day-old rapeseed seedlings were treated with drought stress by restricting water for 7 days, and proteins were extracted from roots and separated by two-dimensional polyacrylamide gel electrophoresis. In the sensitive rapeseed line, 35 protein spots were differentially expressed under drought stress, and proteins related to metabolism, energy, disease/defense, and transport were decreased. In the tolerant line, 32 protein spots were differentially expressed under drought stress, and proteins involved in metabolism, disease/defense, and transport were increased, while energy-related proteins were decreased. Six protein spots in F1 hybrid were common among expressed proteins in the drought-sensitive and -tolerant lines. Notably, tubulin beta-2 and heat shock protein 70 were decreased in the drought-sensitive line and hybrid F1 plants, while jasmonate-inducible protein and 20S proteasome subunit PAF1 were increased in the F1 hybrids and drought-tolerant line. These results indicate that (1) V-type H(+) ATPase, plasma-membrane associated cation-binding protein, HSP 90, and elongation factor EF-2 have a role in the drought tolerance of rapeseed; (2) The decreased levels of heat shock protein 70 and tubulin beta-2 in the drought-sensitive and hybrid F1 lines might explain the reduced growth of these lines in drought conditions. PMID:22543724

  19. Inhibition of Lck enhances glucocorticoid sensitivity and apoptosis in lymphoid cell lines and in chronic lymphocytic leukemia

    PubMed Central

    Harr, MW; Caimi, PF; McColl, KS; Zhong, F; Patel, SN; Barr, PM; Distelhorst, CW

    2011-01-01

    Glucocorticoids are used as part of front-line therapy to treat lymphoid malignancy because of their remarkable ability to induce apoptosis. Yet, in T cells, glucocorticoid-induced apoptosis is readily inhibited by lymphocyte activation and signaling. We have previously shown that the Src family kinase, Lck (lymphocyte cell-specific tyrosine kinase), which is predominantly expressed in T cells, interacts with IP3 receptors to facilitate calcium signaling. Here, we discovered that dexamethasone downregulates Lck, which, in turn, suppresses lymphocyte activation by inhibiting pro-survival calcium oscillations. Moreover, stable expression of shRNAs that selectively targeted Lck or treatment with the Src inhibitor dasatinib (BMS-354825) enhanced apoptosis induction by dexamethasone. To investigate the effect of Lck inhibition in a primary leukemia model, we employed chronic lymphocytic leukemia (CLL) cells that aberrantly expressed Lck and were relatively insensitive to dexamethasone. Lck expression was correlated with resistance to dexamethasone in CLL cells, and its inhibition by dasatinib or other inhibitors markedly enhanced glucocorticoid sensitivity. Collectively, these data indicate that Lck protects cells from glucocorticoid-induced apoptosis and its inhibition enhances sensitivity to dexamethasone. Small-molecule inhibitors of Lck, such as dasatinib, may function to reverse glucocorticoid resistance in some lymphoid malignancies. PMID:20300113

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

    SciTech Connect

    Bernal, Nicols; Martn-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 ?}, ?{sup +}?{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.

  1. 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.

  2. 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.

  3. Probing the local velocity distribution of WIMP dark matter with directional detectors

    SciTech Connect

    Lee, Samuel K.; Peter, Annika H.G. E-mail: annika.peter@uci.edu

    2012-04-01

    We explore the ability of directional nuclear-recoil detectors to constrain the local velocity distribution of weakly interacting massive particle (WIMP) dark matter by performing Bayesian parameter estimation on simulated recoil-event data sets. We discuss in detail how directional information, when combined with measurements of the recoil-energy spectrum, helps break degeneracies in the velocity-distribution parameters. We also consider the possibility that velocity structures such as cold tidal streams or a dark disk may also be present in addition to the Galactic halo. Assuming a CF{sub 4} detector with a 30-kg-yr exposure, a 50-GeV WIMP mass, and a WIMP-nucleon spin-dependent cross-section of 10{sup ?3}pb, we show that the properties of a cold tidal stream may be well constrained. However, measurement of the parameters of a dark-disk component with a low lag speed of ? 50km/s may be challenging unless energy thresholds are improved.

  4. Halo-independent analysis of direct detection data for light WIMPs

    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

    2013-10-01

    We present a halo-independent analysis of direct detection data on ''light WIMPs'', i.e. weakly interacting massive particles with mass close to or below 10 GeV/c{sup 2}. We include new results from silicon CDMS detectors (bounds and excess events), the latest CoGeNT acceptances, and recent measurements of low sodium quenching factors in NaI crystals. We focus on light WIMPs with spin-independent isospin-conserving and isospin-violating interactions with nucleons. For these dark matter candidates we find that a low quenching factor would make the DAMA modulation incompatible with a reasonable escape velocity for the dark matter halo, and that the tension among experimental data tightens in both the isospin-conserving and isospin-violating scenarios. We also find that a new although milder tension appears between the CoGeNT and DAMA annual modulations on one side and the silicon excess events on the other, in that it seems difficult to interpret them as the modulated and unmodulated aspects of the same WIMP dark matter signal.

  5. 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

  6. Glutamine synthetase induction by glucocorticoids in the glucocorticoid-sensitive human leukemic cell line CEM-C7.

    PubMed

    Harmon, J M; Thompson, E B

    1982-02-01

    Treatment of CEM-C7 cells with glucocorticoids produces a 2.5-fold increase in the activity of the enzyme glutamine synthetase (GS). This increase is specific for steroids with glucocorticoid activity adn occurs over a range of steroid concentrations consistent with a receptor-mediated mechanism. Half-maximal and maximal inductions by dexamethasone (dex) occur at 2 X 10(-8) M and 2 X 10(-7) M dex, respectively, concentrations approximately equal to those necessary to produce half and full occupancy of glucocorticoid receptors. GS activity began to increase 1 hour after dex treatment and was complete by 12 hours. This is well before any of the growth inhibitory or cytolytic effects of dex on this cell line occur. This increase was dependent on the presence of glucocorticoid receptors and required both RNA and protein synthesis. Removal of dex following stimulation to maximal levels resulted in a decrease of GS activity to preinduced levels with a half-time of 5 hours. Glutamine deprivation of cells resulted in increased GS activity. However, even in the total absence of glutamine, dex treatment elicited a 2.0-2.5-fold increase in GS activity, ruling out inhibition of glutamine uptake as a mechanism for the dex-induced increase. Experiments with 5'-bromodeoxyuridine (BrdU) demonstrated that GS elevation was sensitive to BrdU substitution of DNA, while dex-induced growth inhibition was not. Therefore GS elevation and growth inhibition in this cell line appear to be independently expressed steroid responses. PMID:6121820

  7. 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 10241024 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 1.8106 Hz without any loses and will report a maximum event rate of 6.11105 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.

  8. 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, Sue; 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

  9. 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

  10. 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 37C at pH 3, 5, 6.5, and 7.4, while drug release kinetics of 5-FU from a pHLNp35-FU formulation were determined at pH 3 and 7.4 at different time points (37C). 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 pHLNp15-FU, pHLNp25-FU and pHLNp35-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

  11. Effect of GABAergic drugs on motor impairment from ethanol, barbital and lorazepam in rat lines selected for differential sensitivity to ethanol.

    PubMed

    Hellevuo, K; Kiianmaa, K; Korpi, E R

    1989-10-01

    The effect of GABAergic drugs on the motor-impairing effects of ethanol, barbital, and lorazepam were studied in the ethanol-sensitive ANT (Alcohol Nontolerant) and ethanol-insensitive AT (Alcohol Tolerant) rat lines, selected for differential ethanol-induced motor impairment on the tilting plane. The basic population from which these rat lines were derived, the mixed (M) line, was also included in the study. The ANT rats were more sensitive to the intoxicating effects of ethanol, barbital, and lorazepam than the AT and M rats at the dose ranges tested. Picrotoxin antagonized motor impairment from all three drugs. Flumazenil (Ro 15-1788) antagonized only the effects of lorazepam, and isoniazid did not modify motor impairment induced by any of the three drugs. These results confirm that the selection of AT and ANT lines has not been specific to ethanol, and that it has increased sensitivity to ethanol, barbital, and lorazepam in the ANT rats rather than decreasing it in the AT rats relative to the M rats. The finding that picrotoxin counteracted motor impairment from ethanol, barbital, and lorazepam support the view that the GABAA receptor complex is important in mediating the intoxicating effects of these drugs. These results also suggest that the genetically-determined difference in sensitivity to ethanol between the rat lines involves GABAergic mechanisms, but it remains to be determined whether any part of the GABAA receptor itself has been affected by the selection program. PMID:2516323

  12. 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.

  13. 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

  14. 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

  15. Altered local field potential activity and serotonergic neurotransmission are further characteristics of the Flinders sensitive line rat model of depression.

    PubMed

    Voget, Mareike; Rummel, Julia; Avchalumov, Yosef; Sohr, Reinhard; Haumesser, Jens K; Rea, Ellis; Math, Aleksander A; Hadar, Ravit; van Riesen, Christoph; Winter, Christine

    2015-09-15

    A significant portion of patients suffering from major depression remains refractory to available antidepressant treatment strategies. This highlights the need for a better understanding of the underlying neuropathology in order to develop rationale-based treatments. Here we aimed to further characterize neurobiological abnormalities of the Flinders Sensitive Line (FSL) rat model of depression. Biochemically, in FSL rats we mainly found increased levels of serotonin in most cortical and subcortical brain regions when compared to controls. Using electrophysiological measurements, in FSL rats we found decreased alpha, beta and low gamma oscillatory activity in the medial prefrontal cortex and nucleus accumbens and decreased alpha and beta as well as increased low gamma oscillatory activity in the subthalamicus nucleus when compared to controls. In summary, we show distinct neurochemical properties in combination with particular oscillatory activity patterns for brain areas thought to be pathophysiologically relevant for depression. Our data contribute to the further understanding of neurobiological alterations in the FSL rat model of depression that could provide a basis for research into future therapeutic strategies. PMID:26025511

  16. 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

  17. 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.

  18. 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.

  19. Differential Mitochondrial Electron Transport through the Cyanide-Sensitive and Cyanide-Insensitive Pathways in Isonuclear Lines of Cytoplasmic Male Sterile, Male Fertile, and Restored Petunia1

    PubMed Central

    Connett, Marie B.; Hanson, Maureen R.

    1990-01-01

    Three pairs of isonuclear lines of cytoplasmic male sterile (CMS) and fertile Petunia cells (Petunia hybrida [Hook] Vilm. and Petunia parodii L.S.M.) grown in suspension culture were examined for sensitivity to inhibitors of respiratory electron transport at time-points after transfer into fresh media. Cells from CMS lines differed from cells of fertile lines in their utilization of the cyanide-insensitive oxidase pathway. Under our culture regime, after approximately 3 days of culture cells from the CMS lines exhibited much lower cyanide-insensitive, salicylhydroxamic acid-sensitive respiration than cells from the fertile lines. This respiratory difference was shown to be specific to the mitochondrial alternative oxidase pathway by using other characteristic inhibitors of mitochondrial electron transport in experiments with isolated mitochondria. Immature anthers from CMS plants also showed lower alternative oxidase activity relative to anthers from male fertile plants, but no such difference was detected in leaf tissue, ovary or perianth tissue, or anthers collected just prior to anthesis. A cell line from a fertile plant carrying a nuclear fertility restorer gene and the CMS cytoplasm exhibited increased activity of the alternative pathway compared with the CMS lines. PMID:16667667

  20. 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

  1. Increased accumulation and retention of micellar paclitaxel in drug-sensitive and P-glycoprotein-expressing cell lines following ultrasound exposure.

    PubMed

    Wan, Chung Ping Leon; Jackson, John K; Pirmoradi, Fatemeh Nazly; Chiao, Mu; Burt, Helen M

    2012-05-01

    Ultrasound treatment has been shown to enhance the uptake of both hydrophilic and hydrophobic compounds into PC3 and Huvec cell lines using an insonation regimen of a single 10-s burst of high-frequency (4 MHz), moderate intensity (32 W/cm(2)) ultrasound. The purpose of this work was to evaluate the effect of this ultrasound regimen on the cellular accumulation of paclitaxel (PTX) loaded in copolymer micellar of methoxy poly(ethylene glycol)-block-poly(D,L-lactide) (MePEG-b-PDLLA) in both drug-sensitive (MDCKII and MCF-7) and P-glycoprotein (Pgp)-expressing (MDCKII-MDR and NCI-ADR) cell lines. There were no effects of ultrasound on hydrodynamic diameters of micelles and the release of FRET pairs, indicating the integrity of micelles was maintained. There was a two-fold increase in intracellular PTX for all ultrasound-treated drug-sensitive cell lines and their respective drug-resistant counterparts compared with no ultrasound. Significant decreases in drug efflux rates were observed at 20, 40 and 60 min for both drug-sensitive and -resistant cell lines receiving ultrasound. The enhanced accumulation and retention of PTX by ultrasound resulted in greater cytotoxicity in both MDCKII and MDCKII-MDR cell lines, as indicated by the MTS assay. These data suggest that ultrasound may facilitate the uptake of intact paclitaxel-loaded micelles into cells, allowing greater retention of drug in both Pgp and non-Pgp-expressing cells. PMID:22425383

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

    PubMed

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

    2015-01-01

    As a population, non-Hodgkin's lymphoma (NHL) cell lines positive for the t(14;18) translocation and/or possessing elevated BCL2 copy number (CN; BCL2(High)) are exquisitely sensitive to navitoclax or the B-cell lymphoma protein-2 (BCL-2)-selective inhibitor venetoclax. Despite this, some BCL2(High) cell lines remain resistant to either agent. Here we show that the MCL-1-specific inhibitor A-1210477 sensitizes these cell lines to navitoclax. Chemical segregation of this synergy with the BCL-2-selective inhibitor venetoclax or BCL-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 BCL2(High) NHL cell lines to a similar extent as A-1210477. A-1210477 also synergized with navitoclax in the majority of BCL2(Low) NHL cell lines. However, chemical segregation with venetoclax or A-1155463 revealed that synergy was driven by BCL-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 (BCL2(Low)) that could benefit from BCL-XL (navitoclax)-driven combination therapy. PMID:26565405

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

    PubMed Central

    Hindle, Allyson G.; Martin, Sandra L.

    2013-01-01

    13-lined ground squirrels, Ictidomys tridecemlineatus, are obligate hibernators that transition annually between summer homeothermy and winter heterothermy wherein they exploit episodic torpor bouts. Despite cerebral ischemia during torpor and rapid reperfusion during arousal, hibernator brains resist damage and the animals emerge neurologically intact each spring. We hypothesized that protein changes in the brain underlie winter neuroprotection. To identify candidate proteins, we applied a sensitive 2D gel electrophoresis method to quantify protein differences among forebrain extracts prepared from ground squirrels in two summer, four winter and fall transition states. Proteins that differed among groups were identified using LC-MS/MS. Only 84 protein spots varied significantly among the defined states of hibernation. Protein changes in the forebrain proteome fell largely into two reciprocal patterns with a strong body temperature dependence. The importance of body temperature was tested in animals from the fall; these fall animals use torpor sporadically with body temperatures mirroring ambient temperatures between 4 and 21C as they navigate the transition between summer homeothermy and winter heterothermy. Unlike cold-torpid fall ground squirrels, warm-torpid individuals strongly resembled the homeotherms, indicating that the changes observed in torpid hibernators are defined by body temperature, not torpor per se. Metabolic enzymes were largely unchanged despite varied metabolic activity across annual and torpor-arousal cycles. Instead, the majority of the observed changes were cytoskeletal proteins and their regulators. While cytoskeletal structural proteins tended to differ seasonally, i.e., between summer homeothermy and winter heterothermy, their regulatory proteins were more strongly affected by body temperature. Changes in the abundance of various isoforms of the microtubule assembly and disassembly regulatory proteins dihydropyrimidinase-related protein and stathmin suggested mechanisms for rapid cytoskeletal reorganization on return to euthermy during torpor-arousal cycles. PMID:23951209

  4. Comparative in vitro sensitivities of human immune cell lines, vaginal and cervical epithelial cell lines, and primary cells to candidate microbicides nonoxynol 9, C31G, and sodium dodecyl sulfate.

    PubMed

    Krebs, Fred C; Miller, Shendra R; Catalone, Bradley J; Fichorova, Raina; Anderson, Deborah; Malamud, Daniel; Howett, Mary K; Wigdahl, Brian

    2002-07-01

    In experiments to assess the in vitro impact of the candidate microbicides nonoxynol 9 (N-9), C31G, and sodium dodecyl sulfate (SDS) on human immune and epithelial cell viability, cell lines and primary cell populations of lymphocytic and monocytic origin were generally shown to be equally sensitive to exposures ranging from 10 min to 48 h. However, U-937 cells were more sensitive to N-9 and C31G after 48 h than were primary monocyte-derived macrophages. Cytokine activation of monocytes and lymphocytes had no effect on cell viability following exposure to these microbicidal compounds. Primary and passaged vaginal epithelial cultures and cell lines differed in sensitivity to N-9 and C31G but not SDS. These studies provide a foundation for in vitro experiments in which cell lines of human immune and epithelial origin can be used as suitable surrogates for primary cells to further investigate the effects of microbicides on cell metabolism, membrane composition, and integrity and the effects of cell type, proliferation, and differentiation on microbicide sensitivity. PMID:12069993

  5. Comparative In Vitro Sensitivities of Human Immune Cell Lines, Vaginal and Cervical Epithelial Cell Lines, and Primary Cells to Candidate Microbicides Nonoxynol 9, C31G, and Sodium Dodecyl Sulfate

    PubMed Central

    Krebs, Fred C.; Miller, Shendra R.; Catalone, Bradley J.; Fichorova, Raina; Anderson, Deborah; Malamud, Daniel; Howett, Mary K.; Wigdahl, Brian

    2002-01-01

    In experiments to assess the in vitro impact of the candidate microbicides nonoxynol 9 (N-9), C31G, and sodium dodecyl sulfate (SDS) on human immune and epithelial cell viability, cell lines and primary cell populations of lymphocytic and monocytic origin were generally shown to be equally sensitive to exposures ranging from 10 min to 48 h. However, U-937 cells were more sensitive to N-9 and C31G after 48 h than were primary monocyte-derived macrophages. Cytokine activation of monocytes and lymphocytes had no effect on cell viability following exposure to these microbicidal compounds. Primary and passaged vaginal epithelial cultures and cell lines differed in sensitivity to N-9 and C31G but not SDS. These studies provide a foundation for in vitro experiments in which cell lines of human immune and epithelial origin can be used as suitable surrogates for primary cells to further investigate the effects of microbicides on cell metabolism, membrane composition, and integrity and the effects of cell type, proliferation, and differentiation on microbicide sensitivity. PMID:12069993

  6. Mitotic Slippage and Expression of Survivin Are Linked to Differential Sensitivity of Human Cancer Cell-Lines to the Kinesin-5 Inhibitor Monastrol

    PubMed Central

    Hershfinkel, Michal; Gheber, Larisa

    2015-01-01

    The mitotic Kinesin-5 motor proteins crosslink and slide apart antiparallel spindle microtubules, thus performing essential functions in mitotic spindle dynamics. Specific inhibition of their function by monastrol-like small molecules has been examined in clinical trials as anticancer treatment, with only partial success. Thus, strategies that improve the efficiency of monastrol-like anticancer drugs are required. In the current study, we examined the link between sensitivity to monastrol and occurrence of mitotic slippage in several human cell-lines. We found that the rank of sensitivity to monastrol, from most sensitive to least sensitive, is: AGS>HepG2>Lovo>Du145?HT29. We show correlation between the sensitivity of a particular cell-line to monastrol and the tendency of the same cell-line to undergo mitotic slippage. We also found that in the monastrol resistant HT29 cells, prolonged monastrol treatments increase mRNA and protein levels of the chromosomal passenger protein survivin. In contrast, survivin levels are not increased by this treatment in the monastrol-sensitive AGS cells. We further show that over-expression of survivin in the monastrol-sensitive AGS cells reduces mitotic slippage and increases resistance to monastrol. Finally, we show that during short exposure to monastrol, Si RNA silencing of survivin expression reduces cell viability in both AGS and HT29 cells. Our data suggest that the efficiency of anti-cancer treatment with specific kinesin-5 inhibitors may be improved by modulation of expression levels of survivin. PMID:26035434

  7. Improved Limits on Spin-Dependent WIMP-Proton Interactions from a Two Liter CF$_3$I Bubble Chamber

    SciTech Connect

    Behnke, E.; Behnke, J.; Brice, S.J.; Broemmelsiek, D.; Collar, J.I.; Cooper, P.S.; Crisler, M.; Dahl, C.E.; Fustin, D.; Hall, J.; Hinnefeld, J.H.; /Indiana U., South Bend /Fermilab /Indiana U., South Bend /Fermilab /Indiana U., South Bend /Fermilab

    2010-08-01

    Data from the operation of a bubble chamber filled with 3.5 kg of CF{sub 3}I in a shallow underground site are reported. An analysis of ultrasound signals accompanying bubble nucleations confirms that alpha decays generate a significantly louder acoustic emission than single nuclear recoils, leading to an efficient background discrimination. Three dark matter candidate events were observed during an effective exposure of 28.1 kg-day, consistent with a neutron background. This observation provides the strongest direct detection constraint to date on WIMP-proton spin-dependent scattering for WIMP masses > 20 GeV/c{sup 2}.

  8. 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

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

    SciTech Connect

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

    2012-11-15

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

  10. Biological heterogeneity and radiation sensitivity of in vitro propagated lung metastatic lines originated from a transplantable squamous cell carcinoma of BALB/c mouse

    SciTech Connect

    Jamasbi, R.J.; Perkins, E.H. )

    1990-03-01

    Seven cell lines established from a diethylnitrosamine (DEN)-induced forestomach carcinoma (DEN3) of a BALB/c mouse and its six pulmonary metastatic foci were used to study the biological and functional diversity of tumor cells. DEN3 is a highly tumorigenic line capable of forming lung metastases readily. Six metastatic nodules were isolated from the lungs of syngeneic mice and six cell lines were established. The cell lines differed in characteristics such as tumorigenicity, metastatic capability, and in vivo and in vitro growth properties. Radiation sensitivity of these cell lines was examined by exposure, at near confluency stage of in vitro growth, to doses of 2.5 to 50 Gray (Gy) X-rays (1 Gy = 100 rads). Shortly after exposure (approximately 5 min), the cells were harvested and 10(5) cells were cultured or inoculated into syngeneic mice, or both. Growth of three of the six cell lines tested was prohibited by 5 Gy. However, some populations from the other cell lines were able to survive 5 or 10 Gy. Progenies of the cells that survived primary radiation exposure after several in vitro passages were able to withstand another exposure of the same magnitude but not a higher dose. The X-rayed survivor cells also maintained their tumorigenic potential.

  11. 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

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

    NASA Astrophysics Data System (ADS)

    Jackson, C. B.; Servant, Graldine; 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.

  13. 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.

  14. 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.

  15. Dark matter spin-dependent limits for WIMP interactions on 19F by PICASSO

    NASA Astrophysics Data System (ADS)

    Archambault, S.; Aubin, F.; Auger, M.; Behnke, E.; Beltran, B.; Clark, K.; Dai, X.; Davour, A.; Farine, J.; Faust, R.; Genest, M.-H.; Giroux, G.; Gornea, R.; Krauss, C.; Kumaratunga, S.; Lawson, I.; Leroy, C.; Lessard, L.; Levy, C.; Levine, I.; MacDonald, R.; Martin, J.-P.; Nadeau, P.; Noble, A.; Piro, M.-C.; Pospisil, S.; Shepherd, T.; Starinski, N.; Stekl, I.; Storey, C.; Wichoski, U.; Zacek, V.

    2009-11-01

    The PICASSO experiment at SNOLAB reports new results for spin-dependent WIMP interactions on 19F using the superheated droplet technique. A new generation of detectors and new features which enable background discrimination via the rejection of non-particle induced events are described. First results are presented for a subset of two detectors with target masses of 19F of 65 g and 69 g respectively and a total exposure of 13.75 0.48 kgd. No dark matter signal was found and for WIMP masses around 24 GeV /c2 new limits have been obtained on the spin-dependent cross section on 19F of ?F = 13.9 pb (90% C.L.) which can be converted into cross section limits on protons and neutrons of ?p = 0.16 pb and ?n = 2.60 pb respectively (90% C.L.). The obtained limits on protons restrict recent interpretations of the DAMA/LIBRA annual modulations in terms of spin-dependent interactions.

  16. Inhibition of PI3K/Akt/mTOR signaling pathway enhances the sensitivity of the SKOV3/DDP ovarian cancer cell line to cisplatin in vitro

    PubMed Central

    Cai, Yunlang; Tan, Xiaoqiang; Liu, Jun; Shen, Yang; Wu, Di; Ren, Mulan; Yu, Dandan

    2014-01-01

    The activation of the PI3K/AKT/mTOR pathway plays a key role in ovarian cancer tumorigenesis, progression and chemotherapy resistance. This study aimed to explore the possible mechanism that PI-103, a dual inhibitor of phosphatidylinositide 3-kinase and mTOR, enhances the sensitivity of SKOV3/DDP ovarian cancer cell line to cisplatin chemotherapy. The results showed that PI-103 could significantly increase the sensitivity of SKVO3/DDP cells to cisplatin through inhibiting the activation of PI3K/Akt/mTOR signaling pathway and inducing cell cycle arrest and apoptosis. PMID:25400422

  17. 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

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

    PubMed Central

    2012-01-01

    Background The epidermal growth factor receptor (EGFR) is an established target for anti-cancer treatment in different tumour types. Two different strategies have been explored to inhibit this pivotal molecule in epithelial cancer development: small molecules TKIs and monoclonal antibodies. ErbB/HER-targeting by monoclonal antibodies such as cetuximab and trastuzumab or tyrosine-kinase inhibitors as gefitinib or erlotinib has been proven effective in the treatment of advanced NSCLC. Results In this study we explored the potential of combining either erlotinib with cetuximab or trastuzumab to improve the efficacy of EGFR targeted therapy in EGFR wild-type NSCLC cell lines. Erlotinib treatment was observed to increase EGFR and/or HER2 expression at the plasma membrane level only in NSCLC cell lines sensitive to the drug inducing protein stabilization. The combined treatment had marginal effect on cell proliferation but markedly increased antibody-dependent, NK mediated, cytotoxicity in vitro. Moreover, in the Calu-3 xenograft model, the combination significantly inhibited tumour growth when compared with erlotinib and cetuximab alone. Conclusion Our results indicate that erlotinib increases surface expression of EGFR and/or HER2 only in EGFR-TKI sensitive NSCLC cell lines and, in turns, leads to increased susceptibility to ADCC both in vitro and in a xenograft models. The combination of erlotinib with monoclonal antibodies represents a potential strategy to improve the treatment of wild-type EGFR NSCLC patients sensitive to erlotinib. PMID:23234355

  19. 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.

  20. 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.

  1. Hormone Resistance in Two MCF-7 Breast Cancer Cell Lines is Associated with Reduced mTOR Signaling, Decreased Glycolysis, and Increased Sensitivity to Cytotoxic Drugs

    PubMed Central

    Leung, Euphemia Yee; Kim, Ji Eun; Askarian-Amiri, Marjan; Joseph, Wayne R.; McKeage, Mark J.; Baguley, Bruce C.

    2014-01-01

    The mTOR pathway is a key regulator of multiple cellular signaling pathways and is a potential target for therapy. We have previously developed two hormone-resistant sub-lines of the MCF-7 human breast cancer line, designated TamC3 and TamR3, which were characterized by reduced mTOR signaling, reduced cell volume, and resistance to mTOR inhibition. Here, we show that these lines exhibit increased sensitivity to carboplatin, oxaliplatin, 5-fluorouracil, camptothecin, doxorubicin, paclitaxel, docetaxel, and hydrogen peroxide. The mechanisms underlying these changes have not yet been characterized but may include a shift from glycolysis to mitochondrial respiration. If this phenotype is found in clinical hormone-resistant breast cancers, conventional cytotoxic therapy may be a preferred option for treatment. PMID:25232533

  2. Hormone Resistance in Two MCF-7 Breast Cancer Cell Lines is Associated with Reduced mTOR Signaling, Decreased Glycolysis, and Increased Sensitivity to Cytotoxic Drugs.

    PubMed

    Leung, Euphemia Yee; Kim, Ji Eun; Askarian-Amiri, Marjan; Joseph, Wayne R; McKeage, Mark J; Baguley, Bruce C

    2014-01-01

    The mTOR pathway is a key regulator of multiple cellular signaling pathways and is a potential target for therapy. We have previously developed two hormone-resistant sub-lines of the MCF-7 human breast cancer line, designated TamC3 and TamR3, which were characterized by reduced mTOR signaling, reduced cell volume, and resistance to mTOR inhibition. Here, we show that these lines exhibit increased sensitivity to carboplatin, oxaliplatin, 5-fluorouracil, camptothecin, doxorubicin, paclitaxel, docetaxel, and hydrogen peroxide. The mechanisms underlying these changes have not yet been characterized but may include a shift from glycolysis to mitochondrial respiration. If this phenotype is found in clinical hormone-resistant breast cancers, conventional cytotoxic therapy may be a preferred option for treatment. PMID:25232533

  3. The transformation of the photo-thermo sensitive genic male-sterile line 261S of rice via an expression vector containing the anti-Waxy gene

    PubMed Central

    Yang, Rui; Zhou, Yongguo; Cao, Yueqin; Yin, Zhongming; Yang, Lijun; Li, Jianyue

    2013-01-01

    Transgenic photo-thermo sensitive genic male sterility Oryza sativa L. cv. 261S plants with the anti-Waxy gene were successfully obtained using an Agrobacterium tumefaciens-mediated co-transformation method. Marker-free homozygous transgenic lines with the anti-Waxy gene were obtained. The setting seed rates of the transgenic plants via self-pollination or via crossing with the restorer line WX99075 rice and the 1000-grain weight of the transgenic plants and the F2 hybrid seeds obtained by crossing the transgenic or non-transgenic plants with the restorer line WX99075 rice, and the number of panicles of the transgenic plants and yields of the F2 hybrid rice, were analysed. Quality indexes of the transgenic plants and of the F2 hybrid seeds were analysed. Our researches results indicate that hybrid female and hybrid descendant edibility could be improved via the introduction of the anti-Waxy gene, but the grain yields of the reserve seeds via self-pollination of the transgenic photo-thermo sensitive genic sterile lines and of the hybrid rice were not affected. PMID:23853508

  4. Gene expression patterns that predict sensitivity to epidermal growth factor receptor tyrosine kinase inhibitors in lung cancer cell lines and human lung tumors

    PubMed Central

    Balko, Justin M; Potti, Anil; Saunders, Christopher; Stromberg, Arnold; Haura, Eric B; Black, Esther P

    2006-01-01

    Background Increased focus surrounds identifying patients with advanced non-small cell lung cancer (NSCLC) who will benefit from treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI). EGFR mutation, gene copy number, coexpression of ErbB proteins and ligands, and epithelial to mesenchymal transition markers all correlate with EGFR TKI sensitivity, and while prediction of sensitivity using any one of the markers does identify responders, individual markers do not encompass all potential responders due to high levels of inter-patient and inter-tumor variability. We hypothesized that a multivariate predictor of EGFR TKI sensitivity based on gene expression data would offer a clinically useful method of accounting for the increased variability inherent in predicting response to EGFR TKI and for elucidation of mechanisms of aberrant EGFR signalling. Furthermore, we anticipated that this methodology would result in improved predictions compared to single parameters alone both in vitro and in vivo. Results Gene expression data derived from cell lines that demonstrate differential sensitivity to EGFR TKI, such as erlotinib, were used to generate models for a priori prediction of response. The gene expression signature of EGFR TKI sensitivity displays significant biological relevance in lung cancer biology in that pertinent signalling molecules and downstream effector molecules are present in the signature. Diagonal linear discriminant analysis using this gene signature was highly effective in classifying out-of-sample cancer cell lines by sensitivity to EGFR inhibition, and was more accurate than classifying by mutational status alone. Using the same predictor, we classified human lung adenocarcinomas and captured the majority of tumors with high levels of EGFR activation as well as those harbouring activating mutations in the kinase domain. We have demonstrated that predictive models of EGFR TKI sensitivity can classify both out-of-sample cell lines and lung adenocarcinomas. Conclusion These data suggest that multivariate predictors of response to EGFR TKI have potential for clinical use and likely provide a robust and accurate predictor of EGFR TKI sensitivity that is not achieved with single biomarkers or clinical characteristics in non-small cell lung cancers. PMID:17096850

  5. Betulinic acid exhibits stronger cytotoxic activity on the normal melanocyte NHEM-neo cell line than on drug-resistant and drug-sensitive MeWo melanoma cell lines.

    PubMed

    Surowiak, Pawel; Drag, Marcin; Materna, Verena; Dietel, Manfred; Lage, Hermann

    2009-01-01

    Betulinic acid is a triterpene isolated from the bark of many plants that exhibits cytotoxicity in several cancer cell lines and is capable of inducing apoptosis. In this study, we examined the cytotoxic activity and apoptotic ability of betulinic acid in the drug-sensitive (MeWo) and drug-resistant melanoma MeWo CIS (cisplatin), MeWo ETO (etoposide), MeWo VIN (vinblastin) and MeWo FOTE (fotemusine) cell lines, as well as in the normal melanocyte NHEM-neo cell line. The results show that betulinic acid exhibited significant cytotoxicity on all the cell lines. However, a sulphorhodamine B cell proliferation assay and immunocytochemical analysis of Ki67 expression revealed the strongest cytotoxicity on the normal melanocyte cell line, NHEM-neo. Flow cytometry and immunocytochemical analysis of caspase 3 expression was used to confirm cell death by apoptosis. In conclusion, betulinic acid is a potential candidate for anticancer research, and may also have an application in the cosmetics industry. PMID:21475863

  6. Effects of a new antioestrogen, idoxifene, on cisplatin- and doxorubicin-sensitive and -resistant human ovarian carcinoma cell lines.

    PubMed Central

    Sharp, S. Y.; Rowlands, M. G.; Jarman, M.; Kelland, L. R.

    1994-01-01

    Pyrrolidino-4-iodotamoxifen (idoxifene) is a new non-steroidal antioestrogen currently undergoing phase I clinical evaluation. Using idoxifene and tamoxifen and two additional analogues of tamoxifen (3-hydroxytamoxifen and 4-iodotamoxifen) and the imidazole-based calmodulin inhibitor, calmidazolium, a strong positive correlation (r2 > 0.95) was observed between cytotoxicity and inhibition of calmodulin-dependent cyclic AMP phosphodiesterase (e.g. mean IC50 across four human ovarian carcinoma cell lines of 4.5 microM for idoxifene and 6.3 microM for tamoxifen). Using two parent human ovarian carcinoma cell lines (41M and CH1; both oestrogen receptor negative) in which acquired resistance to doxorubicin or cisplatin has been generated, we have determined the ability of idoxifene to overcome resistance in these lines. At a non-toxic concentration of 2 microM, idoxifene appeared at least as effective as the clinically used multidrug resistance modifiers verapamil and tamoxifen in overcoming doxorubicin resistance in two acquired resistant cell lines shown to overexpress the P-170 efflux glycoprotein. Non-cross-resistance between cisplatin and idoxifene was observed in two acquired resistant cell lines possessing contrasting mechanisms of resistance to cisplatin (41McisR6 reduced drug transport and CH1cisR6 resistance mediated at the level of DNA). In one of four cell lines (CH1), synergism between idoxifene and cisplatin was observed by median effect analysis. However, with the 41M and its 6-fold cisplatin-resistant variant, antagonism was observed. These observations made by median effect analysis appeared to be unrelated to platinum uptake or removal of platinum-induced DNA interstrand cross-links. These in vitro data suggest that idoxifene may be usefully combined with doxorubicin in the clinical setting, but caution should be exercised in combining it with cisplatin in the treatment of certain tumours. Images Figure 3 PMID:8080723

  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. 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.

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

    PubMed Central

    Marton, Lvia; Nagy, Gergely N.; Ozohanics, Olivr; Lbas, Anik; Krmos, Balzs; Olh, Julianna; Vkey, Kroly; Vrtessy, Beta 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 (40C), 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

  11. 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

  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; ?MURA, 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. 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

  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. 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.

  17. 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

  18. 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

  19. 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.

  20. An improved line list for water vapor in the 1.5 m transparency window by highly sensitive CRDS between 5852 and 6607 cm-1

    NASA Astrophysics Data System (ADS)

    Leshchishina, O.; Mikhailenko, S. N.; Mondelain, D.; Kassi, S.; Campargue, A.

    2013-11-01

    The absorption spectrum of water vapor in natural isotopic abundance has been recorded by high sensitivity Continuous Wave Cavity Ring Down Spectroscopy (CW-CRDS) between 5852 and 6607 cm-1. The investigated region covers the 1.5 ?m transparency window of major importance for atmospheric applications. The achieved sensitivity of the recordings varies from ?min ?210-11 to 210-10 cm-1 and allows for a significant amount of new or more accurate observations compared to previous studies. Measured line intensities cover a range of six orders of magnitude (210-30-210-24 cm/molecule at room temperature). The vibration-rotation assignments were performed using known experimental energy levels and calculated spectra based on variational calculations by Schwenke and Partridge. Five thousand seven hundred and twenty seven lines were assigned to 6379 transitions of six water isotopologues (H216O, H218O, H217O, HD16O, HD18O and HD17O). The first detection of lines due to HD17O in natural water (relative abundance on the order of 1.110-7) illustrates the sensitivity of the recordings. Most of the 1842 newly reported transitions belong to the main isotopologue (1022 transitions) and to the HD16O isotopologue (684 transitions). Sixty-three levels are newly determined and 22 are corrected by more than 0.015 cm-1 compared to those recommended by the water IUPAC task group. Overall, a list of 6589 transitions was constructed for the studied region. The present CRDS line list complemented with 210 strong transitions from the literature is believed to be the most complete empirical list of the region. The obtained results are critically compared to recent IUPAC task group compilations. Overall the agreement between variational and measured intensities is very satisfactory. We nevertheless point out a number of important disagreements for some lines of the highly excited bending bands, mainly 4?2 of H216O.

  1. 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

  2. Use of IL-18 production in a human keratinocyte cell line to discriminate contact sensitizers from irritants and low molecular weight respiratory allergens.

    PubMed

    Corsini, Emanuela; Mitjans, Montserrat; Galbiati, Valentina; Lucchi, Laura; Galli, Corrado L; Marinovich, Marina

    2009-08-01

    Assessment of allergenic potential of chemicals is performed using animal models, such as the murine local lymph node assay, which does not distinguish between respiratory and contact allergens. Progress in understanding the mechanisms of skin sensitization, provides us with the opportunity to develop in vitro tests as an alternative to in vivo sensitization testing. The aim of the present study was to evaluate the possibility to use intracellular interleukin-18 (IL-18) production to assess in vitro the contact sensitization potential of low molecular weight chemicals. The human keratinocyte cell line NCTC2455 was used. Cells were exposed to contact allergens (cinnamaldehyde, dinitrochlorobenzene, glyoxal, isoeugenol, p-phenylediamine, resorcinol, tetramethylthiuram disulfide, 2-mercaptobenzothiazole, 4-nitrobenzylbromide), to proaptens (cinnamyl alcohol, eugenol), to respiratory allergens (diphenylmethane diisocyanate, trimellitic anhydride, ammonium hexachloroplatinate) and to irritants (sodium lauryl sulphate, salicylic acid, phenol). Cell associated IL-18 were evaluated 24 later. At not cytotoxic concentrations (cell viability higher of 75%, as assessed by MTT reduction assay), all contact sensitizers, including proaptens, induced a dose-related increase in IL-18, whereas both irritants and respiratory failed. Similar results were also obtained using primary human keratinocytes. Results were reproducible, and the method could be transferred to another laboratory, suggesting the potential use of the test in immunotoxicity testing strategies. Overall, results obtained indicated that cell-associated IL-18 may provide an in vitro tool for identification and discrimination of contact versus respiratory allergens and/or irritants. PMID:19397996

  3. Deficiency of the Caenorhabditis elegans DNA polymerase eta homologue increases sensitivity to UV radiation during germ-line development.

    PubMed

    Ohkumo, Tsuyoshi; Masutani, Chikahide; Eki, Toshihiko; Hanaoka, Fumio

    2006-01-01

    Defects in the human XPV/POLH gene result in the variant form of the disease xeroderma pigmentosum (XP-V). The gene encodes DNA polymerase eta (Poleta), which catalyzes translesion synthesis (TLS) past UV-induced cyclobutane pyrimidine dimers (CPDs) and other lesions. To further understand the roles of Poleta in multicellular organisms, we analyzed phenotypes caused by suppression of Caenorhabditis elegans POLH (Ce-POLH) by RNA interference (RNAi). F1 and F2 progeny from worms treated by Ce-POLH-specific RNAi grew normally, but F1 eggs laid by worms treated by RNAi against Ce-POLD, which encodes Poldelta did not hatch. These results suggest that Poldelta but not Poleta is essential for C. elegans embryogenesis. Poleta-targeted embryos UV-irradiated after egg laying were only moderately sensitive. In contrast, Poleta-targeted embryos UV-irradiated prior to egg laying exhibited severe sensitivity, indicating that Poleta contributes significantly to damage tolerance in C. elegans in early embryogenesis but only modestly at later stages. As early embryogenesis is characterized by high levels of DNA replication, Poleta may confer UV resistance in C. elegans, perhaps by catalyzing TLS in early embryogenesis. PMID:16565574

  4. 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.

  5. 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.

  6. 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.

  7. Flies who cannot take the heat: genome-wide gene expression analysis of temperature-sensitive lethality in an inbred line of Drosophila melanogaster.

    PubMed

    Vermeulen, C J; Srensen, P; Gagalova, K K; Loeschcke, V

    2014-10-01

    Fitness decreases associated with inbreeding depression often become more pronounced in a stressful environment. The functional genomic causes of these inbreeding-by-environment (IנE) interactions, and of inbreeding depression in general, are poorly known. To further our understanding of IנE interactions, we performed a genome-wide gene expression study of a single inbred line that suffers from temperature-sensitive lethality. We confirmed that increased differential expression between the thermosensitive line and the control line occurs at the restrictive temperature. This demonstrates that IנE interactions in survival are reflected in similar IנE interactions at the gene expression level. To make an impression of the cellular response associated with the lethal effect, we analysed all functional annotation terms that were overrepresented among the differentially expressed genes. Some sets of differentially expressed genes function in the general stress response, and these are more likely to also be differentially expressed in other studies of inbreeding, inbreeding depression, immunity and heat stress. Other sets of differentially expressed genes are shared with studies of gene expression in inbred lines, but not studies of the response to extrinsic stress, and represent a general transcriptomic signature of inbreeding. Finally, some sets of genes have an annotation that is not reported in other studies. These we consider to be candidates for the genes harbouring the mutations responsible for the thermosensitive phenotype, as these mutations are expected to be unique to this line. These genes may also serve as candidate QTL in studies of thermal tolerance and heat resistance. PMID:25233925

  8. Modulation of cisplatin sensitivity in human ovarian carcinoma A2780 and SKOV3 cell lines by sulforaphane.

    PubMed

    Hunakova, Luba; Gronesova, Paulina; Horvathova, Eva; Chalupa, Ivan; Cholujova, Dana; Duraj, Jozef; Sedlak, Jan

    2014-11-01

    Cisplatin resistance is one of the major obstacles in the treatment of ovarian cancer. In an effort to look for new possibilities of how to overcome this difficulty, we studied the mechanisms of the interactions between sulforaphane (SFN) and cisplatin (cisPt) in combined treatment of human ovarian carcinoma A2780 and SKOV3 cell lines. Synergy (A2780) and antagonism (SKOV3) found in MTT assay was confirmed by apoptosis. While SFN significantly potentiated cisPt-induced DNA damage in A2780 cells, it protected SKOV3 cells against cisPt-crosslinking. We revealed a less efficient Nrf-2 pathway inducibility by SFN in A2780 compared to SKOV3 cells, when activation of the Nrf-2 pathway incites its protectivity against cisPt. Thus, different activation of the Nrf-2 pathway may explain the dual effects of SFN. PMID:25159039

  9. 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.

  10. H2 Lyman and Werner band lines and their sensitivity for a variation of the proton-electron mass ratio in the gravitational potential of white dwarfs

    NASA Astrophysics Data System (ADS)

    Salumbides, E. J.; Bagdonaite, J.; Abgrall, H.; Roueff, E.; Ubachs, W.

    2015-06-01

    Recently we published an accurate analysis of molecular hydrogen absorption in the photospheres of the white dwarf stars GD133 and GD29-38, previously observed with the Cosmic Origins Spectrograph aboard the Hubble Space Telescope. Constraints were derived on a possible dependence of the proton-electron mass ratio on gravitational fields that are 10 000 times stronger than at the Earth's surface. Here we present further details of that study, in particular a re-evaluation of the spectrum of the B^1? _u^+ - X^1? _g^+ (v^' },v^' ' }) Lyman bands relevant for the prevailing temperatures (12 000-14 000 K) of the photospheres. The emphasis is on the calculation of so-called Ki-coefficients, that represent the sensitivity of each individual line to a possible change in the proton-electron mass ratio. Such calculations were performed by semi-empirical methods and by ab initio methods providing accurate and consistent values. A full listing is provided for the molecular physics data on the Lyman bands (wavelengths ?i, line oscillator strengths fi, radiative damping rates ?i, and sensitivity coefficients Ki) as required for the analyses of H2-spectra in hot dwarf stars. A similar listing of the molecular physics parameters for the C^1?_u - X^1? _g^+ (v^' },v^' ' }) Werner bands is provided for future use in the analysis of white dwarf spectra.

  11. 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

  12. 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

  13. 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

  14. Findings on H2O2/HNO3 as an indicator of ozoneline-break> sensitivity in Baden-Wrttemberg,line-break> Berlin-Brandenburg, and the Po valleyline-break> based on numerical simulations

    NASA Astrophysics Data System (ADS)

    Hammer, M.-U.; Vogel, B.; Vogel, H.

    2002-09-01

    The usefulness of the indicator H2O2/HNO3 to separate NOx-sensitive and VOC-sensitive regions in the polluted planetary boundary layer on the regional scale is investigated using numerical simulations. The results of box model runs are applied to highlight individual definitions of the NOx-VOC-ozone sensitivity. In particular, different ways to determine the transition value of the indicators H2O2/HNO3 and NOy are explained. Three-dimensional model runs are performed for two model domains in Germany and one domain in the Po valley (Italy). These domains differ significantly in the spatial distribution of the emissions, in the absolute values of the emissions, and in the composition of the VOC. The domains also differ in their meteorological conditions and hence in the involved transport processes. Nevertheless, the transition values of H2O2/HNO3 found for the individual domains differ from 0.2 by less than 15%. This transition value is applied to an emission reduction based on the assumption of all aromatic compound emissions being switched off. It shows that this transition value and the horizontal distribution of H2O2/HNO3 of the base case allow a forecast of those regions where ozone is affected by this emission reduction. This offers the possibility to apply the indicator H2O2/HNO3 and the transition value of 0.2 to observations.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. Low energy nuclear recoils study in noble liquids for low-mass WIMPs

    NASA Astrophysics Data System (ADS)

    Wang, Lu; Mei, Dongming

    2014-03-01

    Detector response to low-energy nuclear recoils is critical to the detection of low-mass dark matter particles-WIMPs (Weakly interacting massive particles). Although the detector response to the processes of low-energy nuclear recoils is subtle and direct experimental calibration is rather difficult, many studies have been performed for noble liquids, NEST is a good example. However, the response of low-energy nuclear recoils, as a critical issue, needs more experimental data, in particular, with presence of electric field. We present a new design using time of flight to calibrate the large-volume xenon detector, such as LUX-Zeplin (LZ) and Xenon1T, energy scale for low-energy nuclear recoils. The calculation and physics models will be discussed based on the available data to predict the performance of the calibration device and set up criteria for the design of the device. A small test bench is built to verify the concepts at The University of South Dakota. This work is supported by DOE grant DE-FG02-10ER46709 and the state of South Dakota.

  20. 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

  1. 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

  2. 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

  3. Study of the radiotherapy sensitization effects and mechanism of capecitabine (Xeloda) against non-small-cell lung cancer cell line A549.

    PubMed

    Zhu, J J; Shan, J J; Sun, L B; Qiu, W S

    2015-01-01

    The purpose of this study was to explore the radiotherapy sensitization effects and the mechanism of capecitabine (Xeloda) against the non-small-cell lung cancer cell line, A549. ?-[(60)Co] radiation was used as the intervention method. Proliferative inhibition of capecitabine on A549 cells was determined by the CCK-8 method. The effects of capecitabine on the apoptosis rate and cell cycle distribution of A549 were detected with the flow cytometric method. We found that capecitabine inhibited the proliferation of A549 in a dose-dependent manner, notably increased the cell apoptosis rate and blocked the cellular G0/G1 phase after radiotherapy by ?-[(60)Co]. Therefore, capecitabine can significantly increase the radiosensitivity of A549; its mechanism may be related to cell cycle arrest and induction of apoptosis. PMID:26662434

  4. 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.

  5. 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-Bayn, Mara; Sierra, Luisa Mara; Blanco-Gonzlez, 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 270nm. 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 (1M, pH 6.9) at a flow rate of 1mLmin(-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?gL(-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

  6. A retinal pigment epithelium-derived cell line from transgenic mouse harboring temperature-sensitive simian virus 40 large T-antigen gene.

    PubMed

    Kato, K; Ishiguro, S; Yamamoto, H; Yanai, N; Obinata, M; Tamai, M

    1996-12-01

    We established a retinal pigment epithelium-derived cell line from transgenic mouse harboring temperature-sensitive simian virus 40 T-antigen gene (tsSV40T) and examined its characteristics. We enucleated both eyes from a 2-month-old transgenic mouse and removed the retinal pigment epithelial (RPE) cells and neuroretinal cells. After cloning the RPE cells, we obtained a cell line (RPET). RPET cells grew well at 33 degrees C but not at 37 degrees C, expressing on the temperature-sensitive character of tsSV40T, and maintained characters of RPE cells such as T1-tyrosinase production, phagocytosis of rod outer segments, and presence of cytokeratin, microvilli on the cell surface and lysosome-like granules around the Golgi apparatus in the cytoplasm. Conditioned medium (CM) from a culture of neuroretinal cells harboring tsSV40T was essentially required for growth. The factor(s) in CM was heat-and acid labile, but was resistant to trypsin digestion. In the presence of 3% CM, epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) and strong effects on RPET cells, whereas insulin, insulin-like growth factor I (IGF-I), and IGF-II had moderate growth effects. Interestingly, none of these growth factors stimulated the RPET cells in the absence of CM. EHS-Matrix had growth effect, whereas laminin, collagen types I and IV, and fibronectin had no marked growth effects on RPET cells. RPET cells were morphologically changed on a laminin-coated dish. They could not spread on the coated dish, and the majority of the cells floated. But when the floating cells were transferred to non-coated dishes, they immediately attached themselves. These results suggest that RPET cells are a good model for for finding novel growth factor(s) and for investigating the mechanism of cell-laminin attachment. PMID:9078403

  7. Automated and sensitive analysis of 28-epihomobrassinolide in Arabidopsis thaliana by on-line polymer monolith microextraction coupled to liquid chromatography-mass spectrometry.

    PubMed

    Wang, Xin; Ma, Qiao; Li, Min; Chang, Cuilan; Bai, Yu; Feng, Yuqi; Liu, Huwei

    2013-11-22

    By on-line solid phase microextraction with polymer monolith coupled to liquid chromatography-mass spectrometry (SPME-LC-MS), an automated and sensitive method for analysis of the endogenous 28-epihomobrassinolide (28-epihomoBR) in Arabidopsis thaliana was developed in this work. Firstly, a poly(methacrylic acid-co-ethylene dimethacrylate) (poly(MAA-co-EDMA)) monolith was prepared in the capillary and applied in in-tube SPME. Polyethylene glycol (PEG) was used as porogen to adjust the specific surface area and hydrophobicity of the target monolith to get satisfactory permeability, high mechanical strength and good stability. The optimized monolith was then served as extraction medium for analysis of the derivatized 28-epihomoBR in plant samples with the cleanup of matrix and enrichment of desired analyte at the same time. Good linearity was obtained in the linear range of 5-500 ng/L with the coefficient of determination (R(2)) of 0.9996. The limit of detection (S/N=3) of 28-epihomoBR was found to be 2.0 ng/L and the limit of quantification (S/N=10) was 5.0 ng/L. Using this method, the endogenous 0.101 ng/g (FW) 28-epihomoBR was successfully detected from only 400mg A. thaliana samples with satisfactory recovery (80.3-92.1%) and reproducibility (RSD 6.8-9.6%). Comparing with other sample pretreatment methods, this automated on-line SPME-LC-MS method is rapid, sensitive, reproducible and laborsaving. PMID:23915641

  8. Development of Oral Epithelial Cell Line ROE2 with Differentiation Potential from Transgenic Rats Harboring Temperature-Sensitive Simian Virus40 Large T-Antigen Gene

    PubMed Central

    Tabuchi, Yoshiaki; Wada, Shigehito; Ikegame, Mika; Kariya, Ayako; Furusawa, Yukihiro; Hoshi, Nobuhiko; Yunoki, Tatsuya; Suzuki, Nobuo; Takasaki, Ichiro; Kondo, Takashi; Suzuki, Yoshihisa

    2014-01-01

    We have developed an immortalized oral epithelial cell line, ROE2, from fetal transgenic rats harboring temperature-sensitive simian virus 40 large T-antigen gene. The cells grew continuously at either a permissive temperature of 33C or an intermediate temperature of 37C. At the nonpermissive temperature of 39C, on the other hand, growth decreased significantly, and the Sub-G1 phase of the cell cycle increased, indicating that the cells undergo apoptosis at a nonpermissive temperature. Histological and immunocytochemical analyses revealed that ROE2 cells at 37C had a stratified epithelial-like morphology and expressed cytokeratins Krt4 and Krt13, marker proteins for oral nonkeratinized epithelial cells. Global-scale comprehensive microarray analysis, coupled with bioinformatics tools, demonstrated a significant gene network that was obtained from the upregulated genes. The gene network contained 16 genes, including Cdkn1a, Fos, Krt13, and Prdm1, and was associated mainly with the biological process of skin development in the category of biological functions, organ development. These four genes were validated by quantitative real-time polymerase chain reaction, and the results were nearly consistent with the microarray data. It is therefore anticipated that this cell line will be useful as an in vitro model for studies such as physiological functions, as well as for gene expression in oral epithelial cells. PMID:24521861

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

    SciTech Connect

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

    1987-12-01

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

  10. 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.

  11. DHFR-mediated effects of methotrexate in medulloblastoma and osteosarcoma cells: the same outcome of treatment with different doses in sensitive cell lines.

    PubMed

    Neradil, Jakub; Pavlasova, Gabriela; Sramek, Martin; Kyr, Michal; Veselska, Renata; Sterba, Jaroslav

    2015-05-01

    Although methotrexate (MTX) is the most well-known antifolate included in many standard therapeutic regimens, substantial toxicity limits its wider use, particularly in pediatric oncology. Our study focused on a detailed analysis of MTX effects in cell lines derived from two types of pediatric solid tumors: medulloblastoma and osteosarcoma. The main aim of this study was to analyze the effects of treatment with MTX at concentrations comparable to MTX plasma levels in patients treated with high-dose or low-dose MTX. The results showed that treatment with MTX significantly decreased proliferation activity, inhibited the cell cycle at S-phase and induced apoptosis in Daoy and Saos-2 reference cell lines, which were found to be MTX-sensitive. Furthermore, no difference in these effects was observed following treatment with various doses of MTX ranging from 1 to 40 M. These findings suggest the possibility of achieving the same outcome with the application of low-dose MTX, an extremely important result, particularly for clinical practice. Another important aspect of treatment with high-dose MTX in clinical practice is the administration of leucovorin (LV) as an antidote to reduce MTX toxicity in normal cells. For this reason, the combined application of MTX and LV was also included in our experiments; however, this application of MTX together with LV did not elicit any detectable effect. The expression analysis of genes involved in the mechanisms of resistance to MTX was a final component of our study, and the results helped us to elucidate the mechanisms of the various responses to MTX among the cell lines included in our study. PMID:25739012

  12. 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

  13. An ionizing radiation-sensitive CHO mutant cell line: irs-20. IV. Genetic complementation, V(D)J recombination and the scid phenotype.

    PubMed

    Lin, J Y; Mhlmann-Diaz, M C; Stackhouse, M A; Robinson, J F; Taccioli, G E; Chen, D J; Bedford, J S

    1997-02-01

    The genetic defect responsible for hypersensitivity of Chinese hamster ovary (CHO) irs-20 cells to ionizing radiation was found to be recessive in nature and could be complemented to produce wild-type radiosensitivity in irs-20/human hybrids. The radiosensitivities of six hybrid clones were determined based on their colony-forming ability under continuous irradiation at 6 cGy/h. A parallel cytogenetic analysis revealed a concordance between the presence or absence of human chromosome 8 and the resistant or sensitive phenotype. Confirming evidence was obtained using human chromosome 8-specific PCR primers. Positive amplification was obtained in hybrids with wild-type radiosensitivity, while no amplification was obtained in sensitive hybrids. Complementation analysis between radiosensitive CHO irs-20 and murine scid cell lines was carried out to determine whether the defects leading to their ionizing radiation hypersensitivity could be corrected by genetic complementation in the hybrids. Complementation did not occur. A transient V(D)J recombination assay after the introduction of the RAG1 and RAG2 genes indicated that the V(D)J recombination ability of the CHO irs-20 cells was about 10% of that for the CHO wild-type cells for signal join formation with an 80% joining fidelity and only 3% of the parental level for coding join formation. These data show that murine scid and irs-20 mutant hamster cells fall into the same complementation group and show similar defects in V(D)J recombination. PMID:9008208

  14. 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

  15. 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

  16. The role of membrane-like stresses in determining the stability and sensitivity of the Antarctic ice sheets: back pressure and grounding line motion.

    PubMed

    Hindmarsh, Richard C A

    2006-07-15

    Membrane stresses act along thin bodies which are relatively well lubricated on both surfaces. They operate in ice sheets because the bottom is either sliding, or is much less viscous than the top owing to stress and heat softening of the basal ice. Ice streams flow over very well lubricated beds, and are restrained at their sides. The ideal of the perfectly slippery bed is considered in this paper, and the propagation of mechanical effects along an ice stream considered by applying spatially varying horizontal body forces. Propagation distances depend sensitively on the rheological index, and can be very large for ice-type rheologies.A new analytical solution for ice-shelf profiles and grounded tractionless stream profiles is presented, which show blow up of the profile in a finite distance upstream at locations where the flux is non-zero. This is a feature of an earlier analytical solution for a floating shelf.The length scale of decay of membrane stresses from the grounding line is investigated through scale analysis. In ice sheets, such effects decay over distances of several tens of kilometres, creating a vertical boundary layer between sheet flow and shelf flow, where membrane stresses adjust. Bounded, physically reasonable steady surface profiles only exist conditionally in this boundary layer. Where bounded steady profiles exist, adjacent profile equilibria for the whole ice sheet corresponding to different grounded areas occur (neutral equilibrium). If no solution in the boundary layer can exist, the ice-sheet profile must change.The conditions for existence can be written in terms of whether the basal rate factor (sliding or internal deformation) is too large to permit a steady solution. The critical value depends extremely sensitively on ice velocity and the back stress applied at the grounding line. High ice velocity and high stress both favour the existence of solutions and stability. Changes in these parameters can cause the steady solution existence criterion to be traversed, and the ice-sheet dynamics to change.A finite difference model which represents both neutral equilibrium and the dynamical transition is presented, and preliminary investigations into its numerical sensitivity are carried out. Evidence for the existence of a long wavelength instability is presented through the solution of a numerical eigenproblem, which will hamper predictability. PMID:16782608

  17. 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.

  18. 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

  19. Measurement of the quenching and channeling effects in a CsI crystal used for a WIMP search

    NASA Astrophysics Data System (ADS)

    Lee, J. H.; Kim, G. B.; Seong, I. S.; Kim, B. H.; Kim, J. H.; Li, J.; Park, J. W.; Lee, J. K.; Kim, K. W.; Bhang, H.; Kim, S. C.; Choi, Seonho; Choi, J. H.; Joo, H. W.; Lee, S. J.; Olsen, S. L.; Myung, S. S.; Kim, S. K.; Kim, Y. D.; Kang, W. G.; So, J. H.; Kim, H. J.; Lee, H. S.; Hahn, I. S.; Leonard, D. S.; Li, J.; Li, Y. J.; Yue, Q.; Li, X. R.

    2015-05-01

    We have studied channeling effects in a cesium iodide (CsI) crystal that is similar in composition to the ones being used in a search for Weakly Interacting Massive Particles (WIMPs) dark matter candidates, and measured its energy-dependent quenching factor, the relative scintillation yield for electron and nuclear recoils. The experimental results are reproduced with a GEANT4 simulation that includes a model of the scintillation efficiency as a function of electronic stopping power. We present the measured and simulated quenching factors and the estimated effects of channeling.

  20. 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}.

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

    PubMed

    Zhu, Yi-Ping; Bian, Xiao-Jie; Ye, Ding-Wei; Yao, Xu-Dong; Zhang, Shi-Lin; Dai, Bo; Shen, Yi-Jun

    2013-04-01

    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

  2. Conformational properties of nickel(II) octaethyl porphyrin insolution. 1. Resonance excitation profiles and temperature dependence of structure-sensitive Raman lines

    SciTech Connect

    Jentzen, W.; Unger, E.; Karvounis, G.; Dreybrodt, W.; Schweitzer-Stenner, R.; Shelnutt, J.A.

    1996-08-15

    We have measured polarized resonance Raman spectra of nickel(II)octaethylporphyrin in CS{sub 2} and CH{sub 2}Cl{sub 2} solution at different excitation wavelengths (430-580nm) and temperatures (190-130 K). The analysis of the spectra revealed that the structure-sensitive Raman lines v{sub 19} and v{sub 10} can be decomposed consistently into two sublines for all excitation wavelengths and temperatures. In the resonance region of the Q{sub O} and Q{sub V} bands, the 0-1 and 0-0 resonances in the excitation profiles of the low-frequency (LF) sublines of v{sub 19} and v{sub 10} are red-shifted by (150 30) cm{sup -1} with respect to the sublines that are at higher frequencies (HF). In accordance with experimental and theoretical results, this indicates that the LF sublines of v{sub 19} and v{sub 10} result from a nonplanar conformer, whereas the HF sublines correspond to an almost planar conformer. The existence of this known conformational equilibrium insolution is further corroborated by the van`t Hoff behavior of the intensity ratios I{sub LF}/I{sub HF} of the sublines of v{sub 19} and v{sub 10}. From the straight lines in van`t Hoff plot, we calculate that the nonplanar conformer in solution is energetically favored by about 3.0 kJ/mol. 28 refs., 7 figs., 2 tabs.

  3. 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

  4. Differential sensitivity of a mouse myeloid leukemia cell line and normal mouse bone marrow cells to X-ray-induced chromosome aberrations

    SciTech Connect

    Aardema, M.J.; Au, W.W.; Hand, R.E. Jr.; Preston, R.J.

    1985-11-01

    Cell line ML-1 was established from a myelogenous leukemia of an RFM mouse. The ML-1 cells and in vitro normal mouse bone marrow cells were analyzed to determine if there was a differential sensitivity to X-ray-induced chromosome aberrations in G1 cells and/or differences in postirradiation cell cycle progression. Cells identified as being in G1 at the time of irradiation by their staining pattern after replication in 5-bromodeoxyuridine were analyzed for all types of chromosomal aberrations following X-ray doses of 0.5, 1.0, 1.5, and 2.0 Gy. ML-1 cells showed a greater sensitivity to the induction of both chromosome-type aberrations and chromatid-type aberrations compared to normal mouse bone marrow cells, which only contained chromosome-type aberrations. The presence of chromatid-type aberrations in the ML-1 cells and not normal bone marrow cells suggested a differential progression through the cell cycle for the two cell types after irradiation. Mitotic index and flow cytometric analyses were performed and showed that both cell types have a delay in progression from G2 into mitosis, but only the normal mouse bone marrow cells have a delay in progression from G1 into S, as well as delayed progression through the S phase following X-irradiation. These results indicate that the ML-1 leukemia cells have an increased radiosensitivity. These same characteristics have been observed in ataxia telangiectasia cells and may well represent a general feature of cells with increased radiosensitivity.

  5. 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

  6. Improved Limits on Spin-Dependent WIMP-Proton Interactions from a Two Liter CF{sub 3}I Bubble Chamber

    SciTech Connect

    Behnke, E.; Behnke, J.; Hinnefeld, J. H.; Levine, I.; Shepherd, T.; Brice, S. J.; Broemmelsiek, D.; Cooper, P. S.; Crisler, M.; Hall, J.; Hu, M.; Ramberg, E.; Sonnenschein, A.; Collar, J. I.; Dahl, C. E.; Fustin, D.; Szydagis, M.

    2011-01-14

    Data from the operation of a bubble chamber filled with 3.5 kg of CF{sub 3}I in a shallow underground site are reported. An analysis of ultrasound signals accompanying bubble nucleations confirms that alpha decays generate a significantly louder acoustic emission than single nuclear recoils, leading to an efficient background discrimination. Three dark matter candidate events were observed during an effective exposure of 28.1 kg day, consistent with a neutron background. This observation provides strong direct detection constraints on weakly interacting massive particle (WIMP)-proton spin-dependent scattering for WIMP masses >20 GeV/c{sup 2}.

  7. Low dose high energy x-ray in-line phase sensitive imaging prototype: Investigation of optimal geometric conditions and design parameters.

    PubMed

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

    2015-12-17

    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 ?m 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 ?m 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 ?m 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

  8. 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

  9. JAK2V617F Drives Mcl-1 Expression and Sensitizes Hematologic Cell Lines to Dual Inhibition of JAK2 and Bcl-xL

    PubMed Central

    Guo, Jun; Roberts, Lisa; Chen, Zhui; Merta, Philip J.; Glaser, Keith B.; Shah, O. Jameel

    2015-01-01

    Constitutive activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) axis is fundamental to the molecular pathogenesis of a host of hematological disorders, including acute leukemias and myeloproliferative neoplasms (MPN). We demonstrate here that the major JAK2 mutation observed in these diseases (JAK2V617F) enforces Mcl-1 transcription via STAT3 signaling. Targeting this lesion with JAK inhibitor I (JAKi-I) attenuates STAT3 binding to the Mcl-1 promoter and suppresses Mcl-1 transcript and protein expression. The neutralization of Mcl-1 in JAK2V617F-harboring myelodyssplastic syndrome cell lines sensitizes them to apoptosis induced by the BH3-mimetic and Bcl-xL/Bcl-2 inhibitor, ABT-263. Moreover, simultaneously targeting JAK and Bcl-xL/-2 is synergistic in the presence of the JAK2V617F mutation. These findings suggest that JAK/Bcl-xL/-2 inhibitor combination therapy may have applicability in a range of hematological disorders characterized by activating JAK2 mutations. PMID:25781882

  10. 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

  11. 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.; Arajo, 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.; Lscher, 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 ?-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 ?-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.

  12. Differential mitochondrial electron transport through the cyanide-sensitive and cyanide-insensitive pathways in isonuclear lines of cytoplasmic male sterile, male fertile, and restored petunia. [Petunia parodii L. S. M

    SciTech Connect

    Connett, M.B.; Hanson, M.R. )

    1990-08-01

    Three pairs of isonuclear lines of cytoplasmic male sterile (CMS) and fertile Petunia cells (Petunia hybrida (Hook) Vilm. and Petunia parodii L.S.M.) grown in suspension culture were examined for sensitivity to inhibitors of respiratory electron transport at time-points after transfer into fresh media. Cells from CMS lines differed from cells of fertile lines in their utilization of the cyanide-insensitive oxidase pathway. Under our culture regime, after approximately 3 days of culture cells from the CMS lines exhibited much lower cyanide-insensitive, salicylhydoxamic acid-sensitive respiration than cells from the fertile lines. This respiratory difference was shown to be specific to the mitochondrial alternative oxidase pathway by using other characteristic inhibitors of mitochondrial electron transport in experiments with isolated mitochondria. Immature anthers from CMS plants also showed lower alternative oxidase activity relative to anthers from male fertile plants, but no such difference was detected in leaf tissue, ovary or perianth tissue, or anthers collected just prior to anthesis. A cell line from a fertile plant carrying a nuclear fertility restorer gene and the CMS cytoplasm exhibited increased activity of the alternative pathway compared with the CMS lines.

  13. 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

  14. 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

  15. 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 ?g/m(3), which is high enough for hygiene management. In the low concentration range lower than 3 ?g/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-?g/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

  16. 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.

  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. 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.

  19. 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 C cm-2 using a 3 nm electron beam.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. Differential sensitivity to x-ray of chromosomes of blood T-lymphocytes and B-and T-cell lines.

    PubMed

    Shiraishi, Y; Minowada, J; Sanberg, A A

    1976-07-01

    Normal T-lymphocytes, B-cell line (CCRF-SB) and T-cell line (CCRF-HSB-2) cells, all diploid in their chromosome constitution, were exposed in vitro to various doses of X-ray and analyzed at their first mitotic division for structural chromosome abnormalities. The irradiation effects were determined also by a viability test of the cells, using trypan blue dye. The irradiated T-cell line (CCRF-HSB-2) showed a remarkably high frequency of chromosome aberrations, including chromosome and chromatid deletions, chromatid exchanges, dicentrics, rings and acentric fragments. On the other hand, the chromosome aberrations observed in the irradiated B-cell line and normal T-lymphocytes consisted mainly of dicentrics, rings, deletions and acentric fragments; the frequency of chromosome and chromatid deletions was low as compared to that of the T-cell line. The cell viability test showed a singificantly higher percent reduction of viable cells at every dose of X-ray in the irradiated T-cell line than in the B-cell line or the normal T-lymphocytes. It is possible that the increased radiosensitivity of the T-cell line is related to the original malignant nature of the cells, which originated from the lymphocytes of a patient with acute lymphoblastic leukemia. PMID:1085743

  5. 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

  6. Limits on Spin-independent Couplings of Light Dark Matter WIMPs with a p-type Point-contact Germanium Detector

    NASA Astrophysics Data System (ADS)

    Lin, S. T.; Wong, H. T.

    New limits on spin-independent WIMP-nucleon coupling using 39.5 kg-days of data taken with a p-type point-contact germanium detector with fiducial mass of 840 g at the Kuo-Sheng Reactor Neutrino Laboratory (KSNL) is presented. Charactering and understanding the anomalous surface behaviour is of particular significance to this study. The slow rise-time of surface events is identified via software pulse shape analysis techniques. In addition, the signal-retaining and background-rejecting efficiencies are implied to clarify the actual bulk and surface events in the mixed regime at sub-keV range. Both efficiencies are evaluated with calibration sources and a novel n-type point-contact germanium detector. Efficiencies-corrected background spectra from the low-background facility at KSNL are derived. Part of the parameter space in cross-section versus WIMP-mass is probed and excluded.

  7. 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

  8. 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.

  9. Atomic Parity Violation, Muon Pair Production in e+e - Collisions and Detection of CDM WIMP-Physics Related to Neutral Vector Boson D1

    NASA Astrophysics Data System (ADS)

    Senju, H.

    1999-11-01

    In our preon model there exists a neutral vector boson D1 which is an isoscalar partner of W(Z) in the vector boson octet. It is shown that the exchange of a D1 of about 1 TeV mass naturally explains a positive excess of the weak charge of atomic cesium recently observed. Other processes occurring through the D1 exchange are discussed, including the detection of CDM WIMP.

  10. Cell lines established by a temperature-sensitive simian virus 40 large-T-antigen gene are growth restricted at the nonpermissive temperature.

    PubMed Central

    Jat, P S; Sharp, P A

    1989-01-01

    The thermolabile large T antigen, encoded by the simian virus 40 early-region mutant tsA58, was used to establish clonal cell lines derived from rat embryo fibroblasts. These cell lines grew continuously at the permissive temperature but upon shift-up to the nonpermissive temperature showed rapidly arrested growth. The growth arrest occurred in either the G1 or G2 phase of the cell cycle. After growth arrest, the cells remained metabolically active as assayed by general protein synthesis and the ability to exclude trypan blue. The inability of these cell lines to divide at the nonpermissive temperature was not readily complemented by the exogenous introduction of other nuclear oncogenes. This finding suggests that either these genes establish cells via different pathways or that immortalization by one oncogene results in a finely balanced cellular state which cannot be adequately complemented by another establishment gene. Images PMID:2542774

  11. 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.

  12. 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

  13. Establishment of a cell line from the ash and privet borer beetle Tylonotus bimaculatus Haldeman and assessment of its sensitivity to diacylhydrazine insecticides.

    PubMed

    Wen, Fayuan; Caputo, Guido; Hooey, Sharon; Bowman, Susan; Pinkney, Kristine; Krell, Peter J; Arif, Basil; Doucet, Daniel

    2015-10-01

    A novel cell line, NRCAN-Tb521, was developed from larvae of the longhorn beetle Tylonotus bimaculatus (Coleoptera: Cerambycidae), a pest of North American ash trees. The cell line has been successfully passaged more than 50 times and displayed very strong attachment to the substrate and a modal chromosomal count distribution of 19. Sequencing of a 649 bp fragment of the mitochondrial cytochrome oxidase I gene confirmed the identity of NRCAN-Tb521 as T. bimaculatus. The response of the cell line to 20-hydroxyecdysone and diacylhydrazine ecdysone agonist insecticides was also studied. At 10(-6) M, 20-hydroxyecdysone, tebufenozide, methoxyfenozide and halofenozide triggered the production of numerous filamentous cytoplasmic extensions, and the cells tended to form aggregates, indicative of a cell differentiation response. This response was followed by a strong decrease in viability after 4 d. Reverse transcription polymerase chain reaction (PCR) experiments and sequencing of PCR fragments showed that the 20E receptor gene EcR is expressed in the cells and that 20E, tebufenozide, methoxyfenozide and halofenozide also induce the expression of the nuclear hormone receptor gene HR3. This report establishes that NRCAN-Tb521 is a valuable in vitro model to study effects of ecdysone agonists in wood-boring cerambycids. PMID:25952767

  14. 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

  15. A highly sensitive method for enantioseparation of fenoprofen and amino acid derivatives by capillary electrophoresis with on-line sample preconcentration.

    PubMed

    Wang, Zhaoyan; Liu, Chao; Kang, Jingwu

    2011-04-01

    A highly sensitive method for enantioseparation of trace fenoprofen and amino acid derivatives by capillary electrophoresis (CE) with vancomycin as the chiral selector was developed. Several CE techniques, such as the partial filling, large-volume sample stacking with EOF as pump plus anion-selective exhaustive injection (LVSEP-ASEI) were involved in the present method to improve the detection sensitivity. With on-column concentration, enantioseparation of racemic fenoprofen and six 9-fluorenylmethyl chloroformate (FMOC)-amino acid derivatives (at the concentration level of ng/mL) with the background electrolyte composed of 100 mmol/L Tris-H(3)PO(4) (pH 6.0) and 2 mmol/L vancomycin was detected readily with the UV detection at 214 nm. Successfully performing LVSEP-ASEI needs a very low EOF that could be depressed by coating the capillary with poly(dimethylacrylamide) solution. The coating also played a role to minimize the adsorption of vancomycin onto the capillary wall. Effect of the injected sample volume and the electrokinetic injection time on the peak area of the enantiomers and their resolution factor were investigated and optimized. Under the optimized conditions, more than 1000-fold enhancement in detection sensitivity compared with the normal injection was achieved. PMID:21342694

  16. Maturation sensitive and resistant t(15;17) NB4 cell lines as tools for APL physiopathology: nomenclature of cells and repertory of their known genetic alterations and phenotypes.

    PubMed

    Roussel, M J; Lanotte, M

    2001-10-29

    Chromosomal translocations, leading to gene rearrangements that generate chimerical proteins, represent one of the initiating events of leukemia. Preleukemia cells eventually develop into overt leukemia by occurrence of secondary genetic alterations (tumor progression). The physiopathology of leukemia has made considerable progress during the last two decades, due to molecular biology investigations on the role played by the altered genes, during neoplasic hemopoiesis. In vitro studies have been facilitated by the establishment of stable leukemia cell lines bearing these gene rearrangements and secondary gene mutations. Investigations on acute promyelocytic leukemia (APL) have benefited from maturation sensitive and resistant cell lines (NB4 and UF-1) derived from APL patient's leukemia cells and bearing the t(15;17). The information concerning the NB4 cell line (responsiveness to retinoid/rexinoid, cAMP, arsenic, mutations causing resistance) is spread in an abundant literature. In this paper, we briefly recapitulate the cellular and molecular features of this cell line and its subclones with the aim of facilitating investigators in their choice of the most appropriate tool for their studies. As redundancy of several names given to NB4 sublines has sometimes created difficulties, we propose a nomenclature for the various NB4 sublines that most investigators certainly would be agreed with. PMID:11704857

  17. 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

  18. Genetic Variants in Cytosolic 5?-Nucleotidase II Are Associated with Its Expression and Cytarabine Sensitivity in HapMap Cell Lines and in Patients with Acute Myeloid LeukemiaS?

    PubMed Central

    Mitra, Amit K.; Crews, Kristine R.; Pounds, Stanley; Cao, Xueyuan; Feldberg, Tanya; Ghodke, Yogita; Gandhi, Varsha; Plunkett, William; Dolan, M. Eileen; Hartford, Christine; Raimondi, Susana; Campana, Dario; Downing, James; Rubnitz, Jeffrey E.; Ribeiro, Raul C.

    2011-01-01

    Cytosolic 5?-nucleotidase II (NT5C2) is involved in the development of 1-?-d-arabinofuranosylcytosine (ara-C) resistance and has been associated with clinical outcome in patients receiving ara-C-based chemotherapy. NT5C2 inactivates ara-C by dephosphorylating ara-C monophosphate to ara-C. In this study, we sequenced NT5C2 in genomic DNA samples from International HapMap project panels with European [Centre d'Etude du Polymorphisme Humain (CEU); n = 90] or African [Yoruba people in Ibadan, Nigeria (YRI); n = 90] ancestry. We identified 41 genetic variants [one insertion-deletion and 40 single nucleotide polymorphisms (SNPs)], including three nonsynonymous SNPs (Y3A, K47R, and Q136R). Twenty-five SNPs were novel and 16 overlapped with the HapMap data. Subjects with African ancestry had NT5C2 mRNA expression levels that was significantly higher than those with European ancestry (p = 0.005). Furthermore, there was a correlation between NT5C2 mRNA expression and ara-C sensitivity in CEU but not in YRI cell lines. None of the nonsynonymous SNPs demonstrated any effect on NT5C2 activity. The genotypes of several SNPs were significantly associated with NT5C2 mRNA expression and/or ara-C sensitivity in CEU cell lines, but very few were significant in YRI cell lines. Of most interest, SNPs (linkage disequilibrium group CEU.12) in the 5?-untranslated region were associated with NT5C2 expression and ara-C sensitivity in HapMap cell lines and with NT5C2 mRNA expression and ara-C sensitivity in diagnostic leukemic blasts from pediatric patients with acute myeloid leukemia. Functional genomics analysis demonstrated that the promoter SNP rs11191612 was associated with altered luciferase activation in reporter assays and altered DNA-protein binding in gel shift assays. These results suggest that genetic variations in NT5C2 influence its expression and, potentially, cellular responses to nucleoside analogs. PMID:21712425

  19. 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

  20. 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

  1. Sensitivity of biochemical test in comparison with other methods for the detection of mycoplasma contamination in human and animal cell lines stored in the National Cell Bank of Iran.

    PubMed

    Molla Kazemiha, Vahid; Amanzadeh, Amir; Memarnejadian, Arash; Azari, Shahram; Shokrgozar, Mohammad Ali; Mahdian, Reza; Bonakdar, Shahin

    2014-10-01

    Mycoplasma contamination in cell culture is considered as serious problem in the manufacturing of biological products. Our goal in this research is to find the best standard and rapid method with high sensitivity, specificity, accuracy and predictive values of positive and negative results for detection of mycoplasma contamination in cell cultures of the National Cell Bank of Iran. In this study, 40 cell lines suspected to mycoplasma contamination were evaluated by three different methods: microbial culture, enzymatic mycoalert() and molecular. Enzymatic evaluation was performed using the mycoalert() kit while in the molecular technique, a universal primer pair was designed based on the common and fixed 16SrRNA ribosomal sequences used. Mycoplasma contaminations in cell cultures with molecular, enzymatic and microbial culture methods were determined as 57.5, 52.5 and 40%, respectively. These results confirmed the higher rate of sensitivity, specificity and accuracy for the molecular method in comparison with enzymatic and microbial methods. Polymerase chain reaction (PCR) assay based on fixed and common sequences in the 16SrRNA, is a useful valuable and reliable technique with high sensitivity, specificity and accuracy for detection of mycoplasma contamination in cell cultures and other biological products. The enzymatic mycoalert() method can be considered as a substitution for conventional microbial culture and DNA staining fluorochrome methods due to its higher sensitivity, specificity and speed of detection (<20 min). PMID:24493067

  2. Volume-sensitive release of organic osmolytes in the human lung epithelial cell line A549: role of the 5-lipoxygenase.

    PubMed

    Holm, Jacob Bak; Grygorczyk, Ryszard; Lambert, Ian Henry

    2013-07-01

    Pathophysiological conditions challenge cell volume homeostasis and perturb cell volume regulatory mechanisms leading to alterations of cell metabolism, active transepithelial transport, cell migration, and death. We report that inhibition of the 5-lipoxygenase (5-LO) with AA861 or ETH 615-139, the cysteinyl leukotriene 1 receptor (CysLT?) with the antiasthmatic drug Zafirlukast, or the volume-sensitive organic anion channel (VSOAC) with DIDS blocks the release of organic osmolytes (taurine, meAIB) and the concomitant cell volume restoration following hypoosmotic swelling of human type II-like lung epithelial cells (A549). Reactive oxygen species (ROS) are produced in A549 cells upon hypotonic cell swelling by a diphenylene iodonium-sensitive NADPH oxidase. The swelling-induced taurine release is suppressed by ROS scavenging (butylated hydroxytoluene, N-acetyl cysteine) and potentiated by H?O?. Ca? mobilization with ionomycin or ATP stimulates the swelling-induced taurine release whereas calmodulin inhibition (W7) inhibits the release. Chelation of the extracellular Ca? (EGTA) had no effect on swelling-induced taurine release but prevented ATP-induced stimulation. H?O?, ATP, and ionomycin were unable to stimulate the taurine release in the presence of AA861 or Zafirlukast, placing 5-LO and CysLT? as essential elements in the swelling-induced activation of VSOAC with ROS and Ca? as potent modulators. Inhibition of tyrosine kinases (genistein, cucurbitacin) reduces volume-sensitive taurine release, adding tyrosine kinases (Janus kinase) as regulators of VSOAC activity. Caspase-3 activity during hypoxia is unaffected by inhibition of 5-LO/CysLT? but reduced when swelling-induced taurine loss via VSOAC is prevented by DIDS excess extracellular taurine, indicating a beneficial role of taurine under hypoxia. PMID:23485709

  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. 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

  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. 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.

  7. 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.).

  8. 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

  9. Calcitonin gene-related peptide rapidly inhibits calcium uptake in osteoblastic cell lines via activation of adenosine triphosphate-sensitive potassium channels.

    PubMed

    Kawase, T; Howard, G A; Roos, B A; Burns, D M

    1996-03-01

    In certain neurons, alternative RNA processing generates calcitonin gene-related peptide (CGRP) from the same gene that encodes the hormone calcitonin. As CGRP-containing nerve fibers are prominent in skeleton, we evaluated the effects of CGRP on osteoblasts. Because the vasodilatory effect of neural CGRP in smooth muscle probably involves inhibition of unstimulated Ca2+ uptake, we examined the acute effects of CGRP on this parameter in rat osteoblastic cells. CGRP inhibits 45Ca2+ uptake in both UMR 106 osteosarcoma and RCOB-3 osteoblastic cells. This inhibition is rapid (0.5 min), occurs with an EC50 of 1 nM, and cannot be demonstrated in the presence of 0.1 mM diltiazem, a blocker of voltage-dependent Ca2+ channels. Depolarization of bone cells with high extracellular potassium (K+) also blocks the effect of CGRP on 45Ca2+ uptake, suggesting a central role for K+ channels in mediating this action. In agreement with this hypothesis, the effect of CGRP is blocked by 1 microM glybenclamide, a specific inhibitor of ATP-sensitive potassium (K(ATP)) channels, or by pretreatment of cells with 1 mM iodoacetic acid to deplete intracellular ATP. Blocking Ca2+-activated potassium channels with 1 mM tetraethylammonium does not prevent CGRP's effect. Pinacidil, a specific activator of K(ATP) channels, mimics CGRP's effect. Both CGRP and pinacidil also produce a small significant stimulation of cellular Ca2+ efflux in UMR 106 cells. These data suggest that inhibition of diltiazem-sensitive Ca2+ channels occurs secondary to the hyperpolarization engendered by CGRP activation of K(ATP) channels in osteoblastic cells, an effect similar to that of CGRP on smooth muscle cells. PMID:8603612

  10. 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.

  11. Evaluation of the neutron background in an HPGe target for WIMP direct detection when using a reactor neutrino detector as a neutron veto system

    SciTech Connect

    Ji, Xiangpan; Xu, Ye Lin, Junsong; Feng, Yulong; Li, Haolin

    2013-11-15

    A direct WIMP (weakly interacting massive particle) detector with a neutron veto system is designed to better reject neutrons. The experimental configuration is studied in this paper involves 984 Ge modules placed inside a reactor-neutrino detector. The neutrino detector is used as a neutron veto device. The neutron background for the experimental design is estimated using the Geant4 simulation. The results show that the neutron background can decrease to O(0.01) events per year per tonne of high-purity germanium and it can be ignored in comparison with electron recoils.

  12. 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.

  13. Calcium insensitivity of FA-6, a cell line derived from a pancreatic cancer associated with humoral hypercalcemia, is mediated by the significantly reduced expression of the Calcium Sensitive Receptor transduction component p38 MAPK

    PubMed Central

    Morgan, Richard; Fairfax, Benjamin; Pandha, Hardev S

    2006-01-01

    The Calcium-Sensing Receptor is a key component of Calcium/Parathyroid hormone homeostatic system that helps maintain appropriate plasma Ca2+ concentrations. It also has a number of non-homeostatic functions, including cell cycle regulation through the p38 MAPK pathway, and recent studies have indicated that it is required for Ca2+ mediated growth arrest in pancreatic carcinoma cells. Some pancreatic cancers produce pathogenic amounts of parathyroid like hormones, however, which significantly increase Ca2+ plasma concentrations and might be expected to block further cell growth. In this study we have investigated the expression and function of the p38 MAPK signaling pathway in Ca2+ sensitive (T3M-4) and insensitive (FA6) pancreatic cancer cell lines. FA-6 cells, which are derived from a pancreatic adenocarcinoma that secretes a parathyroid hormone related peptide, exhibit only very low levels of p38 MAPK expression, relative to T3M-4 cells. Transfecting FA-6 cells with a p38 MAPK expression construct greatly increases their sensitivity to Ca2+. Furthermore, the reduction of p38 MAPK in T3M-4 cells significantly reduces the extent to which high levels of Ca2+ inhibit proliferation. These results suggest that the low levels of p38 MAPK expression in FA-6 cells may serve to reduce their sensitivity to high concentrations of external Ca2+ that would otherwise block proliferation. PMID:17078869

  14. 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

  15. 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.

  16. 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

  17. Antisense RNA of survivin gene inhibits the proliferation of leukemia cells and sensitizes leukemia cell line to taxol-induced apoptosis.

    PubMed

    Li, Wenhan; Wang, Xiaojuan; Lei, Ping; Ye, Qing; Zhu, Huifen; Zhang, Yue; Shao, Jinfang; Yang, Jing; Shen, Guanxin

    2008-02-01

    The effects of survivin antisense RNA on proliferation of leukemia cell line HL-60 and taxol-induced chemotherapy was explored. A cDNA fragment of survivin obtained by RT-PCR was inserted into a plamid vector named pcDNA3 in the reverse direction. The vector encoding antisense RNA of survivin was confirmed by restriction enzyme digestion and DNA sequencing. The recombinant plasmid was delivered into HL-60 cells by electroporation. Growth curves were plotted based on cell counting. Trypan blue dye exclusion assay and MTT assay were carried out after the cells were incubated with taxol. DNA gel electrophoresis and nuclear staining were performed for cell apoptosis assay. The correct construction of the recombinant plasmid has been identified by restriction enzyme digestion and DNA sequencing. A stable down-regulation has been achieved in HL-60 SVVas cells after G418 selection. Compared to HL-60 cells, the proliferation of HL-60 SVVas cells was significantly inhibited (P<0.05). Cytotoxicity assays indicated that IC(50) of HL-60 SVVas for taxol was relatively lower than controls (P<0.01). Apoptosis assays revealed that taxol-induced apoptosis was detected in HL-60 SVVas cells incubated with 50 ng/ml taxol for 12 h, while in HL-60 cells incubated with 100 ng/ml taxol for 72 h. It was suggested that Survivin antisense RNA could inhibit the proliferation of HL-60 cells and enhance taxol-induced apoptosis in HL-60 cells, which may lay an experimental foundation for further research on gene therapy in leukemia. PMID:18278445

  18. The immunomodulatory drug lenalidomide restores a vitamin D sensitive phenotype to the vitamin D resistant breast cancer cell line MDA-MB-231 through inhibition of BCL-2: potential for breast cancer therapeutics.

    PubMed

    Brosseau, Carole; Colston, Kay; Dalgleish, Angus George; Galustian, Christine

    2012-02-01

    1?,25-Dihydroxyvitamin D3, (1,25-D3) the biologically active form of vitamin-D, is well established as a cancer cell growth inhibitor in addition to maintaining bone mineralization. In breast cancer cells, inhibitory effects on angiogenesis, and metastasis have been observed together with enhancement of apoptosis and induction of cell cycle arrest. There is a correlation between vitamin-D receptor expression on breast cancer cells and patient survival. However vitamin-D resistance and hypercalcaemia are key limiting factors in clinical use. The IMiD() immunomodulatory drug lenalidomide, (Revlimid(), CC-5013) used in myeloma, can also modulate apoptotic and growth signalling. We studied whether lenalidomide treated breast cancer cells would acquire sensitivity to 1,25-D3 with resulting growth inhibition. The cell lines MCF-12A, MCF-7 and MDA-MB-231, representing non-tumorogenic, tumorogenic, and vitamin-D resistant lines respectively were treated with lenalidomide and/or 1,25-D3(at 100nM). Whereas lenalidomide alone had no effect on cell growth, a 50% inhibition of cell growth by 1,25-D3 was achieved with additional 1?M lenalidomide in resistant cells. This effect was through apoptosis measured by PARP cleavage and annexin-V expression. An apoptosis protein array showed that the 1,25-D3 and lenalidomide combination increased pro-apoptotic proteins (phosphorylated p53) and decreased BCL-2 expression. BCL-2 inhibition is proposed as a mechanism of action for the combined drugs in the MDA-MB-231 cell line. In vitamin D resistant cell lines MCF-7VDR and HBL-100 where the combination does not affect BCL-2-no inhibitory effect is observed. These results demonstrate the potential for the combinatorial use of lenalidomide and 1,25-D3 for vitamin D refractory tumours. PMID:22109882

  19. 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

  20. 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

  1. 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

  2. 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

  3. Development of bubble chambers with enhanced stability and sensitivity to low-energy nuclear recoils

    NASA Astrophysics Data System (ADS)

    Bolte, W. J.; Collar, J. I.; Crisler, M.; Hall, J.; Holmgren, D.; Nakazawa, D.; Odom, B.; O'Sullivan, K.; Plunkett, R.; Ramberg, E.; Raskin, A.; Sonnenschein, A.; Vieira, J. D.

    2007-07-01

    The viability of using Bubble Chambers as dark matter particle detectors is considered. Techniques leading to the enhanced chamber stability needed for this new application are described in detail. Prototype trials show that sensitivity to the low-energy nuclear recoils induced by Weakly Interacting Massive Particles (WIMP) is possible in conditions of extreme insensitivity to minimum ionizing backgrounds. An understanding of detector response is demonstrated using existing theoretical models. We briefly comment on the prospects for detection of supersymmetric dark matter with large CF3I chambers.

  4. 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.

  5. 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

  6. Cell Lines

    PubMed Central

    Cherbas, Lucy; Gong, Lei

    2014-01-01

    We review the properties and uses of cell lines in Drosophila research, emphasizing the variety of lines, the large body of genomic and transcriptional data available for many of the lines, and the variety of ways the lines have been used to provide tools for and insights into the developmental, molecular, and cell biology of Drosophila and mammals. PMID:24434506

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. Gluten Sensitivity

    MedlinePLUS

    ... like medicines, vitamins, and supplements. People with gluten sensitivity have problems with gluten. It is different from ... small intestine. Some of the symptoms of gluten sensitivity are similar to celiac disease. They include tiredness ...

  13. 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.

  14. On the sensitivity of CTA to gamma-ray boxes from multi-TeV dark matter

    NASA Astrophysics Data System (ADS)

    Ibarra, Alejandro; Lamperstorfer, Anna S.; Lpez-Gehler, Sergio; Pato, Miguel; Bertone, Gianfranco

    2015-09-01

    Collider, direct and indirect searches for dark matter have typically little or no sensitivity to weakly interacting massive particles (WIMPs) with masses above a few TeV. This rather unexplored regime can however be probed through the search for distinctive gamma-ray spectral features produced by the annihilation of WIMPs at very high energies. Here we present a dedicated search for gamma-ray boxessharp spectral features that cannot be mimicked by astrophysical sourceswith the upcoming Cherenkov Telescope Array (CTA). Using realistic projections for the instrument performance and detailed background modelling, a profile likelihood analysis is implemented to derive the expected upper limits and sensitivity reach after 100 h of observations towards a 22 region around the Galactic centre. Our results show that CTA will be able to probe gamma-ray boxes down to annihilation cross sections of 10-27-10-26 cm3/s up to tens of TeV. We also identify a number of concrete particle physics models providing thermal dark matter candidates that can be used as target benchmarks in future search campaigns. This constitutes a golden opportunity for CTA to either discover or rule out multi-TeV thermal dark matter in a corner of parameter space where all other experimental efforts are basically insensitive.

  15. 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

  16. 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

  17. 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.

  18. Sensitive and simplified analysis of natural and synthetic steroids in water and solids using on-line solid-phase extraction and microwave-assisted solvent extraction coupled to liquid chromatography tandem mass spectrometry atmospheric pressure photoionization.

    PubMed

    Snow, Daniel D; Damon-Powell, Teyona; Onanong, Sathaporn; Cassada, David A

    2013-02-01

    Analytical methods for the determination of several natural and synthetic steroids in water and solid samples were developed using liquid chromatography tandem mass spectrometry. Atmospheric pressure photoionization (APPI) in positive mode was used as the source which appeared to reduce background and interferences as compared to electrospray ionization. Toluene was identified as the most appropriate dopant and its concentration optimized to enhance ionization efficiency. Method detection limits were in the low-nanogram-per-liter range for water samples using on-line solid-phase extraction and near 0.2 ng/g using microwave-assisted solvent extraction for solid samples. This on-line method, using APPI as a source and toluene as a dopant, is beneficial as it saves time due to on-line extraction and reduces interference and matrix effects using gas-phase photoionization. Groundwater, wastewater, runoff, and soil samples were collected and analyzed using the method indicating that traces of several androgens, estrogens, and other steroid-like compounds do occur in samples impacted by animal waste. PMID:23208286

  19. 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.

  20. 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

  1. 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)

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. Prospects for the Search for Dark Matter with GLAST

    NASA Astrophysics Data System (ADS)

    Winer, B. L.; Lat Dark Matter; New Physics Working Group

    2008-04-01

    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 2008, The GLAST Large Area Telescope (LAT) will survey the gamma-ray sky in the energy range of 20 MeV-300 GeV. 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.

  7. Dark Matter Searches with GLAST

    NASA Astrophysics Data System (ADS)

    Wai, L.; GLAST Lat Collaboration

    2007-04-01

    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.

  8. 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.

  9. 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)

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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…

  15. 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

  16. 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 skin into ...

  17. 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 ...

  18. 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

  19. 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…

  20. 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

  1. 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.

  2. 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.

  3. The pulmonary extracellular lining.

    PubMed Central

    George, G; Hook, G E

    1984-01-01

    The extracellular lining of the lungs is reviewed. The pulmonary extracellular lining is a complex mixture of phospholipids, proteins and carbohydrates which is absolutely essential for the maintenance of normal pulmonary functions such as gas exchange. Without the lining the lungs would collapse. Alterations in the pulmonary extracellular lining may underlie some disease conditions induced by toxic agents, especially those which interfere with the formation of pulmonary surfactant. The extracellular lining could be used to detect and monitor damage and disease caused by agents toxic to the lungs. The lining contains many hydrolytic enzymes which may act to detoxify certain toxic agents such as those which contain ester groups. The pulmonary extracellular lining could play a significant role mediating the toxic action of inhaled agents as well as the removal of those agents from the lungs. Images FIGURE 1. PMID:6376100

  4. Sensitivity to temozolomide in brain tumor initiating cells

    PubMed Central

    Blough, Michael D.; Westgate, Morgan R.; Beauchamp, Desiree; Kelly, John J.; Stechishin, Owen; Ramirez, Andrea L.; Weiss, Samuel; Cairncross, J. Gregory

    2010-01-01

    Molecular alterations in glioblastoma have the potential to guide treatment. Here, we explore the relationship between temozolomide (TMZ) response and O6-methylguanine DNA methyltransferase (MGMT) status in brain tumor initiating cells (BTICs). Methylation, expression, and sensitivity were assessed in 20 lines; associations were evaluated by Fisher's exact test. Some BTICs were sensitive. Sensitivity to TMZ was only associated with protein expression (P = .001). There were atypical BTICs including TMZ-resistant lines in which the methylation-specific PCR reaction revealed both methylated and unmethylated bands. BTICs are not uniformly resistant to TMZ; some are sensitive. MGMT status does not predict TMZ response with high precision. PMID:20388697

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. Fe XIV line ratios in the sun

    SciTech Connect

    Keenan, F.P.; Dufton, P.L.; Boylan, M.B.; Kingston, A.E.; Widing, K.G. U.S. Navy, E.O. Hulburt Center for Space Research, Washington, DC )

    1991-06-01

    Recent R-matrix calculations of electron-impact excitation rates for Fe XIV are used to derive theoretical electron density-sensitive emission-line ratios involving transitions in the wavelength range 211-274 A. Electron densities deduced from the observed line ratios for solar flares and active regions, obtained with the Naval Research Laboratory's SO82A slitless spectrograph on board Skylab, are in excellent internal agreement and, furthermore, compare favorably with densities determined independently from line ratios in Fe XII and Fe XIII. These results provide experimental support for the accuracy of the atomic data adopted in the analysis, as well as for the techniques used to calculate the line ratios. 36 refs.

  11. 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.

  12. 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

  13. 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.

  14. Temperature measurements via narrow line laser absorption of carbon dioxide

    SciTech Connect

    Wooldridge, M.S.

    1996-12-31

    Theoretical development for temperature measurements via narrow line, infrared absorption of carbon dioxide (CO{sub 2}) is presented. The proposed technique is based on rapid-scanning of two adjacent absorption line shapes. Spectroscopic considerations for sensitivity to temperature measurements are discussed. Several line pairs are evaluated, and the R(58) and R(60) transitions of the (00{sup 0}1){l_arrow}(00{sup 0}0) band are suggested for use in high temperature measurements for combustion systems.

  15. 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

  16. Database of emission lines

    NASA Astrophysics Data System (ADS)

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

    1998-11-01

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

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. On-line surfactant monitoring

    SciTech Connect

    Mullen, K.I.; Neal, E.E.; Soran, P.D.; Smith, B.

    1995-04-01

    This group has developed a process to extract metal ions from dilute aqueous solutions. The process uses water soluble polymers to complex metal ions. The metal/polymer complex is concentrated by ultrafiltration and the metals are recovered by a pH adjustment that frees the metal ions. The metal ions pass through the ultrafiltration membrane and are recovered in a concentrated form suitable for reuse. Surfactants are present in one of the target waste streams. Surfactants foul the costly ultrafiltration membranes. It was necessary to remove the surfactants before processing the waste stream. This paper discusses an on-line device the authors fabricated to monitor the process stream to assure that all the surfactant had been removed. The device is inexpensive and sensitive to very low levels of surfactants.

  2. High-resolution line-scanning optical coherence microscopy

    NASA Astrophysics Data System (ADS)

    Chen, Yu; Huang, Shu-Wei; Aguirre, Aaron D.; Fujimoto, James G.

    2007-07-01

    An optical coherence microscopy system based on line illumination and detection is demonstrated. The system uses a Linnik-type interferometer illuminated by a broadband Ti:sapphire laser and detected by a high-speed, line-scan CCD camera. This approach is less sensitive to incoherent scattering and sample motion than full-field imaging. Spatial resolutions of 2 ?mט3 ?m(transverseaxial) are achieved. The sensitivity of the system is 93 dB with averaging over 30 line scans. En face real time, cellular-level imaging of biological tissues is demonstrated at 2 frames/s.

  3. 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.

  4. Flow line sampler

    DOEpatents

    Nicholls, Colin I. (San Antonio, TX)

    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.

  5. Coherent soliton communication lines

    NASA Astrophysics Data System (ADS)

    Yushko, O. V.; Redyuk, A. A.; Fedoruk, M. P.; Turitsyn, S. K.

    2014-11-01

    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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. Central line infections - hospitals

    MedlinePLUS

    ... samples taken more than once a day Need kidney dialysis Anyone who has a central line can get ... body Make sure everything they touch during the procedure is sterile Cover the catheter with gauze or ...

  13. 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)

  14. Folly Island Tidal Lines

    USGS Multimedia Gallery

    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....

  15. Folly Island Tidal Lines

    USGS Multimedia Gallery

    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....

  16. 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…

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. Phase protection system for ac power lines

    NASA Technical Reports Server (NTRS)

    Wong, W. J. (inventor)

    1974-01-01

    The system described provides protection for phase sensitive loads from being or remaining connected to ac power lines whenever a phase reversal occurs. It comprises a solid state phase detection circuit, a dc power relay circuit, an ac-to-dc converter for energizing the relay circuit, and a bistable four terminal transducer coupled between the phase detection circuit and the power relay circuit, for controlling both circuits.

  2. Measurement of Deflection Line on Bridges

    NASA Astrophysics Data System (ADS)

    Urban, Rudolf; troner, 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.

  3. 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

  4. On-Line and Off-Line Assessment of Metacognition

    ERIC Educational Resources Information Center

    Sara, 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

  5. 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.

  6. 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.

  7. Lunar magnetic permeability studies and magnetometer sensitivity

    NASA Technical Reports Server (NTRS)

    King, J. H.; Ness, N. F.

    1977-01-01

    A regression of quiet magnetic field components simultaneously measured by the two Explorer 35 magnetometers reveals uncertainties in effective sensitivity factors of up to a few percent in one or both of these instruments. Given this, the validity of previous lunar permeability studies based on Explorer 35/ALSEP regressions, wherein inferences are drawn from regression line slopes differing from unity by the order of one percent, is called into question. We emphasize the need to critically address the question of small deviations in magnetometer sensitivity factors from nominal values as a part of any two-magnetometer lunar permeability study.

  8. Tuned cavity magnetometer sensitivity.

    SciTech Connect

    Okandan, Murat; Schwindt, Peter

    2009-09-01

    We have developed a high sensitivity (sensitivity levels.

  9. 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.

  10. Mechanism of cinnamaldehyde sensitization.

    PubMed

    Majeti, V A; Suskind, R R

    1977-02-01

    The skin sensitization of cinnamaldehyde is probably initiated by the reaction of cinnamaldehyde with epsilon-amino groups on protein side chains. Alpha-Substituted cinnamaldehydes, which are known not to be skin sensitizers, react very slowly or not at all with amines in comparison with cinnamaldehyde. PMID:844298

  11. 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

  12. 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.

  13. Ca XV line ratios in solar flares

    SciTech Connect

    Keenan, F.P.; Berrington, K.A.; Aggarwal, K.M.; Widing, K.G.

    1988-04-01

    Recent R-matrix calculations of electron impact excitation rates for Ca XV have been used to obtain theoretical density-sensitive emission line ratios which are applicable to solar flares. Results for electron densities derived from the I(208.71 A)/I(200.95 A), I(181.90 A)/I(200.95 A), and I(215.37 A)/I(200.95 A) values for solar flares obtained by the Skylab NRL S082A slitless spectrograph are in excellant agreement. Ca XV electron densities are found to compare favorably with those determined from the line ratios of ions formed at similar electron temperatures. The results provide support for the accuracy of the adopted atomic data and for the line ratio calculation method. 27 references.

  14. 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.

  15. 27. WILEY CITY LINE, LOOKING WEST ON HENRYBRO LINE FROM ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    27. WILEY CITY LINE, LOOKING WEST ON HENRYBRO LINE FROM WIDE HOLLOW JUNCTION; LINE TO WILEY CITY DIVERGING LEFT - Yakima Valley Transportation Company Interurban Railroad, Connecting towns of Yakima, Selah & Wiley City, Yakima, Yakima County, WA

  16. 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)

  17. 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.

  18. Spectral Line Shapes. Proceedings

    SciTech Connect

    Zoppi, M.; Ulivi, L.

    1997-02-01

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

  19. Line feature matching algorithm

    NASA Astrophysics Data System (ADS)

    Jin, Taisong; Li, Cuihua

    2007-11-01

    This paper presents a line feature matching algorithm. Firstly, it extracts the set of line features in the image, and represents an object using attributed relational graph (ARG). By defining relation vectors between the adjacent features, the graph can describe the structural information of an object. Secondly, the one-to-one correspondences between model features and image features is established by two processes - coarse match and refined match through the analysis of matching ordering and matching number of relation vectors. Finally, the object examples in the image are extracted. Test showed that the proposed algorithm had superior performance to the present line feature matching algorithms, which is robust to shape deformation, or input noise, and decreased the computational cost.

  20. 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...

  1. A high-sensitivity, position-sensitive fission chamber for subcriticality measurements of spent fuel

    NASA Astrophysics Data System (ADS)

    Williams, J. A.; Mihalczo, J. T.; Ricker, C. W.; Glesius, F. L.; Kniss, T. A.

    1990-12-01

    A high-sensitivity fission counter has been developed for subcriticality measurements by the 252Cf-source-driven neutron noise analysis method which requires two neutron counter channels. Performance specifications were provided by ORNL for spent light water reactor (LWR) fuel configurations where multiplication factors ( k-values) could be as low as 0.85. A 3 3 array of 2 in. diameter, 8 ft long counters, fits into storage rack positions occupied by LWR fuel elements. Each counter consists of eight sensitive sections that contain a total of 18 g of 235U. Transmission-line technology is used to minimize capacitances and thus provides broad bandwidths. Each event in the fission counter produces two current pulses propagating in opposite directions on the transmission line. The differences in arrival times of the pulses at the ends of a counter determine the positions of the fission events. Tests on two fission counters show that each counter has a sensitivity of 12.5 cps/nv th and a position sensitivity with 1 ft resolution. Detection efficiency estimates for spent LWR fuel configurations indicate that, using two fission counters, subcriticality measurements can be made down to a k-value of 0.80: for two 3 3 counter arrays, to a k-value of 0.65. The 3 3 counter array or a single counter can be used in applications other than subcriticality measurements where position sensitivity, high sensitivity, and operability in high gamma fields are performance requirements.

  2. Spin line groups.

    PubMed

    Lazi?, Nataa; Milivojevi?, Marko; Damnjanovi?, Milan

    2013-11-01

    Spin line groups describe the symmetries of spin arrangements in quasi-one-dimensional systems. These groups are derived for the first family of line groups. Among them, magnetic groups are singled out as a special case. Spin arrangements generated by the derived groups are first discussed for single-orbit systems and then the conclusions are extended to multi-orbit cases. The results are illustrated by the examples of a CuO2 zigzag chain, a (13)C nanotube and the hexaferrite Ba2Mg2Fe12O22. Applications to neutron diffraction and classical ground-state determination are indicated. PMID:24132222

  3. 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

  4. The EVE Doppler Sensitivity and Flare Observations

    NASA Technical Reports Server (NTRS)

    Hudson, H. S.; Woods, T. N.; Chamberlin, P. C.; Didkovsky, L.; Del Zanna, G.

    2011-01-01

    The Extreme-ultraviolet Variability Experiment (EVE) obtains continuous EUV spectra of the Sun viewed as a star. Its primary objective is the characterization of solar spectral irradiance, but its sensitivity and stability make it extremely interesting for observations of variability on time scales down to the limit imposed by its basic 10 s sample interval. In this paper we characterize the Doppler sensitivity of the EVE data. We find that the 30.4 nm line of He II has a random Doppler error below 0.001 nm (1 pm, better than 10 km/s as a redshift), with ample stability to detect the orbital motion of its satellite, the Solar Dynamics Observatory (SDO). Solar flares also displace the spectrum, both because of Doppler shifts and because of EVE's optical layout, which (as with a slitless spectrograph) confuses position and wavelength. As a flare develops, the centroid of the line displays variations that reflect Doppler shifts and therefore flare dynamics. For the impulsive phase of the flare SOL2010-06-12, we find the line centroid to have a redshift of 16.8 +/- 5.9 km/s relative to that of the flare gradual phase (statistical errors only). We find also that high-temperature lines, such as Fe XXIV 19.2 nm, have well-determined Doppler components for major flares, with decreasing apparent blueshifts as expected from chromospheric evaporation flows.

  5. Interpreting broad emission-line variations - I. Factors influencing the emission-line response

    NASA Astrophysics Data System (ADS)

    Goad, M. R.; Korista, K. T.

    2014-10-01

    We investigate the sensitivity of the measured broad emission-line responsivity dlog fline/dlog fcont to continuum variations in the context of straw-man broad emission-line region (BLR) geometries of varying size with fixed BLR boundaries, and for which the intrinsic emission-line responsivity is known a priori. We find for a generic emission line that the measured responsivity ?eff, delay and maximum of the cross-correlation function are correlated for characteristic continuum variability time-scales Tchar less than the maximum delay for that line ?max(line) for a particular choice of BLR geometry and observer orientation. The above correlations are manifestations of geometric dilution arising from reverberation effects within the spatially extended BLR. When present, geometric dilution reduces the measured responsivity, delay and maximum of the cross-correlation function. Conversely, geometric dilution is minimized if Tchar ? ?max(line). We also find that the measured responsivity and delay show a strong dependence on light-curve duration, with shorter campaigns resulting in smaller than expected values, and only a weak dependence on sampling rate (for irregularly sampled data). The observed strong negative correlation between continuum level and line responsivity found in previous studies cannot be explained by differences in the sampling pattern, light-curve duration or in terms of purely geometrical effects. To explain this and to satisfy the observed positive correlation between continuum luminosity and BLR size in an individual source, the responsivity-weighted radius must increase with increasing continuum luminosity. For a BLR with fixed inner and outer boundaries this requires radial surface emissivity distributions which deviate significantly from a simple power law, and in such a way that the intrinsic emission-line responsivity increases towards larger BLR radii, in line with photoionization calculations.

  6. 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

  7. Method for rapid isolation of sensitive mutants

    DOEpatents

    Freyer, James P. (Los Alamos, NM)

    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.

  8. 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.

  9. 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.

  10. Dark matter detection in two easy steps

    NASA Astrophysics Data System (ADS)

    Pospelov, Maxim; Weiner, Neal; Yavin, Itay

    2014-03-01

    Multicomponent dark matter particles may have a more intricate direct detection signal than simple elastic scattering on nuclei. In a broad class of well-motivated models, the inelastic excitation of dark matter particles is followed by de-excitation via ? decay. In experiments with fine energy resolution, such as many 0?2? decay experiments, this motivates a highly model-independent search for the sidereal daily modulation of an unexpected ? line. Such a signal arises from a two-step weakly interacting massive particle (WIMP) interaction: the WIMP is first excited in the lead shielding and subsequently decays back to the ground state via the emission of a monochromatic ? within the detector volume. We explore this idea in detail by considering the model of magnetic inelastic WIMPs and take a sequence of CUORE-type detectors as an example. We find that under reasonable assumptions about detector performance it is possible to efficiently explore mass splittings of up to a few hundred keV for a WIMP of weak-scale mass and transitional magnetic moments. The modulation can be cheaply and easily enhanced by the presence of additional asymmetric lead shielding. We devise a toy simulation to show that a specially designed asymmetric shielding may result in up to 30% diurnal modulations of the two-step WIMP signal, leading to additional strong gains in sensitivity.

  11. LINE-BY-LINE CALCULATION OF SPECTRA FROM DIATOMIC MOLECULES AND ATOMS ASSUMING A VOIGT LINE PROFILE

    NASA Technical Reports Server (NTRS)

    Whiting, E. E.

    1994-01-01

    This program predicts the spectra resulting from electronic transitions of diatomic molecules and atoms in local thermodynamic equilibrium. The program produces a spectrum by accounting for the contribution of each rotational and atomic line considered. The integrated intensity of each line is distributed in the spectrum by an approximate Voigt profile. The program can produce spectra for optically thin gases or for cases where simultaneous emission and absorption occurs. In addition, the program can compute the spectrum resulting from the absorption of incident radiation by a column of cold gas or the high-temperature, self-absorbed emission spectrum from a nonisothermal gas. The computed spectrum can be output directly or combined with a slit function and sensitivity calibration to predict the output of a grating spectrograph or a fixed wavelength radiometer. Specifically, the program has the capability to include the following features in any computations: (1) Parallel transitions, in which spin splitting and lambda doubling are ignored (ignoring spin splitting and/or lambda doubling means that the total multiple strength is assumed to reside in a single "effective" line), (2) Perpendicular transitions, in which spin splitting and lambda doubling are ignored, (3) Sigma Pi transitions, in which lambda doubling is ignored, (4) Atomic lines, (5) Option to terminate rotational line calculations when the molecule dissociates due to rotation, (6) Option to include the alternation of line intensities for homonuclear molecules, (7) Use of an approximate Voigt profile for the line shape, and (8) Radiative energy transport in a nonisothermal gas. The output options available in the program are: (1) Tabulation of the spontaneous emission spectrum (i.e., optically thin spectrum) for a 1.0 cm path length, (2) Tabulation of the "true" spectrum, which incorporates spontaneous emission, induced emission, absorption, and externally incident radiation through the equation of radiative transfer, (3) Tabulation of the curve of growth for an arbitrary number of wavelength intervals, (4) Tabulation of the integrated intensity over an arbitrary number of wavelength intervals, and (5) Tabulation of the output signal produced by a radiometer or spectrometer by specifying an instrument calibration. The instrument slit function can be approximated by up to 99 straight line segments or by a Gaussian curve. The computation can be made at a fixed wavelength to simulate a radiometer or by scanning across any specified wavelength interval to simulate a grating instrument. In the latter case, the sensitivity can be varied as a function of wavelength to accurately simulate a grating-instrument calibration. This program is written in FORTRAN IV for batch execution and has been implemented on an IBM 7000 Series computer. This program was developed in 1968.

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. Magnetic field line Hamiltonian

    SciTech Connect

    Boozer, A.H.

    1985-02-01

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

  18. 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)

  19. 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…

  20. 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…