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1

Optimized running conditions and sensitivity for direction sensitive detectors of WIMP dark matter  

NASA Astrophysics Data System (ADS)

Optimum fill pressures for direction-sensitive dark matter detectors based on tracking in gases are considered. Given the minimum resolvable track length and the gas fill, the Lindhard-Scharf stopping model leads to the existence of an optimum pressure which maximizes the specific event rate R (event rate per unit detector volume). In addition, maximizing the detectibility of the recoil nucleus diurnal asymmetry is considered. Optimum fill pressures are calculated for Ar, CF 4, CS 2 and Xe gas fills, as a function of the WIMP mass and the minimum resolvable track length. The associated minimum target volumes required to achieve currently competitive WIMP-nucleon cross-section sensitivity are also calculated. The standard isothermal sphere model of the galactic WIMP halo is used throughout, but the method could be extended to use any desired WIMP distribution function.

Tatarowicz, J.; Martoff, C. J.

2011-12-01

2

Towards a depleted argon time projection chamber WIMP search: Darkside prototype analysis and predicted sensitivity  

NASA Astrophysics Data System (ADS)

Scientists have now accumulated overwhelming evidence indicating that over 80% of the mass of the universe is in the form of dark matter, neutral particles with ultra-weak couplings to ordinary matter. One compelling candidate is a Weakly Interacting Massive Particle or WIMP, with mass on the order of 100 GeV.The signal of a WIMP interaction in a detector is a low energy (typically below ˜100 keV) recoiling atomic nucleus. The expected rate is at most a few interactions per year per ton of target. The most critical issue for direct WIMP searches is reducing the background in the detector below this very low rate. Argon is a promising target because measurements of the scintillation pulse shape and the scintillation-to-ionization ratio allow the reduction of gamma-induced signals, the largest source of background, by a factor of 108 or better. One of the major drawbacks of argon is the presence of radioactive 39Ar, which results in a decay rate of ˜1 Bq/kg in natural argon. Because 39Ar is produced primarily in the upper atmosphere, the 39Ar fraction can be reduced significantly by obtaining the argon from underground wells. Our collaboration, DarkSide, is developing a series of two-phase argon time projection chambers (TPCs) utilizing this depleted argon, along with passive shielding and active neutron and muon vetoes, for WIMP searches. I present results from a recent campaign of a 10 kg active mass prototype TPC that demonstrate the successful realization of many of the technical aspects necessary for a full-scale detector, in particular an electron-equivalent light yield of 4.5 photoelectrons per keV deposited, and a free electron lifetime in excess of 200 microseconds. Based on this successful prototype and Monte Carlo simulations, I then conclude that DarkSide-50, a 50 kg active mass TPC to be installed in LNGS, can likely acquire data background-free for three years, accumulating a fiducial exposure of ˜100 kg-years and reaching a sensitivity to the WIMP-nucleon cross section of ˜3x10 -45 cm2. I also present some details on the analysis of Borexino data that resulted in the first real-time, spectroscopic measurement of 7Be solar neutrino interactions.

Loer, Ben Michael

3

New sensitivity to solar WIMP annihilation using low-energy neutrinos  

NASA Astrophysics Data System (ADS)

Dark matter particles captured by the Sun through scattering may annihilate and produce neutrinos, which escape. Current searches are for the few high-energy neutrinos produced in the prompt decays of some final states. We show that interactions in the solar medium lead to a large number of pions for nearly all final states. Positive pions and muons decay at rest, producing low-energy neutrinos with known spectra, including ?¯e through neutrino mixing. We demonstrate that Super-Kamiokande can thereby provide a new probe of the spin-dependent WIMP-proton cross section. Compared to other methods, the sensitivity is competitive and the uncertainties are complementary.

Rott, Carsten; Siegal-Gaskins, Jennifer M.; Beacom, John F.

2013-09-01

4

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

SciTech Connect

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

Barnes, E. J. [School of Physics and Astronomy, University of Edinburgh, Edinburgh, EH9 3JZ (United Kingdom)

2009-09-08

5

Searching for WIMPs with EDELWEISS  

NASA Astrophysics Data System (ADS)

The EDELWEISS-II experiment, operated in the Frejus laboratory in a low-background environment, uses cryogenic germanium detectors to look for WIMPs. We present the results of a WIMP search carried out recently with ten so-called InterDigit detectors. This technology enables a high level of gamma radioactivity rejection within a controlled fiducial volume. A cross-section of 4.4 × 10-8 pb could be excluded for a WIMP mass of 85 GeV. We also present the status of the EDELWEISS-III project, which will operate 40 newly-designed FID detectors in an upgraded installation to improve significantly the sensitivity to low WIMP scattering cross-sections.

Armengaud, Eric; EDELWEISS Collaboration

2012-07-01

6

Columnar recombination: a tool for nuclear recoil directional sensitivity in a xenon-based direct detection WIMP search  

NASA Astrophysics Data System (ADS)

A robust signal for sidereal anisotropy in nuclear recoils would support, perhaps more decisively than any other evidence, a discovery claim for a WIMP component of Dark Matter. I present a concept based on columnar recombination in dense xenon gas, sensing nuclear recoil direction relative to a TPC drift field. The central advance is that nuclear recoil directionality information is obtained through a comparison, event-by-event, of the ionization signal and recombination signal that are produced prior to drifting the track ionization. The optimum xenon density for this concept may be near ten bars, unlike conventional techniques that employ track visualization - with severe restrictions on gas density to about 1/10 bar. No restriction is imposed by diffusion during drift, facilitating the realization of a large monolithic room temperature xenon gas Time Projection Chamber at the ton-scale, with unprecedented sensitivity for both directionality and cross-section. Remarkably, the desired operating conditions for 0-??? 136Xe experiment may be identical.

Nygren, D. R.

2013-10-01

7

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)

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 ?=1.8×10-42 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 ?=3.3×10-41 cm2.

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

2012-06-01

8

Recent Evidence for Gamma-ray Line Emission from Fermi-LAT: WIMP or Artifact?  

NASA Astrophysics Data System (ADS)

The recent claims of a gamma-ray line in the Galactic center at 130 GeV have generated excitement, not least because it could be a signal of dark matter annihilation. I will summarize the current state of the observations of the Galactic center, clusters, and unassociated halo objects. I will also speculate about models of particle dark matter that could explain the data, and possible systematic of the Fermi-LAT instrument that might contaminate the line detection.

Su, Meng; Finkbeiner, D. P.

2013-04-01

9

Probing light WIMPs with directional detection experiments  

NASA Astrophysics Data System (ADS)

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

Morgan, Ben; Green, Anne M.

2012-10-01

10

Lower limits on the strengths of gamma ray lines from WIMP dark matter annihilation  

NASA Astrophysics Data System (ADS)

We study the spectra of gamma ray signals that arise from dark matter annihilation in the Universe. We focus on the large class of theories where the photon spectrum includes both continuum spectrum of gamma rays that arise from annihilation into standard model states at tree level, as well as monochromatic gamma rays arising from annihilation directly into two photons at the one-loop level. In this class of theories we obtain lower bounds on the ratio of the strength of the gamma ray line relative to the gamma ray continuum as a function of the dark matter mass and spin. These limits are obtained from the unitarity relation between the tree-level amplitude of the primary annihilation channel and the imaginary part of the loop-level amplitude for annihilation directly into photons, with the primary decay products running in the loop. These results are exact in the limit that dark matter annihilation at tree level is exclusively to a single standard model species, occurs through the lowest partial wave and respects CP. Away from this limit the bounds are approximate. Our conclusions agree with known results in the literature for the cases of the minimal supersymmetric standard model, universal extra dimensions and the littlest Higgs with T parity. We use the Fermi-LAT observations to translate these limits into upper bounds on the dark matter annihilation cross section into any specific standard model state.

Abazajian, Kevork N.; Agrawal, Prateek; Chacko, Zackaria; Kilic, Can

2012-06-01

11

Vector WIMP miracle  

NASA Astrophysics Data System (ADS)

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.

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

2012-07-01

12

Direct detection of multicomponent secluded WIMPs  

SciTech Connect

Dark matter candidates comprising several substates separated by a small mass gap {delta}m, and coupled to the standard model by (sub-)GeV force carriers, can exhibit nontrivial scattering interactions in direct-detection experiments. We analyze the secluded U(1){sub S}-mediated weakly interacting massive particle (WIMP) scenario, and calculate the elastic and inelastic cross sections for multicomponent WIMP scattering off nuclei. We find that second-order elastic scattering, mediated by virtual excited states, provides strong sensitivity to the parameters of the model for a wide range of mass splittings, while for small {delta}m the WIMP excited states have lifetimes exceeding the age of the Universe, and generically have a fractional relative abundance above 0.1%. This generates even stronger constraints for {delta}m < or approx. 200 keV due to exothermic deexcitation events in detectors.

Batell, Brian [Perimeter Institute for Theoretical Physics, Waterloo, ON, N2J 2W9 (Canada); Pospelov, Maxim [Perimeter Institute for Theoretical Physics, Waterloo, ON, N2J 2W9 (Canada); Department of Physics and Astronomy, University of Victoria, Victoria, BC, V8P 1A1 (Canada); Ritz, Adam [Department of Physics and Astronomy, University of Victoria, Victoria, BC, V8P 1A1 (Canada)

2009-06-01

13

Constraints on Low-Mass WIMP signals from CDMS  

NASA Astrophysics Data System (ADS)

Dark Matter constitutes more than 80% of matter content in known universe. A major candidate to Dark Matter is Weakly Interacting Masive Particle (WIMP). The Cryogenic Dark Matter Search (CDMS) experiment uses cryogenically cooled Germanium detectors to look for recoil signals with the slow moving WIMPs in our galaxy. The most recent results optimized for high mass WIMPs yielded 2 possible candidates, which were statistically consistent with expected background. An updated analysis optimized for low mass WIMP search showed no evidence of low mass WIMPs and disfavors an explanation for the DAMA/LIBRA and CoGeNT signals in terms of spin-independent elastic scattering of low-mass WIMP. Search for annual modulation of our data shows no strong evidence of possible WIMP signature, and rejects the observation of similar phenomenon in CoGeNT at more than 95% confidence level. The next generation SuperCDMS experiment utilizing more advanced detector technology is expected to have much higher sensitivity for WIMP search with very little expected background.

Prasad, Kunj

2012-03-01

14

Nonthermal 'WIMP miracle'  

SciTech Connect

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.

Acharya, Bobby Samir; Kane, Gordon; Watson, Scott; Kumar, Piyush [Abdus Salam International Centre for Theoretical Physics, Strada Costiera 11, Trieste (Italy) and INFN, Sezione di Trieste (Italy); Michigan Center for Theoretical Physics, Ann Arbor, Michigan (United States); Berkeley Center for Theoretical Physics University of California, Berkeley, California 94720 (United States) and Theoretical Physics Group Lawrence Berkeley National Laboratory, Berkeley, California 94720 (United States)

2009-10-15

15

Nonthermal ``WIMP miracle''  

NASA Astrophysics Data System (ADS)

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.

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

2009-10-01

16

A DEAP & CLEAN Program for WIMP Dark Matter  

Microsoft Academic Search

Weakly Interacting Massive Particles (WIMPs) provide a compelling explanation for dark matter that could be directly detected as they recoil in massive and ultra-pure detector targets operating deep underground. Thus far, the direct detection of WIMPs has eluded the most sensitive of experiments and it is desirable to achieve sensitivities some three orders of magnitude beyond the state-of-the-art. This will

Andrew Hime

2007-01-01

17

Median recoil direction as a WIMP directional detection signal  

SciTech Connect

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.

Green, Anne M. [School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, NG7 2RD (United Kingdom); Morgan, Ben [Department of Physics, University of Warwick, Coventry, CV4 7AL (United Kingdom)

2010-03-15

18

Asymmetric WIMP dark matter  

Microsoft Academic Search

In existing dark matter models with global symmetries the relic abundance of dark matter is either equal to that of anti-dark matter (thermal WIMP), or vastly larger, with essentially no remaining anti-dark matter (asymmetric dark matter). By exploring the consequences of a primordial asymmetry on the coupled dark matter and anti-dark matter Boltzmann equations we find large regions of parameter

Michael L. Graesser; Ian M. Shoemaker; Luca Vecchi

2011-01-01

19

Direct detection of WIMPs  

NASA Astrophysics Data System (ADS)

To test the hypothesis according to which Weakly Interacting Massive Particles are a major constituent of Dark Matter, direct detection experiments aim at detecting the spectrum of nuclear recoils induced by WIMPs from the Milky Way halo within a target material. While the detection concept is already more than 20 years old, recent experimental developments have allowed fast progress, which up to now have lead to constrain electroweak theories beyond the standard model in a complementary way to collider experiments.

Armengaud, Eric

2012-07-01

20

The WIMP Paradigm: Current Status  

ScienceCinema

The WIMP paradigm is the glue that joins together much of the high energy and cosmic frontiers. It postulates that most of the matter in the Universe is made of weakly-interacting massive particles, with implications for a broad range of experiments and observations. I will review the WIMP paradigm's underlying motivations, its current status in view of rapid experimental progress on several fronts, and recent theoretical variations on the WIMP paradigm theme.

21

The WIMP Paradigm: Current Status  

SciTech Connect

The WIMP paradigm is the glue that joins together much of the high energy and cosmic frontiers. It postulates that most of the matter in the Universe is made of weakly-interacting massive particles, with implications for a broad range of experiments and observations. I will review the WIMP paradigm's underlying motivations, its current status in view of rapid experimental progress on several fronts, and recent theoretical variations on the WIMP paradigm theme.

Feng, Jonathan (University of California, Irvine)

2011-03-23

22

Development of CsI crystals for WIMP search  

NASA Astrophysics Data System (ADS)

An experimental search for WIMP using CsI(Tl) crystals(KIMS) is being prepared at the underground laboratory, Cheongpyung, Korea. Characteristics and internal background of CsI(Tl) crystal have been investigated in detail to develop highly sensitive detector for WIMP search. The background at the underground laboratory is measured and shielding design has been done with an optimization with a MC study. The result of detector development and prospect of KIMS experiment is reported.

Kim, S. K.; Cho, I. S.; Choi, D. H.; Choi, J. M.; Hahn, I. S.; Hwang, M. J.; Jain, R. K.; Kang, W. K.; Kim, H. J.; Kim, J. H.; Kim, S. C.; Kim, T. Y.; Kim, Y. D.; Kwon, Y. J.; Lee, H. S.; Lee, M. H.; Lee, S. E.; Noh, S. H.; Park, H.; Park, I. H.; Seo, E. S.; Won, E.; Won, H. S.; Yang, H. Y.; Yang, M. S.; Yu, I.

2003-07-01

23

Combined Limits on WIMPs from the CDMS and EDELWEISS Experiments  

SciTech Connect

The CDMS and EDELWEISS collaborations have combined the results of their direct searches for dark matter using cryogenic germanium detectors. The total data set represents 614 kg/days equivalent exposure. A straightforward method of combination was chosen for its simplicity before data were exchanged between experiments. The results are interpreted in terms of limits on spin-independent weakly interacting, massive particle (WIMP)-nucleon cross section. For a WIMP mass of 90 GeV/c{sup 2}, where this analysis is most sensitive, a cross section of 3.3 x 10{sup -44} cm{sup 2} is excluded at 90% C.L. At higher WIMP masses, the combination improves the individual limits, by a factor 1.6 above 700 GeV/c{sup 2}. Alternative methods of combining the data provide stronger constraints for some ranges of WIMP masses and weaker constraints for others.

Ahmed, Z.; /Caltech; Akerib, D.S.; /Case Western Reserve U.; Armengaud, E.; /DAPNIA, Saclay; Arrenberg, S.; /Zurich-Irchel U.; Augier, C.; /Lyon, IPN; Bailey, C.N.; /Case Western Reserve U.; Balakishiyeva, D.; /Florida U.; Baudis, L.; /Zurich-Irchel U.; Bauer, D.A.; /Fermilab; Benoit, A.; /LPSC, Grenoble; Berge, L.; /CSNSM, Orsay /Karlsruhe U., EKP /Karlsruhe, Inst. Technol.

2011-05-01

24

Improved determination of the WIMP mass from direct detection data  

NASA Astrophysics Data System (ADS)

Direct detection experiments searching for weakly interacting massive particle (WIMP) dark matter typically use a simplified model of the Galactic halo to derive parameter constraints. However, there is strong evidence that this Standard Halo Model is not a good approximation to our Galaxy. We discuss previous attempts to extract the WIMP mass, cross section and speed distribution from direct detection data and show that these lead to significant biases in the reconstructed parameter values. We develop and test an alternative model-independent method based on parametrizing the momentum distribution of the WIMPs. This allows us to limit the analysis only to those regions of momentum space to which the experiments are sensitive. The method can be applied to a single experiment to extract information about the distribution function, as well as information on the degenerate WIMP mass and interaction cross section combined in a single parameter. This degeneracy can be broken by including data from additional experiments, meaning that the WIMP mass and speed distribution can be recovered. We test the momentum parametrization method using mock data sets from proposed ton-scale direct detection experiments, showing that it exhibits improved coverage properties over previous methods, as well as significantly reduced bias. We are also able to accurately reconstruct the shape of the WIMP speed distribution but distinguishing between different underlying distributions remains difficult.

Kavanagh, Bradley J.; Green, Anne M.

2012-09-01

25

Post-WIMP user interfaces  

Microsoft Academic Search

arge set of software-engineering tools for building WIMP interfaces. Ifind it rather surprising that the third generation ofWIMP user interfaces has been so dominant for morethan two decades; they are apparently sufficiently goodfor conventional desktop tasks that the field is stuckcomfortably in a rut.I argue in this essay that the status quo does not suffice---that the newer forms of computing

Andries Van Dam

1997-01-01

26

The WIMP Forest: Indirect Detection of a Chiral Square  

SciTech Connect

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).

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

2009-04-01

27

Light WIMPs in the Sun: Constraints from helioseismology  

SciTech Connect

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.

Cumberbatch, Daniel T. [Astroparticle Theory and Cosmology Group, Department of Physics and Astronomy, University of Sheffield, Hicks Building, Hounsfield Road, Sheffield, S3 7RH (United Kingdom); Guzik, Joyce A. [Los Alamos National Laboratory, XTD-2 Mail Stop T086, Los Alamos, New Mexico 87545-2345 (United States); Silk, Joseph [Physics Department, University of Oxford, Oxford, OX1 3RH (United Kingdom); Watson, L. Scott [Sandia National Laboratories, PO Box 5800 Mail Stop 0431, Albuquerque, New Mexico 87185 (United States); West, Stephen M. [Royal Holloway, University of London, Egham, TW20 0EX (United Kingdom); Rutherford Appleton Laboratory, Chilton, Didcot, OX11 0QX (United Kingdom)

2010-11-15

28

Spin-dependent WIMP limits from a bubble chamber.  

PubMed

Bubble chambers were the dominant technology used for particle detection in accelerator experiments for several decades, eventually falling into disuse with the advent of other techniques. We report here on a new application for these devices. We operated an ultraclean, room-temperature bubble chamber containing 1.5 kilograms of superheated CF3I, a target maximally sensitive to spin-dependent and -independent weakly interacting massive particle (WIMP) couplings. An extreme intrinsic insensitivity to the backgrounds that commonly limit direct searches for dark matter was measured in this device under operating conditions leading to the detection of low-energy nuclear recoils like those expected from WIMPs. Improved limits on the spin-dependent WIMP-proton scattering cross section were extracted during our experiments, excluding this type of coupling as a possible explanation for a recent claim of particle dark-matter detection. PMID:18276885

Behnke, E; Collar, J I; Cooper, P S; Crum, K; Crisler, M; Hu, M; Levine, I; Nakazawa, D; Nguyen, H; Odom, B; Ramberg, E; Rasmussen, J; Riley, N; Sonnenschein, A; Szydagis, M; Tschirhart, R

2008-02-15

29

Review of Indirect WIMP Search Experiments  

NASA Astrophysics Data System (ADS)

Observational evidence for dark matter can be explained by Weakly Interacting Massive Particles (WIMPs). These dark matter particle candidates could indirectly be detected through the observation of signals produced as part of WIMP annihilations or decays. Latest results from indirect searches for WIMPs are reviewed. Current and planned experiments are presented and their prospects and discovery potential discussed.

Rott, Carsten

2013-02-01

30

CDMS WIMP detector Fabrication Optimization  

NASA Astrophysics Data System (ADS)

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

Jastram, Andrew

2012-03-01

31

Dark matter in the Solar System. II. WIMP annihilation rates in the Sun  

SciTech Connect

We calculate the annihilation rate of weakly interacting massive particles (WIMPs) in the Sun as a function of their mass and elastic scattering cross section. One byproduct of the annihilation, muon neutrinos, may be observed by the next generation of neutrino telescopes. Previous estimates of the annihilation rate assumed that any WIMPs from the Galactic dark halo that are captured in the Sun by elastic scattering off solar nuclei quickly reach thermal equilibrium in the Sun. Using simulations of WIMP orbits in the Solar System in the case that spin-independent scattering dominates in the Sun (and extrapolating to the case when spin-dependent scattering dominates), we show that the optical depth of the Sun to WIMPs and the gravitational forces from planets both serve to decrease the annihilation rate below these estimates. While we find that the sensitivity of upcoming km{sup 3}-scale neutrino telescopes to {approx}100 GeV WIMPs is virtually unchanged from previous estimates, the sensitivity of these experiments to {approx}10 TeV WIMPs may be an order of magnitude less than the standard calculations would suggest. The new estimates of the annihilation rates should guide future experiment design and improve the mapping from neutrino event rates to WIMP parameter space.

Peter, Annika H. G. [Department of Physics, Princeton University, Princeton, New Jersey 08544 (United States) and California Institute of Technology, Mail Code 105-24, Pasadena, California 91125 (United States)

2009-05-15

32

Directional recoil rates for WIMP direct detection  

SciTech Connect

New techniques for the laboratory direct detection of dark matter weakly interacting massive particles (WIMPs) are sensitive to the recoil direction of the struck nuclei. We compute and compare the directional recoil rates dR/dcos{theta} (where {theta} is the angle measured from a reference direction in the sky) for several WIMP velocity distributions including the standard dark halo and anisotropic models such as Sikivie's late-infall halo model and logarithmic-ellipsoidal models. Since some detectors may be unable to distinguish the beginning of the recoil track from its end (lack of head-tail discrimination), we introduce a folded directional recoil rate dR/d|cos{theta}|, where |cos{theta}| does not distinguish the head from the tail of the track. We compute the CS{sub 2} and CF{sub 4} exposures required to distinguish a signal from an isotropic background noise, and find that dR/d|cos{theta}| is effective for the standard dark halo and some but not all anisotropic models.

Alenazi, Moqbil S.; Gondolo, Paolo [Department of Physics, University of Utah, 115 S 1400 E Rm 201, Salt Lake City, Utah 84112-0830 (United States)

2008-02-15

33

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

NASA Astrophysics Data System (ADS)

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

Ejiri, H.

2006-07-01

34

A DEAP & CLEAN Program for WIMP Dark Matter  

NASA Astrophysics Data System (ADS)

Weakly Interacting Massive Particles (WIMPs) provide a compelling explanation for dark matter that could be directly detected as they recoil in massive and ultra-pure detector targets operating deep underground. Thus far, the direct detection of WIMPs has eluded the most sensitive of experiments and it is desirable to achieve sensitivities some three orders of magnitude beyond the state-of-the-art. This will require development of novel detector technologies exploiting target masses of order a ton and with unprecedented control of radioactive background in order to achieve the desired sensitivity of a single event per ton per year. We have realized a conceptually simple and scalable detector technology using the unique properties of scintillation light in liquid argon and liquid neon. Ultimately, we envision a very massive detector of liquid neon that could serve simultaneously as a detector of WIMP dark matter and low-energy (pp-fusion) solar neutrinos. A DEAP & CLEAN program will be described that makes effective use of liquid argon and liquid neon, interchangeably, in a single detector.

Hime, Andrew

2007-04-01

35

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

NASA Astrophysics Data System (ADS)

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??3×10-26cm3s-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 5.2×10-26cm3s-1 at m?0.3GeV, and is 2.2×10-26cm3s-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.

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

2012-07-01

36

Spin-dependent WIMP scattering off nuclei  

NASA Astrophysics Data System (ADS)

Chiral effective field theory provides a systematic expansion for the coupling of weakly interacting massive particles (WIMPs) to nucleons at the momentum transfers relevant to direct cold dark matter detection. We derive the currents for spin-dependent WIMP scattering off nuclei at the one-body level and include the leading long-range two-body currents, which are predicted in chiral effective field theory. As an application, we calculate the structure factor for spin-dependent WIMP scattering off Xe129,131 nuclei, using nuclear interactions that have been developed to study nuclear structure and double-beta decays in this region. We provide theoretical error bands due to the nuclear uncertainties of WIMP currents in nuclei.

Menéndez, J.; Gazit, D.; Schwenk, A.

2012-11-01

37

WIMP abundance and lepton (flavour) asymmetry  

NASA Astrophysics Data System (ADS)

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 lf = Script O(0.1).

Stuke, Maik; Schwarz, Dominik J.; Starkman, Glenn

2012-03-01

38

Predicted rates for direct WIMP searches  

NASA Astrophysics Data System (ADS)

The differential event rate for direct detection of dark matter, both the time averaged and the modulated one due to the motion of the Earth, are discussed. The calculations focus on relatively light cold dark matter candidates (WIMP) and low energy transfers. It is shown that for some WIMP masses the modulation amplitude may change sign. This effect can be exploited to yield information about the mass of the dark matter candidate.

Vergados, J. D.

2012-09-01

39

Isolation of two chloroethylnitrosourea-sensitive Chinese hamster cell lines  

SciTech Connect

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.

Hata, H.; Numata, M.; Tohda, H.; Yasui, A.; Oikawa, A. (Tohoku Univ., Sendai (Japan))

1991-01-01

40

Improved Detection Sensitivity of Line-Scanning Optical Coherence Microscopy  

PubMed Central

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.

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

2012-01-01

41

Survey of Interferon Production and Sensitivity in Human Cell Lines  

PubMed Central

Seven presumed diploid and 11 established cell lines were studied for their ability to produce free interferon in response to a standardized Newcastle disease virus challenge. Interferon production was evaluated in both serum-containing and serum-free medium. The ability of these cell lines to respond to the application of a standard interferon preparation by becoming resistant to virus was also examined. The diploid lines were distinctly more efficient producers of interferon than were the established lines. They also evidenced a greater requirement for serum to produce their maximum titers, but some were able to produce good titers in serum-free medium. The diploid lines were uniformly more sensitive to the application of exogenous interferon than were the established cell lines and attained greater degrees of virus resistance, but all lines tested displayed measurable sensitivity to interferon.

Moehring, J. M.; Stinebring, W. R.; Merchant, D. J.

1971-01-01

42

Investigation of Magnetically Sensitive FeH Lines  

NASA Astrophysics Data System (ADS)

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.

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

2011-12-01

43

Searching for super-WIMPs in leptonic heavy meson decays  

NASA Astrophysics Data System (ADS)

We study constraints on the models of bosonic super-weakly interacting particle (super-WIMP) dark matter (DM) with DM masses mX˜O(1 - 100) keV from leptonic decays M->l?l+ X, where M=B^,^,s^± is a heavy meson state. We focus on two cases where X denotes either a light pseudoscalar (axion-like), or a light vector state that couples to the standard model (SM) through kinetic mixing. We note that for a small DM mass these decays are separately sensitive to DM couplings to quarks, but not its mass.

Yechan Gunja, Aditya; Healey, Kristopher; Petrov, Alexey

2012-10-01

44

Searching for super-WIMPs in leptonic heavy meson decays  

NASA Astrophysics Data System (ADS)

We study constraints on the models of bosonic super-weakly interacting particle (super-WIMP) dark matter (DM) with DM masses mX˜O(1-100) keV from leptonic decays M???+X, where M=B±,D±,Ds± is a heavy meson state. We focus on two cases where X denotes either a light pseudoscalar (axion-like), or a light vector state that couples to the standard model (SM) through kinetic mixing. We note that for a small DM mass these decays are separately sensitive to DM couplings to quarks, but not its mass.

Aditya, Y. G.; Healey, Kristopher J.; Petrov, Alexey A.

2012-03-01

45

Polymer-bound sensitizer in i-line resist formulations  

NASA Astrophysics Data System (ADS)

An important component of a photoresist formulation is the photoactive compound. In conventional I-line resist, it is the DNQ molecule. In chemically amplified resists, it is the photoacid generator or the PAG. This component acts as the link between the exposure tool and the photoresist system. While PAGs for the 248 nm or DUV application are plenty, there is little effort in the arena of i-line PAGs. Typically, energy transfer in i-line lithography is achieved by using a DUV PAG in conjunction with an i-line energy transfer agent called sensitizer. This combination works very well, as described by workers before. This paper describes a polymer-bound sensitizer, which while maintaining the performance characteristics of a monomeric sensitizer, also enhances the solubility characteristics and the thermal stability of the resist.

Jagannathan, Premlatha; Dewan, Charlotte; Eckert, Andrew R.; Mih, Rebecca D.; Martinek, Kathleen; Richwine, Charles; Linehan, Leo L.; Moreau, Wayne M.; Smith, Randolph S.

1998-06-01

46

Technique for WIMP dark matter detection using pulse-shape discrimination in noble liquids  

NASA Astrophysics Data System (ADS)

The performance of a dual-purpose liquid neon detector (CLEAN) for dark matter and low-energy solar neutrino interactions evaluated with Monte-Carlo simulations will be discussed. The projected sensitivity for CLEAN is less than 10-46 cm^2 for the spin-independent WIMP-nucleon cross-section, and 1% uncertainty for the pp solar neutrino flux measurement. The general technique of using scintillation pulse-shape discrimination in noble liquids will be discussed, and progress on a small-scale argon WIMP-dark matter experiment (DEAP) will be presented.

Boulay, Mark

2005-04-01

47

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

SciTech Connect

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.

Collar, Juan (University of Chicago)

2003-12-03

48

Reconstructing WIMP properties with neutrino detectors  

NASA Astrophysics Data System (ADS)

If the dark matter of the Universe is constituted by weakly interacting massive particles (WIMP), they would accumulate in the core of astrophysical objects as the Sun and annihilate into particles of the Standard Model. High-energy neutrinos would be produced in the annihilations, both directly and via the subsequent decay of leptons, quarks and bosons. While ?erenkov neutrino detectors/telescopes can only count the number of neutrinos above some threshold energy, we study how, by exploiting their energy resolution, large magnetized iron calorimeter and, possibly, liquid argon and totally active scintillator detectors, planned for future long baseline neutrino experiments, have the capability of reconstructing the neutrino spectrum and might provide information on the dark matter properties. In particular, for a given value of the WIMP mass, we show that a future iron calorimeter could break the degeneracy between the WIMP-proton cross section and the annihilation branching ratios, present for ?erenkov detectors, and constrain their values with good accuracy.

Mena, Olga; Palomares-Ruiz, Sergio; Pascoli, Silvia

2008-06-01

49

Gamma rays from warm WIMP dark matter annihilation  

NASA Astrophysics Data System (ADS)

The weakly interacting massive particle (WIMP) often serves as a candidate for the cold dark matter. However, when produced nonthermally, it could behave like warm dark matter. In this paper, we study the properties of the ?-ray emission from annihilation of WIMP dark matter in the halo of our own Milky Way galaxy with high resolution N-body simulations of a Milky-Way-like dark matter halo, assuming a different nature of WIMPs. Due to the large free-streaming length in the scenario of warm WIMPs, the substructure content of the dark matter halo is significantly different from that of the cold WIMP counterpart, resulting in distinct predictions of the ?-ray signals from the dark matter annihilation. We illustrate these by comparing the predicted ?-ray signals from the warm WIMP annihilation to that of cold WIMPs. Pronounced differences from the subhalo sky map and statistical properties between two WIMP models are demonstrated. Due to the potentially enhanced cross section of the nonthermal production mechanism in the warm WIMP scenario, the Galactic center might be prior to the indirect detection of warm WIMPs to dwarf galaxies, which might be different from the cold dark matter scenario. As a specific example, we consider the nonthermally produced neutralino of the supersymmetric model and discuss the detectability of warm WIMPs with the Fermi ?-ray telescope.

Yuan, Qiang; Cao, Yixian; Liu, Jie; Yin, Peng-Fei; Gao, Liang; Bi, Xiao-Jun; Zhang, Xinmin

2012-11-01

50

Neutrino and WIMP detection with CLEAN  

Microsoft Academic Search

CLEAN is an approach to the detection of weakly interacting particles of astrophysical significance, combining large mass and low energy threshold. CLEAN is capable of detecting low energy solar neutrinos, weakly interacting massive particles (WIMPs), and neutrinos released from supernovas. Because liquid neon has a high scintillation yield, has no long-lived radioactive isotopes, and can be easily purified using cold

Daniel McKinsey; Walter Lippincott; James Nikkel; Andrew Hime; Mark Boulay; Jeff Lidgard; Kevin Coakley; Edward Kearns

2004-01-01

51

Searches for WIMP Annihilation with GLAST  

SciTech Connect

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.

Wai, L.; /SLAC

2005-06-21

52

Differentiating hidden sector dark matter from light WIMPs with Germanium detectors  

NASA Astrophysics Data System (ADS)

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

Foot, R.

2013-06-01

53

DNA methylation and sensitivity to antimetabolites in cancer cell lines.  

PubMed

The prediction of the cellular direction of metabolic pathways toward either DNA synthesis or DNA methylation is crucial for determining the susceptibility of cancers to anti-metabolites such as fluorouracil (5-FU). We genotyped the methylenetetrahydrofolate reductase (MTHFR) gene in NCI-60 cancer cell lines, and identified the methylation status of 24 tumor suppressor genes using methylation-specific multiplex ligation-dependent probe amplification. The susceptibility of the cancer cell lines to seven antimetabolites was then determined. Cells homozygous for CC at MTHFR-A1298C were significantly more sensitive to cyclocytidine, cytarabine (AraC) and floxuridine than those with AA or AC (p=0.0215, p=0.0166, and p=0.0323, respectively), and carried more methylated tumor suppressor genes (p=0.0313). Among the 12 tumor suppressor genes which were methylated in >25% of cancer cell lines, the methylation status of TIMP3, APC and IGSF4 significantly correlated with sensitivity to pyrimidine synthesis inhibitors. In particular, cells with methylated TIMP3 had reduced mRNA levels and were significantly more sensitive to aphidicolin-glycinate, AraC and 5-FU than cells with unmethylated TIMP3. We speculate that MTHFR-A1298C homozygous CC might direct the methylation rather than the synthesis of DNA, and result in the methylation of several tumor suppressor genes such as TIMP3. These genes could be useful biological markers for predicting the efficacy of antimetabolites. PMID:18202788

Sasaki, Shin; Kobunai, Takashi; Kitayama, Joji; Nagawa, Hirokazu

2008-02-01

54

Cisplatin sensitivity and thermochemosensitisation in thermotolerant cDDP-sensitive and -resistant cell lines.  

PubMed

Development of thermotolerance is an important phenomenon that must be considered when thermochemotherapy with multiple heat treatments is used clinically. To study the effect of thermotolerance on cellular cisplatin (cDDP) sensitivity at 37 degrees C and 43 degrees C in cell lines with different cDDP sensitivities, two Ehrlich ascites tumour cell lines (one with high cDDP sensitivity and one with in vitro acquired cDDP resistance) were used. The results indicate that in both cell lines the state of thermotolerance per se did not affect the cDDP sensitivity at 37 degrees C. Thus, general elevations in 'all' heat shock protein levels as found in thermotolerant cells apparently do not influence cDDP sensitivity to a considerable extent. The sensitising effect of a (second) heat treatment given simultaneously with a cDDP treatment was less in thermotolerant cells. Thermal enhancement ratios (TERs) at the 10% survival level for heat doses of 43 degrees C for 30 min or 43 degrees C for 60 min were reduced by a factor of 1.6 and 2.1 in cDDP-resistant and -sensitive thermotolerant cells respectively, as compared with control cells. Thus, protection against heat damage in thermotolerant cells seems to be paralleled by diminished thermal chemosensitisation. Although the effect of thermotolerance on the cDDP-sensitising effect was less pronounced in the resistant cells, a modifying effect on the resistance factor was not achieved. PMID:7880730

Hettinga, J V; Lemstra, W; Konings, A W; Kampinga, H H

1995-03-01

55

3D Modelling Is Not for WIMPs  

Microsoft Academic Search

This study compares a traditional 3D WIMP (Window Icon Menu Pointer) modeller to a prototype of a novel system with a 6DOF haptic feedback device, stereovision and a co-located display, both in quantitative and qualitative terms. The novel system was conceived to overcome limitations of traditional interaction techniques and devices when dealing with three-dimensions. Experimental results confirm the fundamental role

Silvia Scali; Mark Wright; Ann Marie Shillito

56

Low Mass WIMP Search Using High Pressure Xenon Gas  

NASA Astrophysics Data System (ADS)

Several groups around the globe employ unique detector technologies in the direct search for dark matter weakly interacting massive particles (WIMPs). One of the leading technologies uses scintillation and ionization signals produced when WIMPs scatter off xenon nuclei. Recent compelling results hint at the possibility of a less massive WIMP (7 -- 10 GeV/c^2), than was previously thought. A plan will be presented for a low mass WIMP search using high pressure xenon, and possibly neon gas. The design, calibration, and expected results will be discussed.

Sofka, Clement

2012-10-01

57

Technique for WIMP dark matter detection using pulse-shape discrimination in noble liquids  

Microsoft Academic Search

The performance of a dual-purpose liquid neon detector (CLEAN) for dark matter and low-energy solar neutrino interactions evaluated with Monte-Carlo simulations will be discussed. The projected sensitivity for CLEAN is less than 10-46 cm^2 for the spin-independent WIMP-nucleon cross-section, and 1% uncertainty for the pp solar neutrino flux measurement. The general technique of using scintillation pulse-shape discrimination in noble liquids

Mark Boulay

2005-01-01

58

Magneto-induced Line Broadening of Magneto-sensitive Lines in Solar Magnetized Atmospheres  

NASA Astrophysics Data System (ADS)

We analyze the spectral line broadening of those magneto-sensitive lines in solar magnetized atmospheres. The broadening at the line wings is due to the increase of the effective width of energy levels involved in Zeeman splitting, and the broadening at the line core also originated in Zeeman splitting under the condition that the Zeeman components are mixed. Therefore, the magneto-induced or Zeeman broadening take effects on the whole line. The observed Stokes parameter data in a sunspot and outside it acquired by Solar Stokes Spectrum Telescope (S3T) are analyzed for the demonstration of this mechanism, and the Zeeman broadening rates are calculated for FeI 6302.5 under some assumptions. Our result shows that the broadening is increased as the magnetic field strength becomes stronger, but the rate of increase at the line core is decreased as the field strength increases, while the rate at the wing does not show such an obvious regularity. The broadening is more effective in the line core than in the wings.

Qu, Zhong-Quan; Wang, Shuai; Xu, Cheng-Lin; Zhang, Xiao-Yu; Sun, Ming-Guo; Jin, Chun-Lan

2005-08-01

59

WIMP diffusion in the Solar System including solar WIMP-nucleon scattering  

NASA Astrophysics Data System (ADS)

Dark matter in the form of Weakly Interacting Massive Particles (WIMPs) can be captured by the Sun and the Earth, sink to their cores, annihilate and produce neutrinos that can be searched for with neutrino telescopes. The calculation of the capture rates of WIMPs in the Sun and especially the Earth are affected by large uncertainties coming mainly from effects of the planets in the Solar System, reducing the capture rates by up to an order of magnitude (or even more in some cases). We show that the WIMPs captured by weak scatterings in the Sun also constitute an important bound WIMP population in the Solar System. Taking this population and its interplay with the population bound through gravitational diffusion into account cancel the planetary effects on the capture rates, and the capture essentially proceeds as if the Sun and the Earth were free in the galactic halo. The neutrino signals from the Sun and the Earth are thus significantly higher than claimed in the scenarios with reduced capture rates.

Sivertsson, Sofia; Edsjö, Joakim

2012-06-01

60

Stringy WIMP detection and annihilation  

SciTech Connect

We calculate the direct dark matter detection spin-independent and proton spin-dependent cross sections for a semirealistic intersecting D6-brane model. The cross sections are compared to the latest constraints of the current dark matter direct detection experiments, as well as the projected results of future dark matter experiments. The allowed parameter space of the intersecting D6-brane model is shown with all current experimental constraints, including those regions satisfying the WMAP and supercritical string cosmology limits on the dark matter density in the Universe. Additionally, we compute the indirect detection gamma-ray flux resulting from neutralino annihilation for the D6-brane model and compare the flux to the projected sensitivity of the Fermi Gamma-ray Space Telescope. Finally, we compute the direct and indirect detection cross sections as well as the gamma-ray flux resulting from weakly interacting massive particle annihilations for the one-parameter model for comparison, where the one-parameter model is a highly constrained subset of the minimal supergravity parameter space such that the soft-supersymmetry-breaking terms are functions of the common gaugino mass, which is common to many string compactifications.

Maxin, James A.; Mayes, Van E. [George P. and Cynthia W. Mitchell Institute for Fundamental Physics, Texas A and M University, College Station, Texas 77843 (United States); Nanopoulos, Dimitri V. [George P. and Cynthia W. Mitchell Institute for Fundamental Physics, Texas A and M University, College Station, Texas 77843 (United States); Astroparticle Physics Group, Houston Advanced Research Center (HARC), Mitchell Campus, Woodlands, Texas 77381 (United States) and Academy of Athens, Division of Natural Sciences, 28 Panepistimiou Avenue, Athens 10679 (Greece)

2009-06-15

61

Hormone Sensitivity is Reflected in the Phospholipid Profiles of Breast Cancer Cell Lines  

Microsoft Academic Search

We have found that the profiles of total phospholipids in malignant breast cancer cell lines change going from hormone sensitive to highly hormone resistant cells lines. In particular, two phospholipid components that were absent or at very low levels in hormone sensitive MCF7 cells and moderately hormone sensitive cell lines (MIII, LCC2) were found in relatively high proportions in highly

Marina Sterin; Jack S. Cohen; Israel Ringel

2004-01-01

62

Delay-Line Three-Dimensional Position Sensitive Radiation Detection  

NASA Astrophysics Data System (ADS)

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.

Jeong, Manhee

63

Use of Twin-Screen-Based WIMPS in Spacecraft Control.  

National Technical Information Service (NTIS)

The ergonomic problems of designing a sophisticated Windows Icons Mouse Pop-up (WIMP) based twin screen workstation are outlined. These same problems will be encountered by future spacecraft controllers. The design of a modern, advanced workstation for us...

R. D. Klim

1990-01-01

64

DARWIN dark matter WIMP search with noble liquids  

NASA Astrophysics Data System (ADS)

DARWIN (dark matter wimp search with noble liquids) is a design study for a next-generation, multi-ton dark matter detector in Europe. Liquid argon and/or liquid xenon are the target media for the direct detection of dark matter candidates in the form of weakly interacting massive particles (WIMPs). Light and charge signals created by particle interactions in the active detector volume are observed via the time projection chamber technique. DARWIN is to probe the spin-independent, WIMP-nucleon cross section down l0-48cm2 and to measure WIMP-induced nuclear recoil spectra with high-statistics, should they be discovered by an existing or near-future experiment. After a brief introduction, I will describe the project, selected R&D topics, expected backgrounds and the physics reach.

Baudis, Laura; DARWIN Consortium

2012-07-01

65

Sensitivity analysis of multiconductor transmission lines and optimization for high-speed interconnect circuit design  

Microsoft Academic Search

Sensitivity analysis of multiconductor transmission lines is derived from a new, all-purpose multi-conductor transmission line model in both frequency domain and time domain. Computer implementation of this new model as well as the sensitivity analysis has been completed. It enables efficient, accurate simulations of interconnect circuit responses as well as sensitivity analysis with respect to both electrical and physical transmission

Cheng Jiao; Andreas C. Cangellaris; Abdul M. Yaghmour; John L. Prince

2000-01-01

66

WIMP-nucleus scattering in chiral effective theory  

NASA Astrophysics Data System (ADS)

We discuss long-distance QCD corrections to the WIMP-nucleon(s) interactions in the framework of chiral effective theory. For scalar-mediated WIMP-quark interactions, we calculate all the next-to-leading-order corrections to the WIMP-nucleus elastic cross-section, including two-nucleon amplitudes and recoil-energy dependent shifts to the single-nucleon scalar form factors. As a consequence, the scalar-mediated WIMP-nucleus cross-section cannot be parameterized in terms of just two quantities, namely the neutron and proton scalar form factors at zero momentum transfer, but additional parameters appear, depending on the short-distance WIMP-quark interaction. Moreover, multiplicative factorization of the cross-section into particle, nuclear and astro-particle parts is violated. In practice, while the new effects are of the natural size expected by chiral power counting, they become very important in those regions of parameter space where the leading order WIMP-nucleus amplitude is suppressed, including the so-called "isospin-violating dark matter" regime. In these regions of parameter space we find order-of-magnitude corrections to the total scattering rates and qualitative changes to the shape of recoil spectra.

Cirigliano, Vincenzo; Graesser, Michael L.; Ovanesyan, Grigory

2012-10-01

67

Limits on the Spin-Dependent WIMP-Nucleon Cross Sections from the First Science Run of the ZEPLIN-III Experiment  

SciTech Connect

We present new experimental constraints on the WIMP-nucleon spin-dependent elastic cross sections using data from the first science run of ZEPLIN-III, a two-phase xenon experiment searching for galactic dark matter weakly interacting massive particles based at the Boulby mine. Analysis of approx450 kgcentre dotdays fiducial exposure allow us to place a 90%-confidence upper limit on the pure WIMP-neutron cross section of sigma{sub n}=1.9x10{sup -2} pb at 55 GeV/c{sup 2} WIMP mass. Recent calculations of the nuclear spin structure based on the Bonn charge-dependent nucleon-nucleon potential were used for the odd-neutron isotopes {sup 129}Xe and {sup 131}Xe. These indicate that the sensitivity of xenon targets to the spin-dependent WIMP-proton interaction could be much lower than implied by previous calculations, whereas the WIMP-neutron sensitivity is impaired only by a factor of approx2.

Lebedenko, V. N.; Bewick, A.; Currie, A.; Davidge, D.; Dawson, J.; Horn, M.; Howard, A. S.; Jones, W. G.; Joshi, M.; Liubarsky, I.; Lyons, K.; Quenby, J. J.; Sumner, T. J.; Thorne, C.; Walker, R. J. [Blackett Laboratory, Imperial College London, London (United Kingdom); Araujo, H. M.; Edwards, B. [Blackett Laboratory, Imperial College London, London (United Kingdom); Particle Physics Department, Rutherford Appleton Laboratory, Chilton (United Kingdom); Barnes, E. J.; Ghag, C.; Murphy, A. StJ. [School of Physics and Astronomy, SUPA University of Edinburgh, Edinburgh (United Kingdom)

2009-10-09

68

Radiation sensitivity and study of glutathione and related enzymes in human colorectal cancer cell lines.  

PubMed

A panel of 13 human colorectal cell lines was studied, with these lines exhibiting a histological profile similar to that observed in clinical practice. In the five lines tested, variable sensitivity to radiation was observed, from the relatively sensitive NCI-H716 to the highly resistant line NCI-H630, with the latter cell line derived from a patient who had previously received radiation treatment. Glutathione levels and glutathione related enzyme activity varied widely between all 13 cell lines, showing no relationship to radiation sensitivity. The variability observed suggests that some colonic tumours may be responsive to radiation, although their identification remains difficult. However, this may prove possible by incorporation of recently developed cell adhesive matrix assays using survival following a 2 Gy radiation dose as a parameter of radiation sensitivity. This panel of human cancer cell lines offers an ideal model for the study of parameters affecting the radiosensitivity and chemosensitivity pattern of colorectal cancer cells. PMID:2901354

Carmichael, J; Park, J G; Degraff, W G; Gamson, J; Gazdar, A F; Mitchell, J B

1988-07-01

69

Detecting Dark Matter annihilation lines with Fermi  

SciTech Connect

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.

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

2009-05-15

70

Caffeine markedly sensitizes human mesothelioma cell lines to pemetrexed  

Microsoft Academic Search

Pemetrexed is a new generation antifolate approved for the treatment of mesothelioma and non-small cell lung cancer. Caffeine\\u000a is known to augment radiation or chemotherapeutic drug-induced cell killing. The current study addresses the impact of caffeine\\u000a on the activity of pemetrexed in mesothelioma cell lines. Caffeine enhanced pemetrexed activity in all four mesothelioma cell\\u000a lines tested (H2052, H2373, H28 and

Sang Hee Min; I. David Goldman; Rongbao Zhao

2008-01-01

71

Electrophysiological Correlates of Ethanol-Induced Sedation in Differentially Sensitive Lines of Mice  

Microsoft Academic Search

Acute electrophysiological effects of ethanol were studied in two lines of mice that differ markedly in their response to the soporific effects of systemic alcohol administration. Cerebellar Purkinje neurons from the genetic line that had long sleep times were one to two orders of magnitude more sensitive to the depressant effects of locally administered ethanol than those from the line

Steve Sorensen; Michael Palmer; Thomas Dunwiddie; Barry Hoffer

1980-01-01

72

Simulation and sensitivity analysis of nonuniform transmission lines using integrated congruence transform  

Microsoft Academic Search

This paper presents a new algorithm for computing sensitivity information of nonuniform multiconductor transmission lines with respect to arbitrary physical parameters. The proposed algorithm provides sensitivity information through a reduced-order system that has a simple representation in the time-domain. This feature enables computing sensitivity in the presence of nonlinear terminations. The proposed algorithm is based on the concept of passive

Emad Gad; Michel Nakhla

2005-01-01

73

A sensitivity-based wiresizing approach to interconnect optimization of lossy transmission line topologies  

Microsoft Academic Search

This paper presents a sensitivity-based wiresizing algorithm for interconnect delay optimization of lossy transmission line topology under MCM technologies. Our approach computes the maximum delay and its sensitivities with respect to the widths of wires in the topology via high order moments based on an exact moment matching model. Compared with other approaches, it achieves analytical sensitivity computation and calculates

Tianxiong Xue; Ernest S. Kuh; Qingjian Yut

1996-01-01

74

Annihilation Lines from Dark Matter with the Fermi-LAT  

SciTech Connect

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.

Ylinen, Tomi [Oskar Klein Centre for Cosmoparticle Physics and Department of Physics, Royal Institute of Technology (KTH), AlbaNova, SE-106 91 Stockholm (Sweden) and School of Pure and Applied Natural Sciences, University of Kalmar, SE-391 82 Kalmar (Sweden)

2010-06-23

75

A High Pressure Noble Gas Approach for WIMP Detection  

NASA Astrophysics Data System (ADS)

Initial measurements of the charge and light yield in pure xenon gas at 20 bar are discussed. Preliminary findings are that the yields are not greatly different from those reported in liquid xenon. Also, they are similar to yields observed in 50 bar Ar(Xe) and 100 bar Ne(Xe) in the same apparatus. In addition, good nuclear recoil discrimination is observed at low recoil energies relevant to WIMP interactions. The findings suggest that a room-temperature, high pressure gas approach may be an attractive alternative to liquid phase detectors for future large scale WIMP measurement experiments.

White, J. T.; Nygren, D.; Ooi, W.; Salinas, G.; Wang, H.

2009-09-01

76

The moment of truth for WIMP dark matter.  

PubMed

We know that dark matter constitutes 85 per cent of all the matter in the Universe, but we do not know of what it is made. Amongst the many dark matter candidates proposed, WIMPs (weakly interacting massive particles) occupy a special place, because they arise naturally from new theories that seek to extend the standard model of particle physics. With the advent of the Large Hadron Collider at CERN, and a new generation of astroparticle experiments, the moment of truth has come for WIMPs: either we will discover them in the next five to ten years, or we will witness their inevitable decline. PMID:21085174

Bertone, Gianfranco

2010-11-18

77

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

SciTech Connect

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.

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

1992-06-01

78

Properties of Liquid Xenon Scintillation for WIMP Searches  

Microsoft Academic Search

The scintillation yields and decay shapes for recoil Xe-ions produced by WIMPs in liquid xenon have been considered. A rough calculation based on biexcitonic diffusion reaction mechanism gives the average energy to produce a vuv photon Wph to be ~90 eV for 60 keV recoil Xe-ions.

Akira Hitachi

2003-01-01

79

Properties of Liquid Xenon Scintillation for WIMP Searches  

NASA Astrophysics Data System (ADS)

The scintillation yields and decay shapes for recoil Xe-ions produced by WIMPs in liquid xenon have been considered. A rough calculation based on biexcitonic diffusion reaction mechanism gives the average energy to produce a vuv photon Wph to be ~90 eV for 60 keV recoil Xe-ions.

Hitachi, Akira

2003-03-01

80

WIMP search by the DAMA experiment at Gran Sasso  

NASA Astrophysics Data System (ADS)

DAMA is searching for rare processes by developing and using several kinds of radiopure scintillators: in particular, NaI(TI), liquid Xenon and CaF2(Eu). Here only the results released so far on the WIMP annual modulation signature are shortly summarized. Next perspectives are briefly mentioned.

Bernabei, R.; Amato, M.; Belli, P.; Cappella, F.; Cerulli, R.; Dai, C. J.; He, H. L.; Ignesti, G.; Incicchitti, A.; Kuang, H. H.; Ma, J. M.; Montecchia, F.; Nozzoli, F.; Prosperi, D.

2003-07-01

81

Simulation and sensitivity computation of nonuniform transmission lines via integrated congruence transform  

Microsoft Academic Search

A new algorithm is presented for sensitivity analysis of nonuniform multi-conductor transmission lines in the presence of nonlinear terminations. The algorithm is based on model-order reduction using integrated congruence transform. The proposed algorithm does not require partitioning the nonuniform line into cascaded connections of uniform sections. In addition, sensitivity information are obtained from solving a reduced-order system, which provides significant

Emad Gad; Michel Nakhla

2003-01-01

82

Baseline gene expression predicts sensitivity to gefitinib in non-small cell lung cancer cell lines.  

PubMed

Tyrosine kinase inhibitors (TKI) of the epidermal growth factor receptor (EGFR) produce objective responses in a minority of patients with advanced-stage non-small cell lung cancer (NSCLC), and about half of all treated patients progress within 6 weeks of instituting therapy. Because the target of these agents is known, it should be possible to develop biological predictors of response, but EGFR protein levels have not been proven useful as a predictor of TKI response in patients and the mechanism of primary resistance is unclear. We used microarray gene expression profiling to uncover a pattern of gene expression associated with sensitivity to EGFR-TKIs by comparing NSCLC cell lines that were either highly sensitive or highly resistant to gefitinib. This sensitivity-associated expression profile was used to predict gefitinib sensitivity in a panel of NSCLC cell lines with known gene expression profiles but unknown gefitinib sensitivity. Gefitinib sensitivity was then determined for members of this test panel, and the microarray-based sensitivity prediction was correct in eight of nine NSCLC cell lines. Gene and protein expression differences were confirmed with a combination of quantitative reverse transcription-PCR, flow cytometry, and immunohistochemistry. This gene expression pattern related to gefitinib sensitivity was independent from sensitivity associated with EGFR mutations. Several genes associated with sensitivity encode proteins involved in HER pathway signaling or pathways that interrelate to the HER signaling pathway. Some of these genes could be targets of pharmacologic interventions to overcome primary resistance. PMID:16877703

Coldren, Christopher D; Helfrich, Barbara A; Witta, Samir E; Sugita, Michio; Lapadat, Razvan; Zeng, Chan; Barón, Anna; Franklin, Wilbur A; Hirsch, Fred R; Geraci, Mark W; Bunn, Paul A

2006-08-01

83

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

Microsoft Academic Search

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

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

1987-01-01

84

9-(beta)-arabinofuranosyladenine preferentially sensitizes radioresistant squamous cell carcinoma cell lines to x-rays.  

National Technical Information Service (NTIS)

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 th...

D. Heaton R. Mustafi J. L. Schwartz

1992-01-01

85

A pulse width modulated power line conditioner for sensitive load centers  

Microsoft Academic Search

Concerns over process disruptions in sensitive load centers, such as semiconductor processing plants, caused by short duration electrical disturbances have prompted development of power line conditioners to supply high quality electric power. Recently, a pulse width modulated power converter suitable for three phase power line conditioning was presented. This paper presents the development of a control strategy for the application

G. Venkataramanan; B. Johnson

1997-01-01

86

Publisher's Note: WIMP diffusion in the solar system including solar WIMP-nucleon scattering [Phys. Rev. D 85, 123514 (2012)  

NASA Astrophysics Data System (ADS)

Dark matter in the form of Weakly Interacting Massive Particles (WIMPs) can be captured by the Sun and the Earth, sink to their cores, annihilate and produce neutrinos that can be searched for with neutrino telescopes. The calculation of the capture rates of WIMPs in the Sun and especially the Earth are affected by large uncertainties coming mainly from effects of the planets in the Solar System, reducing the capture rates by up to an order of magnitude (or even more in some cases). We show that the WIMPs captured by weak scatterings in the Sun also constitute an important bound WIMP population in the Solar System. Taking this population and its interplay with the population bound through gravitational diffusion into account cancel the planetary effects on the capture rates, and the capture essentially proceeds as if the Sun and the Earth were free in the galactic halo. The neutrino signals from the Sun and the Earth are thus significantly higher than claimed in the scenarios with reduced capture rates.

Sivertsson, Sofia; Edsjö, Joakim

2012-06-01

87

Use of human neuroblastoma continuous cell lines for in vitro drug sensitivity screening  

Microsoft Academic Search

We have used three continuous human neuroblastoma cell lines to establish patterns of in vitro drug sensitivities, as judged by clonogenic assay. We evaluated 12 ‘standard’ antitumor drugs already in clinical usage, and tested four newer analogues, one of cisplatin and three of doxorubicin, and the investigational agent desferrioxamine. A certain heterogeneity of drug sensitivities was noted amongst these three

Bridget T. Hill; R. D. H. Whelan; Louise K. Hosking

1988-01-01

88

Fast simulation and sensitivity analysis of lossy transmission lines by the method of characteristics  

Microsoft Academic Search

In this paper we use the method of characteristics to derive a new simulation model of lossy transmission lines, and we present the sensitivity analysis in the time domain. The simulation model is as fast as the recursive convolution model based on moment matching and Pade' approximation, but does not have the stability problem. The sensitivity analysis model is particularly

Jun-Fa Mao; Ernest S. Kuh

1997-01-01

89

Simulation and sensitivity analysis of transmission line circuits by the characteristics method  

Microsoft Academic Search

In this paper we use the method of characteristics to derive a new simulation model of lossy transmission lines, and we present the sensitivity analysis in the time-domain. The simulation model is as fast as the recursive convolution model based on moment matching and Pade' approximation, but does not have the stability problem. The sensitivity analysis model is particularly useful

Jun-Fa Mao; Janet Meiling Wang; Ernest S. Kuh

1996-01-01

90

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

NASA Astrophysics Data System (ADS)

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 ^85Kr, with a relative abundance of about 10-11 (^85Kr/^natKr), 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.

Dobi, Attila

2011-04-01

91

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

NASA Astrophysics Data System (ADS)

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=1.41×10-4 pb (90% C.L.) are excluded.

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

2012-05-01

92

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

NASA Astrophysics Data System (ADS)

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

Cabrera, Blas

2013-04-01

93

Sensitivity studies of high-precision methane column concentration inversion using a line-by-line radiative transfer model  

NASA Astrophysics Data System (ADS)

Hyper-spectral remote sensing may provide an effective solution to retrieve the methane (CH4) concentration in an atmospheric column. As a result of exploring the absorptive characteristics of CH4, an appropriate band is selected from hyperspectral data for the detection of its column concentration with high precision. Following the most recent inversion theory and methods, the line-by-line radiative transfer model (LBLRTM) is employed to forward model the impact of four sensitive factors on inversion precision, including CH4 initial profile, temperature, overlapping gases, and surface albedo. The results indicate that the four optimized factors could improve the inversion precision of atmospheric CH4 column concentration.

Song, Ci; Shu, Jiong; Zhou, Mandi; Gao, Wei

2013-09-01

94

Cosmological radio emission induced by WIMP Dark Matter  

NASA Astrophysics Data System (ADS)

We present a detailed analysis of the radio synchrotron emission induced by WIMP dark matter annihilations and decays in extragalactic halos. We compute intensity, angular correlation, and source counts and discuss the impact on the expected signals of dark matter clustering, as well as of other astrophysical uncertainties as magnetic fields and spatial diffusion. Bounds on dark matter microscopic properties are then derived, and, depending on the specific set of assumptions, they are competitive with constraints from other indirect dark matter searches. At GHz frequencies, dark matter sources can become a significant fraction of the total number of sources with brightness below the microJansky level. We show that, at this level of fluxes (which are within the reach of the next-generation radio surveys), properties of the faint edge of differential source counts, as well as angular correlation data, can become an important probe for WIMPs.

Fornengo, N.; Lineros, R.; Regis, M.; Taoso, M.

2012-03-01

95

An intermediate framework between WIMP, FIMP, and EWIP dark matter  

NASA Astrophysics Data System (ADS)

WIMP (Weakly Interacting Massive Particle), FIMP (Feebly interacting Massive Particle) and EWIP (Extremely Weakly Interacting Particle) dark matter are different theoretical frameworks that have been postulated to explain the dark matter. In this paper we examine an intermediate scenario that combines features from these three frameworks. It consists of a weakly interacting particle — à la WIMP — that does not reach thermal equilibrium in the early Universe — à la FIMP — and whose relic density is determined by the reheating temperature of the Universe — à la EWIP. As an example, an explicit realization of this framework, based on the singlet scalar model of dark matter, is analyzed in detail. In particular, the relic density is studied as a function of the parameters of the model, and the new viable region within this intermediate scenario is determined. Finally, it is shown that this alternative framework of dark matter allows for arbitrarily heavy dark matter particles and that it suggests a connection between dark matter and inflation.

Yaguna, Carlos E.

2012-02-01

96

The zero age main sequence of WIMP burners  

SciTech Connect

We modify a stellar structure code to estimate the effect upon the main sequence of the accretion of weakly-interacting dark matter onto stars and its subsequent annihilation. The effect upon the stars depends upon whether the energy generation rate from dark matter annihilation is large enough to shut off the nuclear burning in the star. Main sequence weakly-interacting massive particles (WIMP) burners look much like proto-stars moving on the Hayashi track, although they are in principle completely stable. We make some brief comments about where such stars could be found, how they might be observed and more detailed simulations which are currently in progress. Finally we comment on whether or not it is possible to link the paradoxically hot, young stars found at the galactic center with WIMP burners.

Fairbairn, Malcolm; Scott, Pat; Edsjoe, Joakim [PH-TH, CERN, Geneva, Switzerland and King's College London, WC2R 2LS (United Kingdom); Cosmology, Particle Astrophysics and String Theory, Physics, Stockholm University and High Energy Astrophysics and Cosmology Centre (HEAC), AlbaNova University Centre, SE-106 91 Stockholm (Sweden)

2008-02-15

97

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

NASA Astrophysics Data System (ADS)

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 ?N? “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 ?N?=0 (“dark radiation without dark radiation”). Conversely, a measurement consistent with Neff=3 is not inconsistent with the presence of dark radiation (?N?>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.

Steigman, Gary

2013-05-01

98

Data analysis on XENON100 detector searching for WIMP  

NASA Astrophysics Data System (ADS)

The XENON100 detector is a dual-phase xenon time projection chamber (LXeTPC) installed underground at the Laboratori Nazionali del Gran Sasso (Italy) and used to search for dark matter in the form of weakly interacting massive particles (WIMPs) by simultaneously measuring the scintillation and ionization signals produced by nuclear recoils. The 62 kg LXeTPC is instrumented by 178 PMTs and surrounded by a 99 kg Lxe active veto with 64 PMTs. XENON100 has set the most stringent limits on WIMP-nucleon interaction cross section to date, above 7E-45cm^2 at 90% C.L., and continues to accrue blinded data towards a first robust discovery. We present the analysis techniques developed for the experiment and detail data selection procedures, quality cuts and efficiencies, as well the unblinding procedures for the experiment. Finally the methods for establishing presence of signal or for establishing a limit on interaction cross-section for WIMPs with matter are described.

Rizzo, Alfio

2012-03-01

99

Can WIMP dark matter overcome the nightmare scenario?  

SciTech Connect

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.

Kanemura, Shinya; Nabeshima, Takehiro [Department of Physics, University of Toyama, Toyama 930-8555 (Japan); Matsumoto, Shigeki; Okada, Nobuchika [Department of Physics and Astronomy, University of Alabama, Tuscaloosa, Alabama 35487 (United States)

2010-09-01

100

On-line capillary electrophoresis for enhanced detection sensitivity of feline panleukopenia virus.  

PubMed

A rapid on-line capillary electrophoresis (CE) method for highly sensitive detection of DNA molecules with specific lengths was developed based on the combination of base stacking (BS) and programmed field strength gradients (PFSG). The BS method has been performed for on-column concentration to improve detection sensitivity without any modification of the CE system. PFSG increased the electrophoretic velocity of DNA molecules, which effectively decreased analysis time. Using the BS and PFSG combination, the amplified PCR product (340-bp DNA) of cats infected with feline panleukopenia virus was detected within 6.5min. Detection sensitivity (?10-fold) was enhanced compared to conventional CE analysis. The combined on-line CE/BS-PFSG methodology could be an effectively rapid analysis technique for the highly sensitive detection of disease-related specific DNA molecules. PMID:23153639

Shin, Ahram; Lee, Mijin; Kim, Sangduk; Kang, Seong Ho

2012-10-11

101

A comparison of heat and radiation sensitivity of three human glioma cell lines  

SciTech Connect

Three human glioma cell lines were tested for radiation and hyperthermia sensitivity and compared to the responses of a normal human fibroblast cell line. The radiation response of the glioma cell lines exhibited a large shoulder on the radiation survival curve indicating radioresistance when compared to the more radiosensitive fibroblast cell line. The hyperthermia response for the glioma cell lines was qualitatively similar to responses reported for other cell lines. When compared to normal human fibroblasts the glioma cells were found to be more sensitive to hyperthermia than the normal fibroblasts indicating hyperthermia may be a promising method or adjunct to radiotherapy in the treatment of resistant glioma cells or tumors. The results also show that both the radiation and thermal response is influenced by cell culture conditions and growth status. Two of the cell lines grown to confluency and treated in confluency showed an increased radiation resistance at low doses and the cell lines showed decreased resistance at high doses compared to cells plated to confluency. An increased thermal resistance, especially at the lower heating temperatures, was also observed for cells grown to confluency. Measurements of residual glucose in the culture medium at the time of irradiation was about the same for the two culture methods (55%-65%). Cell cycle analysis showed that the differences were not related to changes in cell cycle distribution.

Raaphorst, G.P.; Feeley, M.M.; Da Silva, V.F.; Danjoux, C.E.; Gerig, L.H. (Ottawa Regional Cancer Centre, Ontario (Canada))

1989-09-01

102

Effects of In Utero and Lactational TCDD Exposure on Bone Development in Differentially Sensitive Rat Lines  

Microsoft Academic Search

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a notorious model compound of highly toxic environmental pollutants, poly- chlorinated dibenzo-p-dioxins (PCDDs). Their toxic effects are mediated via cytosolic aryl hydrocarbon receptor (AHR). We studied the effects of several dose levels of TCDD on developing rat bone after maternal exposure at different times of gestation and lactation in three differentially sensitive rat lines. Rat lines A,

Hanna M. Miettinen; Pasi Pulkkinen; Timo Jamsa; Jaana Koistinen; Ulla Simanainen; Jouko Tuomisto; Juha Tuukkanen; Matti Viluksela

2005-01-01

103

Multidrug resistance-associated antigens on drug-sensitive and -resistant human tumour cell lines  

Microsoft Academic Search

In this paper the biochemical properties of the antigens detected by six murine monoclonal antibodies (MAbs) are described. These MAbs react selectively with the multidrug-resistant small cell lung cancer (SCLC) cell line, H69AR, compared to its sensitive parent cell line, H69 (Mirski & Cole, 1989). Because H69AR cells do not overexpress P-glycoprotein, the antigens detected by these MAbs may be

SEL Mirski; SPC Cole

1991-01-01

104

Improvement of the Determination of the WIMP Mass from Direct Dark Matter Detection Data  

SciTech Connect

Weakly Interacting Massive Particles (WIMPs) are one of the leading candidates for Dark Matter. We developed a model--independent method for determining the WIMP mass by using data (i.e., measured recoil energies) of direct detection experiments. Our method is independent of the as yet unknown WIMP density near the Earth, of the form of the WIMP velocity distribution, as well as of the WIMP-nucleus cross section. It requires however positive signals from at least two detectors with different target nuclei. At the first phase of this work we found a systematic deviation of the reconstructed WIMP mass from the real one for heavy WIMPs. Now we improved this method so that this deviation can be strongly reduced for even very high WIMP mass. The statistical error of the reconstructed mass has also been reduced. In a background-free environment, a WIMP mass of {approx}50 GeV could in principle be determined with an error of {approx}35% with only 2x50 events.

Drees, Manuel [Physikalisches Institut der Universitaet Bonn, D-53115 Bonn, Germany School of Physics, KIAS, Seoul 130-012, Republic of Korea Bethe Center of Theoretical Physics, Universitaet Bonn, D-53115 Bonn (Germany); Shan, Chung-Lin [School of Physics and Astronomy, Seoul National University, Seoul 151-747 (Korea, Republic of)

2008-11-23

105

A line voltage regulator\\/conditioner for harmonic-sensitive load isolation  

Microsoft Academic Search

A technique is presented for the isolation of harmonic-sensitive loads from harmonic-producing loads, such as rectifiers and power converters. The solution, referred to as a line voltage regulator\\/conditioner (LVRC), utilizes a combination of a series and a parallel active power filter. The series filter isolates the sensitive loads on the output side of the LVRC from the nonlinear, distortion-producing loads

Steven Moran

1989-01-01

106

Determinants of the sensitivity of human small-cell lung cancer cell lines to methotrexate.  

PubMed Central

We have characterized the determinants of methotrexate (MTX) responsiveness in eight patient-derived cell lines of small-cell lung cancer (SCLC). Clonogenic survival was correlated with factors known to affect sensitivity to drug. NCI-H209 and NCI-H128 were most drug sensitive, with drug concentrations required to inhibit clonogenic survival by 50% with less than 0.1 microM MTX. Six cell lines (NCI-H187, NCI-H345, NCI-H60, NCI-H524, NCI-H146, and NCI-N417D) were relatively drug resistant. In all cell lines studied, higher molecular weight MTX-polyglutamates (MTX-PGs) with 3-5 glutamyl moieties (MTX-Glu3 through MTX-Glu5) were selectively retained. Relative resistance to low (1.0 microM) drug concentrations appeared to be largely due to decreased intracellular metabolism of MTX. Five of the six resistant lines were able to synthesize polyglutamates at higher (10 microM) drug concentrations, although one resistant cell line (NCI-N417D) did not synthesize higher molecular weight MTX-PGs, even after exposure to 10 microM drug. Two cell lines with resistance to 10 microM MTX (NCI-H146 and NCI-H524) synthesized and retained higher molecular weight MTX-PGs in excess of binding capacity after exposure to 10 microM drug. However, the specific activity of thymidylate synthase in these cell lines was low. MTX sensitivity in patient-derived cell lines of SCLC requires the ability of cells to accumulate and retain intracellular drug in the form of polyglutamate metabolites in excess of dihydrofolate reductase, as well as a high basal level of consumption of reduced folates in the synthesis of thymidylate.

Curt, G A; Jolivet, J; Carney, D N; Bailey, B D; Drake, J C; Clendeninn, N J; Chabner, B A

1985-01-01

107

A frequency domain sensitivity analysis of closed-loop multiconductor transmission lines  

Microsoft Academic Search

A frequency domain technique for the optimization, sensitivity, and robustness analysis of a large high-speed lossy multiconductor transmission line networks in VLSI regimes is presented. The technique is used to demonstrate the superiority of closed-loop topologies in terms of their electrical performance. To demonstrate this superiority, the numerical frequency domain results are validated by independent time domain simulations and measurements

Tawfik Rahal-Arabi; R. Suarez-Gartner; Martin Rausch; Kristine M. Lape

1993-01-01

108

Phenotypic Instability of Drug Sensitivity in a Human Colon Carcinoma Cell Line1  

Microsoft Academic Search

Colon cancer is one of the tumors most refractory to treatment by chemotherapy, and this may be due to inherent phenotypic instability of such tumor cells with respect to the biochemical determinants of drug sensitivity. To test this hypothesis, a clonal human colon carcinoma cell line, clone A, was passaged in culture in the absence of selection condi tions or

Peter J. Ferguson; Yung-chi Cheng

1989-01-01

109

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

PubMed

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. PMID:20430010

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

2010-04-27

110

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

Microsoft Academic Search

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.

Alvarado Tarun; Julius Jecong; Caesar Saloma

2005-01-01

111

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

NASA Astrophysics Data System (ADS)

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.

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

2013-10-01

112

Sensitivity of gastric adenocarcinoma and normal cell lines against combined or conjugated antimetabolites.  

PubMed

The in-vitro growth inhibition of cancer and normal cell lines caused by mixed or covalently linked antimetabolites should clarify whether the conjugation of antimetabolites influences cell sensitivity and growth inhibition in a manner that differs from an equimolar mixture of the same antimetabolites or not. Growth inhibition of the human gastric adenocarcinoma cell lines 23132/87 and MKN-45 in comparison with normal gastric intestinal CCL-241 and the dermal fibroblast cell line NHDF was evaluated using CASY technology. The cell lines were incubated with an equimolar mixture of 5-fluoro-2'-deoxyuridine (5FdU)+3'-C-ethynylcytidine (ECyd) or the covalently linked duplex drug 5FdU(5'?5')ECyd. The drug and metabolites of the assays and medium were determined semiquantitatively using high-performance liquid chromatography. The sensitivity of cancer and nonmalignant cell lines was clearly different against the duplex drug. A measure of 0.65 µmol/l 5FdU(5'?5')ECyd, for example, reduced the growth of MKN-45 or 23132/87 gastric cancer cells from 100% on day 0 to about 50 or 20% on day 10, respectively. However, under the same conditions, the growth of the nonmalignant NHDF and CCL-241 cell lines was not markedly inhibited. The cytostatic activity of the duplex drug is based on the active metabolites in and outside the cell formed by the degradation of 5FdU(5'?5')ECyd. The sensitivity of cell lines against the duplex drug depended on its ability to metabolize the duplex drug. 5FdU(5'?5')ECyd should be more advantageous for specific and efficient polychemotherapy of gastric cancer than the corresponding equimolar mixture of 5FdU+ECyd or a standard combination regime of single drugs. PMID:23358120

Weinreich, Jürgen; Struller, Florian; Küper, Markus; Hack, Anita; Königsrainer, Alfred; Schott, Timm C

2013-04-01

113

Differential sensitivity of melanoma cell lines with BRAFV600E mutation to the specific Raf inhibitor PLX4032  

PubMed Central

Blocking oncogenic signaling induced by the BRAFV600E mutation is a promising approach for melanoma treatment. We tested the anti-tumor effects of a specific inhibitor of Raf protein kinases, PLX4032/RG7204, in melanoma cell lines. PLX4032 decreased signaling through the MAPK pathway only in cell lines with the BRAFV600E mutation. Seven out of 10 BRAFV600E mutant cell lines displayed sensitivity based on cell viability assays and three were resistant at concentrations up to 10 ?M. Among the sensitive cell lines, four were highly sensitive with IC50 values below 1 ?M, and three were moderately sensitive with IC50 values between 1 and 10 ?M. There was evidence of MAPK pathway inhibition and cell cycle arrest in both sensitive and resistant cell lines. Genomic analysis by sequencing, genotyping of close to 400 oncogeninc mutations by mass spectrometry, and SNP arrays demonstrated no major differences in BRAF locus amplification or in other oncogenic events between sensitive and resistant cell lines. However, metabolic tracer uptake studies demonstrated that sensitive cell lines had a more profound inhibition of FDG uptake upon exposure to PLX4032 than resistant cell lines. In conclusion, BRAFV600E mutant melanoma cell lines displayed a range of sensitivities to PLX4032 and metabolic imaging using PET probes can be used to assess sensitivity.

2010-01-01

114

Goodbye to WIMPs: A Scalable Interface for ALMA Operations  

NASA Astrophysics Data System (ADS)

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.

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

2011-07-01

115

Search for low-mass WIMPs with EDELWEISS-II heat-and-ionization detectors  

NASA Astrophysics Data System (ADS)

We report on a search for low-energy (E<20keV) WIMP-induced nuclear recoils using data collected in 2009-2010 by EDELWEISS from four germanium detectors equipped with thermal sensors and an electrode design (ID) which allows to efficiently reject several sources of background. The data indicate no evidence for an exponential distribution of low-energy nuclear recoils that could be attributed to WIMP elastic scattering after an exposure of 113kg·d. For weakly interacting massive particles (WIMPs) of mass 10 GeV, the observation of one event in the WIMP search region results in a 90% C.L. limit of 1.0×10-5pb on the spin-independent WIMP-nucleon scattering cross-section, which constrains the parameter space associated with the findings reported by the CoGeNT, DAMA and CRESST experiments.

Armengaud, E.; Augier, C.; Benoît, A.; Bergé, L.; Bergmann, T.; Blümer, J.; Broniatowski, A.; Brudanin, V.; Censier, B.; Chapellier, M.; Charlieux, F.; Couëdo, F.; Coulter, P.; Cox, G. A.; Domange, J.; Drillien, A. A.; Dumoulin, L.; Eitel, K.; Filosofov, D.; Fourches, N.; Gascon, J.; Gerbier, G.; Gironnet, J.; Gros, M.; Henry, S.; Heuermann, G.; Hervé, S.; Juillard, A.; Kleifges, M.; Kluck, H.; Kozlov, V.; Kraus, H.; Kudryavtsev, V. A.; Le Sueur, H.; Loaiza, P.; Marnieros, S.; Menshikov, A.; Navick, X.-F.; Nones, C.; Olivieri, E.; Pari, P.; Paul, B.; Robinson, M.; Rozov, S.; Sanglard, V.; Schmidt, B.; Siebenborn, B.; Tcherniakhovski, D.; Torrento-Coello, A. S.; Vagneron, L.; Walker, R. J.; Weber, M.; Yakushev, E.; Zhang, X.

2012-09-01

116

Folate depletion increases sensitivity of solid tumor cell lines to 5-fluorouracil and antifolates.  

PubMed

Cancer cell lines in standard cell culture medium or in animal models are surrounded by an environment with relatively high folate (HF) levels, compared with folate levels in human plasma. In the present study we adapted 4 colon cancer (C26-A, C26-10, C26-G and WiDr) and 3 squamous cell carcinoma of the head and neck (HNSCC) cell lines (11B, 14C and 22B) to culture medium with low folate (LF) levels (2.5, 1.0 and 0.5 nM, respectively) and investigated whether folate depletion had an effect on sensitivity to antifolates and which mechanisms were involved. All LF cell lines showed a higher sensitivity to 5-fluorouracil (5-FU) alone or in combination with leucovorin (LV) (2-5-fold), to the thymidylate synthase (TS) inhibitors, AG337 (2-7-fold), ZD1694 (3-49-fold), ZD9331 (3-40-fold), LY231514 (2-21-fold) or GW1843U89 (4-29-fold) or to the dihydrofolate reductase (DHFR) inhibitor PT523 (2-50-fold) compared with their HF variants cultured in standard medium containing up to 8 microM folic acid. LV could only increase sensitivity to 5-FU in HNSCC cell lines 14C and 14C/F. The differences in sensitivity could partially be explained by a 2-7-fold increased transport activity of the reduced folate carrier (RFC) in LF cell lines, whereas no significant change in folylpolyglutamate synthetase (FPGS) activity was observed. Furthermore, the protein expression and catalytic activity of the target enzyme TS were up to 7-fold higher in HF colon cancer cells compared with the LF variants (p < 0.05). Although the TS protein expression in LF HNSCC cells was also lower than in HF variants, the TS catalytic activity and FdUMP binding sites were up to 3-fold higher (p < 0.05). Thus, changes in TS levels were associated with differences in sensitivity. These results indicate that folate depletion was associated with changes in TS and RFC levels which resulted in an increase in sensitivity to 5-FU and antifolates. The folate levels in LF medium used in this study are more representative for folate levels in human plasma and therefore these data could be more predictive for the activity of 5-FU and antifolates in a clinical setting than results obtained from cell lines cultured in HF medium or in animal models. PMID:10956384

Backus, H H; Pinedo, H M; Wouters, D; Padrón, J M; Molders, N; van Der Wilt, C L; van Groeningen, C J; Jansen, G; Peters, G J

2000-09-15

117

Sensitivity of BRCA2 mutated human cell lines to Aurora kinase inhibition.  

PubMed

Aurora kinases play a vital part in successful mitosis and cell division. Aberrant Aurora-A and -B expression is commonly seen in various types of tumors. Small molecule Aurora inhibitors have already entered clinical trials. Aurora-A amplification has been shown to be associated with breast tumors from BRCA2-mutation carriers and such patients might therefore be candidates for treatment with Aurora kinase inhibitors. There is a need to identify markers that can predict sensitivity to Aurora inhibition. In this study sensitivity to the inhibitor ZM447439 was tested on a panel of 15 non-malignant and malignant epithelial cell lines that differed with respect to BRCA2 and p53 status and related to level of Aurora kinase expression. The IC(50) value for cell survival ranged from 1.9-8.1 ?M and was not related to presence or absence of BRCA2 mutation. The levels of Aurora-A and -B expression correlated with each other but sensitivity towards ZM447439 did not correlate with levels of Aurora-A and -B mRNA expression, alone. Cells treated with the Aurora kinase inhibitor completed mitosis but cytokinesis was inhibited resulting in polyploidy and multinucleation. Different levels of polyploidy could not be fully explained by defects in p53. Only cell lines with a combination of high Aurora-A and -B expression, BRCA2 mutation and p53 defects showed more sensitivity towards Aurora inhibition than other cell lines. In conclusion, BRCA2-mutated cells showed variable sensitivity towards Aurora kinase inhibition. The level of sensitivity could not be predicted by Aurora expression levels alone but BRCA2 mutated tumors with high Aurora expression and non-functional p53 are likely candidates for treatment with Aurora inhibitors. PMID:20960027

Vidarsdottir, Linda; Steingrimsdottir, Gudridur; Bodvarsdottir, Sigridur Klara; Ogmundsdottir, Helga Margret; Eyfjord, Jorunn Erla

2010-10-20

118

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

SciTech Connect

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.

Perunicic, B.; Levi, S. (Sarajevo Univ. (Yugoslavia)); Kezunovic, M.; Soljanin, E. (Texas A and M Univ., College Station, TX (USA))

1990-04-01

119

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

SciTech Connect

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.

Kiyohara, Chikako; Hirohata, Tomio; Nagayama, Junya (Kyushu Univ., Fukuoka (Japan)); Kuratsune, Masanori (Nakamura Gakuen Coll., Fukuoka (Japan) Nakamura Junior Coll., Fukuoka (Japan))

1991-01-01

120

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

SciTech Connect

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

Denne, B.; Hinnov, E.

1984-04-01

121

Induction of resistance to hexadecylphosphocholine in the highly sensitive human epidermoid tumour cell line KB  

Microsoft Academic Search

Hexadecylphosphocholine (HePC, Miltefosine) is a representative of the group of alkyl-lysophosphocholines showing remarkable antitumoral activity in in vitro experiments and in experimental animal tumour models. The epidermoid tumour cell line KB, which is highly sensitive to HePC (half-maximal growth inhibiting concentration, ic50: 1.2 ?M; half lethal concentration, lc50: 2.8 ?M), was slowly adapted to increasing concentrations of HePC. After 14

E. A. M. Fleer; D. Berkovic; U. Grunwald; W. Hiddemann

1996-01-01

122

Characterising WIMPs at a future e + e - linear collider  

NASA Astrophysics Data System (ADS)

We investigate the prospects for detecting and measuring the parameters of WIMP dark matter in a model-independent way at the International Linear Collider. The signal under study is direct WIMP pair production with associated initial state radiation e + e -? ???. The analysis accounts for the beam energy spectrum of the ILC and the dominant machine induced backgrounds. The influence of the detector parameters are incorporated by full simulation and event reconstruction within the framework of the ILD detector concept. We show that by using polarised beams, the detection potential is significantly increased by reduction of the dominant SM background of radiative neutrino production e+e- rightarrow ? bar {? }? . The dominant sources of systematic uncertainty are the precision of the polarisation measurement and the shape of the beam energy spectrum. With an integrated luminosity of {L}= 500 fb^{-1} the helicity structure of the interaction involved can be inferred, and the masses and cross sections can be measured with a relative accuracy of the order of 1 %.

Bartels, Christoph; Berggren, Mikael; List, Jenny

2012-11-01

123

Differential sensitivities of glioblastoma cell lines towards metabolic and signaling pathway inhibitions.  

PubMed

In glioblastoma multiforme (GBM), the activation of the phosphatidylinositol 3-kinase (PI3-K) pathway is known to promote aerobic glycolysis. The relative sensitivity of GBM towards PI3-K and metabolic inhibitors was examined in a panel of human GBM lines. We observed differential sensitivities towards oligomycin, an ATP synthase inhibitor that suppresses oxidative phosphorylation (OXPHOS). GBMs that were sensitive to oligomycin have greater intrinsic oxygen consumption. They also failed to undergo adaptive glycolytic switches in response to oligomycin, as reflected in the failure to activate AMPK?. On the other hand, GBM lines that were less sensitive to oligomycin could be rendered non-viable when simultaneously treated with the glycolysis inhibitor, 2-Deoxyglucose (2DG). Furthermore, inhibiting either PI3-K pathway or glycolysis was effective in suppressing cell migration. Inhibiting OXPHOS alone did not have any significant effects on cell motility. However, both oligomycin and 2DG acted synergistically in suppressing cell migration. We conclude that while there was less synergy by the combined inhibition of PI3-K and glycolysis, the simultaneous targeting of glycolysis and OXPHOS is highly effective in blocking GBM tumorigenic phenotypes. PMID:23523615

Kennedy, Colin R; Tilkens, Sarah B; Guan, Hong; Garner, Justine A; Or, Penelope M Y; Chan, Andrew M

2013-03-21

124

Inhibition of Iron Uptake Is Responsible for Differential Sensitivity to V-ATPase Inhibitors in Several Cancer Cell Lines  

PubMed Central

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

Straud, Sarah; Zubovych, Iryna; De Brabander, Jef K.; Roth, Michael G.

2010-01-01

125

Delivery of Plasmid DNA into Mammalian Cell Lines Using pH-Sensitive Liposomes: Comparison with Cationic Liposomes  

Microsoft Academic Search

We compare the transfection efficiency of plasmid DNA encoding either luciferase or (ß-galactosidase encapsulated in pH-sensitive liposomes or non-pH-sensitive liposomes or DNA complexed with cationic liposomes composed of dioleoyloxypropyl-trimethylammonium:dioleoylphosphatidyl-ethanolamine (1:1, w\\/w) (Lipofectin) and delivered into various mammalian cell lines. Cationic liposomes mediate the highest transient transfection level in all cell-lines examined. pH-sensitive liposomes, composed of cholestryl hemisuccinate and dioleoylphosphatidylethanolamine at

Jean-Yves Legendre; Francis C. Szoka Jr

1992-01-01

126

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

PubMed

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

Frahm, Björn; Brod, Helmut; Langer, Uwe

2009-03-25

127

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

SciTech Connect

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.

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

2006-01-04

128

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

PubMed Central

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.

2012-01-01

129

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

NASA Astrophysics Data System (ADS)

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.

McDonald, John

2012-09-01

130

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

SciTech Connect

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

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

2005-09-01

131

Drug sensitivity patterns of HHV8 carrying body cavity lymphoma cell lines  

PubMed Central

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.

2011-01-01

132

Expected Sensitivity of the Nuclear Compton Telescope to Gamma-Ray Line Emission  

NASA Astrophysics Data System (ADS)

The Nuclear Compton Telescope (NCT) is a balloon-borne soft gamma-ray (0.2-10 MeV) telescope designed to study astrophysical sources of nuclear line emission and gamma-ray polarization. NCT consists of twelve 3D position-sensitive germanium strip detectors. The ultra-compact design and new technologies allow NCT to achieve high efficiency with excellent spectral resolution and background reduction. We are currently preparing for a conventional balloon flight ( 36 hr) of the NCT instrument from New Mexico in September 2008 and a long-duration balloon flight (LDBF) ( 20 days) from Australia in December 2009. Here we focus on the LDBF in 2009. Our source and background simulations are performed using the Monte Carlo simulation package MGGPOD, and events are reconstructed using the Medium Energy Gamma-ray Astronomy library (MEGAlib). We use the same tools that were successfully used for background simulations of the 2005 prototype flight (see J. Bowen, this conference). Sensitivity is optimized using standard cuts such as photon energy, angular resolution measure (ARM), and event quality factor. In this work, we present realistic line sensitivities for NCT for the LDBF in 2009.

Chiu, Jeng-Lun; Bandstra, M. E.; Boggs, S. E.; NCT Collaboration

2008-03-01

133

Sensitive Ewing sarcoma and neuroblastoma cell lines have increased levels of BAD expression and decreased levels of BAR expression compared to resistant cell lines.  

PubMed

The purpose of the study is to compare the mRNA expression of pro-apoptotic and anti-apoptotic genes by using the GeneSystem 320 (Capital Genomix Inc., Gaithersburg, MD) to examine the differential expression in Ewing sarcoma and neuroblastoma cell lines. This is an alternate method for which internal controls have been built into the system for comparing mRNA. The tumor cell lines were chosen based on their previously characterized Fas-resistance or Fas-sensitive properties in order to determine the differences in their response to apoptotic signals. Two representative pro-apoptotic genes (BAD and SMAC) and one anti-apoptotic gene (BAR) were chosen for the study. The results of mRNA expression were correlated with protein expression by Western analysis. BAD was highly expressed in the Fas-sensitive cell lines while SMAC was equally expressed in both Fas-sensitive and Fas-resistant cell lines. On the other hand, BAR was highly expressed in Fas-resistant cell lines and minimally expressed in the Fas-sensitive cell lines. Our data suggests that levels of BAD and BAR mRNA expression predict sensitivity to apoptosis. PMID:16690206

Lee, Betty; Galli, Susanna; Tsokos, Maria

2006-05-11

134

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

SciTech Connect

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

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

2008-01-17

135

Consequences of statistical sense determination for WIMP directional detection  

SciTech Connect

We study the consequences of limited recoil sense reconstruction on the number of events required to reject isotropy and detect a WIMP signal using a directional detector. For a constant probability of determining the sense correctly, 3-d readout and zero background, we find that as the probability is decreased from 1.0 to 0.75 the number of events required increases by a factor of a few. As the probability is decreased further the number of events increases sharply, and isotropy can be rejected more easily by discarding the sense information and using axial statistics. This however requires an order of magnitude more events than vectorial data with perfect sense determination. We also consider energy dependent probabilities of correctly measuring the sense. Our main finding is that correctly determining the sense of the abundant, but less anisotropic, low energy recoils is most important.

Green, Anne M.; Morgan, Ben [School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, NG7 2RD (United Kingdom); Department of Physics, University of Warwick, Coventry, CV4 7AL (United Kingdom)

2008-01-15

136

Gravitational diffusion of solar system WIMPs. [Weakly interacting massive particles  

SciTech Connect

It is shown here that, because of purely gravitational diffusion, the most important solar-bound weakly interacting massive particles (WIMPs) are populated at the same phase-space density as low-velocity unbound orbits. This diffusion occurs on time scales short compared both to the lifetime of the earth and to weak-interaction depletion. The effect is that direct capture from bound and unbound orbits together is very nearly equal to direct capture by the earth considered as a body in free space. The same gravitational diffusion virtually eliminates indirect capture. The net result is that free-space formulas for capture reported in a previous paper may be used without modification despite the fact that the earth is bound in the potential well of the sun. 10 refs.

Gould, A. (Institute for Advanced Study, Princeton, NJ (USA))

1991-02-01

137

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

PubMed

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. PMID:20307559

Emter, Roger; Ellis, Graham; Natsch, Andreas

2010-03-20

138

The flinders sensitive line rat model of depression--25 years and still producing.  

PubMed

Approximately 25 years have passed since the first publication suggesting the Flinders sensitive line (FSL) rat as an animal model of depression. At least 6 years of research on these rats was completed before that seminal paper, and there has been a steady stream of publications (130+) over the years. The present review will focus on several issues not previously covered in earlier reviews, summarize the several lines of ongoing investigations, and propose a novel mechanism that accounts for a number of previously unexplained observations. A key observation in the FSL rat relates to the antidepressant (AD)-like effects of known and putative antidepressants. The FSL rat typically exhibits an AD-like effect in behavioral tests for AD-like activity following chronic (14 days) treatment, although some studies have found AD-like effects after fewer days of treatment. In other observations, exaggerated swim test immobility in the FSL rat has been found to have a maternal influence, as shown by cross-fostering studies and observations of maternal behavior; the implications of this finding are still to be determined. Ongoing or recently completed studies have been performed in the laboratories of Marko Diksic of Canada, Aleksander Mathé of Sweden, Gregers Wegener of Denmark, Brian Harvey of South Africa, Paul Pilowsky and Rod Irvine of Australia, and Gal Yadid of Israel. Jennifer Loftis of Portland, Oregon, and Lynette Daws of San Antonio, Texas, have been working with the FSL rats in the United States. A puzzling feature of the FSL rat is its sensitivity to multiple chemicals, and its greater sensitivity to a variety of drugs with different mechanisms of action. It has been recently shown that each of these drugs feeds through G protein-coupled receptors to potassium-gated channels. Thus, an abnormality in the potassium channel could underlie the depressed-like behavior of the FSL rats. PMID:23319547

Overstreet, David H; Wegener, Gregers

2013-01-10

139

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

PubMed Central

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

Kasai, H; Neher, E

1992-01-01

140

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

PubMed

Individual differences in nutrient sensitivity have been suggested to be related with differences in stress sensitivity. Here we used layer hens divergently selected for high and low specific antibody responses to SRBC (i.e., low line hens and high line hens), reflecting a genetically based differential immune competence. The parental line of these hens was randomly bred as the control line and was used as well. Recently, we showed that these selection lines differ in their stress reactivity; the low line birds show a higher hypothalamic-pituitary-adrenal (HPA) axis reactivity. To examine maternal effects and neonatal nutritional exposure on nutrient sensitivity, we studied 2 subsequent generations. This also created the opportunity to examine egg production in these birds. The 3 lines were fed 2 different nutritionally complete layer feeds for a period of 22 wk in the first generation. The second generation was fed from hatch with the experimental diets. At several time intervals, parameters reflecting humoral immunity were determined such as specific antibody to Newcastle disease and infectious bursal disease vaccines; levels of natural antibodies binding lipopolysaccharide, lipoteichoic acid, and keyhole limpet hemocyanin; and classical and alternative complement activity. The most pronounced dietary-induced effects were found in the low line birds of the first generation: specific antibody titers to Newcastle disease vaccine were significantly elevated by 1 of the 2 diets. In the second generation, significant differences were found in lipoteichoic acid natural antibodies of the control and low line hens. At the end of the observation period of egg parameters, a significant difference in egg weight was found in birds of the high line. Our results suggest that nutritional differences have immunomodulatory effects on innate and adaptive humoral immune parameters in birds with high HPA axis reactivity and affect egg production in birds with low HPA axis reactivity. PMID:19687271

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

2009-09-01

141

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

Microsoft Academic Search

Langerhans cells (LC) are key mediators of contact allergenicity in the skin. However, no in vitro methods exist which are based on the activation process of LC to predict the sensitization potential of chemicals. In this study, we have evaluated the performances of MUTZ-3, a cytokine-dependent human monocytic cell line, in its response to sensitizers. First, we compared undifferentiated MUTZ-3

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

2006-01-01

142

Participation of poly(ADP-robose) polymerase in the drug sensitivity in human lung cancer cell lines  

Microsoft Academic Search

Summary Poly(ADP-ribose) polymerase has been generally assumed to be involved in DNA repair. The level of the enzyme in various lung cancer cell lines was examined to determine if it is involved in drug resistance. Among nine cell lines of lung cancer tested, small-cell lung cancer lines, which showed higher sensitivity to cisplatin and etoposide, were unexpectedly found to contain

Sachiyo Kubo; Mitsuko Matsutani; Kazuhiko Nakagawa; Tsutomu Ogura; Hiroyasu Esumi; Nagahiro Saijo

1992-01-01

143

Comparative evaluation of the cytotoxicity sensitivity of six fish cell lines to four heavy metals in vitro.  

PubMed

To establish the potential use of cell cultures as a simple and sensitive biological tool to detect environmental pollutants, six cell lines established from several fish species including GCF (grass carp fins), CIK (Ctenopharyngodon idellus kidney), EPC (epithelioma papulosum cyprini), CCO (channel catfish ovary), BB (brown bullhead caudal trunk) and FHM (fathead minnow muscle) were tested and compared for their cytotoxic sensitivity to four heavy metals: cadmium (Cd), chromium (Cr), zinc (Zn), and copper (Cu). Following a 24-h exposure to these metal salts at selected concentrations, test cells were characterized by morphology, viability and proliferation. Our results indicate that all these metal salts are cytotoxic to these fish cell lines, but at varied levels. Calculated inhibitory concentration (IC(50)) values revealed that the cytotoxicity of Cr and Cd was significantly more pronounced than that of the other two metal salts. Comparative analysis of these fish cell lines showed that C. idellus kidney (CIK) cells are the most sensitive cell line to copper, epithelioma papulosum cyprini (EPC) cells are more sensitive than other cells to Cr and Zn, while channel catfish ovary (CCO) cell line is the most sensitive one to Cd. In conclusion, CIK, EPC and CCO could potentially be sensitive bio-indicators for the initial monitoring and assessment of acute cytotoxicity of heavy metals in the aquatic environment. PMID:17931828

Tan, Fengxia; Wang, Min; Wang, Weimin; Lu, Yuanan

2007-09-07

144

A Transmission Renewal Planning Method using Supply-end Reserves and Line Flow Sensitivities  

NASA Astrophysics Data System (ADS)

With the high economic growth era until 1990s, the power demand increased sharply year by year. Therefore, the electric power utilities installed many electric power facilities along with the predicted demand. However, in recent years, fewer infrastructures have been installed because electric power demand growth is saturated due to low economic growth. Therefore, in electric power facilities planning, it has been necessary to form a rational renewal planning which also considers social influence factors such as the construction quantity. In this paper, we propose a new transmission renewal planning method using Supply-end Reserves and Line Flow Sensitivities. We carry out simulations for the IEEJ EAST 10-machine -O/V model system and determine the transmission planning priority order to confirm the validity of the proposed method.

Ueda, Keisuke; Takamizawa, Yu; Iwamoto, Shinichi; Kato, Yoshinori; Shimazu, Masayuki

145

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

SciTech Connect

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.

Tarun, Alvarado; Jecong, Julius; Saloma, Caesar

2005-12-01

146

Multiple mechanisms account for variation in base-line sensitivity to azole fungicides in field isolates of Mycosphaerella graminicola.  

PubMed

Molecular mechanisms that account for variation in base-line sensitivity to azole fungicides were examined in a collection of twenty field isolates, collected in France and Germany, of the wheat pathogen Mycosphaerella graminicola (Fuckel) Schroeter. The isolates tested represent the wide baseline sensitivity to the azole fungicide tebuconazole described previously. The isolates were cross-sensitive to other azoles tested, such as cyproconazole and ketoconazole, but not to unrelated chemicals like cycloheximide, kresoxim-methyl or rhodamine 6G. Progenies from a genetic cross between an isolate with an intermediate and a high sensitivity to azoles displayed a continuous range of phenotypes with respect to cyproconazole sensitivity, indicating that variation in azole sensitivity in this haploid organism is polygenic. The basal level of expression of the ATP-binding cassette transporter genes MgAtr1-MgAtr5 from Mgraminicola significantly varied amongst the isolates tested, but no clear increase in the transcript level of a particular MgAtr gene was found in the less sensitive isolates. Cyproconazole strongly induced expression of MgAtr4, but no correlation between expression levels of this gene and azole sensitivity was observed. One isolate with intermediate sensitivity to azoles over-expressed CYP51, encoding cytochrome P450 sterol 14alpha-demethylase from M graminicola. Isolates with a low or high sensitivity to azoles were tested for accumulation of cyproconazole, but no clear correlation between reduced accumulation of the fungicide in mycelium and sensitivity to azoles was observed. Therefore, differences in accumulation cannot account exclusively for the variation in base-line sensitivity of the isolates to azoles. The results indicate that multiple mechanisms account for differences in base-line sensitivity to azoles in field isolates of M graminicola. PMID:14667055

Stergiopoulos, Ioannis; van Nistelrooy, Johannes G M; Kema, Gert H J; De Waard, Maarten A

2003-12-01

147

Position sensitive VUV gaseous photomultiplier based on Thick-multipliers with resistive line readout  

NASA Astrophysics Data System (ADS)

In this work, a new position sensitive gas photomultiplier (GPM) based on a cascade configuration is proposed. The GPM is composed by two THGEMs, followed by a 2D-THCOBRA being operated in Ne/CH4(5%), at a pressure of 1 bar in VUV single photon mode. The 2D-THCOBRA is a hybrid microstructure which combines the benefits of a THGEM and a 2D-MHSP, presenting two independent charge multiplication stages. The position capability is performed by using two orthogonal resistive lines crossing each one the readout electrodes. The position is obtained by measuring the charge sharing in both ends of each resistive line, by using only 2 readout channels. This work focuses the study of the detector gain, Ion Back Flow (IBF) and spatial resolution. A charge gain of 106 and an Ion Back Flow (IBF) values of about 20% were measured. Position resolutions below 300 ?m (FWHM) were obtained for single VUV photon counting mode operation.

Lopes, T.; Silva, A. L. M.; Azevedo, C. D. R.; Carramate, L. F. N. D.; Covita, D. S.; Veloso, J. F. C. A.

2013-09-01

148

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

PubMed

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. PMID:19133282

Ho, Tsing-Fen; Peng, Yu-Ta; Chuang, Show-Mei; Lin, Shin-Chang; Feng, Bo-Lin; Lu, Chien-Hsing; Yu, Wan-Ju; Chang, Jo-Shu; Chang, Chia-Che

2008-12-24

149

WIMP dark matter from gravitino decays and leptogenesis  

NASA Astrophysics Data System (ADS)

The spontaneous breaking of B-L symmetry naturally accounts for the small observed neutrino masses via the seesaw mechanism. We have recently shown that the cosmological realization of B-L breaking in a supersymmetric theory can successfully generate the initial conditions of the hot early universe, i.e. entropy, baryon asymmetry and dark matter, if the gravitino is the lightest superparticle (LSP). This implies relations between neutrino and superparticle masses. Here we extend our analysis to the case of very heavy gravitinos which are motivated by hints for the Higgs boson at the LHC. We find that the nonthermal production of 'pure' wino or higgsino LSPs, i.e. weakly interacting massive particles (WIMPs), in heavy gravitino decays can account for the observed amount of dark matter while simultaneously fulfilling the constraints imposed by primordial nucleosynthesis and leptogenesis within a range of LSP, gravitino and neutrino masses. For instance, a mass of the lightest neutrino of 0.05 eV would require a higgsino mass below 900 GeV and a gravitino mass of at least 10 TeV.

Buchmüller, W.; Domcke, V.; Schmitz, K.

2012-06-01

150

Neutrino signals from electroweak bremsstrahlung in solar WIMP annihilation  

NASA Astrophysics Data System (ADS)

Bremsstrahlung of W and Z gauge bosons, or photons, can be an important dark matter annihilation channel. In many popular models in which the annihilation to a pair of light fermions is helicity suppressed, these bremsstrahlung processes can lift the suppression and thus become the dominant annihilation channels. The resulting dark matter annihilation products contain a large, energetic, neutrino component. We consider solar WIMP annihilation in the case where electroweak bremsstrahlung dominates, and calculate the resulting neutrino spectra. The flux consists of primary neutrinos produced in processes such as ???bar nu?Z and ???bar nulW, and secondary neutrinos produced via the decays of gauge bosons and charged leptons. After dealing with the neutrino propagation and flavour evolution in the Sun, we consider the prospects for detection in neutrino experiments on Earth. We compare our signal with that for annihilation to W+W-, and show that, for a given annihilation rate, the bremsstrahlung annihilation channel produces a larger signal by a factor of a few.

Bell, Nicole F.; Brennan, Amelia J.; Jacques, Thomas D.

2012-10-01

151

Short-term Selection for Acute Ethanol Tolerance and Sensitization from an F2 Population Derived from the High and Low Alcohol Sensitive Selectively Bred Rat Lines  

PubMed Central

Previous studies have identified quantitative trait loci (QTL) in the inbred High and Low Alcohol Sensitive Rat (IHAS1 and ILAS1) strains. The original development of the strains involved selection for ethanol sensitivity based on duration of the loss of the righting reflex (LORR) following a standard dose of ethanol. This paper confirms some of these QTL using a short-term selection procedure based on the difference between the blood ethanol level at loss and regain of the righting response. An F2 population of rats was developed by a reciprocal cross of IHAS1 and ILAS1 rats. Selection for 5 generations was carried out using delta-blood ethanol concentration (dBEC) as the selection trait, where dBEC = BECLR (BEC at loss of righting reflex) – BECRR (BEC at regain of righting reflex). The lines were labeled Tolerant (TOL) or Sensitive (SENS). Approximately one-third of the offspring for each generation in each line were genotyped using DNA markers that had been previously found to be linked to QTL on chromosomes 1, 2, 5, 12, and 13. By the fifth generation of selection, the lines showed a very large difference in dBEC, BECRR, and duration of LORR; BECLR showed little segregation during the selection, and latency to lose the righting reflex showed none. IHAS allele frequency increased in the SENS line for markers on chromosomes 1, 5, 12, and 13 while ILAS allele frequency increased in the TOL line. These results were in good agreement with the two previous QTL studies. On chromosome 2, the selection resulted in an accumulation of ILAS alleles in both lines. This study provides independent confirmation of the location of QTL on chromosomes 1, 5, 12, and 13 for ethanol sensitivity. It also suggests that genetic differences in duration of LORR are mediated primarily by the dBEC phenotype.

Radcliffe, Richard A.; Bludeau, Pequita; Deng, Xin-Sheng; Erwin, V. Gene; Deitrich, Richard A.

2008-01-01

152

Direct and indirect detection of higgsino-like WIMPs: Concluding the story of electroweak naturalness  

NASA Astrophysics Data System (ADS)

Supersymmetric models which fulfill the conditions of electroweak naturalness generally contain light higgsinos with mass not too far from mh?125 GeV, while other sparticles can be much heavier. In R-parity conserving models, the lightest neutralino is then a higgsino-like WIMP (albeit with non-negligible gaugino components), with thermal relic density well below measured values. This leaves room for axions to function as co-dark matter particles. The local WIMP abundance is then expected to be below standard estimates, and direct and indirect detection rates must be accordingly rescaled. We calculate rescaled direct and indirect higgsino-like WIMP detection rates in SUSY models that fulfill the electroweak naturalness condition. In spite of the rescaling, we find that ton-scale noble liquid detectors can probe the entire higgsino-like WIMP parameter space, so that these experiments should either discover WIMPs or exclude the concept of electroweak naturalness in R-parity conserving natural SUSY models. Prospects for spin-dependent or indirect detection are more limited due in part to the rescaling effect.

Baer, Howard; Barger, Vernon; Mickelson, Dan

2013-10-01

153

Sensitive quantitative analysis of murine LINE1 DNA methylation using high resolution melt analysis  

PubMed Central

We present here the first high resolution melt (HRM) assay to quantitatively analyze differences in murine DNA methylation levels utilizing CpG methylation of Long Interspersed Elements-1 (LINE1 or L1). By calculating the integral difference in melt temperature between samples and a methylated control, and biasing PCR primers for unmethylated CpGs, the assay demonstrates enhanced sensitivity to detect changes in methylation in a cell line treated with low doses of 5-aza-2’-deoxycytidine (5-aza). The L1 assay was confirmed to be a good marker of changes in DNA methylation of L1 elements at multiple regions across the genome when compared with total 5-methyl-cytosine content, measured by Liquid Chromatography-Mass Spectrometry (LC-MS). The assay design was also used to detect changes in methylation at other murine repeat elements (B1 and Intracisternal-A-particle Long-terminal Repeat elements). Pyrosequencing analysis revealed that L1 methylation changes were non-uniform across the CpGs within the L1-HRM target region, demonstrating that the L1 assay can detect small changes in CpG methylation among a large pool of heterogeneously methylated DNA templates. Application of the assay to various tissues from Balb/c and CBA mice, including previously unreported peripheral blood (PB), revealed a tissue hierarchy (from hypermethylated to hypomethylated) of PB > kidney > liver > prostate > spleen. CBA mice demonstrated overall greater methylation than Balb/c mice, and male mice demonstrated higher tissue methylation compared with female mice in both strains. Changes in DNA methylation have been reported to be an early and fundamental event in the pathogenesis of many human diseases, including cancer. Mouse studies designed to identify modulators of DNA methylation, the critical doses, relevant time points and the tissues affected are limited by the low throughput nature and exorbitant cost of many DNA methylation assays. The L1 assay provides a high throughput, inexpensive and sensitive screening tool for identifying and characterizing DNA methylation changes to L1 elements at multiple regions across the genome.

Newman, Michelle; Blyth, Benjamin J.; Hussey, Damian J.; Jardine, Daniel; Ormsby, Rebecca J.

2012-01-01

154

A Model-Independent Understanding of WIMP Dark Matter Searches  

NASA Astrophysics Data System (ADS)

I explore the hypothesis that dark matter is composed of Weakly Interacting Massive Particles, as motivated by various theories which solve the gauge hierarchy problem in the Standard Model of particle physics, and the interplay between various methods which can be sensitive to the presence of such a new particle. I present a model-independent parametrization of dark matter interactions and derive bounds on the various possible interactions from hadron collider studies sensitive to the presence of dark matter as well as from searches for new spectral lines in cosmic gamma rays, comparing the bounds from those two searches to those from direct detection experiments. I find that colliders provide the most strenuous constraints on spin-dependent scattering of dark matter, and that collider and indirect searches are highly complementary with direct detection searches, allowing derivations of the nature of dark matter interactions when a discovery does take place. I also present an exploration of how robust these collider bounds are to corrections from the presence of additional, related particles in the spectrum of new physics. As long as the additional, mediating particles are heavy enough to resonantly produce the final state that is searched for at colliders I find that the bounds from the effective theory are sound.

Shepherd, William Madsen

155

Comparisons between Sensitive and Resistant Human Tumor Cell Lines Regarding Effects of Polyamine Depletion on Chloroethylnitrosourea Efficacy1  

Microsoft Academic Search

We have reported that 2-difluoromethylornithine (DFMO)-induced polyamine (PA) depletion sensitized five Chloroethylnitrosourea (CENU)- resistant, O6-alkylguanine repair-proficient (Mer*) human tumor cell lines to l,3-bis(2-chloroethyl)-l-nitrosourea (BCNU), but failed to alter BCNU efficacy in a single CENU-sensitive, repair-deficient (Mer~) line. Further, alkaline elution assays of DNA ¡nterstrandcross-links (ISC) found no BCNU-induced ISC in either PA-depleted or control Mer* cells, suggesting that targets other

Jerome Seidenfeld; Wendy S. Sprague

1990-01-01

156

Indirect WIMP search for the Sun, Earth, and galactic center using upward going muon event in Super-Kamiokande  

NASA Astrophysics Data System (ADS)

We present the result of indirect search for WIMPs using upward-going muon(upmu) events at the Super-Kamiokande detector. We searched upmu events for the direction of the Sun, Earth and galactic center(GC), and set the limits on upmu fluxes and WIMP-nucleon cross sections.

Super-Kamiokande Collaboration; Tanaka, Takayuki

2012-08-01

157

Accurate calculations of the WIMP halo around the Sun and prospects for its gamma-ray detection  

SciTech Connect

Galactic weakly interacting massive particles (WIMPs) may scatter off solar nuclei to orbits gravitationally bound to the Sun. Once bound, the WIMPs continue to lose energy by repeated scatters in the Sun, eventually leading to complete entrapment in the solar interior. While the density of the bound population is highest at the center of the Sun, the only observable signature of WIMP annihilations inside the Sun is neutrinos. It has been previously suggested that although the density of WIMPs just outside the Sun is lower than deep inside, gamma rays from WIMP annihilation just outside the surface of the Sun, in the so-called WIMP halo around the Sun, may be more easily detected. We here revisit this problem using detailed Monte Carlo simulations and detailed composition and structure information about the Sun to estimate the size of the gamma-ray flux. Compared to earlier simpler estimates, we find that the gamma-ray flux from WIMP annihilations in the solar WIMP halo would be negligible; no current or planned detectors would be able to detect this flux.

Sivertsson, Sofia; Edsjoe, Joakim [Department of Theoretical Physics, Royal Institute of Technology (KTH), AlbaNova University Center, 106 91 Stockholm (Sweden) and Oskar Klein Centre for Cosmoparticle Physics, Department of Physics, Stockholm University, AlbaNova University Center, 106 91 Stockholm (Sweden); Oskar Klein Centre for Cosmoparticle Physics, Department of Physics, Stockholm University, AlbaNova University Center, 106 91 Stockholm (Sweden)

2010-03-15

158

A Radiometrie Method for Evaluation of Chemotherapy Sensitivity: Results of Screening a Panel of Human Breast Cancer Cell Lines1  

Microsoft Academic Search

We have used a radiometrie method to screen for chemotherapy sensitivity among a panel of human breast cancer cell lines. This method utilizes the inhibition of conversion of (>4C)glucose to I4CO2as an index of cytotoxicity. Nine different breast cancer cell lines were exposed for 1 h to 4 different concentrations of several antineoplastic agents with and without documented clinical activity

Carlos L. Arteaga; Barbara J. Forseth; Gary M. Clark; Daniel D. Von Hoff

159

The role of sensitivity of ALA (PpIX)-based PDT on Human embryonic kidney cell line (HEK293T)  

Microsoft Academic Search

Present study evaluates the effects of photodynamic therapy (PDT) with aminolevulinic acid (5-ALA) as photo sensitizer using\\u000a Human embryonic kidney (HEK293T) cell line as an experimental model. Porphyrins derivatives are used as active cytotoxic antitumor\\u000a agents in PDT. Above mentioned cell line were irradiated with red light (a diode laser, ? = 635 nm) at different doses (0–160\\u000a J\\/cm2) of

M. Fakhar-E-Alam; M. Atif; T. Rehman; H. Sadia; S. Firdous

2011-01-01

160

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

SciTech Connect

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.

Donato, F.; Maurin, D.; Brun, P.; Delahaye, T.; Salati, P. [Dipartimento di Fisica Teorica, Universita di Torino Istituto Nazionale di Fisica Nucleare, via P. Giuria 1, I-10125 Torino (Italy); Laboratoire de Physique Nucleaire et Hautes Energies, CNRS-IN2P3/Universite Paris VII, 4 Place Jussieu, Tour 33, 75252 Paris Cedex 05 (France); CEA, Irfu, Service de Physique des Particules, Centre de Saclay, F-91191 Gif-sur-Yvette (France); LAPTH, Universite de Savoie, CNRS, B.P. 110 74941 Annecy-le-Vieux (France)

2009-02-20

161

The XENON10 WIMP Direct Detection Search at the Gran Sasso Underground Laboratory  

SciTech Connect

The direct detection search for WIMPs with the XENON10 detector has produced among the best results in the field to date. The detector is a dual-phase liquid xenon time projection chamber, capable of 3-D position reconstruction and nuclear recoil discrimination. We summarize 58.6 live-days of WIMP search data collected at the Gran Sasso Underground Laboratory (LNGS) in Italy. With this data we have been able to set stringent upper limits on the spin-dependent and spin-independent WIMP scattering cross sections, in addition to a lower limit of 2.2 TeV/c{sup 2} on the mass of the heavy Majorana neutrino.

Manalaysay, Aaron [Department of Physics, University of Florida, Gainesville, FL 32611 (United States) and Physics Institute, University of Zuerich, Zuerich, CH-8057 (Switzerland)

2009-09-08

162

Limits on Spin-Dependent WIMP-Nucleon Cross Sections from the XENON10 Experiment  

SciTech Connect

XENON10 is an experiment to directly detect weakly interacting massive particles (WIMPs), which may comprise the bulk of the nonbaryonic dark matter in our Universe. We report new results for spin-dependent WIMP-nucleon interactions with {sup 129}Xe and {sup 131}Xe from 58.6 live days of operation at the Laboratori Nazionali del Gran Sasso. Based on the nonobservation of a WIMP signal in 5.4 kg of fiducial liquid xenon mass, we exclude previously unexplored regions in the theoretically allowed parameter space for neutralinos. We also exclude a heavy Majorana neutrino with a mass in the range of {approx}10 GeV/c{sup 2}-2 TeV/c{sup 2} as a dark matter candidate under standard assumptions for its density and distribution in the galactic halo.

Angle, J. [Department of Physics, University of Florida, Gainesville, Florida 32611 (United States); Physics Institute, University of Zuerich, Zuerich, CH-8057 (Switzerland); Aprile, E.; Giboni, K. L.; Monzani, M. E.; Plante, G.; Santorelli, R.; Yamashita, M. [Department of Physics, Columbia University, New York, New York 10027 (United States); Arneodo, F. [INFN-Laboratori Nazionali del Gran Sasso, Assergi, 67100 (Italy); Baudis, L.; Ferella, A. D. [Physics Institute, University of Zuerich, Zuerich, CH-8057 (Switzerland); Bernstein, A.; Madden, N.; Winant, C. [Lawrence Livermore National Laboratory, 7000 East Avenue, Livermore, California 94550 (United States); Bolozdynya, A.; Dahl, C. E.; Kwong, J.; Shutt, T. [Department of Physics, Case Western Reserve University, Cleveland, Ohio 44106 (United States); Coelho, L. C. C.; Fernandes, L. M. P.; Lopes, J. A. M. [Department of Physics, University of Coimbra, Coimbra 3004-516 (Portugal)] (and others)

2008-08-29

163

WIMP-nucleon cross-section results from the second science run of ZEPLIN-III  

NASA Astrophysics Data System (ADS)

We report experimental upper limits on WIMP-nucleon elastic scattering cross sections from the second science run of ZEPLIN-III at the Boulby Underground Laboratory. A raw fiducial exposure of 1344 kg?days was accrued over 319 days of continuous operation between June 2010 and May 2011. A total of eight events was observed in the signal acceptance region in the nuclear recoil energy range 7-29 keV, which is compatible with background expectations. This allows the exclusion of the scalar cross-section above 4.8×10 pb near 50 GeV/c WIMP mass with 90% confidence. Combined with data from the first run, this result improves to 3.9×10 pb. The corresponding WIMP-neutron spin-dependent cross-section limit is 8.0×10 pb. The ZEPLIN programme reaches thus its conclusion at Boulby, having deployed and exploited successfully three liquid xenon experiments of increasing reach.

Akimov, D. Yu.; Araújo, H. M.; Barnes, E. J.; Belov, V. A.; Bewick, A.; Burenkov, A. A.; Chepel, V.; Currie, A.; Deviveiros, L.; Edwards, B.; Ghag, C.; Hollingsworth, A.; Horn, M.; Jones, W. G.; Kalmus, G. E.; Kobyakin, A. S.; Kovalenko, A. G.; Lebedenko, V. N.; Lindote, A.; Lopes, M. I.; Lüscher, R.; Majewski, P.; Murphy, A. St. J.; Neves, F.; Paling, S. M.; Pinto da Cunha, J.; Preece, R.; Quenby, J. J.; Reichhart, L.; Scovell, P. R.; Silva, C.; Solovov, V. N.; Smith, N. J. T.; Stekhanov, V. N.; Sumner, T. J.; Thorne, C.; Walker, R. J.

2012-03-01

164

Predicted Modulated Differential Rates for Direct WIMP Searches at Low Energy Transfers  

NASA Astrophysics Data System (ADS)

The differential event rate for direct detection of dark matter, both the time averaged and the modulated one due to the motion of the Earth, are discussed. The calculations focus on relatively light cold dark matter candidates (WIMP) and low energy transfers. It is shown that for sufficiently light WIMPs the extraction of relatively large nucleon cross sections is possible. Furthermore for some WIMP masses the modulation amplitude may change sign, meaning that, in such a case, the maximum rate may occur six months later than naively expected. This effect can be exploited to yield information about the mass of the dark matter candidate, if and when the observation of the modulation of the event rate is established.

J. D., Vergados

2012-03-01

165

In-line prediction of drug release profiles for pH-sensitive coated pellets.  

PubMed

A new method for the prediction of the drug release profiles during a running pellet coating process from in-line near infrared (NIR) measurements has been developed. The NIR spectra were acquired during a manufacturing process through an immersion probe. These spectra reflect the coating thickness that is inherently connected with the drug release. Pellets sampled at nine process time points from thirteen designed laboratory-scale coating batches were subjected to the dissolution testing. In the case of the pH-sensitive Acryl-EZE coating the drug release kinetics for the acidic medium has a sigmoid form with a pronounced induction period that tends to grow along with the coating thickness. In this work the autocatalytic model adopted from the chemical kinetics has been successfully applied to describe the drug release. A generalized interpretation of the kinetic constants in terms of the process and product parameters has been suggested. A combination of the kinetic model with the multivariate Partial Least Squares (PLS) regression enabled prediction of the release profiles from the process NIR data. The method can be used to monitor the final pellet quality in the course of a coating process. PMID:21968477

Pomerantsev, Alexey L; Rodionova, Oxana Ye; Melichar, Michael; Wigmore, Anthony J; Bogomolov, Andrey

2011-10-03

166

Limits on spin-dependent WIMP-nucleon cross sections from 225 live days of XENON100 data.  

PubMed

We present new experimental constraints on the elastic, spin-dependent WIMP-nucleon cross section using recent data from the XENON100 experiment, operated in the Laboratori Nazionali del Gran Sasso in Italy. An analysis of 224.6 live days×34 kg of exposure acquired during 2011 and 2012 revealed no excess signal due to axial-vector WIMP interactions with 129Xe and 131Xe nuclei. This leads to the most stringent upper limits on WIMP-neutron cross sections for WIMP masses above 6 GeV/c², with a minimum cross section of 3.5×10(-40) cm² at a WIMP mass of 45 GeV/c², at 90% confidence level. PMID:23889382

Aprile, E; Alfonsi, M; Arisaka, K; Arneodo, F; Balan, C; Baudis, L; Bauermeister, B; Behrens, A; Beltrame, P; Bokeloh, K; Brown, A; Brown, E; Bruno, G; Budnik, R; Cardoso, J M R; Chen, W-T; Choi, B; Colijn, A P; Contreras, H; Cussonneau, J P; Decowski, M P; Duchovni, E; Fattori, S; Ferella, A D; Fulgione, W; Gao, F; Garbini, M; Ghag, C; Giboni, K-L; Goetzke, L W; Grignon, C; Gross, E; Hampel, W; Kaether, F; Kish, A; Lamblin, J; Landsman, H; Lang, R F; Le Calloch, M; Lellouch, D; Levy, C; Lim, K E; Lin, Q; Lindemann, S; Lindner, M; Lopes, J A M; Lung, K; Marrodán Undagoitia, T; Massoli, F V; Melgarejo Fernandez, A J; Meng, Y; Messina, M; Molinario, A; Ni, K; Oberlack, U; Orrigo, S E A; Pantic, E; Persiani, R; Plante, G; Priel, N; Rizzo, A; Rosendahl, S; dos Santos, J M F; Sartorelli, G; Schreiner, J; Schumann, M; Scotto Lavina, L; Scovell, P R; Selvi, M; Shagin, P; Simgen, H; Teymourian, A; Thers, D; Vitells, O; Wang, H; Weber, M; Weinheimer, C

2013-07-09

167

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

PubMed

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

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

2008-05-21

168

MD simulations of electron and WIMP scattering from neutron star crust  

NASA Astrophysics Data System (ADS)

Neutron star crust is composed of a crystal lattice of atomic nuclei embedded in a relativistic degenerate electron gas. We use molecular dynamics simulations to determine the crystal structure of neutron star crust material. From these simulations, we calculated the static structure factor S(q) that describes the scattering of electrons, neutrinos, or weakly interacting dark matter particles (WIMPs) from ions in the crust. The scattering of electrons determines the crust thermal conductivity, while WIMP scattering from the crust may allow dark matter particles to be trapped in neutron stars.

Fish, Jake; Horowitz, Charles

2012-10-01

169

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

PubMed

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

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

2013-05-23

170

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

SciTech Connect

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

Azam, Philippe [AFSSAPS, Unite BCM, 635 Rue de la Garenne, 34740 Vendargues (France); Peiffer, Jean-Luc [AFSSAPS, Unite BCM, 635 Rue de la Garenne, 34740 Vendargues (France); Chamousset, Delphine [AFSSAPS, Unite BCM, 635 Rue de la Garenne, 34740 Vendargues (France); Tissier, Marie-Helene [AFSSAPS, Unite BCM, 635 Rue de la Garenne, 34740 Vendargues (France); Bonnet, Pierre-Antoine [AFSSAPS, Unite BCM, 635 Rue de la Garenne, 34740 Vendargues (France); Vian, Laurence [Laboratoire de Toxicologie, Faculte de Pharmacie (UM1), 15 av Charles Flahault, BP 14491, 34093 Montpellier Cedex 5 (France); Fabre, Isabelle [AFSSAPS, Unite BCM, 635 Rue de la Garenne, 34740 Vendargues (France); Ourlin, Jean-Claude [AFSSAPS, Unite BCM, 635 Rue de la Garenne, 34740 Vendargues (France)]. E-mail: jean-claude.ourlin@afssaps.sante.fr

2006-04-01

171

Development of an in vitro skin sensitization test using human cell lines: The human Cell Line Activation Test (h-CLAT)  

Microsoft Academic Search

The aim of this study is to optimize the experimental conditions for an in vitro skin sensitization test using the human cell lines THP-1 and U-937. As regards pre-culturing time, the expression of CD86 on DNCB-treated THP-1 cells tended to be higher after 48h and 72h pre-culture compared with other time points evaluated. Next, we investigated the effect of chemical

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

2006-01-01

172

Morphometric and Colorimetrie Analyses of Human Tumor Cell Line Growth and Drug Sensitivity in Soft Agar Culture1  

Microsoft Academic Search

Previous studies have demonstrated the suitability of image analysis of tetrazolium-stained colonies to assess growth and drug sensitivity of human tumor cells cultivated in soft agar culture. In the present study, the potential utility of colorimetrie analysis to expedite experimental drug evaluations using human tumor cell lines was investigated. The same culture dishes were assessed by image analysis and by

M. C. Alle; C. M. Pacula-Co; M. L. Hursey; L. R. Rubinstein; M. R. Boy

1991-01-01

173

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

Microsoft Academic Search

A detailed electron microscopy study of cadmium sensitive and resistant muntjac fibroblast cell lines has identified a wide range of intracellular damage following exposure to cadmium. Damaged organelles included cell membrane, mitochondria, Golgi cisternae and tubular network, chromatin, nucleoli, microfilaments and ribosomes. Although cell membrane damage was generally the earliest indication of adverse cadmium action, particularly with continuous cadmium exposures,

Muriel J. Ord; Simon D. Bouffler; Rakesh Chibber

1988-01-01

174

Resolution, Line-Edge Roughness, Sensitivity Tradeoff, and Quantum Yield of High Photo Acid Generator Resists for Extreme Ultraviolet Lithography  

Microsoft Academic Search

Ultrahigh loadings of photoacid generators (PAGs) in phenolic extreme ultraviolet (EUV) resists have generated the highest known film quantum yields (FQYs). We evaluate the performance of these resists in terms of resolution, line-edge roughness (LER), and sensitivity and collectively evaluate these three parameters (known as RLS) in terms of KLUP and Z-Parameter figures of merit. An analytical model describing the

Craig D. Higgins; Charles R. Szmanda; Alin Antohe; Greg Denbeaux; Jacque Georger; Robert L. Brainard

2011-01-01

175

Lethal and Mutagenic Effects of 4-Nitroquinoline 1-Oxide in Uv-Sensitive and Wild-Type CHO Cell Lines.  

National Technical Information Service (NTIS)

A wild-type Chinese hamster ovary cell line (CHO-9) and its uv-sensitive subclone (43-3B) have been used in characterizing the lethal and mutagenic effects of the chemical carcinogen, 4-nitroquinoline 1-oxide (4NQO). Cell survival as a function of 4NQO do...

B. P. Tincknell

1982-01-01

176

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

PubMed Central

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

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

1995-01-01

177

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

NASA Astrophysics Data System (ADS)

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

Nygren, David

2013-04-01

178

RasGRP1 sensitizes an immature B cell line to antigen receptor-induced apoptosis.  

PubMed

RasGRP1 is a guanine nucleotide exchange factor that activates Ras GTPases and is activated downstream of antigen receptors on both T and B lymphocytes. Ras-GRP1 provides signals to immature T cells that confer survival and proliferation, but RasGRP1 also promotes T cell receptor-mediated deletion of mature T cells. We used the WEHI-231 cell line as an experimental system to determine whether RasGRP1 can serve as a quantitative modifier of B cell receptor-induced deletion of immature B cells. A 2-fold elevation in RasGRP1 expression markedly increased apoptosis of WEHI-231 cells following B cell receptor ligation, whereas a dominant negative mutant of RasGRP1 suppressed B cell receptor-induced apoptosis. Activation of ERK1 or ERK2 kinases was not required for RasGRP1-mediated apoptosis. Instead, elevated RasGRP1 expression caused down-regulation of NF-kappaB and Bcl-x(L), which provide survival signals counter-acting apoptosis induction by B cell receptor. Inhibition of NF-kappaB was sufficient to enhance B cell receptor-induced apoptosis of WEHI-231 cells, and ligation of co-stimulatory receptors that activate NF-kappaB suppressed the ability of RasGRP1 to promote B cell receptor-induced apoptosis. These experiments define a novel apoptosis-promoting pathway leading from B cell receptor to the inhibition of NF-kappaB and demonstrate that differential expression of RasGRP1 has the potential to modulate the sensitivities of B cells to negative selection following antigen encounter. PMID:14970203

Guilbault, Benoit; Kay, Robert J

2004-02-17

179

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

Code of Federal Regulations, 2011 CFR

...traffic-sensitive, and tandem-switched transport services. 69.713 Section 69...traffic-sensitive, and tandem-switched transport services. (a) Scope. This paragraph...traffic-sensitive components of tandem-switched transport services, as described in §§...

2011-10-01

180

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

Code of Federal Regulations, 2012 CFR

...traffic-sensitive, and tandem-switched transport services. 69.713 Section 69...traffic-sensitive, and tandem-switched transport services. (a) Scope. This paragraph...traffic-sensitive components of tandem-switched transport services, as described in §§...

2012-10-01

181

The role of sensitivity of ALA (PpIX)-based PDT on Human embryonic kidney cell line (HEK293T)  

NASA Astrophysics Data System (ADS)

Present study evaluates the effects of photodynamic therapy (PDT) with aminolevulinic acid (5-ALA) as photo sensitizer using Human embryonic kidney (HEK293T) cell line as an experimental model. Porphyrins derivatives are used as active cytotoxic antitumor agents in PDT. Above mentioned cell line were irradiated with red light (a diode laser, ? = 635 nm) at different doses (0-160 J/cm2) of light. The influence/effectiveness of incubation time, various concentrations of aminolevulinic acid (5-ALA) and light doses on the cellular viability was studied. HEK293T cells were deliberated by exposing the ALA-PpIX (0-1000 ?g/ml) of concentrations. The optimal uptakes of photosensitizer (PS) in cell lines were investigated by means of spectro photo metric measurements. Cells viability was determined by means of neutral red assay (NRA). It was observed that alone, neither photosensitizer nor light dose have significant effect on cells viability, but optimal concentration of PS along with suitable dose of light exhibit effective impact on the viability of cell. Our results showed that light doses of 40 J/cm2 demonstrates effective PDT outcome for HEK293T cell line when incubated with 400 ?g/ml, with wrapping up view that HEK293T cell line is very sensitive to ALA-mediated PDT as compared to cell line published in our data. At the end results has been verified by using reactive oxygen species (ROS) measure test.

Fakhar-e-Alam, M.; Atif, M.; Rehman, T.; Sadia, H.; Firdous, S.

2011-08-01

182

Differential modulation of CXCR4 and CD40 protein levels by skin sensitizers and irritants in the FSDC cell line.  

PubMed

The development of non-animal methods for skin sensitization testing is an urgent challenge. Some of the most promising in vitro approaches are based on the analysis of phenotypical and functional modifications induced by sensitizers in dendritic cell models. In this work, we evaluated, for the first time, a fetal skin-derived dendritic cell line (FSDC) as a model to discriminate between sensitizers and irritants, through analysis of their effects on CD40 and CXCR4 protein expression. The chemicals concentrations were chosen based on a slight cytotoxicity effect (up to 15%). Protein levels were evaluated by Western blot and immunocytochemistry, after stimulation with the skin sensitizers 2,4-dinitrofluorobenzene (DNFB), 1,4-phenylenediamine (PPD) and nickel sulphate (NiSO(4)), the non-sensitizer 2,4-dichloronitrobenzene (DCNB), and the irritants sodium dodecyl sulphate (SDS) and benzalkonium chloride (BC). All sensitizers tested increased CD40 and CXCR4 levels. In contrast, irritants decreased both proteins levels, with a more pronounced effect on CXCR4. In agreement with these results, dendritic cells derived from human peripheral blood monocytes-derived dendritic cells (MoDC) showed a similar response pattern to the skin sensitizer and irritant tested, PPD and SDS, respectively. In conclusion, evaluation of CD40 and CXCR4 proteins in chemical-treated FSDC may represent a useful tool in a future in vitro test for sensitizing assessment. PMID:18281165

Neves, Bruno Miguel; Cruz, Maria Teresa; Francisco, Vera; Gonçalo, Margarida; Figueiredo, Américo; Duarte, Carlos B; Lopes, Maria Celeste

2007-12-24

183

Characterization of kinase suppressor of Ras-1 expression and anticancer drug sensitivity in human cancer cell lines.  

PubMed

Previous studies have indicated that the ERK1/2 MAP kinase signaling pathway plays an important role not only in cell growth, cell cycle regulation, and differentiation, but also in determining the sensitivity of cells to anticancer agents as well. Furthermore, expression of kinase suppressor of Ras-1 (KSR1), a molecular scaffold that modulates signaling through the ERK1/2 MAP kinase pathway, has been shown to influence the cellular sensitivity to the anticancer agent cisplatin. To further define the role of KSR1 expression on drug sensitivity, the expression of KSR1 was examined in the NCI60 anticancer drug screen, a panel of cancer cell lines representing nine tissue types, established by the Developmental Therapeutics Program (DTP) at the National Cancer Institute (NCI). The expression of thousands of molecular targets has been examined in the NCI60 panel as well as the cellular toxicity for greater than 400,000 compounds. KSR1 expression varied almost 30-fold difference between the highest and lowest expressing cell lines in the NCI60. Using the COMPARE analysis algorithm, KSR1 expression was correlated with sensitivity of the compounds screened by DTP and several novel agents were identified whose sensitivity correlated with KSR1 expression in the NCI60 panel. Cytotoxicity of two agents, cytochalasin H and tunicamycin, identified through the COMPARE analysis of KSR1 expression and drug sensitivity, was also examined in wild type (KSR(+/+)) mouse embryo fibroblasts (MEFs) and MEFs deficient in KSR1 expression (KSR1(-/-)). These studies demonstrated enhanced sensitivity, as well as increased ERK activation, in KSR(-/-) MEFs following exposure to tunicamycin or cytochalasin H compared to KSR(+/+) MEFs. Furthermore, restoration of KSR1 expression in KSR(-/-) MEFs following stable transduction of cells with a KSR1 expression vector, enhanced sensitivity of cells to tunicamycin and cytochalasin H and decreased ERK1/2 activation following exposure to these drugs. In addition, the sensitivity to cytochalasin H and tunicamycin of breast cancer cell lines with low KSR1 expression, (HS578T and MDA-MB-231/ATCC), was increased relative to the sensitivity of breast cancer cells with higher levels of KSR1 (MCF7). These studies indicate that KSR1 may play an important role in the determination of cellular sensitivity to anticancer agents. PMID:18661133

Stoeger, Scott M; Cowan, Kenneth H

2008-07-26

184

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

NASA Astrophysics Data System (ADS)

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.

McDonald, John

2011-11-01

185

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

Microsoft Academic Search

Neutrino-less double beta decays (0???) and direct observation of cold dark matter (DM) are of great interest for studying fundamental properties of neutrinos and weakly interacting massive particles (WIMPs). These are crucial for particle physics and cosmology beyond the standard electro-weak theory. The present seminar in the Erice neutrino school reports briefly (1) the effective neutrino mass studied by 0???,

H. Ejiri

2006-01-01

186

Sensitivities of NIH/3T3-derived clonal cell lines to ionizing radiation: Significance for gene transfer studies  

SciTech Connect

Rodent cells are frequently used as recipients in experiments involving gene transfer, isolation, and characterization. The present studies were designed to investigate the clonal responses to ionizing radiation of NIH/3T3 cells subjected to DNA-mediated gene transfer. Radiation sensitivity (D0) values were determined for the parental NIH/3T3 cell strain, six clonal cell lines transfected with DNA from radiation-resistant human tumor cells, and six nontransfected clonal cell lines. The radiation sensitivities of four transfected and two nontransfected clonal cell lines differed significantly from parental NIH/3T3 cells (P less than 0.05). Detailed karyotype analysis of two nontransfected clonal cell lines with differing radiation sensitivities showed variation in chromosomal composition. Specifically, a minute chromosome was observed to segregate consistently (in 49 of 50 metaphases) with the genome of one NIH/3T3 clone (D0 2.07 Gy) and was completely absent (from 50 metaphases) in another NIH/3T3 clone (D0 1.06 Gy). In the parental NIH/3T3 strain (D0 2.02 Gy) 10% of cells (3 of 30 metaphases) had such minute chromosomes. These findings demonstrate that the clonal cellular heterogeneity of NIH/3T3 cells is characterized by genotypic and phenotypic variations which must be considered in the experimental design involving gene transfer and expression.

Kasid, U.N.; Weichselbaum, R.R.; Brennan, T.; Mark, G.E.; Dritschilo, A. (Georgetown Univ. School of Medicine, Washington, DC (USA))

1989-06-15

187

Highly Sensitive Fetal Goat Tongue Cell Line for Detection and Isolation of Foot-and-Mouth Disease Virus ?  

PubMed Central

A fetal goat cell line (ZZ-R 127) supplied by the Collection of Cell Lines in Veterinary Medicine of the Friedrich Loeffler Institute was examined for susceptibility to infection by foot-and-mouth disease (FMD) virus (FMDV) and by two other viruses causing clinically indistinguishable vesicular conditions, namely, the viruses of swine vesicular disease and vesicular stomatitis. Primary bovine thyroid (BTY) cells are generally the most sensitive cell culture system for FMDV detection but are problematic to produce, particularly for laboratories that infrequently perform FMD diagnostic tests and for those in countries where FMD is endemic that face problems in sourcing thyroid glands from FMD-negative calves. Strains representing all seven serotypes of FMDV could be isolated in ZZ-R 127 cells with a sensitivity that was considerably higher than that of established cell lines and within 0.5 log of that for BTY cells. The ZZ-R 127 cell line was found to be a sensitive, rapid, and convenient tool for the isolation of FMDV and a useful alternative to BTY cells for FMD diagnosis.

Brehm, K. E.; Ferris, N. P.; Lenk, M.; Riebe, R.; Haas, B.

2009-01-01

188

Arsenic trioxide (As2O3) sensitivity of carcinoma cell lines and cancer cells from patients with carcinomatosis peritonei.  

PubMed

The effectiveness of As2O3 treatment was studied in 3 carcinoma cell lines, LoVo, OVCAR-3, and PA-1, and in cancer cells obtained from ascites fluids of 8 patients with carcinomatosis peritonei. LoVo, OVCAR-3, and PA-1 cell lines, and cancer cells from the patients were cultured in As2O3 gradient media; As2O3 sensitivity was evaluated by trypan blue dye exclusion and by morphologic examination after Wright staining. PA-1 was the most sensitive cell line to As2O3; OVCAR-3 and LoVo were resistant to As2O3. Cancer cells from 2 of 8 patients were sensitive to As2O3. The in vivo tumoricidal effect of As2O3 (100 microg/day, i.p.) was studied in 30 BALB/c nude mice following i.p. implantation of PA-1 tumor cells. The 17 As2O3-injected mice died of extensive intratumoral hemorrhage, necrosis, and hemorrhagic ascites within 48 hr after initial treatment. In 10 As2O3-untreated tumor-bearing control mice, only focal intratumoral hemorrhage and necrosis were noted. In summary, solid tumor cell lines and cancer cells from patients showed various As2O3 sensitivities in vitro, and As2O3 had a marked tumoricidal effect on PA-1 cells in vivo. These results suggest that As2O3 treatment might possibly be beneficial in patients with carcinomatosis peritonei who are resistant to conventional therapy and whose tumors show in vitro sensitivity to As2O3. However, to minimize the life-threatening tumor lysis effect, it would be better to administer As2O3 after removal of the peritoneal tumor masses. PMID:15487701

Moon, Yeonsook; Park, Gyeongsin; Kim, Yonggoo; Kim, Myungshin; Lim, Jihyang; Pai, Soo Hwan; Lee, Eun Jung; Kang, Chang Suk; Han, Kyungja

2004-01-01

189

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

Microsoft Academic Search

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.

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

2010-01-01

190

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

Microsoft Academic Search

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

Roger Emter; Graham Ellis; Andreas Natsch

2010-01-01

191

Cerebellar GABA A receptor binding and function in vitro in two rat lines developed for high and low alcohol sensitivity  

Microsoft Academic Search

TheBmax of the [3H]muscimol binding in the cerebellum of ethanol-naive alcohol-sensitive ANT (Alcohol Non-Tolerant) rats was only about 70% of that in the alcohol-insensitive AT (Alcohol Tolerant) rats. There were no line differences in the muscimol binding to cerebrocortical and hippocampal membranes. In the alcohol-sensitive rats, the cerebellar [3H]muscimol binding (5 nM) negatively correlated with the ethanol-induced motor-impairment measured in

M. Uusi-Oukari; E. R. Korpi

1989-01-01

192

Stem-like Cells in Bladder Cancer Cell Lines with Differential Sensitivity to Cisplatin  

PubMed Central

Background Recurrence is a common problem in bladder cancer; this has been attributed to cancer stem cells. In this study, we characterized potential cancer stem cell populations isolated from three cell lines that demonstrate different responses to cisplatin. Materials and Methods The ALDEFLUOR® assay was used to isolate cells from TCCSUP, T24, and 5637 cell lines, and these cells were evaluated for their ability to form colonies, differentiate, migrate and invade. Results The cell lines demonstrate a spectrum of aldehyde dehydrogenase high (ALDHHigh)populations that correlate with resistance to cisplatin. In the two resistant cell lines, T24 and 5637, the ALDHHigh cells demonstrate increased colony formation, migration, invasion, and ability to differentiate. The resistant T24 and 5637 cell lines may serve as models to investigate alternative therapies for bladder cancer.

Sarachine Falso, Miranda J.; Buchholz, Bruce A.; deVere White, Ralph W.

2013-01-01

193

microRNA-34a sensitizes lung cancer cell lines to DDP treatment independent of p53 status.  

PubMed

miR-34a was identified as one of the downregulated microRNAs (miRNAs) in human lung cancer. However, the precise biological role of miR-34a in p53 deficient lung cancer cell lines remains largely elusive. In the present study, we aimed to identify the role of miR-34a in the regulation of lung cancer cell proliferation. Using quantitative RT-PCR analysis, we found that miR-34a was highly upregulated in the p53 wild-type A549 human lung cancer cell line when treated with the DNA damaging agent adriamycin (ADR), but not in the SBC-5 cells harboring mutated p53. Transient introduction of miR-34a into A549 and SBC-5 cell lines caused complete suppression of cell proliferation and induced the cell cycle arrested at the G(1) phase. When we knockdown the miR-34a downstream target--Sitr1--using the small-interfering RNA, there was also a cell growth inhibition in both cell lines though not as much as miR-34a did. Moreover, we demonstrated that pretransfection of miR-34a could increase the sensitivity of both lung cancer cell lines to cisplatin (DDP), and this could be reverted by the miR-34a inhibitor. Moreover, when cells pretreated with siR-Sirt1, they are more sensitive to DDP than the control pretreated cells as well. We thus hypothesize the miR-34a/Sirt1 cascade involved with p53-independent functions. Overall, in this study, we found the proliferation inhibition function of miR-34a in vitro in lung cancer cell lines is p53 independent, and also demonstrated the combination therapeutic potential of miR-34a and DDP in lung cancer cell lines. PMID:23036084

Wang, Xi; Dong, Ke; Gao, Ping; Long, Min; Lin, Fang; Weng, Yuanyuan; Ouyang, Yongri; Ren, Jihong; Zhang, Huizhong

2012-10-04

194

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

Microsoft Academic Search

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

MF Pera; B Köberle; JRW Masters

1995-01-01

195

Associations of ErbB2, ?1-integrin and lipid rafts on Herceptin (Trastuzumab) resistant and sensitive tumor cell lines  

Microsoft Academic Search

ErbB2-mediated transmembrane signaling is a key target of novel anticancer agents such as Herceptin. Our comparison of Herceptin resistant (JIMT-1, MKN-7) and sensitive (SKBR-3, N-87) cell lines demonstrates the importance of ErbB2 association patterns involving integrins and lipid rafts. Flow cytometric FRET and confocal microscopic measurements revealed colocalization and molecular proximity between ?1-integrins and ErbB2, as well as their association

Maria-Magdalena Mocanu; Zsolt Fazekas; Miklós Petrás; Péter Nagy; Zsolt Sebestyén; Jorma Isola; József Tímár; John W. Park; György Vereb; János Szöll?si

2005-01-01

196

Activation of voltage-sensitive Ca 2+ currents by vasopressin in an insulin-secreting cell line  

Microsoft Academic Search

Summary The effect of vasopressin on voltage-sensitive Ca2+ currents in the rat insulinoma cell line RINm5F has been investigated in patch-clamp whole-cell and single-channel current recording experiments. In the whole-cell recording configuration the dominant inward current in the presence of tetrodotoxin was noninactivating and had a high voltage threshold. This current was much enhanced when external Ca2+ was replaced by

P. Thorn; O. H. Petersen

1991-01-01

197

The sensitivity of a malignant cell line to hyperthermia (42°C) at low intracellular pH  

Microsoft Academic Search

The postulate that low intracellular pH acts as a preconditioner for the destructuve effects of hyperthermia (42 degrees C) was examined, using a heat-sensitive line of malignant cells derived from rat mammary gland (SDB). Intracellular pH (pHi) was measured indirectly, from the distribution of the weak, non-metabolizable organic acid 5,5-dimethyl-2,4-oxazolidinedione (DMO) between intra- and extra-cellular water. Respiration, aerobic and anaerobic

J A Dickson; B E Oswald

1976-01-01

198

Transformation of Rat Ovarian Epithelial and Rat1 Fibroblast Cell Lines by RAST24 Does Not Influence Cisplatin Sensitivity1  

Microsoft Academic Search

Recent reports suggest that expression of an activated c-Ha-ros onco gene is associated with cisplatin resistance in NIH-3T3 fibroblasts. To investigate the generality of these observations, cisplatin cytotoxicity was determined in a series of clonal Rat-1 fibroblast and rat ovarian surface epithelial (ROSE) cell lines carrying a zinc-inducible metallothionein- RAST24 fusion gene, MTR4ST24. Cisplatin sensitivity in RAS-trsms- formed fibroblast sublines

Raymond P. Perez; Kinya Hamaguchi; Pamela A. Tracey; Laura M. Handel; Thomas C. Hamilton; Andrew K. Godwin

199

A simple and sensitive chromium speciation procedure by hyphenating flow injection on-line preconcentration with catalytic spectrophotometry  

Microsoft Academic Search

A high sensitive chromium speciation procedure based on spectrophotometric detection was developed by coupling flow injection on-line preconcentration with a catalytic indicator reaction. Chromium(VI) is retained on a mini-column packed with polystyrene anion exchange resin (strong basic 717 resin), which was afterwards eluted with a small volume of NaNO3 solution. The eluted Cr(VI) is then directed to catalyze the decoloration

Han Cui; Ronghuan He; Jianhua Wang

2006-01-01

200

Restoring E-cadherin expression increases sensitivity to epidermal growth factor receptor inhibitors in lung cancer cell lines.  

PubMed

The epidermal growth factor receptor (EGFR) is overexpressed in the majority of non-small cell lung cancers (NSCLC). EGFR tyrosine kinase inhibitors, such as gefitinib and erlotinib, produce 9% to 27% response rates in NSCLC patients. E-Cadherin, a calcium-dependent adhesion molecule, plays an important role in NSCLC prognosis and progression, and interacts with EGFR. The zinc finger transcriptional repressor, ZEB1, inhibits E-cadherin expression by recruiting histone deacetylases (HDAC). We identified a significant correlation between sensitivity to gefitinib and expression of E-cadherin, and ZEB1, suggesting their predictive value for responsiveness to EGFR-tyrosine kinase inhibitors. E-Cadherin transfection into a gefitinib-resistant line increased its sensitivity to gefitinib. Pretreating resistant cell lines with the HDAC inhibitor, MS-275, induced E-cadherin along with EGFR and led to a growth-inhibitory and apoptotic effect of gefitinib similar to that in gefitinib-sensitive NSCLC cell lines including those harboring EGFR mutations. Thus, combined HDAC inhibitor and gefitinib treatment represents a novel pharmacologic strategy for overcoming resistance to EGFR inhibitors in patients with lung cancer. PMID:16424029

Witta, Samir E; Gemmill, Robert M; Hirsch, Fred R; Coldren, Christopher D; Hedman, Karla; Ravdel, Larisa; Helfrich, Barbara; Dziadziuszko, Rafal; Chan, Daniel C; Sugita, Michio; Chan, Zeng; Baron, Anna; Franklin, Wilbur; Drabkin, Harry A; Girard, Luc; Gazdar, Adi F; Minna, John D; Bunn, Paul A

2006-01-15

201

Glucocorticoid Sensitivity and Receptors in Cells of HumanMyelogenous Leukemia Line  

Microsoft Academic Search

cells are ASD-chboroacetateestenase positive, and the line retainsthe samekaryotypic abnormalitythat was present in the fresh leukemia cells of the patient. The HL-60 cell line was derivedfrom a patient with promyebocyticleukemia.Thesecells are predominantly at the pnomyebocyte stage of development and stain positive for peroxidase and ASD-chboroacetatees terase. The cells retain the karyotype of the fresh beukemic cells and are abbeto produce

H. Phillip Koeffber; David W. Golde; Marc E. Lippman

202

Association of amphiregulin with the cetuximab sensitivity of gastric cancer cell lines.  

PubMed

The therapeutic activity of the epidermal growth factor receptor (EGFR)-directed monoclonal antibody cetuximab in gastric cancer is currently being investigated in clinical studies. Reliable biomarkers for the identification of patients who are likely to benefit from this treatment are not available. In this study, we assessed the activity of cetuximab in five gastric cancer cell lines (AGS, AZ521, Hs746T, LMSU and MKN1). The viability of two of these cell lines, AZ521 and MKN1, was significantly reduced by cetuximab treatment. High expression and secretion levels of the EGFR-binding ligand, amphiregulin (AREG), were associated with cetuximab responsiveness. MET activation and mutations in Kirsten-Ras gene (KRAS) were associated with cetuximab resistance. By introducing a hierarchy between these markers, we established a model that facilitated the correct classification of all five gastric cancer cell lines as cetuximab responsive or non-responsive. The highest priority was allocated to activating KRAS mutations, followed by MET activation and finally by the levels of secreted AREG. In order to validate these results, we used three additional human gastric cancer cell lines (KATOIII, MKN28 and MKN45). In conclusion, we propose that our model allows the response of gastric cancer cell lines to cetuximab treatment to be predicted. PMID:22614881

Kneissl, Julia; Keller, Simone; Lorber, Thomas; Heindl, Stefan; Keller, Gisela; Drexler, Ingo; Hapfelmeier, Alexander; Höfler, Heinz; Luber, Birgit

2012-05-14

203

Radiation sensitivities of 31 human oesophageal squamous cell carcinoma cell lines  

PubMed Central

The purpose of this study was to determine the radiosensitivities of 31 human oesophageal squamous cell carcinoma cell lines with a colony-formation assay. A large variation in radiosensitivity existed among 31 cell lines. Such a large variation may partly explain the poor result of radiotherapy for this cancer. One cell line (KYSE190) demonstrated an unusual radiosensitivity. Ataxia-telangiectasia-mutated (ATM) gene in these cells had five missense mutations, and ATM protein was truncated or degraded. Inability to phosphorylate Chk2 in the irradiated KYSE190 cells suggests that the ATM protein in these cells had lost its function. The dysfunctional ATM protein may be a main cause of unusual radiosensitivity of KYSE190 cells. Because the donor of these cells was not diagnosed with ataxia telangiectasia, mutations in ATM gene might have occurred during the initiation and progression of cancer. Radiosensitive cancer developed in non-hereditary diseased patients must be a good target for radiotherapy.

Ban, Sadayuki; Michikawa, Yuichi; Ishikawa, Ken-ichi; Sagara, Masashi; Watanabe, Koji; Shimada, Yutaka; Inazawa, Johji; Imai, Takashi

2005-01-01

204

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

NASA Astrophysics Data System (ADS)

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.

Rao, Gottipaty N.; Karpf, Andreas

2011-05-01

205

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...

206

Hepatocyte Growth Factor Sensitizes Human Ovarian Carcinoma Cell Lines to Paclitaxel and Cisplatin  

Microsoft Academic Search

The hepatocyte growth factor (HGF) receptor, encoded by the MET oncogene, is expressed in 70% of human ovarian carcinomas and over- expressed in 30% of cases. Because HGF is known to protect cells from apoptosis, we investigated whether receptor expression modifies ovarian cancer cell response to chemotherapy. The apoptotic effect of the front- line chemotherapeutic drugs paclitaxel and cisplatin on

Andrea Rasola; Sergio Anguissola; Norma Ferrero; Daniela Gramaglia; Antonella Maffe; Piera Maggiora; Paolo M. Comoglio; M. Flavia Di Renzo

2004-01-01

207

Basal drag pattern and grounding line sensitivity of the ice flow of Totten Glacier, East Antarctica  

NASA Astrophysics Data System (ADS)

Increased ice thinning has been detected on Totten Glacier, East Antarctica, but the cause of thinning and its timing are unclear. Most of the observed changes are taking place in the proximity of the grounding line. In this work, we apply an inverse method part of the JPL/UCI Ice Sheet System Model (ISSM) to infer the spatial pattern of basal drag on Totten Glacier from satellite radar interferometry observations of ice motion combined with a gridded thickness map using IceBridge data. A particularity of Totten Glacier is that its grounding line migrates back and forth over more than 15 km along the glacier sides as a result of changes in oceanic tides. We use the model set up and our observations of grounding line migration to study the impact of oceanic tides and changes in ice shelf bottom melting on the ice speed of the glacier. We conclude on the likelihood that observed glacier thinning is indeed controlled by its grounding line dynamics and whether the current rate of ice thinning might be explained from a change in thermal forcing from the ocean. Preliminary results are presented. This work is performed at University of California, Irvine under a contract with NASA Cryosphere Science Program.

Li, X.; Rignot, E. J.; Morlighem, M.; Seroussi, H. L.; Larour, E. Y.; Mouginot, J.; Scheuchl, B.; Young, D. A.; Blankenship, D. D.

2011-12-01

208

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

NASA Astrophysics Data System (ADS)

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

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

2005-09-01

209

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

PubMed Central

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

2011-01-01

210

The Flinders Sensitive Line of rats, a rat model of depression, has elevated brain glucose utilization when compared to normal rats and the Flinders Resistant Line of rats.  

PubMed

The Flinders Sensitive Line (FSL) of rats, developed as a line of rats with behavioral supersensitivity to diisopropyl fluorophosphates, a cholinesterase inhibitor, has been used as a rat model of depression. This line has many behavioral and neurochemical similarities to human depression. Because brain regional glucose utilization has been extensively studied in patients with depression with a rather heterogeneous outcome, it became necessary to evaluate this parameter in a well defined and homogeneous animal model. In the present study, the regional glucose utilization measured in thirty-six distinct brain regions and the pineal body was determined in FSL rats and the values were compared to those found in normal Sprague-Dawley (SPD) rats and the Flinders Resistant Line of rats (FRL: animals which have a high resistance to the above noted cholinesterase inhibitor). The measurements were performed by autoradiography with 2-[(14)C]deoxyglucose (2-DG) as the tracer. SPD and FRL groups consisted of six and FSL had 8 rats. The rats were sacrificed 45min following the start of the tracer injection. The results showed that the global, and, in many brain areas, regional, glucose utilization is higher in the FSL rats than in the control SPD rats. The synthesis in the FRL rats was very similar to that of the SPD rats, but it was different in many brain regions from the FSL rats. Because the FSL rats have many neurochemical and behavioral differences, in particular, those parameters having lower values, the results presented here suggest that the biochemical processes in the brain of FSL rats occur with lower efficiency than in either the normal SPD rats or FRL rats. PMID:19560506

Kanemaru, Kazuya; Diksic, Mirko

2009-06-26

211

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

PubMed

Mammalian telomeres are transcribed into long non-coding telomeric repeat-containing RNA (TERRA) molecules that seem to play a role in the maintenance of telomere stability. In human cells, CpG-island promoters drive TERRA transcription and are regulated by methylation. It was suggested that the amount of TERRA may be related to telomere length. To test this hypothesis we measured telomere length and TERRA levels in single clones isolated from five human cell lines: HeLa (cervical carcinoma), BRC-230 (breast cancer), AKG and GK2 (gastric cancers), and GM847 (SV40 immortalized skin fibroblasts). However, these two parameters did not correlate with each other. Moreover, cell survival to ?-rays did not show a significant variation among the clones, suggesting that, in this cellular system, the intra-population variability in telomere length and TERRA levels does not influence sensitivity to ionizing radiation. This conclusion was supported by the observation that in a cell line in which telomeres were greatly elongated by the ectopic expression of telomerase, TERRA expression levels and radiation sensitivity were similar to the parental HeLa cell line. PMID:23717814

Smirnova, Alexandra; Gamba, Riccardo; Khoriauli, Lela; Vitelli, Valerio; Nergadze, Solomon G; Giulotto, Elena

2013-05-10

212

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

PubMed Central

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

Smirnova, Alexandra; Gamba, Riccardo; Khoriauli, Lela; Vitelli, Valerio; Nergadze, Solomon G.; Giulotto, Elena

2013-01-01

213

Neutron Background in WIMP Dark Matter Detectors Using Liquid Argon and Liquid Neon  

NASA Astrophysics Data System (ADS)

Neutron-induced nuclear recoil represents an irreducible background in detectors aimed at the direct detection of WIMP dark matter. Muon-induced neutrons can be adequately suppressed by staging experiments sufficiently deep underground, however, it is also critical to suppress neutron production via (,) interactions due to naturally occurring radioactivity in detector construction materials. We present the results of simulations for the mini-CLEAN detector under development to search for WIMP dark matter using 100 kg of liquid argon or liquid neon as the target material. We show that neutron backgrounds can be sufficiently suppressed in a conceptually simple detector using the coincidence between the prompt nuclear recoil signal and the delayed neutron capture gamma ray.

Hime, Andrew; Mei, Dongming

2006-04-01

214

Indirect Detection of Dark Matter WIMPs in a Liquid Argon TPC  

Microsoft Academic Search

We assess the prospects for indirect detection of Weakly Interacting Massive\\u000aParticles using a large Liquid Argon TPC detector. Signal events will consist\\u000aof energetic electron (anti)neutrinos coming from the decay of $\\\\tau$ leptons\\u000aand $b$ quarks produced in WIMP annihilation in the core of the Sun. Background\\u000acontamination from atmospheric neutrinos is expected to be low, thanks to the

A. Bueno; R. Cid; S. Navas-Concha; D. Hooper; T. J. Weiler

2004-01-01

215

A WIMP detector with two-phase xenon to search for dark matter  

NASA Astrophysics Data System (ADS)

In this thesis I would like to introduce an experimental approach to solve the dark matter problem that is one of the hottest unsolved physics problems today. I have been involved for several years to solve that problem in UCLA- Torino Dark Matter search team at CERN, Geneva. The UCLA- Torino dark matter team is searching for the Super Symmetric dark matter particle named neutralino, that is a candidate for the WIMPs (Weakly Interactive Massive Particles). So, many parts of this thesis will be filled with description of the dark matter search work of the UCLA-Univ. of Torino collaboration with 1-kg two-phase xenon detector that was supposed to be mounted at the laboratory in the middle of the Mt. Blanc tunnel with an expecting event rate of 3 ~ 4 events/kg/day. Even though most physicists believe the existence of dark matter, I would like to review the inventory of the dark matter in the universe, cosmological approach for the dark matter, and astrophysical approach for that problem in the first few chapters. I will introduce the already found evidences of the non-baryonic dark matter, for example MACHO, gravitational lensing, super nova, etc. Theoretical approaches and several direct detection methods will be reviewed also. The direct WIMPs searching detectors need the extremely powerful background discrimination because there is a huge amount of background in that energy range of dark matter signal. Xenon and xenon detector meet all the requirements well for the background rejection. Especially, a two-phase xenon WIMP detector provides much better background rejection than a single phase one. Also we will show the outstanding effect of the electroluminescence plates with CsI internal photo cathode that magnify the primary scintillation and increase the efficiency of the background rejection. Applying the CsI internal photo cathode to the xenon WIMP detector is one of major topics for this dissertation.

Woo, Jong-Kwan

2000-08-01

216

Fission-product gamma-ray line pairs sensitive to fissile material and neutron energy  

Microsoft Academic Search

The beta-delayed gamma-ray spectra from the fission of 235U, 238U, and 239Pu by thermal and near-14-MeV neutrons have been measured for delay times ranging from 1 min to 14 h. Spectra at all delay times contain sets of prominent gamma-ray lines with intensity ratios that identify the fissile material and distinguish between fission induced by low-energy or high-energy neutrons.

R. E. Marrs; E. B. Norman; J. T. Burke; R. A. Macri; H. A. Shugart; E. Browne; A. R. Smith

2008-01-01

217

Fission-product gamma-ray line pairs sensitive to fissile material and neutron energy  

NASA Astrophysics Data System (ADS)

The beta-delayed gamma-ray spectra from the fission of 235U, 238U, and 239Pu by thermal and near-14-MeV neutrons have been measured for delay times ranging from 1 min to 14 h. Spectra at all delay times contain sets of prominent gamma-ray lines with intensity ratios that identify the fissile material and distinguish between fission induced by low-energy or high-energy neutrons.

Marrs, R. E.; Norman, E. B.; Burke, J. T.; Macri, R. A.; Shugart, H. A.; Browne, E.; Smith, A. R.

2008-07-01

218

Fission-product gamma-ray line pairs sensitive to fissile material and neutron energy  

Microsoft Academic Search

The beta-delayed gamma-ray spectra from the fission of 235U, 238U, and 239Pu by thermal and near-14-MeV neutrons have been measured for delay times ranging from 1min to 14h. Spectra at all delay times contain sets of prominent gamma-ray lines with intensity ratios that identify the fissile material and distinguish between fission induced by low-energy or high-energy neutrons.

R. E. Marrs; E. B. Norman; J. T. Burke; R. A. Macri; H. A. Shugart; E. Browne; A. R. Smith

2008-01-01

219

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

PubMed Central

We have studied the radiation dose responses of two human fibroblast lines: cells from a patient with Ataxia telangiectasia (AT-2SF) and an established line of human T-1 cells. Aerobic and hypoxic 225 kVp X-ray survival curves were used as controls to the heavy ion exposures. 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 microns-1 to over 1,000 keV microns-1. All Ataxia survival curves were exponential functions of the dose. Their radiosensitivity reached peak values at 100-200 keV microns-1. 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. At high LET their radiosensitivity approached that of the Ataxia cells. The repair-misrepair model has been used to interpret these results. According to this model, the molecular repair processes culminate either in eurepair or in misrepair. 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. 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. T-1 cells have efficient repair mechanisms at low LET, and the repair-misrepair model suggests that at high LET the T-1 cells can still efficiently repair individual lesions, but that as the lesions become closely spaced along the tracks, the probability of misrepair increases.

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

1984-01-01

220

Repetitive DNA sequences in methotrexate- and methasquin-sensitive and -resistant Chinese hamster cell lines  

Microsoft Academic Search

DNA purified from a Chinese hamster cell line of lung fibroblast origin (DC83F) was analyzed by density gradient centrifugation and by gel electrophoresis after restriction endonuclease digestion in order to fractionate discrete repetitive fractions within the total DNA. No obvious satellite DNAs were resolved using the CsCl or Ag-Cs2SO4 density gradient conditions described herein. However, analysis of the digestion products

Debra J. Wolgemuth; June L. Biedler; Peter W. Melera

1980-01-01

221

Variation in sensitizing effect of caffeine in human tumour cell lines after ?-irradiation  

Microsoft Academic Search

Background and purpose: We have investigated whether the protective role of the G2 checkpoint has increasing importance when the p53-dependent G1 checkpoint is inactivated.Materials and methods: We have studied the differential effect of caffeine by clonogenic assays and flow cytometry in three human tumour cell lines with different functionality of p53 protein.Results: The radiosensitizing effect of caffeine (2 mM) expressed

Maria Teresa Valenzuela; Santiago Mateos; J. Mariano Ruiz de Almodóvar; Trevor J McMillan

2000-01-01

222

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

SciTech Connect

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.

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

1983-07-01

223

Halo-independent analysis of direct detection data for light WIMPs  

NASA Astrophysics Data System (ADS)

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/c2. 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.

Del Nobile, Eugenio; Gelmini, Graciela B.; Gondolo, Paolo; Huh, Ji-Haeng

2013-10-01

224

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

NASA Astrophysics Data System (ADS)

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 CF4 detector with a 30-kg-yr exposure, a 50-GeV WIMP mass, and a WIMP-nucleon spin-dependent cross-section of 10-3pb, 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.

Lee, Samuel K.; Peter, Annika H. G.

2012-04-01

225

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

Microsoft Academic Search

Although the importance of animal cell culture for the industrial (large scale) production of pharmaceutical products is continuously\\u000a increasing, the sensibility of the cells towards their cultivation environment is still a challenging issue. In comparison\\u000a to microbial cultures, cell cultures which are not protected by a cell wall are much more sensitive to shear stress and foam\\u000a formation. Reactor design

Björn Frahm; Helmut Brod; Uwe Langer

2009-01-01

226

CD40-ligation-mediated protection from apoptosis of a Fas-sensitive Hodgkin's-disease-derived cell line.  

PubMed

Modulation of Fas expression and function by CD40 ligation was investigated in the Fas-sensitive human Hodgkin's disease cell line HDLM2. The recombinant human trimeric soluble CD40L (sCD40L) protected this cell line from apoptosis induced by an agonistic Fas antibody at all concentrations tested. sCD40L also protected HDLM2 when added up to 2 h after Fas ligation. Apoptosis induced by a cell-permeable synthetic ceramide could not be prevented by sCD40L. Thus, CD40 ligation is likely to intervene in the early phases of the Fas signal transduction pathway. When CD40 ligation preceded Fas ligation, it rendered the cells refractory to Fas-induced apoptosis. sCD40L-mediated protection could not be attributed to reduction in surface Fas expression, increase in Bcl-2 levels or to increase in the levels of soluble Fas isoforms. PMID:9769119

Metkar, S S; Naresh, K N; Redkar, A A; Nadkarni, J J

1998-10-01

227

Usutu virus growth in human cell lines: induction of and sensitivity to type I and III interferons.  

PubMed

The mechanisms of Usutu virus (USUV) pathogenesis are largely unknown. The aim of this study was to evaluate the sensitivity of USUV to interferon (IFN) and the capacity of USUV to stimulate IFN production. Initial experiments were conducted to characterize the susceptibility of human cell lines to USUV infection and to evaluate the single-growth cycle replication curve of USUV. Results indicate that USUV is able to infect a variety of human cell lines, completing the replication cycle in Hep-2 and Vero cells within 48 h. Pre-treatment of cells with types I and III IFNs significantly inhibited the replication of USUV. However, the inhibitory effects of IFNs were considerably less if IFN was added after viral infection had been initiated. Also, USUV weakly induced types I and III IFNs. PMID:23255619

Scagnolari, Carolina; Caputo, Beniamino; Trombetti, Simona; Cacciotti, Giulia; Soldà, Annalisa; Spano, Lucia; Villari, Paolo; della Torre, Alessandra; Nowotny, Norbert; Antonelli, Guido

2012-12-19

228

Software modules of DAQ PCI board (DeLiDAQ) for positive-sensitive MWPC detectors with delay line readout  

NASA Astrophysics Data System (ADS)

The data acquisition system for the position-sensitive delay line detectors on basis of the reprogrammable PCI DAQ board (DeLiDAQ) began to be used for scientific measurements with one- and two-dimensional position-sensitive MWPC detectors on the neutron reactors IBR-2 (JINR, Dubna) and BERII (HMI, Berlin). A stand-alone version of the system with the graphical user interface on the basis of packet ROOT can be used on any PC with the operating system Windows 2000 or Windows XP. Architecture of the created software ensures several ways of interfacing to experiment control systems. In the paper we provide a description of the DeLiDAQ software modules, their features and results of some performance tests.

Levchanovsky, F. V.; Litvinenko, E. I.; Nikiforov, A. S.; Gebauer, B.; Schulz, Ch.; Wilpert, Th.

2006-12-01

229

Fission Product Gamma-Ray Line Pairs Sensitive to Fissile Material and Neutron Energy  

Microsoft Academic Search

The beta-delayed gamma-ray spectra from the fission of ²³⁵U, ²³⁸U, and ²³⁹Pu by thermal and near-14-MeV neutrons have been measured for delay times ranging from 1 minute to 14 hours. Spectra at all delay times contain sets of prominent gamma-ray lines with intensity ratios that identify the fissile material and distinguish between fission induced by low-energy or high-energy neutrons.

R E Marrs; E B Norman; J T Burke; R A Macri; H A Shugart; E Browne; A R Smith

2007-01-01

230

Identification of Proteins Sensitive to Thermal Stress in Human Neuroblastoma and Glioma Cell Lines  

PubMed Central

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

Xu, Guilian; Stevens, Stanley M.; Kobiessy, Firas; Brown, Hilda; McClung, Scott; Gold, Mark S.; Borchelt, David R.

2012-01-01

231

Organization of actin cytoskeleton during meiosis I in a wheat thermo-sensitive genic male sterile line.  

PubMed

BS366 is a thermo-sensitive male sterile line of wheat (Triticum aestivum L.) for two-line hybrid breeding, which exhibits aberrant meiotic cytokinesis under low temperature. Through transcriptome analysis, a possible regulatory role for plant actin cytoskeleton was suggested. However, the organization of actin cytoskeleton in meiosis has been poorly understood so far. Here, fixed microsporocytes during meiosis were labeled with tetramethylrhodamine isothiocyanate-phalloidin and 4',6-diamidino-2-phenylindole. Quantities of fluorescent micrographs were captured using a confocal microscope, including the transient state from metaphase to telophase. We observed that actin filaments were abundant in typical kariokinetic spindle, central spindle (parallel microtubules or actin fibers between two separated chromosomes in anaphase), and phragmoplast. Interestingly, we identified the Chinese lantern-shaped actin phragmoplast in wheat meiosis for the first time. Under low temperature, phragmoplast actin filaments were chaotic and normal cell plate failed to form. These data provide new insights into the organization of actin filaments during male meiosis of plant and support a role of actin cytoskeleton in bringing about thermo-sensitive male sterility in wheat. PMID:22350736

Xu, Chenguang; Liu, Zetao; Zhang, Liping; Zhao, Changping; Yuan, Shaohua; Zhang, Fengting

2012-02-16

232

Position and time sensitive photon counting detector with image charge delay-line readout  

NASA Astrophysics Data System (ADS)

We have developed single photon counting image intensifier tubes combining position and time information read-out with at least 500x500 pixels and sub-nanosecond time resolution. This image intensifier type uses a resistive screen instead of a phosphor screen and the image charge pickup anode is placed outside the sealed tube. We present a novel delay-line anode design which allows for instance detecting simultaneously arriving pairs of photons. Due to the very low background this technique is suited for applications with very low light intensity and especially if a precise time tagging for each photon is required. We show results obtained with several anode types on a 25 mm image intensifier tube and a 40 mm open-face MCP detector and discuss the performance in neutron radiography, e.g. for homeland security, and the prospects for applications like Fluorescence Life-time Imaging Microscopy (FLIM), astronomy and X-ray polarimetry.

Czasch, Achim; Dangendorf, Volker; Milnes, James; Schössler, Sven; Lauck, Ronald; Spillmann, Uwe; Howorth, Jon; Jagutzki, Ottmar

2007-10-01

233

Evaluation of the anti-proliferative activity of three new pyrazole compounds in sensitive and resistant tumor cell lines.  

PubMed

Background: In previous papers we demonstrated that the activity of short heteroretinoids as anti-proliferative and pro-apoptotic compounds was deeply linked to their heterocyclic moiety and that ionone-derived 1,5-pyrazoles had the highest anti-proliferative activity in our preliminary experiments. We then demonstrated the high and pharmacologically significant anti-proliferative and apoptotic activities of the pyrazole compounds 2-(1-(4-chlorophenyl)-1H-pyrazol-5-yl)-5-methoxyphenol (EN12-4), 5-methoxy-2-(1-(pyridin-2-yl)-1H-pyrazol-5-yl)phenol (EN12-2A) and 2-(5-(4-methoxyphenyl)-1H-pyrazol-1-yl)pyridine (EN7-2) establishing, especially for EN12-2A, a possible mechanism of action involving the cell microtubular system. Methods: Here, the anti-proliferative activity of these pyrazole compounds was analyzed in vitro by the MTT assay in six drug-resistant cell lines, five of which were selected after exposure to increasing concentrations of cisplatin (L1210/DDP), doxorubicin (A2780/DX3), 5-fluorouracil (HCT-8/5FU), taxol (A549/T24) and etoposide (MCF-7/VP), and one was obtained by transfection of the ABCG2 membrane transporter (HEK-293/R2). Results: Our data show that these compounds have a similar anti-proliferative activity in nearly all resistant and sensitive cell lines, demonstrating their ability to overcome the most common mechanisms of drug resistance with two exceptions regarding the MCF-7/VP cell line over-expressing the ABCC1 (MRP1) transporter, and the MDR1 over-expressing A2780/DX3 cells, with a calculated RI = 3.2 for EN12-2A, relative to their sensitive cellular counterpart. On the other hand, the taxol-resistant A549/T24 cell line showed a significantly increased sensitivity to our compounds. Conclusions: Our data suggest that our pyrazole compounds are able to overcome in vitro the most common drug-resistance mechanisms demonstrating a significant anti-proliferative activity and confirming a mechanism of action involving the depolymerization of microtubules. PMID:23950595

Viale, Maurizio; Anzaldi, Maria; Aiello, Cinzia; Fenoglio, Carla; Albicini, Federica; Emionite, Laura; Gangemi, Rosaria; Balbi, Alessandro

2013-01-01

234

Hsp90 inhibitor NVP-AUY922 enhances radiation sensitivity of tumor cell lines under hypoxia.  

PubMed

NVP-AUY922, a novel inhibitor of Hsp90, was shown to enhance the effect of ionizing radiation (IR) on tumor cells under normoxic conditions. Since low oxygen tension is a common feature of solid tumors, we explore in the present study the impact of hypoxia on the combined treatment of lung carcinoma A549 and glioblastoma SNB19 cell lines with NVP-AUY922 and IR. Cellular analysis included the colony-forming ability, expression of CAIX, Hsp90, Hsp70, Raf-1, Akt, cell cycle progression and associated proteins, as well as DNA damage measured by histone ?H2AX.   The clonogenic assay revealed that in both cell lines NVP-AUY922 enhanced the radiotoxicity under hypoxic exposure to a level similar to that observed under oxic conditions. Irrespective of oxygen supply during drug treatment, NVP-AUY922 also reduced the expression of anti-apoptotic proteins Raf-1 and Akt. As judged by the levels of histone ?H2AX, drug-treated hypoxic cells exhibited a lower repair rate of DNA double-strand breaks than normoxic cells. The drug-IR mediated changes in the cell cycle, i.e., S-phase depletion and G 2/M arrest, developed not directly during hypoxic exposure but first upon 24 h reoxygenation. Under both oxygen tensions, Hsp90 inhibition downregulated the cell cycle-associated proteins, Cdk1, Cdk4 and pRb. The finding that NVP-AUY922 can enhance the in vitro radiosensitivity of hypoxic tumor cells may have implications for the combined modality treatment of solid tumors. PMID:22286776

Djuzenova, Cholpon S; Blassl, Christina; Roloff, Konstanze; Kuger, Sebastian; Katzer, Astrid; Niewidok, Natalia; Günther, Nadine; Polat, Bülent; Sukhorukov, Vladimir L; Flentje, Michael

2012-04-01

235

Sensitivity to noise and ergodicity of an assembly line of cellular automata that classifies density  

NASA Astrophysics Data System (ADS)

We investigate the sensitivity of the composite cellular automaton of H. Fuk? [Phys. Rev. EPNASA61539-375510.1103/PhysRevE.55.R2081 55, R2081 (1997)] to noise and assess the density classification performance of the resulting probabilistic cellular automaton (PCA) numerically. We conclude that the composite PCA performs the density classification task reliably only up to very small levels of noise. In particular, it cannot outperform the noisy Gacs-Kurdyumov-Levin automaton, an imperfect classifier, for any level of noise. While the original composite CA is nonergodic, analyses of relaxation times indicate that its noisy version is an ergodic automaton, with the relaxation times decaying algebraically over an extended range of parameters with an exponent very close (possibly equal) to the mean-field value.

Mendonça, J. Ricardo G.

2011-03-01

236

A high-resolution HCANH experiment with enhanced sensitivity via multiple quantum line narrowing.  

PubMed

We report a 3D constant-time HCANH experiment (CTSL-HCANH) that uses the slower relaxation of multiple-quantum coherence to increase sensitivity and provides high C(?) resolution. In this experiment the H(?) of the (H(?), C(?)) multiple quanta are selectively spin locked, so that H(?) chemical shift evolution and (1) H-(1)H J-dephasing become ineffective during the relatively long delay needed for C(?) to N coherence transfer. As compared to an HCANH experiment that uses C(?) single-quantum coherence, an average enhancement of 20% was observed on calmodulin in complex with the binding domain of the transcription factor SEF2-1. Compared to CBCANH the signal intensity is approximately twice as good. The favorable relaxation properties of multiple quanta, together with the outstanding C(?) resolution, make the experiment a very good complement to CBCANH and CBCA(CO)NH for sequential assignment of larger proteins for which deuteration is not yet necessary. PMID:21080255

Larsson, G; Wijmenga, S S; Schleucher, J

1999-06-01

237

Highly sensitive detection of l-glutamate by on-line amperometric micro-flow analysis based on enzymatic substrate recycling  

Microsoft Academic Search

A highly selective and sensitive on-line monitoring system is proposed for amperometric assay of trace amounts of l-glutamate. The system includes a microdialysis probe, immobilized enzyme reactor, and poly(1,2-diaminobenzene)-coated platinum electrode. The enzyme reactor prepared by the co-immobilization of l-glutamate oxidase and glutamate dehydrogenase are here employed to enhance the sensitivity of l-glutamate as an on-line amplifier based on the

Toshio Yao; Seita Suzuki; Taketoshi Nakahara; Hirohito Nishino

1998-01-01

238

High-sensitivity determination of tyrosine-phosphorylated peptides by on-line enzyme reactor and electrospray ionization mass spectrometry.  

PubMed Central

We describe a simple, fast, sensitive, and nonisotopic bioanalytical technique for the detection of tyrosine-phosphorylated peptides and the determination of sites of protein tyrosine phosphorylation. The technique employs a protein tyrosine phosphatase micro enzyme reactor coupled on-line to either capillary electrophoresis or liquid chromatography and electrospray ionization mass spectrometry instruments. The micro enzyme reactor was constructed by immobilizing genetically engineered, metabolically biotinylated human protein tyrosine phosphatase beta onto the inner surface of a small piece of a 50-microns inner diameter, 360-microns outer diameter fused silica capillary or by immobilization of the phosphatase onto 40-90-microns avidin-activated resins. By coupling these reactors directly to either a capillary electrophoresis column or a liquid chromatography column, we were able to rapidly perform enzymatic dephosphorylation and separation of the reaction products. Detection and identification of the components of the reaction mixture exiting these reactors were done by mass analysis with an on-line electrospray ionization mass spectrometer. Tyrosine-phosphorylated peptides, even if present in a complex peptide mixture, were identified by subtractive analysis of peptide patterns generated with or without phosphatase treatment. Two criteria, namely a phosphatase-induced change in hydropathy and charge, respectively, and a change in molecular mass by 80 Da, were used jointly to identify phosphopeptides. We demonstrate that, with this technique, low picomole amounts of a tyrosine-phosphorylated peptide can be detected in a complex peptide mixture generated by proteolysis of a protein and that even higher sensitivities can be realized if more sensitive detection systems are applied.

Amankwa, L. N.; Harder, K.; Jirik, F.; Aebersold, R.

1995-01-01

239

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

SciTech Connect

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.

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

2007-01-01

240

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

PubMed Central

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.

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

241

Relationship between DNA Cross-Links, Cell Cycle, and Apoptosis in Burkitt's Lymphoma Cell Lines Differing in Sensitivity to Nitrogen Mustard  

Microsoft Academic Search

We surveyed 11 Burkitt's lymphoma cell lines for chemosensitivity to nitrogen mustard (HN2) in order to determine whether any simple correlates to cytotoxic response might be revealed. The lines tested varied over a 5-fold range in concentration of HN2 required to inhibit tumor cell growth by 50%. Drug sensitivity correlated neither with continental origin of tumor, growth fraction, presence of

Patrick M. O'Connor; Karsten Wassermann; Monica Sarang; Ian Magrath; Vilhelm A. Bohr; Kurt W. Kohn

1991-01-01

242

Administration of antidepressants, diazepam and psychomotor stimulants further confirms the utility of Flinders Sensitive Line rats as an animal model of depression  

Microsoft Academic Search

Flinders Sensitive Line (FSL) rats have been proposed as an animal model of depression because they resemble depressed humans in that they have elevated REM sleep, reduced activity, and increased immobility and anhedonia after exposure to stressors. The present paper reviews experiments on the drug treatment of FSL and control Flinders Resistant Line (FRL) rats related to their utility as

D. H. Overstreet; O. Pucilowski; A. H. Rezvani; D. S. Janowsky

1995-01-01

243

Sensitivity of human lung adenocarcinoma cell lines to targeted inhibition of BET epigenetic signaling proteins  

PubMed Central

Bromodomain and extra terminal domain (BET) proteins function as epigenetic signaling factors that associate with acetylated histones and facilitate transcription of target genes. Inhibitors targeting the activity of BET proteins have shown potent antiproliferative effects in hematological cancers through the suppression of c-MYC and downstream target genes. However, as the epigenetic landscape of a cell varies drastically depending on lineage, transcriptional coactivators such as BETs would be expected to have different targets in cancers derived from different cells of origin, and this may influence the activity and mechanism of action of BET inhibitors. To test this hypothesis, we treated a panel of lung adenocarcinoma (LAC) cell lines with the BET inhibitor JQ1 and found that a subset is acutely susceptible to BET inhibition. In contrast to blood tumors, we show that LAC cells are inhibited by JQ1 through a mechanism independent of c-MYC down-regulation. Through gene expression profiling, we discovered that the oncogenic transcription factor FOSL1 and its targets are suppressed by JQ1 in a dose-dependant manner. Knockdown of BRD4 also decreased FOSL1 levels, and inhibition of FOSL1 phenocopied the effects of JQ1 treatment, suggesting that loss of this transcription factor may be partly responsible for the cytotoxic effects of BET inhibition in LAC cells, although ectopic expression of FOSL1 alone did not rescue the phenotype. Together, these findings suggest that BET inhibitors may be useful in solid tumors and that cell-lineage–specific differences in transcriptional targets of BETs may influence the activity of inhibitors of these proteins in different cancer types.

Lockwood, William W.; Zejnullahu, Kreshnik; Bradner, James E.; Varmus, Harold

2012-01-01

244

Sensitivity of human lung adenocarcinoma cell lines to targeted inhibition of BET epigenetic signaling proteins.  

PubMed

Bromodomain and extra terminal domain (BET) proteins function as epigenetic signaling factors that associate with acetylated histones and facilitate transcription of target genes. Inhibitors targeting the activity of BET proteins have shown potent antiproliferative effects in hematological cancers through the suppression of c-MYC and downstream target genes. However, as the epigenetic landscape of a cell varies drastically depending on lineage, transcriptional coactivators such as BETs would be expected to have different targets in cancers derived from different cells of origin, and this may influence the activity and mechanism of action of BET inhibitors. To test this hypothesis, we treated a panel of lung adenocarcinoma (LAC) cell lines with the BET inhibitor JQ1 and found that a subset is acutely susceptible to BET inhibition. In contrast to blood tumors, we show that LAC cells are inhibited by JQ1 through a mechanism independent of c-MYC down-regulation. Through gene expression profiling, we discovered that the oncogenic transcription factor FOSL1 and its targets are suppressed by JQ1 in a dose-dependant manner. Knockdown of BRD4 also decreased FOSL1 levels, and inhibition of FOSL1 phenocopied the effects of JQ1 treatment, suggesting that loss of this transcription factor may be partly responsible for the cytotoxic effects of BET inhibition in LAC cells, although ectopic expression of FOSL1 alone did not rescue the phenotype. Together, these findings suggest that BET inhibitors may be useful in solid tumors and that cell-lineage-specific differences in transcriptional targets of BETs may influence the activity of inhibitors of these proteins in different cancer types. PMID:23129625

Lockwood, William W; Zejnullahu, Kreshnik; Bradner, James E; Varmus, Harold

2012-11-05

245

Topoisomerase II? content and topoisomerase II catalytic activity cannot explain drug sensitivities to topoisomerase II inhibitors in lung cancer cell lines  

Microsoft Academic Search

Purpose:?Topoisomerase II? content, topoisomerase II catalytic activity and drug sensitivities to the topoisomerase II inhibitors,\\u000a doxorubicin and etoposide, were examined in a panel of 14 unselected human lung cancer cell lines in order to determine the\\u000a relationship between topoisomerase II and drug sensitivities to the topoisomerase II inhibitors. Methods: Drug sensitivities were determined using a microculture tetrazolium assay. The topoisomerase

Kohichi Yamazaki; Hiroshi Isobe; Tarou Hanada; Tomoko Betsuyaku; Atsushi Hasegawa; Nobuyuki Hizawa; Shigeaki Ogura; Yoshikazu Kawakami

1996-01-01

246

The relationship between CD86\\/CD54 expression and THP1 cell viability in an in vitro skin sensitization test – human cell line activation test (h-CLAT)  

Microsoft Academic Search

Recent regulations for cosmetics in Europe prohibit animal testing for evaluating the sensitization potential of chemicals\\u000a to improve animal welfare. Yet, there is not an acceptable Organization for Economic Co-operation and Development non-animal\\u000a skin sensitization test method. Several in vitro skin sensitization methods that focus on the activation of Langerhans cells,\\u000a including human cell lines, are being evaluated as possible

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

2009-01-01

247

Evaluation of the antiproliferative activity of diterpene isonitriles from the sponge Pseudoaxinella flava in apoptosis-sensitive and apoptosis-resistant cancer cell lines.  

PubMed

One new (1) and three known (2-4) isonitrile diterpenes, isolated from the Caribbean sponge Pseudoaxinella flava, were assayed in human cancer cell lines in vitro using an MTT colorimetric assay and quantitative videomicroscopy. Compounds 1-4 displayed activity for human PC3 prostate apoptosis-sensitive cancer cell lines. Compounds 3 and 4 demonstrated similar growth inhibitory effects for three apoptosis-sensitive and three apoptosis-resistant cancer cell lines. Quantitative videomicroscopy analysis revealed that compounds 1 and 2 exerted their activity through cytotoxic effects, and compounds 3 and 4 through cytostatic effects. These results identify marine diterpene isonitriles as potential lead compounds for anticancer drug discovery. PMID:21985105

Lamoral-Theys, Delphine; Fattorusso, Ernesto; Mangoni, Alfonso; Perinu, Cristina; Kiss, Robert; Costantino, Valeria

2011-10-10

248

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

NASA Astrophysics Data System (ADS)

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

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

2002-03-01

249

Fundamental Studies on the Acid Generator to Improve the Resolution, Line Width Roughness, and Sensitivity Tradeoff under Ionizing Radiation  

NASA Astrophysics Data System (ADS)

The effects of acid generation efficiency and other properties on the resolution, line width roughness (LWR), and sensitivity (RLS) tradeoff for extreme ultraviolet (EUV) photoresists were evaluated under electron beam (EB) exposure. The acid generators (AGs) introducing a trifluoromethyl group as an electron-withdrawing group on the sulfur atom had a much higher reduction potential than current AGs. We determined acid generation efficiency by the 13C-NMR method and standard titration. The dissolution inhibitory effect on the alkaline developer and the thermal property of the resist film using each AG were also evaluated. The RLS performance of resists containing AGs with a higher acid generation efficiency than conventional AGs was characterized using the relative Z-factor under EB exposure.

Yoshiyuki Utsumi,; Makiko Irie,; Yoshitaka Komuro,; Kensuke Matsuzawa,; Hideo Hada,; Takashi Haga,; Satoshi Ogawa,

2010-06-01

250

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

PubMed

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

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

2012-04-28

251

The Sensitivity of Diffuse Large B-Cell Lymphoma Cell Lines to Histone Deacetylase Inhibitor-Induced Apoptosis Is Modulated by BCL-2 Family Protein Activity  

PubMed Central

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

Thompson, Ryan C.; Vardinogiannis, Iosif; Gilmore, Thomas D.

2013-01-01

252

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

SciTech Connect

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

Wai, Larry; /SLAC

2007-02-05

253

On-line capillary electrophoresis derivatization method for high sensitivity analysis of ubiquitin in filtered cerebrospinal fluid.  

PubMed

Electrophoretically mediated microanalysis was implemented for on-line fluorescence derivatization of ubiquitin (UBI), a potential biomarker of Alzheimer disease. Ubiquitin was labeled on its amino groups by the Fluoprobes® 488 N-hydroxysuccinimide. The pH of the BGE, the applied electric field, and the washing process of the capillary were optimized. The best derivatization yield was obtained at pH 9.5 under an electric field of ?210 V/cm. The concentration and volume of the fluorescent dye as well as the sample medium and volume of injected UBI were also optimized. In order to improve further the LOD of UBI, electrophoretically mediated microanalysis was performed in a wider (100 ?m id) and longer (110 cm) capillary. As expected, these capillary dimensions improved the analytical sensitivity of UBI when compared to the 50 ?m id capillary. Under the optimized conditions, this analytical methodology allowed the analysis of free UBI in standard solution with a LOD of ?15 nM. Finally, the on-line fluorescent derivatization of UBI was applied to the detection and the quantification of UBI in cerebrospinal fluid (CSF) samples. Due to the high salt concentration of biological samples, desalting of CSF was required prior to the CE analysis. Quantification of UBI in CSF either by a direct evaluation of peak areas or using the standard addition method was achieved. PMID:23857291

Mesbah, Kiarach; Oukacine, Farid; Lehnert, Stefan; Otto, Markus; Taverna, Myriam

2013-08-16

254

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

NASA Astrophysics Data System (ADS)

The XRCC1 gene (X-ray repair cross complementing) complements the DNA repair deficiency of the radiation sensitive Chinese hamster ovary (CHO) mutant cell line EM9 but the mechanism of the correction is not elucidated yet. XRCC1 shows substantial homology to the RAG2 gene (recombination activating gene) and we therefore tried to answer the question, whether structural similarities (sequence of a putative recombination activating domain, aa 332-362 for XRCC1 and aa 286-316 in RAG2) would reflect similar functions of the homologous, putative recombination activating domain. PCR experiments revealed that no sequence homologous to the structural part of human XRCC1 was present in cDNA of CHO. Differential display demonstrated two putative recombination activating 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 inserts of the recombinant plasmids. The recombination activating activity of XRCC1 analogues could explain a mechanism responsible for the correction of the DNA repair defect in EM9.

Golubnitchaya-Labudová, O.; Portele, A.; Vaçata, V.; Lubec, G.; Rink, H.; Höfer, M.

1997-10-01

255

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

PubMed Central

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

2011-01-01

256

Inhibition of MDR1 expression by retinol treatment increases sensitivity to etoposide (VP16) in human neoplasic cell line.  

PubMed

Multidrug resistance (MDR) is the major obstacle to cancer chemotherapy. MDR phenotype is mainly related to the over-expression of MDR1 gene, being responsible for tumor resistance to several chemotherapeutic drugs. It has been suggested that MDR1 expression is redox-regulated and we have recently described a pro-oxidative effect of retinol. Here we tested the therapeutic use of retinol as a modulator of MDR1 gene expression in tumor cell lines, and verified in situ the enhancement of anticancer drug efficacy. Two human colorectal adenocarcinoma cell lines (HT29, SW620) with different degrees of MDR1 expression were used. Cells were pre-treated with a sublethal dose of retinol and then challenged with the etoposide (VP16) drug. The drug GI50 was assessed by SRB method and levels of MDR1 expression were determined by semi-quantitative rtPCR. Retinol treatment caused a 40% decrease in MDR1 expression and increased VP16 toxicity. MDR1 expression and drug sensitivity were restored to control values when mannitol (a hydroxyl radical scavenger) was co-administrated. Our data point a role to the use of retinol as an adjuvant in the treatment of tumors with MDR phenotype. PMID:18282684

Klamt, Fábio; Passos, Daniel Thompsen; Castro, Mauro Antônio Alves; Gelain, Daniel Pens; Grivicich, Ivana; Moreira, José Cláudio Fonseca

2008-01-15

257

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

PubMed Central

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.

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

2013-01-01

258

Suppression of manganese superoxide dismutase augments sensitivity to radiation, hyperthermia and doxorubicin in colon cancer cell lines by inducing apoptosis  

PubMed Central

Increased expression of manganese superoxide dismutase (Mn-SOD), one of the mitochondrial enzymes involved in the redox system, has been shown to diminish the cytotoxic effects of several anti-cancer modalities, including tumour necrosis factor-?, ionizing radiation, certain chemotherapeutic agents and hyperthermia. We asked if Mn-SOD is a potential target to augment the sensitivity of cancer cells to various anti-cancer treatments and for this we established stable Mn-SOD antisense RNA expressing cell clones from two human colon cancer cell lines, HCT116 (p53 wild-type) and DLD1 (p53 mutant-type). Suppression of Mn-SOD in HCT116 was accompanied by an increased sensitivity to radiation, hyperthermia and doxorubicin, as compared with findings in controls. The mitochondrial permeability transition, as measured by a decrease of the mitochondrial transmembrane potential was more intensely induced by radiation in HCT116 antisense clones than in the control, an event followed by a greater extent of DNA fragmentation. Apoptosis was also induced by hyperthermia more intensely in HCT116 antisense clones than in the control. On the other hand, DLD1 antisense clones did not exhibit any enhancement of sensitivity to any of these treatments. These data support the possibility that inhibition of Mn-SOD activity renders colon cancer cells with wild-type p53 susceptible to apoptosis induced by radiation, hyperthermia and selected anti-cancer drugs. Therefore, we suggest that Mn-SOD could be a target molecule to overcome the resistance to anti-cancer treatments in some colon cancer cells carrying wild-type p53. © 2000 Cancer Research Campaign

Kuninaka, S; Ichinose, Y; Koja, K; Toh, Y

2000-01-01

259

Closer look at CMB constraints on WIMP dark matter  

NASA Astrophysics Data System (ADS)

We use cosmic microwave background data from the WMAP, SPT, BICEP, and QUaD experiments to obtain constraints on the dark matter particle mass m?, and show that the combined data requires m?>7.6GeV at the 95% confidence level for the ???bb¯ channel assuming s-wave annihilation and a thermal cross section ??av?=3×10-26cm3/s. We examine whether the bound on m? is sensitive to ?8 measurements made by galaxy cluster observations. The large uncertainty in ?8 and the degeneracy with ?m allow only small improvements in the dark matter mass bound. Increasing the number of effective neutrinolike degrees of freedom to Neff=3.85 improves the mass bound to m?>8.6GeV at 95% confidence, for the ???bb¯ channel. We also study models in which dark matter halos at z<60 reionize the Universe. We compute the Ostriker-Vishniac power resulting from partial reionization at intermediate redshifts 10

Natarajan, Aravind

2012-04-01

260

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

SciTech Connect

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}.

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

2010-08-01

261

Improved limits on spin-dependent WIMP-proton interactions from a two liter CF3I bubble chamber.  

PubMed

Data from the operation of a bubble chamber filled with 3.5 kg of CF3I 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/c2. PMID:21405218

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; Hu, M; Levine, I; Ramberg, E; Shepherd, T; Sonnenschein, A; Szydagis, M

2011-01-10

262

Improved Limits on Spin-Dependent WIMP-Proton Interactions from a Two Liter CF3I Bubble Chamber  

NASA Astrophysics Data System (ADS)

Data from the operation of a bubble chamber filled with 3.5 kg of CF3I 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 28.1kgday, 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 >20GeV/c2.

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.; Hu, M.; Levine, I.; Ramberg, E.; Shepherd, T.; Sonnenschein, A.; Szydagis, M.

2011-01-01

263

Consequences of DM/antiDM oscillations for asymmetric WIMP dark matter  

NASA Astrophysics Data System (ADS)

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 ?(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.

Cirelli, Marco; Panci, Paolo; Servant, Géraldine; Zaharijas, Gabrijela

2012-03-01

264

A new analysis method for WIMP searches with dual-phase liquid Xe TPCs  

NASA Astrophysics Data System (ADS)

A new data analysis method based on physical observables for WIMP dark matter searches with noble liquid Xe dual-phase TPCs is presented. Traditionally, the nuclear recoil energy from a scatter in the liquid target has been estimated by means of the initial prompt scintillation light (S1) produced at the interaction vertex. The ionization charge (C2), or its secondary scintillation (S2), is combined with the primary scintillation in log10(S2/S1) vs. S1 only as a discrimination parameter against electron recoil background. Arguments in favor of C2 as the more reliable nuclear recoil energy estimator than S1 are presented. The new phase space of log10(S1/C2) vs. C2 is introduced as more efficient for nuclear recoil acceptance and exhibiting superior energy resolution. This is achieved without compromising the discrimination power of the LXe TPC, nor its 3D event reconstruction and fiducialization capability, as is the case for analyses that exploit only the ionization channel. Finally, the concept of two independent energy estimators for background rejection is presented: E2 as the primary (based on C2) and E1 as the secondary (based on S1). log10(E1/E2) vs. E2 is shown to be the most appropriate phase space in which to evaluate WIMP signal candidates.

Arisaka, K.; Beltrame, P.; Ghag, C.; Lung, K.; Scovell, P. R.

2012-09-01

265

Enhanced expression of the neuronal K+/Cl- cotransporter, KCC2, in spontaneously depressed Flinders Sensitive Line rats.  

PubMed

We used Flinder Sensitive Line (FSL) rats, a genetic model of unipolar depression, to examine whether changes in central GABAergic transmission are associated with a depressed phenotype. FSL rats showed an increased behavioral response to low doses of diazepam, as compared to either Sprague Dawley (SD) or Flinder Resistant Line (FRL) rats used as controls. Diazepam at a dose of 0.3 mg/kg, i.p., induced a robust impairment of motor coordination in FSL rats, but was virtually inactive in SD or FRL rats. The increased responsiveness of FSL rats was not due to changes in the brain levels of diazepam or its active metabolites, or to increases in the number or affinity of benzodiazepine recognition sites, as shown by the analysis of [(3)H]-flunitrazepam binding in the hippocampus, cerebral cortex or cerebellum. We therefore examined whether FSL rats differed from control rats for the expression levels of the K(+)/Cl(-) cotransporter, KCC2, which transports Cl(-) ions out of neurons, thus creating the concentration gradient that allows Cl(-) influx through the anion channel associated with GABA(A) receptors. Combined immunoblot and immunohistochemical data showed a widespread increase in KCC2 expression in FSL rats, as compared with control rats. The increase was more prominent in the cerebellum, where KCC2 was largely expressed in the granular layer. These data raise the interesting possibility that a spontaneous depressive state in animals is associated with an amplified GABAergic transmission in the CNS resulting from an enhanced expression of KCC2. PMID:20153734

Matrisciano, F; Nasca, C; Molinaro, G; Riozzi, B; Scaccianoce, S; Raggi, M A; Mercolini, L; Biagioni, F; Mathè, A A; Sanna, E; Maciocco, E; Pignatelli, M; Biggio, G; Nicoletti, F

2010-02-11

266

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

PubMed

It was reported that the radiation-sensitive Medaka mutant "ric1" has a defect in the repair of DNA double-strand breaks (DSBs) induced by gamma-rays during early embryogenesis. To study the cellular response of a ric1 mutant to ionizing radiation (IR), we established the mutant embryonic cell lines RIC1-e9, RIC1-e42, RIC1-e43. Following exposure to gamma-irradiation, the DSBs in wild-type cells were repaired within 1 h, while those in RIC1 cells were not rejoined even after 2 h. Cell death was induced in the wild-type cells with cell fragmentation, but only a small proportion of the RIC1 cells underwent cell death, and without cell fragmentation. Although both wild-type and RIC1 cells showed mitotic inhibition immediately after gamma-irradiation, cell division was much slower to resume in the wild-type cells (20 h versus 12 h). In both wild-type and RIC1 cells, Ser139 phosphorylated H2AX (gammaH2AX) foci were formed after gamma-irradiation, however, the gammaH2AX foci disappeared more quickly in the RIC1 cell lines. These results suggest that the instability of gammaH2AX foci in RIC1 cells cause an aberration of the DNA damage response. As RIC1 cultured cells showed similar defective DNA repair as ric1 embryos and RIC1 cells revealed defective cell death and cell cycle checkpoint, they are useful for investigating DNA damage responses in vitro. PMID:19952493

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

2009-12-01

267

On the sensitivity of FeI 617.3 and 630.2 nm line shapes to unresolved magnetic fields  

NASA Astrophysics Data System (ADS)

Our study was aimed at obtaining line diagnostics sensitive to effects of small scale magnetic features that are unresolved in observations. We studied the dependence on the magnetic flux of parameters describing the two Fe I lines at 630.2 and 617.3 nm. In particular, we analyzed the line core intensity (IC), full width half maximum (FWHM), and equivalent width (EQW) of Stokes I in NOAA 11172 observed with IBIS at the Dunn Solar Telescope on March 17th, 2011. Our results show that IC is sensitive to both temperature and magnetic flux variations, while FWHM is sensitive mostly to magnetic flux variations. The EQW is almost insensitive to magnetic flux and mostly sensitive to temperature. Variations of a few percents of line parameters are found in data spatially degraded to represent quiet Sun, disk-centre conditions in medium resolution observations. Such variations can be observed with instruments as SOLIS/VSM, SDO/HMI, HINODE/SOT. Shapes of investigated lines can therefore be employed to investigate physical properties of quiet Sun regions, and in particular to disentangle magnetic and thermodynamic effects an d their variations over the magnetic cycle.

Criscuoli, S.; Ermolli, I.; Uitenbroek, H.; Giorgi, F.

268

Lack of Correlation between Sensitivity to Growth Inhibition and Receptor Number for Transforming Growth Factor ß in Human Squamous Carcinoma Cell Lines  

Microsoft Academic Search

Four human squamous carcinoma cell lines, SCC-9, SCC-12F, SCC- 15G, and SCC-25, were examined for sensitivity to the growth-inhibitory and differentiation-inducing effects of transforming growth factor ß (TGF-\\/3). None of the four cell lines was induced to differentiate, as measured by staining for keratin and by competence of cells to form cross-linked envelopes, by concentrations of TGF-\\/Sas high as 1000

Charles D. HÃ; Linda S. Birnbaum

269

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

Microsoft Academic Search

Regulatory policies in Europe prohibited the testing of cosmetic ingredients in animals for a number of toxicological endpoints. Currently no validated non-animal test methods exist for skin sensitization. Evaluation of changes in cell surface marker expression in dendritic cell (DC)-surrogate cell lines represents one non-animal approach. The human Cell Line Activation Test (h-CLAT) examines the level of CD86 and CD54

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

2010-01-01

270

Two Wistar Rat Lines Selectively Bred for Anxiety-Related Behavior Show Opposite Reactions in Elevated Plus Maze and Fear-Sensitized Acoustic Startle Tests  

Microsoft Academic Search

Two Wistar rat lines selectively bred for high (HAB), and low anxiety-related behavior (LAB) on the elevated plus maze were tested for the fear-sensitized acoustic startle response. The study of male rats from the F9 generation revealed a higher anxiety level of HAB rats on the elevated plus maze. However, the LAB rats displayed a higher baseline and fear-sensitized acoustic

D. M. Yilmazer-Hanke; A. Wigger; R. Linke; R. Landgraf; H. Schwegler

2004-01-01

271

Large-scale nuclear structure calculations for spin-dependent WIMP scattering with chiral effective field theory currents  

NASA Astrophysics Data System (ADS)

We perform state-of-the-art large-scale shell-model calculations of the structure factors for elastic spin-dependent WIMP scattering off Xe129,131, I127, Ge73, F19, Na23, Al27, and Si29. This comprehensive survey covers the nonzero-spin nuclei relevant to direct dark matter detection. We include a pedagogical presentation of the formalism necessary to describe elastic and inelastic WIMP-nucleus scattering. The valence spaces and nuclear interactions employed have been previously used in nuclear structure calculations for these mass regions and yield a good spectroscopic description of these isotopes. We use spin-dependent WIMP-nucleus currents based on chiral effective field theory at the one-body level and including the leading long-range two-body currents due to pion exchange, which are predicted in chiral effective field theory. Results for all structure factors are provided with theoretical error bands due to the nuclear uncertainties of WIMP currents in nuclei.

Klos, P.; Menéndez, J.; Gazit, D.; Schwenk, A.

2013-10-01

272

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

NASA Astrophysics Data System (ADS)

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.

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

2013-07-01

273

Identification of expression signatures predictive of sensitivity to the Bcl-2 family member inhibitor ABT-263 in small cell lung carcinoma and leukemia/lymphoma cell lines.  

PubMed

ABT-263 inhibits the antiapoptotic proteins Bcl-2, Bcl-x(L), and Bcl-w and has single-agent efficacy in numerous small cell lung carcinoma (SCLC) and leukemia/lymphoma cell lines in vitro and in vivo. It is currently in clinical trials for treating patients with SCLC and various leukemia/lymphomas. Identification of predictive markers for response will benefit the clinical development of ABT-263. We identified the expression of Bcl-2 family genes that correlated best with sensitivity to ABT-263 in a panel of 36 SCLC and 31 leukemia/lymphoma cell lines. In cells sensitive to ABT-263, expression of Bcl-2 and Noxa is elevated, whereas expression of Mcl-1 is higher in resistant cells. We also examined global expression differences to identify gene signature sets that correlated with sensitivity to ABT-263 to generate optimal signature sets predictive of sensitivity to ABT-263. Independent cell lines were used to verify the predictive power of the gene sets and to refine the optimal gene signatures. When comparing normal lung tissue and SCLC primary tumors, the expression pattern of these genes in the tumor tissue is most similar to sensitive SCLC lines, whereas normal tissue is most similar to resistant SCLC lines. Most of the genes identified using global expression patterns are related to the apoptotic pathway; however, all but Bcl-rambo are distinct from the Bcl-2 family. This study leverages global expression data to identify key gene expression patterns for sensitivity to ABT-263 in SCLC and leukemia/lymphoma and may provide guidance in the selection of patients in future clinical trials. PMID:20179162

Tahir, Stephen K; Wass, John; Joseph, Mary K; Devanarayan, Viswanath; Hessler, Paul; Zhang, Haichao; Elmore, Steve W; Kroeger, Paul E; Tse, Christin; Rosenberg, Saul H; Anderson, Mark G

2010-02-23

274

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

Microsoft Academic Search

Recent regulatory changes have placed a major emphasis on in vitro safety testing and alternative models. In regard to skin sensitization tests, dendritic cells (DCs) derived from human peripheral blood have been considered in the development of new in vitro alternatives. Human cell lines have been also reported recently. In our previous study, we suggested that measuring CD86 and\\/or CD54

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

2006-01-01

275

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  

Microsoft Academic Search

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

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

2002-01-01

276

Next-generation sequencing of paired tyrosine kinase inhibitor-sensitive and -resistant EGFR mutant lung cancer cell lines identifies spectrum of DNA changes associated with drug resistance.  

PubMed

Somatic mutations in kinase genes are associated with sensitivity of solid tumors to kinase inhibitors, but patients with metastatic cancer eventually develop disease progression. In EGFR mutant lung cancer, modeling of acquired resistance (AR) with drug-sensitive cell lines has identified clinically relevant EGFR tyrosine kinase inhibitor (TKI) resistance mechanisms such as the second-site mutation, EGFR T790M, amplification of the gene encoding an alternative kinase, MET, and epithelial-mesenchymal transition (EMT). The full spectrum of DNA changes associated with AR remains unknown. We used next-generation sequencing to characterize mutational changes associated with four populations of EGFR mutant drug-sensitive and five matched drug-resistant cell lines. Comparing resistant cells with parental counterparts, 18-91 coding SNVs/indels were predicted to be acquired and 1-27 were lost; few SNVs/indels were shared across resistant lines. Comparison of two related parental lines revealed no unique coding SNVs/indels, suggesting that changes in the resistant lines were due to drug selection. Surprisingly, we observed more CNV changes across all resistant lines, and the line with EMT displayed significantly higher levels of CNV changes than the other lines with AR. These results demonstrate a framework for studying the evolution of AR and provide the first genome-wide spectrum of mutations associated with the development of cellular drug resistance in an oncogene-addicted cancer. Collectively, the data suggest that CNV changes may play a larger role than previously appreciated in the acquisition of drug resistance and highlight that resistance may be heterogeneous in the context of different tumor cell backgrounds. PMID:23733853

Jia, Peilin; Jin, Hailing; Meador, Catherine B; Xia, Junfeng; Ohashi, Kadoaki; Liu, Lin; Pirazzoli, Valentina; Dahlman, Kimberly B; Politi, Katerina; Michor, Franziska; Zhao, Zhongming; Pao, William

2013-06-03

277

Sensitive, high-resolution chromatin and chromosome mapping in situ: Presence and orientation of two closely integrated copies of EBV in a lymphoma line  

Microsoft Academic Search

Summary Here we describe development and application of highly sensitive fluorescence methodology for local- ization of single-copy sequences in interphase nuclei and metaphase chromosomes by nonisotopic in situ hybridization. Application of this methodology to the investigation of Epstein-Barr virus integration in the Namalwa lymphoma cell line has revealed two EBV ge- nomes closely integrated at the known site on chro-

J BENTLEYLAWRENCE; Carol A. Villnave; Robert H. Singer

1988-01-01

278

SENSITIVE HPLC METHOD WITH FLUORESCENCE DETECTION AND ON-LINE WAVELENGTH SWITCHING FOR SIMULTANEOUS DETERMINATION OF VALSARTAN AND AMLODIPINE IN HUMAN PLASMA  

Microsoft Academic Search

This study describes the development and validation of a highly sensitive high-performance liquid chromatographic method with fluorescence detection and on-line emission wavelength switching for the simultaneous determination of valsartan (VAL) and amlodipine (AML) in human plasma. Irbesartan (IRB) was used as internal standard (IS). VAL, AML, and IRB were isolated from plasma by nonextractive procedure; simple protein precipitation with methanol.

Nasr Y. Khalil; Tanveer A. Wani; Mohamed A. Abunassif; Ibrahim A. Darwish

2011-01-01

279

NSAIDs and butyrate sensitize a human colorectal cancer cell line to TNF-? and Fas ligation: the role of reactive oxygen species  

Microsoft Academic Search

The nonsteroidal antiinflammatory drugs (NSAIDs) indomethacin and salicylic acid and the short chain fatty acid butyrate are effective colon cancer chemopreventive agents that increase reactive oxygen species (ROS) generation in colon cancer cells. Here we demonstrate that these agents sensitize the normally resistant human HT-29 colon cancer cell line to apoptosis induced by TNF-? or a Fas ligating antibody. The

Charles Giardina; Hamid Boulares; Mehmet Sait Inan

1999-01-01

280

Replicative Function and Neutralization Sensitivity of Envelope Glycoproteins from Primary and T-Cell Line-Passaged Human Immunodeficiency Virus Type 1 Isolates  

Microsoft Academic Search

The structure, replicative properties, and sensitivity to neutralization by soluble CD4 and monoclonal antibodies were examined for molecularly cloned envelope glycoproteins derived from human immunodefi- ciency virus type 1 (HIV-1) viruses either isolated directly from patients or passaged in T-cell lines. Comple- mentation of virus entry into peripheral blood mononuclear cell targets by primary patient envelope glyco- proteins exhibited efficiencies

NANCY SULLIVAN; YING SUN; JOHN LI; WOLFGANG HOFMANN; ANDJOSEPH SODROSKI

1995-01-01

281

Heating, moisture, and water budgets of tropical and midlatitude squall lines: Comparisons and sensitivity to longwave radiation  

SciTech Connect

A two-dimensional, time-dependent, nonhydrostatic numerical cloud model is used to estimate the heating (Q[sub 1]), moisture (Q[sub 2]), and water budgets in the convective and stratiform regions for a tropical and a midlatitude squall line (EMEX and PRE-STORM). The model is anelastic and includes a parameterized three-class ice-phase microphysical scheme and longwave radiative transfer processes. A quantitative estimate of the impact of the longwave radiative cooling on the total surface precipitation and on the development and structure of these squall lines is presented. The vertical eddy moisture fluxes are a major contribution to the model-derived Q[sub 2] budgets in both squall cases. The vertical eddy heat flux is important for the PRE-STORM case due to the stronger vertical velocities in the PRE-STORM convective cells. The convective region plays an important role in the generation of stratiform rainfall for both cases. The transfer of condensate from the convective region became less important than the time in the stratiform water budget of the PRE-STORM system as it developed from its initial stage, such that the relative contribution to the stratiform water budget made by the horizontal transfer of hydrometeors from the convective region is similar at the mature stages of both systems. Longwave radiative cooling enhanced the total surface precipitation about 14% and 31% over a 16-h simulation time for the PRE-STORM and EMEX cases. The relative contribution to the stratiform water budget from the convective region is more sensitive to the longwave radiative cooling for the PRE-STORM case than for the EMEX case. The effect of radiative cooling is shown to increase as systems age in both cases. It was determined that the Q[sub 1] and Q[sub 2] budgets in the convective and stratiform regions are only quantitatively, not qualitatively, altered by the inclusion or exclusion of longwave radiative transfer processes. 55 refs., 9 figs., 5 tabs.

Tao, W.K.; Simpson, J.; Chou, M.D.; Sui, C.H.; Ferrier, B.; Pickering, K. (NASA, Goddard Space Flight Center, Greenbelt, MD (United States)); Lang, S. (Science Systems and Applications, Inc., Greenbelt, MD (United States)); Scala, J. (National Research Council, Washington, DC (United States))

1993-03-01

282

WIMPs in a 3-3-1 model with heavy sterile neutrinos  

NASA Astrophysics Data System (ADS)

In this work we build a gauge model based on the SU(3)c?SU(3)L?U(1)N symmetry with heavy neutrinos and show that we can have two weakly interacting cold dark matter candidates in its spectrum. This is achieved by noticing that a global U(1) symmetry can be imposed on the model in such a way that the stability of the dark matter is guaranteed. We obtain their relic abundance and analyze their compatibility with recent direct detection experiments, also exploring the possibility of explaining the two events reported by CDMSII. An interesting outcome of this 3-3-1 model, concerning direct detection of these WIMPs, is a strong bound on the symmetry breaking scale, which imposes it to be above 3 TeV.

Mizukoshi, J. K.; de S. Pires, C. A.; Queiroz, F. S.; Rodrigues da Silva, P. S.

2011-03-01

283

WIMPs in a 3-3-1 model with heavy sterile neutrinos  

SciTech Connect

In this work we build a gauge model based on the SU(3){sub c} x SU(3){sub L} x U(1){sub N} symmetry with heavy neutrinos and show that we can have two weakly interacting cold dark matter candidates in its spectrum. This is achieved by noticing that a global U(1) symmetry can be imposed on the model in such a way that the stability of the dark matter is guaranteed. We obtain their relic abundance and analyze their compatibility with recent direct detection experiments, also exploring the possibility of explaining the two events reported by CDMSII. An interesting outcome of this 3-3-1 model, concerning direct detection of these WIMPs, is a strong bound on the symmetry breaking scale, which imposes it to be above 3 TeV.

Mizukoshi, J. K. [Centro de Ciencias Naturais e Humanas, Universidade Federal do ABC, R. Santa Adelia 166, 09210-170, Santo Andre - SP (Brazil); Pires, C.A. de S; Queiroz, F. S.; Rodrigues da Silva, P. S. [Departamento de Fisica, Universidade Federal da Paraiba, Caixa Postal 5008, 58051-970, Joao Pessoa - PB (Brazil)

2011-03-15

284

Gamma-ray constraints on the first stars from annihilation of light WIMPs  

NASA Astrophysics Data System (ADS)

We calculate the limits on the fraction of viable dark matter minihalos in the early universe to host Population III.1 stars, surviving today as dark matter spikes in our Milky Way halo. Motivated by potential hints of light dark matter from the DAMA and CoGeNT direct dark matter searches, we consider thermal relic WIMP dark matter with masses of 5, 10, and 20 GeV, and annihilation to ?+?-, ?+?-, and qq¯. From this brief study we conclude that, if dark matter is light, either the typical black hole size is ?100M? (i.e. there is no significant Dark Star phase), and/or dark matter annihilates primarily to ?+?- or other final states that result in low gamma-ray luminosity, and/or that an extremely small fraction of minihalos in the early universe that seem suitable to host the formation of the first stars actually did.

Sandick, Pearl; Diemand, Juerg; Freese, Katherine; Spolyar, Douglas

2012-04-01

285

Conservative upper limits on WIMP annihilation cross section from Fermi-LAT ?-rays  

NASA Astrophysics Data System (ADS)

The spectrum of an isotropic extragalactic ?-ray background (EGB) has been measured by the Fermi-LAT telescope at high latitudes. Two new models for the EGB are derived from the subtraction of unresolved point sources and extragalactic diffuse processes, which could explain from 30% to 70% of the Fermi-LAT EGB. Within the hypothesis that the two residual EGBs are entirely due to the annihilation of dark matter (DM) particles in the Galactic halo, we obtain conservative upper limits on their annihilation cross section langle??rangle. Severe bounds on a possible Sommerfeld enhancement of the annihilation cross section are set as well. Finally, would langle??rangle be inversely proportional to the WIMP velocity, very severe limits are derived for the velocity-independent term of the annihilation cross section.

Donato, F.; Calore, F.; De Romeri, V.

2012-07-01

286

Differential sensitivity and responsiveness of three human cell lines HepG2, 1321N1 and HEK 293 to cadmium.  

PubMed

Cadmium (Cd) is a toxic heavy metal with no uniform mechanism of toxicity. In this the present study, the toxic effect of 5, 10 and 50 microM of Cd chloride was compared in three human cell lines; a human hepatoma cell line HepG2, a human astrocytoma cell line 1321N1, and a human embryonic kidney cell HEK 293. The results indicate a decrease in the viability of all three cell lines following exposure to Cd with HepG2 cells (IC50=13.96 microM) showing the most sensitivity when measured using the MTT assay. There was significant increase in lactate dehydrogenase leakage, DNA damage, malondialdeyde and antioxidant enzymes activities in all three cell lines especially at 50 microM Cd. Significant decreases in ATP production were also observed at all Cd concentrations in HepG2 and HEK 293 cell lines. ROS levels significantly increase and GSH/GSSG ratio significantly decrease in all the three cell lines after Cd exposure, but these effects were attenuated by the presence of N-acetylcysteine (NAC). The present study therefore shows that ROS production and glutathione (GSH) depletion may play a role in Cd-induced toxicity in all the three cell lines. The endogenous levels of protective enzymes as well as their responsiveness are likely to determine a cell's susceptibility to Cd. PMID:20686333

Lawal, Akeem Olalekan; Ellis, Elizabeth

2010-08-01

287

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

NASA Astrophysics Data System (ADS)

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

Kundu, Susmita; Bhattacharjee, Pijushpani

2012-06-01

288

Factors responsible for levels of male sterility in photoperiod-sensitive cytoplasmic male sterile (PCMS) wheat lines  

Microsoft Academic Search

A `two-line system' using photoperiod-sensitivecytoplasmic male sterility (PCMS) caused by Aegilops crassa cytoplasm has been proposed as a newmeans of producing hybrid wheat. The PCMS line ismaintained by self-pollination under short-dayconditions (?14.5 h light period), and F1 seedscan be produced by outcrossing of the PCMS line witha pollinator under long-day conditions (?15 h lightperiod). As the levels of male sterility

Koji Murai

2001-01-01

289

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

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.

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

1995-01-01

290

Comparative in vitro cytotoxicity of taxol and Taxotere against cisplatin-sensitive and-resistant human ovarian carcinoma cell lines  

Microsoft Academic Search

Using the sulforhodamine B assay, we compared the cytotoxic properties of the novel microtubule agent taxol and the semi-synthetic related compound Taxotere in nine human ovarian-carcinoma cell lines, including three pairs of cell lines rendered resistant to cisplatin or carboplatin. In addition, the cytotoxicity of the commonly used anticancer drugs cisplatin and adriamycin and the topoisomerase II inhibitor etoposide was

Lloyd R. Kelland; George Abel

1992-01-01

291

Inheritance of photoperiod sensitive genic male sterility and breeding of photoperiod sensitive genic male-sterile lines in rice (Oryza sativa L.) through anther culture  

Microsoft Academic Search

The fertility segregations of F1, F2, BCF1 descended from crosses between PSGMR and japonica varieties, and F1's anther cultured homozygous diploid pollen plant populations (H2) were studied to reveal the genetic mechanism of photoperiod sensitive genic male sterility in PSGMR under natural daylight\\u000a length at Shanghai. Rate of bagged seed-setting was used as an indicator of fertility. Fifteen F1 showed

Yang Zhuping

1997-01-01

292

Effects of retinoids and phorbol esters on the sensitivity of different cell lines to the polypeptide toxins modeccin, abrin, ricin and diphtheria toxin.  

PubMed

The effects of retinoic acid and 12-O-tetradecanoylphorbol 13-acetate on the sensitivities of a number of cell lines to the toxins modeccin, abrin, ricin and diphtheria toxin were studied. Retinoic acid and some other retinoids were found to protect a number of the cell lines against the toxins. HeLa cells that were protected bound much more retinoic acid than L-cells that were not protected. The tumour promoter 12-O-tetradecanoylphorbol 13-acetate was found to increase the sensitivity of cells to abrin, ricin and modeccin in the absence as well as in the presence of retinoic acid. Neither retinoic acid nor 12-O-tetradecanoylphorbol 13-acetate affected the extent of binding and pinocytotic uptake of toxins by the cells. Apparently retinoic acid and 12-O-tetradecanoylphorbol 13-acetate interfere with the entry of the toxins through the cell membrane. PMID:7306026

Sandvig, K; Olsnes, S

1981-03-15

293

Enhanced one-loop corrections to WIMP annihilation and their thermal relic density in the coannihilation region  

NASA Astrophysics Data System (ADS)

We consider quantum corrections to coannihilation processes of weakly interacting massive particles (WIMPs) due to the exchange of light bosons in the initial state (“Sommerfeld corrections”). We work at the one-loop level, i.e. we assume that these corrections can be treated perturbatively. Coannihilation is important if there is at least one additional new particle with mass close to the lightest WIMP, which is a dark matter candidate. In this case the exchange of a (relatively light) boson in the initial state can change the identity of the annihilating particles. The corrections we are interested in factorize, as in the case of WIMP self-annihilation treated previously, but they can mix different tree-level amplitudes. Moreover, even small mass splittings between the external particles and those in the loop can change the relevant loop functions significantly. We find exact analytical expressions for these functions and illustrate the effects by considering the cases of wino- or Higgsino-like neutralinos as examples.

Drees, Manuel; Gu, Jie

2013-03-01

294

ATP-sensitive K + channels in an insulin-secreting cell line are inhibited by d -glyceraldehyde and activated by membrane permeabilization  

Microsoft Academic Search

Summary  The control of K+ channels in the insulin-secreting cell line RINm5F has been investigated by patch-clamp singlechannel current recording experiments. The unitary current events recorded from cell-attached patches are due to large and small inwardly rectifying ATP-sensitive K+ channels with conductance properties similar to the two channels previously identified in primary cultured rat islet cells (Findlay, I., Dunne, M.J., &

M. J. Dunne; I. Findlay; O. H. Petersen; C. B. Wollheim

1986-01-01

295

Prediction of preservative sensitization potential using surface marker CD86 and\\/or CD54 expression on human cell line, THP1  

Microsoft Academic Search

Preservatives are important components in many products, but have a history of purported allergy. Several assays [e.g., guinea\\u000a pig maximization test (GPMT), local lymph node assay (LLNA)] are used to evaluate allergy potential of preservatives. We recently\\u000a developed the human Cell Line Activation Test (h-CLAT), an in vitro skin sensitization test using human THP-1 cells. This\\u000a test evaluates the augmentation

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

2007-01-01

296

Differential sensitivity to X-ray of chromosomes of blood T-lymphocytes and B and T-cell lines  

Microsoft Academic Search

Summary  Normal T-lymphocytes, B-cell line (CCRF-SB) and T-cell line (CCRF-HSB-2) cells, all diploid in their chromosome constitution,\\u000a were exposed in vitro to various doses of X-ray and analyzed at their first mitotic division for structural chromosome abnormalities.\\u000a The irradiation effects were determined also by a viability test of the cells, using trypan blue dye. The irradiated T-cell\\u000a line (CCRF-HSB-2) showed a

Yukimasa Shiraishi; Jun Minowada; Avery A. Sandberg

1976-01-01

297

Differential sensitivity of melanoma cell lines with BRAF V600E mutation to the specific Raf inhibitor PLX4032  

Microsoft Academic Search

Blocking oncogenic signaling induced by the BRAF\\u000a V600E mutation is a promising approach for melanoma treatment. We tested the anti-tumor effects of a specific inhibitor of Raf\\u000a protein kinases, PLX4032\\/RG7204, in melanoma cell lines. PLX4032 decreased signaling through the MAPK pathway only in cell\\u000a lines with the BRAF\\u000a V600E mutation. Seven out of 10 BRAF\\u000a V600E mutant cell lines displayed

Jonas N Søndergaard; Ramin Nazarian; Qi Wang; Deliang Guo; Teli Hsueh; Stephen Mok; Hooman Sazegar; Laura E MacConaill; Jordi G Barretina; Sarah M Kehoe; Narsis Attar; Erika von Euw; Jonathan E Zuckerman; Bartosz Chmielowski; Begoña Comin-Anduix; Richard C Koya; Paul S Mischel; Roger S Lo; Antoni Ribas

2010-01-01

298

Camptothecin analog (CPT-11)-sensitive human pancreatic tumor cell line QGP-1N shows resistance to SN-38, an active metabolite of CPT-11.  

PubMed

In the course of our study to determine the cross-sensitivity between CPT-11 and its active metabolite, SN-38, we found a SN-38-resistant human pancreatic tumor cell line, QGP-1N, which shows sensitivity to CPT-11. The IC50 of SN-38 was 152 times greater for QGP-1N than for SUIT-2, also a human pancreatic tumor cell line, whose IC50 of CPT-11 was similar to that for QGP-1N. The uptakes of CPT-11 and SN-38 and the intracellular conversion of CPT-11 to SN-38 could not explain the difference in sensitivity. DNA synthesis of QGP-1N cells was inhibited by CPT-11 which did not affect that of SUIT-2, while SN-38 inhibited the DNA synthesis of SUIT-2 at lower concentrations than that of QGP-1N. The inhibition test of topoisomerase I catalytic activity by CPT-11 or SN-38 revealed no difference in the biochemical properties of the topoisomerase I enzymes to the compounds between these two cell lines. These results indicate that CPT-11 should have its own inhibitory effect on DNA synthesis through a yet unknown mechanism in QGP-1N cells, although SN-38 plays an essential role in the antitumor activity of CPT-11 in SUIT-2 cells. In some cases, the antitumor effect of CPT-11 might be consequent not only on SN-38 but also on CPT-11 itself. PMID:1329748

Takeda, S; Shimazoe, T; Kuga, H; Sato, K; Kono, A

1992-10-15

299

High cytotoxic sensitivity of the human small cell lung doxorubicin-resistant carcinoma (GLC4/ADR) cell line to prodigiosin through apoptosis activation.  

PubMed

In the present study, we describe the cytotoxicity of the new drug prodigiosin (PG) in two small cell lung carcinoma (SCLC) cell lines, GLC4 and its derived doxorubicin-resistant GLC4/ADR cell line, which overexpresses multidrug-related protein 1 (MRP-1). We observed through Western blot that PG mediated cytochrome c release, caspase cascade activation and PARP cleavage, thereby leading to apoptosis in a dose-response manner. MRP-1 expression increased after PG treatment, although that does not lead to protein accumulation. The MTT assay showed no difference in sensitivity to PG between the two cell lines. Our results support PG as a potential drug for the treatment of lung cancer as it overcomes the multidrug resistance phenotype produced by MRP-1 overexpression. PMID:15746575

Llagostera, Esther; Soto-Cerrato, Vanessa; Joshi, Ricky; Montaner, Beatriz; Gimenez-Bonafé, Pepita; Pérez-Tomás, Ricardo

2005-04-01

300

Radiation Sensitivity, H2AX Phosphorylation, and Kinetics of Repair of DNA Strand Breaks in Irradiated Cervical Cancer Cell Lines  

Microsoft Academic Search

Six human cervical cancer cell lines (five human papillomavirus (HPV) positive, one HPV negative) for induction and rejoining of DNA strand breaks and for kinetics of formation and loss of serine 139 phosphorylated histone H2AX (H2AX). X-rays induced the same level of DNA breakage for all cell lines. By 8 hours after 20 Gy, <2% of the initial single-strand breaks

Judit P. Banath; Susan H. MacPhail; Peggy L. Olive

2004-01-01

301

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

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.

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

2013-01-01

302

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

PubMed

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

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

2013-06-01

303

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

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.

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

2006-01-01

304

Securing Continuous Clean Power. Considerations to be Made When Constructing Facilities Utilizing Sensitive or Never Off Line Electrical Equipment.  

National Technical Information Service (NTIS)

With today's computers and other highly sensitive and sophisticated electronic equipment, commercial grade electric power can no longer be relied on to provide the quality of power needed. Due to the stricter power quality requirements of electronic equip...

C. A. Bigelow

1986-01-01

305

High-speed spectral domain polarization-sensitive OCT using a single InGaAs line-scan camera and an optical switch  

NASA Astrophysics Data System (ADS)

We demonstrated high-speed spectral domain polarization-sensitive optical coherence tomography (SD-PSOCT) using a single InGaAs line-scan camera and an optical switch at 1.3-?m region. The polarization-sensitive low coherence interferometer in the system was based on the original free-space PS-OCT system published by Hee et al. The horizontal and vertical polarization light rays split by polarization beam splitter were delivered and detected via an optical switch to a single spectrometer by turns instead of dual spectrometers. The SD-PSOCT system had an axial resolution of 8.2 ?m, a sensitivity of 101.5 dB, and an acquisition speed of 23,496 Alines/s. We obtained the intensity, phase retardation, and fast axis orientation images of a biological tissue. In addition, we calculated the averaged axial profiles of the phase retardation in human skin.

Lee, Sang-Won; Jeong, Hyun-Woo; Kim, Beop-Min

2010-02-01

306

Dark Matter as Fossil Turbulence---Primordial Fog Particles and WIMPs  

NASA Astrophysics Data System (ADS)

Most of the matter of the universe is ``dark''. Based on the Schwarz viscous and turbulence self-gravitational condensation scales, most dark matter has two forms: ``primordial fog particles'' (PFPs---now moon-mass black dwarfs in galaxy halos) which condensed when the plasma universe neutralized to an inviscid, weakly-turbulent gas about 0.3 By (billion years after the big bang); plus WIMP fluids whose weakly-interacting-massive-particles may still be condensing slowly at large scales to form halos about galaxy clusters. Recent Hubble Space Telescope (HST) photos show evidence of PFPs as cometary globules in planetary nebulae (see http:www-acs.ucsd.edu ir118 for illustrations). Recent HST deep field photos show red galaxies existed at only 0.75 By, also suggesting a gentle, weak-turbulence, PFP condensation scenario for the first (small red) stars, within preexisting galaxy mass PFP ``fog patches''. The generally accepted Jeans criterion permits no such condensations of protogalaxies in the plasma epoch, and requires a strongly turbulent (big blue star) initial gas condensation scenario that is inconsistent with fossil non-turbulence evidence such as ancient globular star clusters and the extreme temperature uniformity observed in the cosmic microwave background radiation.

Gibson, Carl H.

1996-11-01

307

Differential anthracycline sensitivity in two related human colon carcinoma cell lines expressing similar levels of P-glycoprotein.  

PubMed

Chemosensitivity of the human colon carcinoma HCT-15 cell line to 4'-epidoxorubicin proved to be 100-fold higher than that of its variant HCT-15 EDR. Confocal scanning microscopy showed significant less drug accumulation in HCT-15 EDR. A 2-fold increase in hsp27 expression was found in HCT-15 EDR, with no alteration in hsp70. The expression of the drug exporter Pgp was similar in both cell lines, despite the lower drug accumulation shown by HCT-15 EDR in respect to HCT-15. Other molecules implicated in the acquisition of enhanced chemoresistance or a more active Pgp variant present in HCT-15 EDR, could explain the phenomenon. PMID:11248426

Boquete, A L; Vargas Roig, L; López, G A; Gude, R; Binda, M M; González, A D; Ciocca, D R; Bonfil, R D

2001-04-10

308

Relationships between intermediate filaments and cell-specific functions in renal cell lines derived from transgenic mice harboring the temperature-sensitive T antigen.  

PubMed

Four renal cell lines were derived from glomeruli, proximal, distal, and cortical collecting tubules microdissected from the kidneys of transgenic mice carrying the temperature-sensitive mutant of the simian virus 40 large T antigen under the control of the vimentin promoter. All four cell lines contained large T antigen in their nuclei, grew rapidly, and contained vimentin filaments when grown in serum-enriched medium at the permissive temperature of 33 degrees C. The glomerular cell line formed multiple layers of cells and contained smooth muscle actin and desmin filaments, features of mesangial cells. The three tubule cell lines formed monolayers of polarized cuboid cells separated by tight junctions and having a patchy distribution of cytokeratins K8-K18. A shift from 33 degrees C to the restrictive temperature (39.5 degrees C) stopped cell growth in all cell lines and caused profound changes in the content of intermediate filaments. Vimentin was still present in mesangial-like cells, but the proximal, distal, and collecting tubule cells contained uniform networks of cytokeratins K8-K18 and desmoplakin I and II around the cell peripheries. Potassium transport, mediated by Na+-K+ ATPase pumps and specific cAMP hormonal sensitivities, significantly increased in proximal, distal, and collecting tubule cells when shifted from 33 degrees C to 39.5 degrees C. Thus, the temperature-dependent inactivation of large T antigen, responsible for the arrest of cell growth, did not affect the phenotype of mesangial-like glomerular cells but induced some changes in the expression of intermediate filaments and restored, at least partially, the main parental cell-specific functions in proximal, distal, and collecting tubule cultured cells. PMID:8698837

Cluzeaud, F; Bens, M; Wu, M S; Li, Z; Vicart, P; Paulin, D; Vandewalle, A

1996-04-01

309

Interactions between ice and ocean observed with phase-sensitive radar near an Antarctic ice-shelf grounding line  

Microsoft Academic Search

Precise measurements of basal melting have been made at a series of 14 sites lying within a few kilometres of the grounding line of the Ronne Ice Shelf, Antarctica, where the ice thickness ranges from 1570 to 1940 m. The study was conducted over the course of 1 year and included a detailed survey of the horizontal deformation, as well

Adrian Jenkins; Hugh F. J. Corr; Keith W. Nicholls; Craig L. Stewart; Christopher S. M. Doake

2006-01-01

310

Hepsulfam Sensitivity in Human Breast Cancer Cell Lines: The Role of Glutathione and Glutathione S-Transferase in Resistance1  

Microsoft Academic Search

Hepsulfam (NSC 329680, 1,7-heptanediol disulfamate) is an alkylat- ing agent that showed excellent activity against mouse and human mam mary carcinoma in preclinical studies. We therefore studied the cytotox- icity of this drug in six human breast cancer cell lines (Adr\\

Deborah K. Armstrong; Gary B. Gordon; John Hilton; Robert T. Streeper; O. Michael Colvin; Nancy E. Davidson

311

Highly sensitive detection of l-glutamate by on-line amperometric micro-flow analysis based on enzymatic substrate recycling.  

PubMed

A highly selective and sensitive on-line monitoring system is proposed for amperometric assay of trace amounts of l-glutamate. The system includes a microdialysis probe, immobilized enzyme reactor, and poly(1,2-diaminobenzene)-coated platinum electrode. The enzyme reactor prepared by the co-immobilization of l-glutamate oxidase and glutamate dehydrogenase are here employed to enhance the sensitivity of l-glutamate as an on-line amplifier based on the substrate recycling. The l-glutamate in the dialysate from the probe are recycled enzymatically during passage through the reactor in the presence of sufficient amounts of NADH and oxygen to produce a large amount of hydrogen peroxide, which is detected if selectively at a downstream poly(1,2-diaminobenzene)-coated platinum electrode without interference from oxidizable species such as l-ascorbate in the sample and NADH added to the carrier buffer. The cycle is also initiated with 2-oxoglutarate, and so saccharopine dehydrogenase reactor is positioned in series before the amplifier reactor to remove 2-oxoglutarate in the dialysate. By the present method, l-glutamate is selectively assayed with a 160-fold increase in sensitivity compared with the unamplified responses. The detection limit is 0.5x10(-7) M of l-glutamate. PMID:18967078

Yao, T; Suzuki, S; Nakahara, T; Nishino, H

1998-03-01

312

Development of photoperiod-sensitive cytoplasmic male sterile (PCMS) wheat lines showing high male sterility under long-day conditions and high seed fertility under short-day conditions  

Microsoft Academic Search

A “two-line system” using photoperiod-sensitive cytoplasmic male sterility (PCMS) caused by Aegilops crassa cytoplasm under long-day photoperiods (?15 h) has been proposed as a means of producing hybrid varieties in common wheat\\u000a (Triticum aestivum). The PCMS line is maintained by self-pollination under short-day conditions, and hybrid seeds can be produced through outcrossing\\u000a of the PCMS line with a pollinator line under

Koji Murai; Ichiro Tsutui; Yuki Kawanishi; Shojiro Ikeguchi; Mikiko Yanaka; Naoyuki Ishikawa

2008-01-01

313

How dark are Majorana WIMPs? Signals from magnetic inelastic dark matter and Rayleigh dark matter  

NASA Astrophysics Data System (ADS)

The effective interactions of dark matter with photons are fairly restricted. Yet both direct detection as well as monochromatic ?-ray signatures depend sensitively on the presence of such interactions. For a Dirac fermion, electromagnetic dipoles are possible but are very constrained. For Majorana fermions, no such terms are allowed. We consider signals of an effective theory with a Majorana dark matter particle and its couplings to photons. In the presence of a nearby excited state, there is the possibility of a magnetic dipole transition (magnetic inelastic dark matter), which yields both direct and indirect detection signals and, intriguingly, yields essentially the same size over a wide range of dipole strengths. Absent an excited state, the leading interaction of weakly interacting massive particles is similar to the Rayleigh scattering of low-energy photons from neutral atoms, which may be captured by an effective operator of dimension 7 of the form ?¯?F??F??. While it can be thought of as a phase of the magnetic inelastic dark matter scenario where the excited state is much heavier than the ground state, it can arise from other theories as well. We study the resulting phenomenology of this scenario: gamma-ray lines from the annihilation of weakly interacting massive particles; nuclear recoils in direct detection; and direct production of the weakly interacting massive particle pair in high-energy colliders. Considering recent evidence in particular for a 130 GeV line from the Galactic center, we discuss the detection prospects at upcoming experiments.

Weiner, Neal; Yavin, Itay

2012-10-01

314

Characterization of kinase suppressor of Ras1 expression and anticancer drug sensitivity in human cancer cell lines  

Microsoft Academic Search

Previous studies have indicated that the ERK1\\/2 MAP kinase signaling pathway plays an important role not only in cell growth,\\u000a cell cycle regulation, and differentiation, but also in determining the sensitivity of cells to anticancer agents as well.\\u000a Furthermore, expression of kinase suppressor of Ras-1 (KSR1), a molecular scaffold that modulates signaling through the ERK1\\/2\\u000a MAP kinase pathway, has been

Scott M. Stoeger; Kenneth H. Cowan

2009-01-01

315

SELECTIVE LOSS OF ACETYLCHOLINE SENSITIVITY IN A NERVE CELL LINE CULTURED IN HORMONE-SUPPLEMENTED SERUM-FREE MEDIUM  

Microsoft Academic Search

When clonal rat pheochromocytoma PC12h cells were cultured in a hormone-supplemented serum-free medium, the carbamylcholine-elicited catecholamine release from cells cultured in serum- free medium was completely abolished. On the other hand, the high potassium-induced catechol- amine release was not changed, even in PC12h cells cultured in serum-free medium. The lack of carbamylcholine sensitivity was confirmed directly by measuring carbamylcholine-induced 22Na

MASAYUKI MITSUKA; HIROSHI HATANAKA

1983-01-01

316

Factors affecting the sensitivity of human-derived esophageal carcinoma cell lines to 5-fluorouracil and cisplatin  

PubMed Central

Effective chemotherapy against esophageal carcinoma is considered achievable with a combination of 5-fluorouracil (5-FU) and cisplatin (CDDP). However, chemo-therapy remains ineffective in certain patients. The aim of this study was to clarify the factors which affect sensitivity to 5-FU and CDDP. The effects of factors known to influence sensitivity to 5-FU and CDDP, namely transporters, DNA repair enzymes and metabolic enzymes, were examined. mRNA levels of four transporters, SLC22A2, SLC23A2, ABCB1 and ABCC2, two DNA repair-related enzymes, Rad51 and MSH2, and one metabolic enzyme, dihydropyrimidine dehydrogenase (DPYD), showed a strong correlation (|r|>0.7) with IC50 values for 5-FU. In addition, the mRNA levels of ABCC2, MSH2 and DPYD showed a strong correlation (|r|>0.7) with the IC50 values for CDDP. Gimeracil, a DPYD inhibitor, enhanced the sensitivity of some cells to 5-FU but decreased the sensitivity of all the cells to CDDP. The inhibitory effects of ABCC2 with MK571 did not correspond to those observed in the correlation analysis. In conclusion, mRNA levels of SLC22A2, SLC23A2, ABCB1, ABCC2, Rad51, MSH2 and DPYD were confirmed to be strongly correlated with IC50 values for 5-FU, and mRNA levels of ABCC2, MSH2 and DPYD were confirmed to be strongly correlated with IC50 values for CDDP. In addition, the inhibition of DPYD appeared to affect the cytotoxicity of CDDP.

MINEGAKI, TETSUYA; TAKARA, KOHJI; HAMAGUCHI, RYOHEI; TSUJIMOTO, MASAYUKI; NISHIGUCHI, KOHSHI

2013-01-01

317

High sensitivity CW-Cavity Ring Down Spectroscopy of N2O between 6950 and 7653 cm-1 (1.44-1.31 ?m): II. Line intensities  

NASA Astrophysics Data System (ADS)

The room temperature absorption spectra of nitrous oxide, N2O, have been recorded in the 6950-7653 cm-1 spectral region at 2 and 10 Torr using a CW-CRDS spectrometer based on 24 fibered DFB lasers. The achieved sensitivity (noise equivalent absorption ?min?5×10-11 cm-1) allowed detecting lines with intensities as low as 1×10-29 cm/molecule. In the preceding contribution (Lu Y, Mondelain D, Liu AW, Perevalov VI, Kassi S, Campargue A, J Quant Spectros and Radiat Transfer 2012;113:749-62), we reported the assignment of more than 7200 N2O lines in the region and the derivation of the corresponding spectroscopic parameters Gv, Bv, Dv and Hv. In the present work, more than 1300 14N216O absolute line intensities of cold and hot bands belonging to the ?P=12, 13 and 14 series of transitions have been measured (P=2V1+V2+4V3 is the polyad number). The uncertainty of the obtained line intensity values varies from 4 to 7% for the majority of the lines. The obtained dataset extends importantly the set of measurements available in the literature, in particular for the ?P =13 series for which previous data were very limited. The ?P=12-14 effective dipole moment parameters were fitted to the intensity values measured in this work and available in the literature. The obtained sets of the dipole moment parameters allow reproducing the observed line intensities within their experimental uncertainties. The calculated intensities of the ?P=12, 13 and 14 bands of 14N216O assigned by CRDS in the 6950-7653 cm-1 region are provided as supplementary material.

Karlovets, E. V.; Lu, Y.; Mondelain, D.; Kassi, S.; Campargue, A.; Tashkun, S. A.; Perevalov, V. I.

2013-03-01

318

MRI compatibility of position-sensitive photomultiplier depth-of-interaction PET detectors modules for in-line multimodality preclinical studies  

NASA Astrophysics Data System (ADS)

This work addresses the feasibility of a small-animal, in-line PET/MR system based on Position-Sensitive Photo Multiplier Tubes (PS-PMTs). To this end, we measured the effects of static magnetic fields on the PS-PMTs performance in order to explore the minimal tandem separation between the PET and MR subsystems to preserve their respective performances. We concluded that it is possible to achieve minimal degradation of the PET scanner performance (after a system recalibration) if the magnetic field strength influencing the PET detectors is less than 1 mT and if it is oriented perpendicularly to the longitudinal axis of the tube. Therefore, we predict that it will be possible to maintain the PET image quality if it is placed outside the 1 mT line.

Vaquero, J. J.; Sánchez, J. J.; Udías, J. M.; Cal-González, J.; Desco, M.

2013-02-01

319

An improved line list for water vapor in the 1.5 µm transparency window by highly sensitive CRDS between 5852 and 6607 cm?1  

NASA Astrophysics Data System (ADS)

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 µm transparency window of major importance for atmospheric applications. The achieved sensitivity of the recordings varies from ?min ˜2×10?11 to 2×10?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 (2×10?30?2×10?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.

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

2013-11-01

320

Purine analogs sensitize the multidrug resistant cell line (NCI-H460/R) to doxorubicin and stimulate the cell growth inhibitory effect of verapamil.  

PubMed

The resistant cell line NCI-H460/R and its counterpart NCI-H460 were used to investigate the ability of purine analogs to overcome multidrug resistance (MDR) that seriously limit the efficacy of lung cancer regimens with chemotherapeutic agents. Two purine analogs, sulfinosine (SF) and 8-Cl-cAMP, exerted dose-dependent effects on cell growth in both parental and resistant cell lines. They significantly decreased mdr1 expression in NCI-H460/R cells. Low concentrations (1 microM) of SF and 8-Cl-cAMP in combination with doxorubicin (DOX) exerted synergistic growth inhibition in both cell lines. Pretreatment with SF and 8-Cl-cAMP improved the sensitivity to DOX more than verapamil (VER), the standard modulator of MDR. The increased accumulation of DOX observed after the treatment with SF and 8-Cl-cAMP was consistent with the results obtained with VER. VER stimulated the effect of 8-Cl-cAMP on DOX cytotoxicity and mdr1 expression. Combinations of either SF or 8-Cl-cAMP with VER at clinically acceptable concentrations exhibited synergistic effects on cell growth inhibition in the resistant cell line. SF and 8-Cl-cAMP modulated MDR in NCI-H460/R cells, especially when applied before DOX administration. This feature, together with their ability to reverse MDR, renders the purine analogs (in combination with VER) as potential candidates for improving the clinical activity of existing lung cancer therapeutics. PMID:19533022

Pesi?, Milica; Podolski, Ana; Raki?, Ljubisa; Ruzdiji?, Sabera

2009-06-18

321

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 leukemia.  

PubMed

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

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; Lamba, Jatinder K

2011-06-28

322

Characterization of the androgen-sensitive MDA-kb2 cell line for assessing complex environmental mixtures.  

PubMed

Synthetic and natural steroidal androgens and estrogens and many other non-steroidal endocrine-active compounds commonly occur as complex mixtures in aquatic environments. It is important to understand the potential interactive effects of these mixtures to properly assess their risk. Estrogen receptor agonists exhibit additivity in mixtures when tested in vivo and in vitro. Little is known, however, concerning possible mixture interactions of androgen receptor agonists. In these studies we used the MDA-kb2 cell line, a human breast cancer cell line with endogenous androgen receptors and a stably transfected luciferase reporter gene construct to quantify the androgenic activity of seven natural and synthetic androgens: 17beta-trenbolone, dihydrotestosterone, methyltestosterone, testosterone, trendione, 17alpha-trenbolone, and androstenedione. We tested combinations of these androgens and compared the observed activity to expected androgenic activity based on a concentration addition model. Our analyses support the hypothesis that androgen receptor agonists cause additive responses in a mixture. Binary mixtures of 17beta-trenbolone with 17beta-estradiol or triclocarban (an anti-microbial found in the environment) were also tested. 17beta-Estradiol induced androgenic activity, but only at concentrations 600-fold greater than those found in the environment. Triclocarban enhanced the activity of 17beta-trenbolone. Additionally, three anti-androgens were each paired with three androgens of varying potencies. The relative potencies of the antagonists were a vinclozolin metabolite (M2) > procymidone > prochloraz regardless of the androgen used. The results of our studies demonstrate the potential utility of the androgen-responsive MDA-kb2 cell line for quantifying the activity of mixtures of endocrine-active chemicals in complex wastes such as municipal effluents and feedlot discharges. PMID:20821581

Blake, Lindsey S; Martinovi?, Dalma; Gray, L Earl; Wilson, Vickie S; Regal, Ron R; Villeneuve, Daniel L; Ankley, Gerald T

2010-06-01

323

Characterization of Glutathione S-Transferase Isoforms in Three Maize Inbred Lines Exhibiting Differential Sensitivity to Alachlor.  

PubMed Central

Glutathione S-transferases (GSTs) are a family of isozymes that catalyze the conjugation of glutathione to several xenobiotics, including a number of important herbicides. Several GST isoforms have been identified in maize (Zea mays L.). In this study we focused on three isoforms, GST I, II, and IV, derived from homo-or heterodimerization of two subunits GST-29 and GST-27, which have been shown to be responsible for reactivity to alachlor. The expression of these isoforms was examined in three inbred lines of maize that showed tolerance, susceptibility, and intermediate resistance to alachlor (2-Cl-N-[2,6-diethylphenyl]-N-[methoxymethyl]acetamide) treatment. The different isoforms were separated by anion-exchange chromatography and subunits were quantified by western blot analysis. GST assays were performed against both 1-Cl-2,4-dinitrobenzene and alachlor. This analysis showed that the susceptible and intermediate lines exhibit impaired function in the GST-27 and GST-29 subunits, respectively. In addition, this study suggests that GST IV is the principal, detoxifying enzyme for alachlor, although GST I and II are required to achieve tolerance to high rates of the herbicide.

Rossini, L.; Jepson, I.; Greenland, A. J.; Gorla, M. S.

1996-01-01

324

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

SciTech Connect

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}.

Behnke, E.; Behnke, J.; Hinnefeld, J. H.; Levine, I.; Shepherd, T. [Indiana University South Bend, South Bend, Indiana (United States); Brice, S. J.; Broemmelsiek, D.; Cooper, P. S.; Crisler, M.; Hall, J.; Hu, M.; Ramberg, E.; Sonnenschein, A. [Fermi National Accelerator Laboratory, Batavia, Illinois (United States); Collar, J. I.; Dahl, C. E.; Fustin, D.; Szydagis, M. [Enrico Fermi Institute, KICP and Department of Physics, University of Chicago, Chicago, Illinois (United States)

2011-01-14

325

Associations of ErbB2, beta1-integrin and lipid rafts on Herceptin (Trastuzumab) resistant and sensitive tumor cell lines.  

PubMed

ErbB2-mediated transmembrane signaling is a key target of novel anticancer agents such as Herceptin. Our comparison of Herceptin resistant (JIMT-1, MKN-7) and sensitive (SKBR-3, N-87) cell lines demonstrates the importance of ErbB2 association patterns involving integrins and lipid rafts. Flow cytometric FRET and confocal microscopic measurements revealed colocalization and molecular proximity between beta1-integrins and ErbB2, as well as their association with lipid rafts. A weak functional interaction between ErbB2 and beta1-integrin and the fact that ErbB2 did not co-patch with beta1-integrins upon crosslinking imply that ErbB2 and beta1-integrin define two distinct molecular association clusters from a functional point of view. Although Herceptin-sensitive cell lines expressed more ErbB2 and fewer beta1-integrin molecules on their surface than their resistant counterparts, this finding probably does not explain the Herceptin resistant phenotype due to the weak interaction between beta1-integrins and ErbB2. Our results imply that the true significance of the expression profile of proteins involved in oncogenesis can only be understood after characterizing their molecular interactions. PMID:16112423

Mocanu, Maria-Magdalena; Fazekas, Zsolt; Petrás, Miklós; Nagy, Péter; Sebestyén, Zsolt; Isola, Jorma; Tímár, József; Park, John W; Vereb, György; Szöllosi, János

2005-09-28

326

Comparison of primary human fibroblasts and keratinocytes with immortalized cell lines regarding their sensitivity to sodium dodecyl sulfate in a neutral red uptake cytotoxicity assay.  

PubMed

Cell lines present a valuable tool for in vitro assessment of skin damage caused by application of cosmeticals or pharmaceuticals. They form a reproducible test system under controllable test conditions and, in many cases, can be used as alternatives to animal testing in order to assess the compatibility of drugs or cosmetics and human skin. Yet, it can not necessarily be assumed that the behavior of cultured cells, when treated with different substances, is exactly consistent with the behavior of cells being part of a live organism. Becoming immortal, cells exhibit changes in genotype and/or phenotype, possibly resulting in modified reactions to external influences. Therefore, to obtain results close to in vivo studies, it seems apparent to use primary cells for testing that have not yet undergone any modifications. To compare the properties of primary fibroblasts (Normal Human Dermal Fibroblasts, NHDF) and primary keratinocytes (Normal Human Epidermal Keratinocytes, NHEK) with those of immortal cell lines (3T3 (ACC 173) Swiss albino mouse fibroblasts and HaCaT (human, adult, low calcium, high temperature, human adult skin keratinocytes) cells), their sensitivities in cytotoxicity assays have been assessed. While both fibroblast cell cultures showed similar sensitivities towards sodium dodecyl sulfate (SDS), primary keratinocytes died at SDS concentrations about three times lower than the immortal HaCaT cells. PMID:19402346

Olschläger, Veronika; Schrader, Andreas; Hockertz, Stefan

2009-01-01

327

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

PubMed Central

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

2011-01-01

328

Intrinsically lower AKT, mTOR and HIF activity correlates with increased sensitivity to 2-deoxy-D-glucose under hypoxia in lung cancer cell lines  

PubMed Central

Down regulation by siRNA or absence of Hypoxic Inducible Factor (HIF-1?) has been shown to lead to increased sensitivity to glycolytic inhibitors in hypoxic tumor cells. In surveying a number of tumor types for differences in intrinsic levels of HIF under hypoxia we find that the reduction of the upstream pathways of HIF, AKT and mammalian target of rapamycin (mTOR) correlate with increased toxic effects of 2-DG in lung cancer cell lines when treated under hypoxia. Since HIF-1? translation is regulated by the mammalian target of rapamycin (mTOR), we examined the effects of blocking mTOR under hypoxia with an analog of rapamycin (CCI-779) in those cell lines that showed increased mTOR and AKT activity and found that HIF-1? down-regulation coincided with increased 2-DG killing. CCI-779 however was ineffective in increasing 2-DG toxicity in cell lines that do not express HIF. This result supports the hypothesis that although mTOR inhibition leads to blockage of numerous downstream targets, CCI-779 increases the toxicity of 2-DG in hypoxic cells through down-regulation of HIF-1?. Overall, our findings show that CCI-779 hyper-sensitizes hypoxic tumor cells to 2-DG and suggest that the intrinsic expression of AKT, mTOR, and HIF in lung cancer, as well as other tumor types, may be important in dictating the decision on how best to use 2-DG alone or in combination with CCI-799 to kill hypoxic tumor cells clinically.

Wangpaichitr, Medhi; Savaraj, Niramol; Maher, Johnathan; Kurtoglu, Metin; Lampidis, Theodore J.

2008-01-01

329

Development of an automated on-line pre-column derivatization procedure for sensitive determination of histamine in food with high-performance liquid chromatography-fluorescence detection.  

PubMed

An improved sensitive method was developed and validated for the determination of histamine in food samples by using automated on-line pre-column derivatization coupled with high performance liquid chromatography and fluorescence detection (HPLC-FLD). o-Phthaldialdehyde (OPA) was adopted as derivatization reagent, and a "sandwich" (OPA+histamine+OPA) aspiration mode for the automated on-line pre-column derivatization was found to efficiently enhance the method sensitivity and precision. Histamine in food samples was efficiently extracted with a methanol-phosphate buffer solution (50:50, v/v) at 60 degrees C for 30 min, and purified with Waters Oasis MCX solid-phase extraction (SPE) cartridge. The limit of quantification for this method is 0.2 mg/kg, which is very sensitive for histamine determination. With the "sandwich" injection program, 3.7% of relative standard deviation (RSD) was achieved by five replicative determinations of a sample blank spiked with 0.25 mg/kg histamine standard. Histamine in food samples such as fumitory skipjack and mackerel was analyzed with relative recoveries over 95% at spiking level of 150 mg/kg, as well as canned tuna fish and cheese with relative recoveries up to 98% at spiking levels of 0.50 and 5.0 mg/kg, respectively. The proposed method was validated with a sample from the Food Analysis Performance Assessment Scheme (FAPAS) as a standard certified material; and the results (140+/-6 mg/kg) agreed well with the assigned value (139 mg/kg). PMID:18822416

Peng, Jin-Feng; Fang, Ke-Teng; Xie, Dong-Hua; Ding, Bin; Yin, Ju-Yi; Cui, Xiao-Mei; Zhang, Ying; Liu, Jing-Fu

2008-09-13

330

Novel mast cell lines with enhanced proliferative and degranulative abilities established from temperature-sensitive SV40 large T antigen transgenic mice.  

PubMed

Mast cells (MCs) play crucial roles in innate immunity to parasitic and bacterial infections as well as in hypersensitivity, such as the induction and exacerbation of allergy and autoimmune diseases. The regulatory mechanisms for MC development and effector functions are of great interest for developing novel therapeutic strategies against such disorders. Here we report the establishment of novel, immortalized MC lines from bone marrow (BM) cells of a temperature-sensitive mutant of SV40 large T antigen-transgenic mice (termed SVMCs). BM cells from tsSV40LT mice were cultured in the presence of interleukin (IL)-3 for 3 weeks, and then subjected to limiting dilution and single-cell cloning, yielding 27 independent MC clones, three of which were subjected to further analysis. On culture with nerve growth factor, stem cell factor and IL-3, these SVMC clones showed morphologic and biochemical changes from mucosal MC-like to connective-tissue MC-like phenotypes. These SVMC lines exhibited a significantly enhanced proliferation rate, and a higher responsiveness to the high affinity Fc receptor for IgE-mediated intracellular calcium mobilization and degranulation than those of BM-derived cultured MCs. These cell lines should facilitate studies on the mechanisms for the development, differentiation and effector functions of MCs in health and diseases. PMID:16822814

Kanehira, Masahiko; Kaifu, Tomonori; Maya, Kozue; Kaji, Mitsuji; Nakamura, Akira; Obinata, Masuo; Takai, Toshiyuki

2006-07-05

331

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

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

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

1999-01-01

332

Activation of the amiloride-sensitive epithelial sodium channel by the serine protease mCAP1 expressed in a mouse cortical collecting duct cell line.  

PubMed

This study examines whether serine proteases can activate the amiloride-sensitive sodium channel (ENaC) in mammalian kidney epithelial cells. The transepithelial sodium transport assessed by amiloride-sensitive short-circuit current appears to be sensitive to aprotinin, a protease inhibitor in a mouse cortical collecting duct cell line (mpkCCD(c14)). This result indicated that serine proteases may be implicated in the regulation of ENaC-mediated sodium transport. Using degenerated oligonucleotides to a previously isolated serine protease from Xenopus, xCAP1 (channel activating protease), a novel full-length serine protease (mCAP1), has been isolated and characterized. RNA analysis showed a broad pattern of expression in tissues (kidney, lung, colon, and salivary glands) expressing ENaC. Reverse transcription-PCR experiments also showed that mCAP1 was abundantly expressed in proximal tubule cells and was also expressed in intact and cultured collecting duct cells. Coexpression of the Xenopus, rat, or human alpha-, beta-, and gamma-ENaC subunits in Xenopus oocytes also showed that mCAP1 induces a significant increase in ENaC-mediated current accompanied by a decrease of channel molecules at the cell surface. It is proposed that this novel mouse channel activating protease may act as a regulator of ENaC within the kidney. PMID:10770960

Vuagniaux, G; Vallet, V; Jaeger, N F; Pfister, C; Bens, M; Farman, N; Courtois-Coutry, N; Vandewalle, A; Rossier, B C; Hummler, E

2000-05-01

333

Constraints on WIMP and Sommerfeld-enhanced dark matter annihilation from HESS observations of the galactic center  

NASA Astrophysics Data System (ADS)

We examine the constraints on models of weakly interacting massive particle (WIMP) dark matter from the recent observations of the Galactic Center by the High Energy Spectroscopic System (HESS) telescope. We analyze canonical WIMP annihilation into Standard Model particle final states, including bbar b, tbar t and W+W-. The constraints on annihilation into bbar b is within an order of magnitude of the thermal cross section at ~ 3 TeV, while the ?+?- channel is within a factor of ~ 2 of thermal. We also study constraints on Sommerfeld-enhanced dark matter annihilation models, and find that the gamma-ray observational constraints here rule out all of the parameter space consistent with dark matter annihilation interpretations of PAMELA and the Fermi-LAT e+e- spectrum, in specific classes of models, and strongly constrains these interpretations in other classes. The gamma-ray constraints we find are more constraining on these models, in many cases, than current relic density, cosmic microwave background, halo shape and naturalness constraints.

Abazajian, Kevork N.; Harding, J. Patrick

2012-01-01

334

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

NASA Astrophysics Data System (ADS)

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 bbar b and ?+?? or W+W? 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 ?+?? 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.

Gómez-Vargas, Germán A.; Sánchez-Conde, Miguel A.; Huh, Ji-Haeng; Peiró, Miguel; Prada, Francisco; Morselli, Aldo; Klypin, Anatoly; Cerdeño, David G.; Mambrini, Yann; Muñoz, Carlos

2013-10-01

335

Rapid and sensitive on-line solid phase extraction-ultra high performance liquid chromatography-electrospray-tandem mass spectrometry analysis of pesticides in surface waters.  

PubMed

A simple, fast and sensitive method has been developed for the determination of 37 LC-amenable pesticides in surface water samples. On-line solid phase extraction (SPE) coupled to ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS. was employed for pre-concentration and analysis of all compounds in 16min. SPE parameters were evaluated in order to increase sample throughput and detectability. Thus, injected sample volume, sample loading flow, carryover effects and reusability of the cartridges employed were studied, observing that 70 extractions can be performed with the same cartridge. Validation parameters were performed and good linearity (R(2)>0.99 in all cases) and precision (interday relative standard deviation values were lower than 14%) were obtained. Limits of detection (LOD) and limits of quantification (LOQ) were lower than 6.0 and 18.0ngL(-1) applying an injection sample volume of 1.5mL, respectively, with exception of thifensulfuron methyl, whose limits were 10.0 and 33.0ngL(-1), respectively. On-line SPE recoveries were evaluated for three concentration levels (0.01, 0.03, 0.10 and 0.20?gL(-1)) and acceptable values were found. The on-line SPE method was also compared with off-line SPE. Matrix effects were observed for majority of compounds and standard addition method was selected for analysis of real water samples. Finally, surface water samples were analyzed and, in all cases, the pesticide concentrations were below than the allowable limit in water for human consumption. PMID:23885668

Hurtado-Sánchez, M C; Romero-González, R; Rodríguez-Cáceres, M I; Durán-Merás, I; Frenich, A Garrido

2013-07-16

336

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

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 ?M) and inhibited by diphenyliodonium (5 ?M). 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.

Wang, Dashou; Youngson, Charlotte; Wong, Veronica; Yeger, Herman; Dinauer, Mary C.; de Miera, Eleazar Vega-Saenz; Rudy, Bernardo; Cutz, Ernest

1996-01-01

337

Genotype-Dependent Sensitivity of Uveal Melanoma Cell Lines to Inhibition of B-Raf, MEK, and Akt Kinases: Rationale for Personalized Therapy  

PubMed Central

Purpose. Inhibitors of B-Raf and MEK kinases hold promise for the management of cutaneous melanomas harboring BRAF mutations. BRAF mutations are rare in uveal melanomas (UMs), but somatic mutations in the G protein ? subunits G?q and G?11 (encoded by GNAQ and GNA11, respectively) occur in a mutually exclusive pattern in ?80% of UMs. The impact of B-Raf and MEK inhibitors on G?-mutant UMs remains unknown. Methods. The impact of the B-Raf inhibitor PLX4720, the MEK inhibitor AZD6244, and the Akt inhibitor MK2206 on UM cell lines was assessed with the use of cell viability, proliferation, and apoptosis assays and immunoblot analysis. Results. BRAF-mutant UM cells were sensitive to both PLX4720 and AZD6244, undergoing cell cycle arrest but not apoptosis. UM cells with a G?-protein mutation (GNAQ or GNA11) were mildly sensitive to AZD6244 but completely resistant to PLX4720. In fact, PLX4720 paradoxically increased ERK phosphorylation in G?-mutant UM cells. The combination of AZD6244 with PLX4720 had synergistic anticancer activity in BRAF-mutant cells but not in G?-mutant cells. The Akt inhibitor MK2206 sensitized BRAF-mutant cells to both PLX4720 and AZD6244 and sensitized G?-mutant cells to AZD6244 but did not overcome the resistance of the G?-mutant cells to PLX4720. Conclusions. The response of UM cells to inhibition of B-Raf, MEK, and Akt depends on their genotype. Future use of such targeted therapies in clinical trials of UM patients will require careful design and patient selection based on genotype to provide personalized and effective therapy.

Chew, Sue Anne; He, Bin; Riechardt, Aline I.; Karadedou, Theano; Kotoula, Vassiliki; Poulaki, Vassiliki

2011-01-01

338

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

PubMed Central

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 ?-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.

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

2009-01-01

339

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

PubMed

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 11beta-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 tonicity-responsive enhancer binding protein, an osmoregulatory transcription factor capable of binding tonicity-responsive enhancer 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 that, by binding to the AU-rich sequences of the 3'-untranslated region 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 posttranscriptional 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

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

2009-10-21

340

Combined modalities of resistance in an oxaliplatin-resistant human gastric cancer cell line with enhanced sensitivity to 5-fluorouracil  

PubMed Central

To identify mechanisms underlying oxaliplatin resistance, a subline of the human gastric adenocarcinoma TSGH cell line, S3, was made resistant to oxaliplatin by continuous selection against increasing drug concentrations. Compared with the parental TSGH cells, the S3 subline showed 58-fold resistance to oxaliplatin; it also displayed 11-, 2-, and 4.7-fold resistance to cis-diammine-dichloroplatinum (II) (CDDP), copper sulphate, and arsenic trioxide, respectively. Interestingly, S3 cells were fourfold more susceptible to 5-fluorouracil-induced cytotoxicity due to downregulation of thymidylate synthase. Despite elevated glutathione levels in S3 cells, there was no alteration of resistant phenotype to oxaliplatin or CDDP when cells were co-treated with glutathione-depleting agent, l-buthionine-(S,R)-sulphoximine. Cellular CDDP and oxaliplatin accumulation was decreased in S3 cells. In addition, amounts of oxaliplatin- and CDDP–DNA adducts in S3 cells were about 15 and 40% of those seen with TSGH cells, respectively. Western blot analysis showed increased the expression level of copper transporter ATP7A in S3 cells compared with TSGH cells. Partial reversal of the resistance of S3 cells to oxaliplatin and CDDP was observed by treating cell with ATP7A-targeted siRNA oligonucleotides or P-type ATPase-inhibitor sodium orthovanadate. Besides, host reactivation assay revealed enhanced repair of oxaliplatin- or CDDP-damaged DNA in S3 cells compared with TSGH cells. Together, our results show that the mechanism responsible for oxaliplatin and CDDP resistance in S3 cells is the combination of increased DNA repair and overexpression of ATP7A. Downregulation of thymidylate synthase in S3 cells renders them more susceptible to 5-fluorouracil-induced cytotoxicity. These findings could pave ways for future efforts to overcome oxaliplatin resistance.

Chen, C-C; Chen, L-T; Tsou, T-C; Pan, W-Y; Kuo, C-C; Liu, J-F; Yeh, S-C; Tsai, F-Y; Hsieh, H-P; Chang, J-Y

2007-01-01

341

Contrasted effects of the multitarget TKi vandetanib on docetaxel-sensitive and docetaxel-resistant prostate cancer cell lines.  

PubMed

OBJECTIVES: Overexpression of epidermal growth factor receptor (EGFR) and angiogenic factors is associated with the progression of androgen-independent prostate cancer (AIPC). We examined the effects of vandetanib, an inhibitor of vascular endothelial growth factor (VEGFR), EGFR, and rearranged during transfection (RET) tyrosine-kinase activities, alone or combined with docetaxel, on PC3 docetaxel-sensitive (PC3wt) or docetaxel-resistant (PC3R) AIPC cell growth in vivo and in vitro. METHODS: Mice bearing PC3wt or PC3R tumors were treated for 3 weeks with vandetanib (25 or 50 mg/kg/d p.o., 5 d/wk), docetaxel (10 or 30 mg/kg i.p., 1 d/wk), or their combination (low or high doses). Xenograft tumors were analyzed for expression of Ki-67, EGFR, VEGFR2, and production of VEGFA. RESULTS: On PC3wt, vandetanib at both doses stimulated tumor growth, whereas docetaxel at both doses exerted strong growth-inhibiting effects. The low-dose vandetanib-docetaxel combination resulted in tumor growth similar to that of control, whereas the high-dose combination induced a significant antiproliferative effect. In contrast, on PC3R, the low-dose of vandetanib had no effect on tumor growth, whereas the high-dose of vandetanib significantly inhibited tumor growth. Docetaxel at both doses exerted moderate and transient antitumor effects. The combination of high-dose vandetanib with high-dose docetaxel resulted in antiproliferative effects, which were lower than expected from the sum of individual drug effects. Importantly, tumor analyses revealed overexpression of the EGFR/VEGFR pathways in PC3R relative to PC3wt. CONCLUSION: Present results suggest that vandetanib should not be associated with docetaxel in treatment-naive or docetaxel-resistant prostate cancer (CaP). The use of high-dose vandetanib alone may warrant further investigation in patients with docetaxel-resistant AIPC overexpressing VEGFR/EGFR pathways. PMID:22608542

Guérin, Olivier; Etienne-Grimaldi, Marie-Christine; Monteverde, Martino; Sudaka, Anne; Brunstein, Marie-Christine; Formento, Patricia; Lattanzio, Laura; Maffi, Monica; Tonissi, Federica; Ortholan, Cécile; Pagès, Gilles; Fischel, Jean-Louis; Lo Nigro, Cristiana; Merlano, Marco; Milano, Gérard

2012-05-17

342

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

SciTech Connect

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

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

2005-09-01

343

Activity- and schedule-dependent interactions of paclitaxel, etoposide and hydroperoxy-ifosfamide in cisplatin-sensitive and -refractory human ovarian carcinoma cell lines.  

PubMed

Paclitaxel has demonstrated broad clinical activity in a variety of malignancies both alone and in combination with other chemotherapeutic agents. The in vitro cytotoxicity of a 2 h exposure to paclitaxel, hydroperoxy-ifosfamide and etoposide alone, in combination and in sequence, was evaluated against established cisplatin-sensitive and cisplatin-refractory human ovarian carcinoma cell lines using isobologram analysis. The combinations of either paclitaxel-hydroperoxy-ifosfamide or paclitaxel-etoposide were found to be additive or synergistic when the drugs were given simultaneously or when paclitaxel was given 24 h before hydroperoxy-ifosfamide or etoposide respectively. However, when etoposide or hydroperoxy-ifosfamide were given before paclitaxel, antagonistic interactions were observed. With regard to etoposide this antagonism was evident for up to 24 h. In agreement with our data with the schedule-dependent interactions of paclitaxel and cisplatin in human gastric and ovarian carcinoma cell lines, these data demonstrate that the interactions of paclitaxel, etoposide and hydroperoxy-ifosfamide are also highly schedule dependent and applications of etoposide or ifosfamide before paclitaxel may result in pronounced antagonism. These findings could have implications for the design of further clinical protocols. PMID:8688325

Klaassen, U; Harstrick, A; Schleucher, N; Vanhoefer, U; Schröder, J; Wilke, H; Seeber, S

1996-07-01

344

Activity- and schedule-dependent interactions of paclitaxel, etoposide and hydroperoxy-ifosfamide in cisplatin-sensitive and -refractory human ovarian carcinoma cell lines.  

PubMed Central

Paclitaxel has demonstrated broad clinical activity in a variety of malignancies both alone and in combination with other chemotherapeutic agents. The in vitro cytotoxicity of a 2 h exposure to paclitaxel, hydroperoxy-ifosfamide and etoposide alone, in combination and in sequence, was evaluated against established cisplatin-sensitive and cisplatin-refractory human ovarian carcinoma cell lines using isobologram analysis. The combinations of either paclitaxel-hydroperoxy-ifosfamide or paclitaxel-etoposide were found to be additive or synergistic when the drugs were given simultaneously or when paclitaxel was given 24 h before hydroperoxy-ifosfamide or etoposide respectively. However, when etoposide or hydroperoxy-ifosfamide were given before paclitaxel, antagonistic interactions were observed. With regard to etoposide this antagonism was evident for up to 24 h. In agreement with our data with the schedule-dependent interactions of paclitaxel and cisplatin in human gastric and ovarian carcinoma cell lines, these data demonstrate that the interactions of paclitaxel, etoposide and hydroperoxy-ifosfamide are also highly schedule dependent and applications of etoposide or ifosfamide before paclitaxel may result in pronounced antagonism. These findings could have implications for the design of further clinical protocols.

Klaassen, U.; Harstrick, A.; Schleucher, N.; Vanhoefer, U.; Schroder, J.; Wilke, H.; Seeber, S.

1996-01-01

345

Synthesis and biological evaluation of novel pyrido[2,3-b]pyrazines inhibiting both erlotinib-sensitive and erlotinib-resistant cell lines.  

PubMed

A series of novel pyrido[2,3-b]pyrazines were synthesized as potential antitumor agents for erlotinib-resistant tumors. Known signal inhibitor compounds from our Nested Chemical Library were tested in phenotypic assays on erlotinib-sensitive PC9 and erlotinib-resistant PC9-ER cell lines to find a compound class to be active on erlotinib resistant cell lines. Based on the screening data, novel pyrido[2,3-b]pyrazines were designed and synthesized. The effect of the substituent position of the heteroaromatic moiety in position 7 and the importance of unsubstituted position 2 of the pyridopyrazine core were explored. Compound 7n had an IC50 value of 0.09?M for the inhibition of PC9 and 0.15?M for the inhibition of PC9-ER. We found that some lead compounds of these structures overcome erlotinib-resistance which might become promising drug candidates to fight against NSCLC with EGFR T790M mutation. The signaling network(s) involved in the mechanism(s) of action of these novel compounds in overcoming erlotinib resistance remain to be elucidated. PMID:24095095

Kékesi, László; Sipos, Anna; Németh, Gábor; Pató, János; Breza, Nóra; Baska, Ferenc; Orfi, László; Kéri, György

2013-09-08

346

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

SciTech Connect

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.

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

1987-12-01

347

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

PubMed Central

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.

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

2012-01-01

348

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

PubMed

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

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

2012-01-01

349

Decreased DNA topoisomerase II alpha expression and cold-sensitive growth in a mouse mammary cancer cell line resistant to etoposide and doxorubicin.  

PubMed

A mouse mammary carcinoma FM3A cell line resistant to the DNA topoisomerase (topo) II-targeting agent, etoposide (VP-16), FM3A/VP-2B, had a markedly reduced growth rate at a low temperature (33 degrees C). The cells had the following properties: (a) FM3A/VP-2B, which had 24-fold higher resistance to VP-16 than its parental line, FM3A, was cross-resistant to doxorubicin, but not to a camptothecin derivative, CPT-11. (b) Cold-resistant revertants from FM3A/VP-2B, R-6 and R-11, remained 8- to 9-fold more resistant to VP-16 and 2- to 3-fold more resistant to doxorubicin. (c) FM3A/VP-2B had one-fourth the level of topo II activity and one-third of the topo II alpha content and mRNA of FM3A. R-6 and R-11, however, had levels similar to FM3A. (d) FM3A/VP-2B and FM3A had a 3-base deletion at position 4170 on one allele on the topo II alpha cDNA, but expression of the wild-type and the deletion allele was not appreciably changed in both cell lines. Decreased topo II alpha expression might have led to the acquisition of drug resistance to etoposide in FM3A/VP-2B, and appeared to be linked with the cold-sensitive growth. We also present a corrected mouse topo II alpha cDNA sequence. PMID:8884812

Kawanami, K; Nakamura, T; Ono, M; Kusano, T; Okada, K; Kikuchi, A; Adachi, N; Kohno, K; Higashi, K; Kuwano, M

1996-01-01

350

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

PubMed

Preservatives are important components in many products, but have a history of purported allergy. Several assays [e.g., guinea pig maximization test (GPMT), local lymph node assay (LLNA)] are used to evaluate allergy potential of preservatives. We recently developed the human Cell Line Activation Test (h-CLAT), an in vitro skin sensitization test using human THP-1 cells. This test evaluates the augmentation of CD86 and CD54 expression, which are key events in the sensitization process, as an indicator of allergy following treatment with test chemical. Earlier, we found that a sub-toxic concentration was needed for the up-regulation of surface marker expression. In this study, we further evaluate the capability of h-CLAT to predict allergy potential using eight preservatives. Cytotoxicity was determined using propidium iodide with flow cytometry analysis and five doses that produce a 95, 85, 75, 65, and 50% cell viability were selected. If a material did not have any cytotoxicity at the highest technical dose (HTD), five doses are set using serial 1.3 dilutions of the HTD. The test materials used were six known allergic preservatives (e.g., methylchloroisothiazolinone/methylisothiazolinone, formaldehyde), and two non-allergic preservatives (methylparaben and 4-hydroxybenzoic acid). All allergic preservatives augmented CD86 and/or CD54 expression, indicating h-CLAT correctly identified the allergens. No augmentation was observed with the non-allergic preservatives; also correctly identified by h-CLAT. In addition, we report two threshold concentrations that may be used to categorize skin sensitization potency like the LLNA estimated concentration that yield a three-fold stimulation (EC3) value. These corresponding values are the estimated concentration which gives a relative fluorescence intensity (RFI) = 150 for CD86 and an RFI = 200 for CD54. These data suggest that h-CLAT, using THP-1 cells, may be able to predict the allergy potential of preservatives and possibility classify the potency of an allergen. PMID:17119987

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

2006-11-21

351

Genetic variants in urinary bladder cancer: collective power of the "wimp SNPs".  

PubMed

In recent years, genome-wide association studies (GWAS) have identified more than 300 validated associations between genetic variants and risk of approximately 70 common diseases. A small number of rare variants with a frequency of usually less than 1% are associated with a strongly enhanced risk, such as genetic variants of TP53, RB1, BRCA1, and BRCA2. Only a very small number of SNPs (with a frequency of more that 1% of the rare allele) have effects of a factor of two or higher. Examples include APOE4 in Alzheimer's disease, LOXL1 in exfoliative glaucoma, and CFH in age-related macular degeneration. However, the majority of all identified SNPs have odds ratios between 1.1 and 1.5. In the case of urinary bladder cancer, all known SNPs that have been validated in sufficiently large populations are associated with odds ratios smaller than 1.5. These SNPs are located next to the following genes: MYC, TP63, PSCA, the TERT-CLPTM1L locus, FGFR3, TACC3, NAT2, CBX6, APOBEC3A, CCNE1, and UGT1A. It is likely that these moderate risk or "wimp SNPs" interact, and because of their high number, collectively have a strong influence on whether an individual will develop cancer or not. It should be considered that variants identified so far explain only approximately 5-10% of the overall inherited risk. Possibly, the remaining variance is due to an even higher number of SNPs with odds ratios smaller than 1.1. Recent studies have provided the following information: (1) The functions of genes identified as relevant for bladder cancer focus on detoxification of carcinogens, control of the cell cycle and apoptosis, as well as maintenance of DNA integrity. (2) Many novel SNPs are far away from the protein coding regions, suggesting that these SNPs are located on distant-acting transcriptional enhancers. (3) The low odds ratio of each individual bladder cancer-associated SNP is too low to justify reasonable preventive measures. However, if the recently identified SNPs interact, they may collectively result in a substantial risk that is of preventive relevance. In addition to the "novel SNPs" identified by the recent GWAS, at least 163 further variants have been reported in relation to bladder cancer, although they have not been consistently validated in independent case-control series. Moreover, given that only 60 of these 163 "old SNPs" are covered by the SNP chips used in the recent GWAS, there are in principle 103 published variants still awaiting validation or disproval. In future, besides identifying novel disease-associated rare variants by deep sequencing, it will also be important to understand how the already identified variants interact. PMID:21380501

Golka, Klaus; Selinski, Silvia; Lehmann, Marie-Louise; Blaszkewicz, Meinolf; Marchan, Rosemarie; Ickstadt, Katja; Schwender, Holger; Bolt, Hermann M; Hengstler, Jan G

2011-03-05

352

Leucovorin and fluorouracil plus oxaliplatin or leucovorin and fluorouracil plus irinotecan as individualized first-line therapy based on a drug sensitivity test  

PubMed Central

The purpose of this study was to determine the effect of the addition of oxaliplatin (l-OHP) or irinotecan (SN-38) to 5-fluorouracil (5-FU) using the collagen gel droplet embedded culture-drug sensitivity test (CD-DST) to establish whether leucovorin plus 5-FU should be administered in combination with l-OHP (FOLFOX) or SN-38 (FOLFIRI) in individualized first-line chemotherapy for the treatment of advanced colorectal cancer (CRC). Specimens of primary tumors were obtained from 24 CRC patients who had received no preoperative chemotherapy. CD-DST was performed, and the inhibition rate (IR) was obtained under multiple incubation conditions. The effects of addition of l-OHP or SN-38 were evaluated for the same area under the concentration curve (AUC) of 5-FU based on linear regression analysis. Approximate expression and correlation coefficients (5-FU vs. 5-FU + l-OHP, 5-FU vs. 5-FU + SN-38; AUC of 5-FU=72 and 5-FU vs. 5-FU + l-OHP, 5-FU vs. 5-FU + SN-38; AUC of 5-FU=144) were y=0.94x+8.53 (R2=0.95, p<0.0004), y=0.77x+26.18 (R2=0.76, p<0.0004) and y= 0.91x+10.90 (R2=0.94, p<0.0004), y=0.52x+44.61 (R2=0.60, p<0.0004), respectively. Approximate expression of 5-FU vs. 5-FU + l-OHP almost fit the regression line (y=x+b1). This suggests that addition of l-OHP yields a constant additive effect, independent of the IR of 5-FU. However, approximate expression of 5-FU vs. 5-FU + SN-38 fit the regression line (y=ax+b2, a<1, b2?b1). This suggests that addition of SN-38 yields a greater additive effect due to the lower IR of 5-FU. These results indicate that FOLFIRI should be selected as the first-line chemotherapy for the treatment of poor responders to 5-FU.

OCHIAI, TAKUMI; NISHIMURA, KAZUHIKO; WATANABE, TOMOO; KITAJIMA, MASAYUKI; HASHIGUCHI, TADASUKE; NAKATANI, AKINORI; MARUSASA, TAKASHI; MURAKI, AKIRA; NAGAOKA, ISAO; FUTAGAWA, SHUNJI

2010-01-01

353

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

NASA Astrophysics Data System (ADS)

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.

Falkowski, Adam; No, Jose M.

2013-02-01

354

Non-perturbative QCD effects in eta_b decays into baryons and WIMP scattering off nuclei  

NASA Astrophysics Data System (ADS)

In this work we estimate the helicity suppressed decay rates of $\\eta_b$ resonances into baryon pairs due to instanton-induced effects by rescaling the corresponding partial widths of the experimentally measured branching ratios for the $\\eta_c(1S) \\to p\\bar{p}$ and $\\eta_c(1S) \\to \\Lambda\\bar(\\Lambda)$ decay modes. Thus we point out that both $\\eta_b(1S) \\to p\\bar{p}$ and $\\eta_b(1S) \\to \\Lambda\\bar(\\Lambda)$ channels could be detected at a Super B factory and LHC experiments. Furthermore, we examine related instanton-induced effects on WIMP scattering off nuclei concluding, albeit with large uncertainties, that they might enhance the spin-dependent cross section for a light pseudoscalar Higgs boson mediator, thereby inducing a dependence on the momentum transfer to the recoling nucleus.

Sanchis-Lozano, M.

355

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

PubMed Central

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

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

2005-01-01

356

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

PubMed Central

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

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

2011-01-01

357

Resting Glutamate Levels and Rapid Glutamate Transients in the Prefrontal Cortex of the Flinders Sensitive Line Rat: A Genetic Rodent Model of Depression  

PubMed Central

Despite the numerous drugs targeting biogenic amines for major depressive disorder (depression), the search for novel therapeutics continues because of their poor response rates (?30%) and slow onset of action (2–4 weeks). To better understand role of glutamate in depression, we used an enzyme-based microelectrode array (MEA) that was selective for glutamate measures with fast temporal (2?Hz) and high spatial (15 × 333??m) resolution. These MEAs were chronically implanted into the prefrontal cortex of 3- to 6-month-old and 12- to 15-month-old Flinders Sensitive Line (FSL) and control Flinders Resistant Line (FRL) rats, a validated genetic rodent model of depression. Although no changes in glutamate dynamics were observed between 3 and 6 months FRL and FSL rats, a significant increase in resting glutamate levels was observed in the 12- to 15-month-old FSL rats compared with the 3- to 6-month-old FSL and age-matched FRL rats on days 3–5 post-implantation. Our MEA also recorded, for the first time, a unique phenomenon in all the four rat groups of fluctuations in resting glutamate, which we have termed glutamate transients. Although these events lasted only for seconds, they did occur throughout the testing paradigm. The average concentration of these glutamate-burst events was significantly increased in the 12- to 15-month-old FSL rats compared with 3- to 6-month-old FSL and age-matched FRL rats. These studies lay the foundation for future studies of both tonic and phasic glutamate signaling in rat models of depression to better understand the potential role of glutamate signaling in depression.

Hascup, Kevin N; Hascup, Erin R; Stephens, Michelle L; Glaser, Paul EA; Yoshitake, Takashi; Mathe, Aleksander A; Gerhardt, Greg A; Kehr, Jan

2011-01-01

358

Silencing of microRNA-21 confers radio-sensitivity through inhibition of the PI3K/AKT pathway and enhancing autophagy in malignant glioma cell lines.  

PubMed

Radiation is a core part of therapy for malignant glioma and is often provided following debulking surgery. However, resistance to radiation occurs in most patients, and the underlying molecular mechanisms of radio-resistance are not fully understood. Here, we demonstrated that microRNA 21 (miR-21), a well-known onco-microRNA in malignant glioma, is one of the major players in radio-resistance. Radio-resistance in different malignant glioma cell lines measured by cytotoxic cell survival assay was closely associated with miR-21 expression level. Blocking miR-21 with anti-miR-21 resulted in radio-sensitization of U373 and U87 cells, whereas overexpression of miR-21 lead to a decrease in radio-sensitivity of LN18 and LN428 cells. Anti-miR-21 sustained ?-H2AX DNA foci formation, which is an indicator of double-strand DNA damage, up to 24 hours and suppressed phospho-Akt (ser473) expression after exposure to ?-irradiation. In a cell cycle analysis, a significant increase in the G?/M phase transition by anti-miR-21 was observed at 48 hours after irradiation. Interestingly, our results showed that anti-miR-21 increased factors associated with autophagosome formation and autophagy activity, which was measured by acid vesicular organelles, LC3 protein expression, and the percentage of GFP-LC3 positive cells. Furthermore, augmented autophagy by anti-miR-21 resulted in an increase in the apoptotic population after irradiation. Our results show that miR-21 is a pivotal molecule for circumventing radiation-induced cell death in malignant glioma cells through the regulation of autophagy and provide a novel phenomenon for the acquisition of radio-resistance. PMID:23077620

Gwak, Ho-Shin; Kim, Tae Hoon; Jo, Guk Heui; Kim, Youn-Jae; Kwak, Hee-Jin; Kim, Jong Heon; Yin, Jinlong; Yoo, Heon; Lee, Seung Hoon; Park, Jong Bae

2012-10-15

359

Silencing of MicroRNA-21 Confers Radio-Sensitivity through Inhibition of the PI3K/AKT Pathway and Enhancing Autophagy in Malignant Glioma Cell Lines  

PubMed Central

Radiation is a core part of therapy for malignant glioma and is often provided following debulking surgery. However, resistance to radiation occurs in most patients, and the underlying molecular mechanisms of radio-resistance are not fully understood. Here, we demonstrated that microRNA 21 (miR-21), a well-known onco-microRNA in malignant glioma, is one of the major players in radio-resistance. Radio-resistance in different malignant glioma cell lines measured by cytotoxic cell survival assay was closely associated with miR-21 expression level. Blocking miR-21 with anti-miR-21 resulted in radio-sensitization of U373 and U87 cells, whereas overexpression of miR-21 lead to a decrease in radio-sensitivity of LN18 and LN428 cells. Anti-miR-21 sustained ?-H2AX DNA foci formation, which is an indicator of double-strand DNA damage, up to 24 hours and suppressed phospho-Akt (ser473) expression after exposure to ?-irradiation. In a cell cycle analysis, a significant increase in the G2/M phase transition by anti-miR-21 was observed at 48 hours after irradiation. Interestingly, our results showed that anti-miR-21 increased factors associated with autophagosome formation and autophagy activity, which was measured by acid vesicular organelles, LC3 protein expression, and the percentage of GFP-LC3 positive cells. Furthermore, augmented autophagy by anti-miR-21 resulted in an increase in the apoptotic population after irradiation. Our results show that miR-21 is a pivotal molecule for circumventing radiation-induced cell death in malignant glioma cells through the regulation of autophagy and provide a novel phenomenon for the acquisition of radio-resistance.

Jo, Guk Heui; Kim, Youn-Jae; Kwak, Hee-Jin; Kim, Jong Heon; Yin, Jinlong; Yoo, Heon; Lee, Seung Hoon; Park, Jong Bae

2012-01-01

360

Two active copies of the X-linked gene spermidine/spermine N1-acetyltransferase (SSAT) in a female lung cancer cell line are associated with an increase in sensitivity to an antitumor polyamine analogue.  

PubMed

The expression of the polyamine catabolic enzyme, spermidine/spermine N1-acetyltransferase (SSAT), has been associated with tumor sensitivity to antitumor polyamine analogues. In the sensitive cell types the level of SSAT is greatly induced by these agents. Although SSAT expression is regulated at many levels, the initial regulation of this X-linked gene occurs at the level of transcription. Because most previous work in human cell lines has been performed in cells of male origin and because the SSAT gene is located near the pseudoautosomal region of the X chromosome, we investigated the possibility that both copies of SSAT could be expressed in normal and tumor cells in women. DNA methyl-sensitive restriction enzyme analysis of DNA from normal peripheral lymphocytes suggested that like most X-linked genes, only one copy of SSAT is actively transcribed. However, in an examination of four representative human lung tumor cell lines derived from women, two were found to have a methylation pattern identical to male-derived cells, suggesting a reactivation of the normally inactive allele or loss of the inactive allele. Microsatellite repeat polymorphism analysis indicated that one of the lines, a female carcinoid line, NCI H727, had reactivated the previously inactive copy, thus providing H727 with two active alleles, whereas a small cell lung cancer line, H889, appears to have lost the inactive allele. Most importantly, the H727 line expressed high amounts of SSAT mRNA and protein in response to treatment with the polyamine analogue, N1,N12-bis(ethyl)spermine, a compound known to increase SSAT transcription in sensitive cell types. H727 was also the only female line that responded to treatment in a cytotoxic manner. These data suggest that both copies of the SSAT allele may be expressed and that the inappropriate expression of the second copy can lead to an increase in tumor sensitivity to polyamine analogues that induce SSAT. PMID:9717831

Mank-Seymour, A R; Murray, T R; Berkey, K A; Xiao, L; Kern, S; Casero, R A

1998-08-01

361

Differential effects of all-trans-retinoic acid, docosahexaenoic acid, and hexadecylphosphocholine on cisplatin-induced cytotoxicity and apoptosis in a cisplantin-sensitive and resistant human embryonal carcinoma cell line  

Microsoft Academic Search

Apart from modulation of tumor-cell drug sensitivity, induction of differentiation might be an alternative in the treatment\\u000a of tumors resistant to cytotoxic drugs. In this report the capacity to induce differentiation and to modulate the cis-diamminedichloroplatinum(II)\\u000a (CDDP) sensitivity of all-trans-retinoic acid (RA), docosahexaenoic acid (DCHA), and hexadecylphosphocholine (HePC) is examined in human germ-cell tumor cell\\u000a lines. In the embryonal carcinoma

Hetty Timmer-Bosscha; Elisabeth G. E. de Vries; C. Meijer; J. Wolter Oosterhuis; Nanno H. Mulder

1998-01-01

362

miR-181a sensitizes a multidrug-resistant leukemia cell line K562/A02 to daunorubicin by targeting BCL-2.  

PubMed

The aim of this study was to investigate whether miR-181a could modulate the sensitivity of the leukemia drug-resistant cell line K562/A02 to the chemotherapeutic agent daunorubicin (DNR), and explore the mechanism of miR-181a on the DNR sensitivity of K562/A02 cells. MicroRNA microarray and stem-loop reverse transcription-polymerase chain reaction were used to detect the expression of miR-181a. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay was performed to quantify the effect of miR-181a on K562 cells growth and viability. Apoptotic cells were quantitatively detected using Annexin V/FITC and PI apoptosis detection kit. BCL-2 protein expression was measured by western blot. Luciferase reporter vector with the putative BCL-2 3' untranslated region was constructed to explore whether BCL-2 was a direct target gene of miR-181a. BCL-2 siRNA was transfected into the cell to explore the relationship between BCL-2 and DNR resistance. The miR-181a expression level was lower in the K562/A02 cells than in the K562 cells (P< 0.05). K562 cells that were transfected with miR-181a inhibitor had a significantly higher survival than K562 cells, and K562/A02 cells that were transfected with the miR-181a mimic had a significantly lower survival than K562/A02 cells (P< 0.05). miR-181a could enhance DNR-induced apoptosis in K562/A02 cells. BCL-2 siRNA transfected K562/A02 cells had decreased survival compared with the K562/A02 control group. In conclusion, miR-181a could play a role in the development of DNR resistance in K562/A02 cells and the over-expression of miR-181a could sensitize K562/A02 cells to DNR by targeting BCL-2. PMID:22285729

Li, Hao; Hui, Lulu; Xu, Wenlin

2012-01-26

363

Enhanced sensitivity of small cell lung cancer cell lines to cisplatin and etoposide after infection with adeno-associated virus type 2.  

PubMed

In previous studies we have reported the sensitisation of human tumour cells to gamma irradiation and chemotherapeutic drugs upon infection with the human non-pathogenic adeno-associated virus type 2 (AAV-2) in vitro and in vivo. Treatment of small cell lung cancer (SCLC) is consistently hampered by relapses due to the selection of chemotherapy-resistant cell clones. Hence, we were interested to test whether selection of chemotherapy-resistant SCLC cells might be reduced or even prevented if chemotherapy is applied in combination with AAV-2 infection. In vitro proliferation assays indicated that the number of proliferating cells, after combined treatment with cisplatin and etoposide, can be significantly reduced by concomitant AAV-2 infection, as compared with treated but non-infected controls. H446 SCLC cells, which show resistance to etoposide/cisplatin chemotherapy (compared with a cell line which was never chemotherapeutically treated before, like NCI-H209) were significantly more sensitive after AAV-2 infection, suggesting that the therapeutic efficacy of chemotherapy in SCLC can be enhanced even if the cells are already relatively resistant to chemotherapy. Similarly, in vivo growth of tumours induced by inoculation of SCLC cells into immunocompromised nude mice was reduced more efficiently in AAV-2-infected animals compared with tumours in mice treated with chemotherapeutic drugs alone. These data extend and further support our previous reports on AAV functions which might be useful in improving the efficacy of chemotherapeutic drugs used in human cancer treatment. PMID:10211097

Hillgenberg, M; Schlehofer, J R; von Knebel Doeberitz, M; Klein-Bauernschmitt, P

1999-01-01

364

Curcumin induces cell death and restores tamoxifen sensitivity in the antiestrogen-resistant breast cancer cell lines MCF-7/LCC2 and MCF-7/LCC9.  

PubMed

Curcumin, a principal component of turmeric (Curcuma longa), has potential therapeutic activities against breast cancer through multiple signaling pathways. Increasing evidence indicates that curcumin reverses chemo-resistance and sensitizes cancer cells to chemotherapy and targeted therapy in breast cancer. To date, few studies have explored its potential antiproliferation effects and resistance reversal in antiestrogen-resistant breast cancer. In this study, we therefore investigated the efficacy of curcumin alone and in combination with tamoxifen in the established antiestrogen-resistant breast cancer cell lines MCF-7/LCC2 and MCF-7/LCC9. We discovered that curcumin treatment displayed anti-proliferative and pro-apoptotic activities and induced cell cycle arrest at G2/M phase. Of note, the combination of curcumin and tamoxifen resulted in a synergistic survival inhibition in MCF-7/LCC2 and MCF-7/LCC9 cells. Moreover, we found that curcumin targeted multiple signals involved in growth maintenance and resistance acquisition in endocrine resistant cells. In our cell models, curcumin could suppress expression of pro-growth and anti-apoptosis molecules, induce inactivation of NF-?B, Src and Akt/mTOR pathways and downregulate the key epigenetic modifier EZH2. The above findings suggested that curcumin alone and combinations of curcumin with endocrine therapy may be of therapeutic benefit for endocrine-resistant breast cancer. PMID:23299550

Jiang, Min; Huang, Ou; Zhang, Xi; Xie, Zuoquan; Shen, Aijun; Liu, Hongchun; Geng, Meiyu; Shen, Kunwei

2013-01-08

365

Development of a sensitive and selective LC-MS/MS method for the determination of urea in human epithelial lining fluid.  

PubMed

A sensitive, selective, and quantitative method for the determination of urea has been developed and validated in human epithelial lining fluid (ELF; the supernatant from bronchoalveolar lavage). The method employs a simple derivatization of urea with camphanic chloride to improve the chromatographic retention and separation. The derivatization was performed after drying an aliquot of ELF (20?L) without prior sample clean-up. Ultra High Performance Liquid Chromatography (UHPLC) on a HSS-T3 stationary phase column with 1.8?m particle size was used for chromatographic separation coupled to tandem mass spectrometry. The method was validated over the concentration range of 8.78-103.78?g/mL, however the dynamic range can be further lowered if needed. The results from assay validation show that the method is rugged, precise, accurate, and well-suited to support analysis of urea in ELF samples. In addition, the relatively small sample volume (20?L) and a run time of 1.5min facilitate automation and allow for high-throughput analysis. This derivatization method was compared to a commercially available colorimetric assay kit, and it was used in a preclinical non-GLP mouse study where urea measurements were used as marker of bronchoalveolar lavage fluid dilution. PMID:23353811

Bowen, Chester L; Licea-Perez, Hermes

2013-01-09

366

[Alteration of protein and amino acid components and Rubisco activity in leaves of thermo-sensitive mutant line of rice during induced of green and yellow banding].  

PubMed

We have determined the Rubisco components and activity, whole leaf protein and amino acid components of thermo-sensitive mutant line 1103s of rice (Oryza sativa ssp. indica) leaves during induces green and yellow banding in this study. The results are as follows: The structure and components of Rubisco in the mutant are the same as in the wild form and relatively stable, but the activity of the mutant Rubisco greatly changes as a special protein of molecular weight 56.2 kD (PI=4.5) appears and disappears. When the green-yellow bands appear, the special protein disappears, and the activity of the mutant-rice Rubisco decreases, whereas when the green-yellow bands in the same part of the leaves disappear, the special protein appears and the activity of Rubisco is increase. The above shows the changes of the activity of the mutant-rice Rubisco during photosynthesis are closely related to the special protein in the leaves and its structure and components, and possibly to the regulating protein of Rubisco. The protein particularly regulates metabolic processes of amino acids preventing regulation of the preceding amino acids, such that the formation of the structural material in chloroplast is prevented, and finally the chloroplast thylakoid structure degenerates. PMID:15323419

Shao, Ji Rong; Zhu, Xue Mei; Xie, Rong; Ren, Zheng Long; Sun, Jing San

2004-06-01

367

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

Microsoft Academic Search

The in vitro response to radiation and chemotherapeutic drugs of cell lines established from 7 patients with small cell (SC) lung cancer were tested using a soft agarose clonogenic assay. Five cell lines retained the typical morphological and biochemical amine precursor uptake decarboxylation characteristics of SC, while two cell lines had undergone ''transformation'' to large cell (LC) morphological variants with

Desmond N. Carney; James B. Mitchell; T. J. Kinsella

1983-01-01

368

Characterization of galanin receptors in the insulin-secreting cell line Rin m 5F: evidence for coupling with a pertussis toxin-sensitive guanosine triphosphate regulatory protein.  

PubMed

The present work characterizes galanin receptors in the insulin-secreting pancreatic beta-cell line Rin m 5F and documents their regulation by guanine nucleotides. Binding of [125I]galanin to cell membranes was found to be temperature dependent, rapid, saturable, reversible, and highly peptide specific. Optimal steady state conditions were achieved after a 60-min incubation at 15 C. The concentration dependence of galanin binding determined by adding increasing concentrations of [125I]galanin indicated that galanin receptors were saturated at 2-3 nM peptide. Scatchard analysis revealed a single class of receptors, with a Kd of 0.3 nM and a binding capacity of 82 fmol/mg protein. Guanyl 5'-yl imidodiphosphate dramatically enhanced the dissociation of bound [125I]galanin. Some guanine nucleotides inhibited [125I]galanin binding to membranes with the following order of potency: guanyl 5'-yl imidodiphosphate greater than GTP = GDP. Other nucleotides had no effect. The effect of the guanine nucleotides was Mg2+ dependent, but Na+ independent, although Mg2+ ions alone (5 mM) slightly enhanced [125I]galanin binding, and Na+ ions alone (100 mM) induced a 60% decrease in the binding. Finally, overnight treatment of Rin m 5F cells with pertussis toxin (0.4 microgram/ml) dramatically reduced [125I]galanin binding to cell membranes. This was related to a 4-fold decrease in receptor affinity, with no change in binding capacity. In conclusion, for the first time evidence of the existence of galanin receptors on functional pancreatic beta-cells is presented. Also, other findings support the fact that galanin receptors are functionally associated with a pertussis toxin-sensitive GTP-binding protein mediating guanine nucleotide control of galanin binding. PMID:2468476

Lagny-Pourmir, I; Amiranoff, B; Lorinet, A M; Tatemoto, K; Laburthe, M

1989-05-01

369

A high-fat diet exacerbates depressive-like behavior in the Flinders Sensitive Line (FSL) rat, a genetic model of depression.  

PubMed

Major depressive disorder (MDD) and diabetes mellitus type II (T2DM) are two of the major health challenges of our time. It has been shown that MDD and T2DM are highly co-morbid, and recent work has proposed a bi-directional connection between the diseases. The aim of the current study was to investigate the effect of a high-fat diet (HFD) on behavior and metabolism in a genetic rat model of depression, the Flinders Sensitive and Resistant Line (FSL/FRL) rats. Age and weight matched rats were fed a HFD or control diet for 10 weeks and subjected to behavioral testing and metabolic assessment. We found that HFD exacerbated the depressive-like behavior of the FSL rat in the Forced Swim Test (FST), a depression screening tool, although it did not affect the non-depressed FRL rat despite a higher caloric intake. Moreover, the depressive-like phenotype was associated with reduced anxiety and impairment in novel object recognition memory, while HFD consumption led to diminished object recognition memory as well. In both strains HFD increased insulin levels during an oral glucose tolerance test, although fasting blood glucose levels were only significantly increased by HFD in the FSL rat, suggesting a greater metabolic susceptibility in this rat strain. We conclude that compared with the FRL rat, the FSL rat is more susceptible to developing aberrant behaviors related to depression following metabolic stress induced by HFD. Further studies with a mechanistic focus could potentially lead to a better understanding of a possible pathophysiological link between T2DM and MDD. PMID:20888697

Abildgaard, Anders; Solskov, Lasse; Volke, Vallo; Harvey, Brian H; Lund, Sten; Wegener, Gregers

2010-10-02

370

Gene-specific repair of Pt/DNA lesions and induction of apoptosis by the oral platinum drug JM216 in three human ovarian carcinoma cell lines sensitive and resistant to cisplatin  

PubMed Central

JM216, an oral platinum drug entering into phase III clinical trial, exhibited comparable cytotoxicity to cisplatin in three human ovarian carcinoma cell lines: the sensitive (CH1), acquired resistant (CH1cisR) and intrinsically resistant (SKOV-3). Platinum accumulation and binding to DNA were similar in each of the three cell lines at equimolar doses, indicating that the resistant cell lines could tolerate higher intracellular platinum levels and platinum bound to DNA at IC50 concentrations of drug. Comparison with cisplatin demonstrated that intracellular platinum levels were marginally higher with JM216, but that platinum binding to DNA was similar for the two drugs in each of the cell lines. Each of the cell lines exhibited an ability to repair JM216 induced platinum/DNA lesions in the N-ras gene (gene-specific repair) at equitoxic concentrations of drug. However, this occurred to a greater extent in the two resistant cell lines such that by 24 h the CH1cisR and SKOV-3 had removed 72% and 67% respectively compared with approximately 32% for the CH1. Reduced gene-specific repair capacity in CH1 cells was also seen following incubation with 25 ?M (or 5 ?M – 2 × IC50) cisplatin, whereas the CH1cisR and SKOV-3 cell lines were repair proficient. JM216 induced apoptosis in the three cell lines following a 2h incubation with 2 × the IC50 of drug. Fluorescent microscopy of cells stained with propidium iodide showed that the detached cell population displayed typical apoptotic nuclei. Furthermore, field inversion gel electrophoresis demonstrated the presence of DNA fragments approximately 23–50 kb in size, indicative of apoptosis, in the detached cells. JM216 induced an S phase slow down in each of the three cell lines accompanied by a G2 block in the CH1 pair. Incubation with this concentration of JM216 also resulted in the induction of p53 in the CH1 and CH1cisR. These studies suggest that the relative sensitivity of the CH1 cell line to cisplatin and JM216 is at least partly attributable to a deficiency in gene-specific repair. The oral platinum drug, JM216, exerts its cytotoxic effects through the induction of apoptosis following a slow-down in S phase in both the sensitive and resistant lines. © 1999 Cancer Research Campaign

O'Neill, C F; Koberle, B; Masters, J R W; Kelland, L R

1999-01-01

371

Nitric oxide sensitizes prostate carcinoma cell lines to TRAIL-mediated apoptosis via inactivation of NF-?B and inhibition of Bcl-xL expression  

Microsoft Academic Search

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to be selective in the induction of apoptosis in cancer cells with minimal toxicity to normal tissues and this prompted its potential therapeutic application in cancer. However, not all cancers are sensitive to TRAIL-mediated apoptosis and, therefore, TRAIL-resistant cancer cells must be sensitized first to become sensitive to TRAIL. Treatment of

Sara Huerta-Yepez; Mario Vega; Ali Jazirehi; Hermes Garban; Fumiya Hongo; Genhong Cheng; Benjamin Bonavida

2004-01-01

372

Response to mTOR inhibition: activity of eIF4E predicts sensitivity in cell lines and acquired changes in eIF4E regulation in breast cancer  

PubMed Central

Background Inhibitors of the kinase mTOR, such as rapamycin and everolimus, have been used as cancer therapeutics with limited success since some tumours are resistant. Efforts to establish predictive markers to allow selection of patients with tumours likely to respond have centred on determining phosphorylation states of mTOR or its targets 4E-BP1 and S6K in cancer cells. In an alternative approach we estimated eIF4E activity, a key effector of mTOR function, and tested the hypothesis that eIF4E activity predicts sensitivity to mTOR inhibition in cell lines and in breast tumours. Results We found a greater than three fold difference in sensitivity of representative colon, lung and breast cell lines to rapamycin. Using an assay to quantify influences of eIF4E on the translational efficiency specified by structured 5'UTRs, we showed that this estimate of eIF4E activity was a significant predictor of rapamycin sensitivity, with higher eIF4E activities indicative of enhanced sensitivity. Surprisingly, non-transformed cell lines were not less sensitive to rapamycin and did not have lower eIF4E activities than cancer lines, suggesting the mTOR/4E-BP1/eIF4E axis is deregulated in these non-transformed cells. In the context of clinical breast cancers, we estimated eIF4E activity by analysing expression of eIF4E and its functional regulators within tumour cells and combining these scores to reflect inhibitory and activating influences on eIF4E. Estimates of eIF4E activity in cancer biopsies taken at diagnosis did not predict sensitivity to 11-14 days of pre-operative everolimus treatment, as assessed by change in tumour cell proliferation from diagnosis to surgical excision. However, higher pre-treatment eIF4E activity was significantly associated with dramatic post-treatment changes in expression of eIF4E and 4E-binding proteins, suggesting that eIF4E is further deregulated in these tumours in response to mTOR inhibition. Conclusions Estimates of eIF4E activity predict sensitivity to mTOR inhibition in cell lines but breast tumours with high estimated eIF4E activity gain changes in eIF4E regulation in order to enhance resistance.

2011-01-01

373

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

Microsoft Academic Search

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

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

2006-01-01

374

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  

Microsoft Academic Search

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

Dashou Wang; Charlotte Youngson; Veronica Wong; Herman Yeger; Mary C. Dinauer; Eleazar Vega-Saenz de Miera; Bernardo Rudy; Ernest Cutz

1996-01-01

375

Behavioral, Physiological, and Neuroendocrine Stress Responses and Differential Sensitivity to Diazepam in Two Wistar Rat Lines Selectively Bred for High and Low-Anxiety–Related Behavior  

Microsoft Academic Search

Two Wistar rat lines, selectively bred for high-anxiety–related behavior (HAB) and low-anxiety–related behavior (LAB) in the elevated plus-maze test, were tested for the susceptibility of their behavioral characteristics to anxiolytic treatment and for their endocrine and physiological reactivity to different stressors. Injection of 1mg\\/kg diazepam failed to affect line differences in coping strategy but resulted in a marked (20-fold) decrease

Gudrun Liebsch; Astrid CE Linthorst; Inga D Neumann; Johannes MHM Reul; Florian Holsboer; Rainer Landgraf

1998-01-01

376

The isolation of abscisic acid (ABA) deficient mutants by selection of induced revertants in non-germinating gibberellin sensitive lines of Arabidopsis thaliana (L.) heynh  

Microsoft Academic Search

By selecting for germinating seeds in the progeny of mutagen-treated non-germinating gibberellin responsive dwarf mutants of the ga-1 locus in Arabidopsis thaliana, germinating lines (revertants) could be isolated. About half of the revertants were homozygous recessive for a gene (aba), which probably regulates the presence of abscisic acid (ABA). Arguments for the function of this gene were obtained from lines

M. Koornneef; M. L. Jorna; D. L. C. Brinkhorst-van der Swan; C. M. Karssen

1982-01-01

377

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

Microsoft Academic Search

DNA methylation is known to play an important role in the regulation of gene expression in eukaryotes. In this study, we\\u000a assessed the extent and pattern of cytosine methylation in the rice genome, using the technique of methylation-sensitive amplified\\u000a polymorphism (MSAP), which is a modification of the amplified fragment length polymorphism (AFLP) method that makes use of\\u000a the differential sensitivity

L. Z. Xiong; C. G. Xu; M. A. Saghai Maroof; Qifa Zhang

1999-01-01

378

Case for a 700+GeV WIMP: Cosmic ray spectra from PAMELA, Fermi, and ATIC  

SciTech Connect

Multiple lines of evidence indicate an anomalous injection of high-energy e{sup +}e{sup -} in the galactic halo. The recent e{sup +} fraction spectrum from the payload for antimatter matter exploration and light-nuclei astrophysics (PAMELA) shows a sharp rise up to 100 GeV. The Fermi gamma-ray space telescope has found a significant hardening of the e{sup +}e{sup -} cosmic-ray spectrum above 100 GeV, with a break, confirmed by HESS at around 1 TeV. The advanced thin ionization calorimeter (ATIC) has also detected a similar excess, falling back to the expected spectrum at 1 TeV and above. Excess microwaves towards the galactic center in the WMAP data are consistent with hard synchrotron radiation from a population of 10-100 GeV e{sup +}e{sup -} (the WMAP 'Haze'). We argue that dark matter annihilations can provide a consistent explanation of all of these data, focusing on dominantly leptonic modes, either directly or through a new light boson. Normalizing the signal to the highest energy evidence (Fermi and HESS), we find that similar cross sections provide good fits to PAMELA and the Haze, and that both the required cross section and annihilation modes are achievable in models with Sommerfeld-enhanced annihilation. These models naturally predict significant production of gamma rays in the galactic center via a variety of mechanisms. Most notably, there is a robust inverse-Compton scattered (ICS) gamma-ray signal arising from the energetic electrons and positrons, detectable at Fermi/GLAST energies, which should provide smoking gun evidence for this production.

Cholis, Ilias; Goodenough, Lisa; Weiner, Neal [Center for Cosmology and Particle Physics, Department of Physics, New York University, New York, New York 10003 (United States); Dobler, Gregory; Finkbeiner, Douglas P. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, Massachusetts 02138 (United States)

2009-12-15

379

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

PubMed Central

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

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

1975-01-01

380

The local dark matter phase-space density and impact on WIMP direct detection  

NASA Astrophysics Data System (ADS)

We present a new determination of the local dark matter phase-space density. This result is obtained implementing, in the limit of isotropic velocity distribution and spherical symmetry, Eddington's inversion formula, which links univocally the dark matter distribution function to the density profile, and applying, within a Bayesian framework, a Markov Chain Monte Carlo algorithm to sample mass models for the Milky Way against a broad and variegated sample of dynamical constraints. We consider three possible choices for the dark matter density profile, namely the Einasto, NFW and Burkert profiles, finding that the velocity dispersion, which characterizes the width in the distribution, tends to be larger for the Burkert case, while the escape velocity depends very weakly on the profile, with the mean value we obtain being in very good agreement with estimates from stellar kinematics. The derived dark matter phase-space densities differ significantly — most dramatically in the high velocity tails — from the model usually taken as a reference in dark matter detection studies, a Maxwell-Boltzmann distribution with velocity dispersion fixed in terms of the local circular velocity and with a sharp truncation at a given value of the escape velocity. We discuss the impact of astrophysical uncertainties on dark matter scattering rates and direct detection exclusion limits, considering a few sample cases and showing that the most sensitive ones are those for light dark matter particles and for particles scattering inelastically. As a general trend, regardless of the assumed profile, when adopting a self-consistent phase-space density, we find that rates are larger, and hence exclusion limits stronger, than with the standard Maxwell-Boltzmann approximation. Tools for applying our result on the local dark matter phase-space density to other dark matter candidates or experimental setups are provided.

Catena, Riccardo; Ullio, Piero

2012-05-01

381

Effects of Serum and Insulin on the Sensitivity of the Human Breast Cancer Cell Line MCF7 to Estrogen and Antiestrogens1  

Microsoft Academic Search

The effect of the antiestrogens tamoxifen and nafoxidine on the growth of the human breast cancer cell line MCF-7 is modified by both serum and insulin. Tamoxifen inhibition of the growth of MCF-7 cells in culture is reduced as the concentra tion of serum in the medium is increased from 0.1% to 5 to 10%. Estradiol does not stimulate cell

W. Barkley Butler; William H. Kelsey; Nicolene Goran

382

Transforming Growth Factor A Expression Drives Constitutive Epidermal Growth Factor Receptor Pathway Activation and Sensitivity to Gefitinib(Iressa) in Human Pancreatic Cancer Cell Lines  

Microsoft Academic Search

The epidermal growth factor receptor (EGFR) is considered an important therapeutic target in pancreatic cancer, but it is currently impossible to identify those patients who are most likely to benefit from EGFR-directed therapy. We examined the biological effects of the EGFR tyrosine kinase inhibitor gefitinib (ZD1839, Iressa) in a panel of nine human pancreatic cancer cell lines. The drug strongly

Maria S. Pino; Marissa Shrader; Cheryl H. Baker; Francesco Cognetti; Henry Q. Xiong; James L. Abbruzzese; David J. McConkey

383

Transfection of rat dermal papilla cells with a gene encoding a temperature- sensitive polyomavirus large T antigen generates cell lines retaining a differentiated phenotype  

Microsoft Academic Search

The dermal papilla is a discrete group of cells at the base of the hair follicle and is implicated in controlling the hair growth cycle. Early passage dermal papilla cells can induce hair growth in vivo, but, upon further culturing, this property is lost. In order to study the events occurring in hair induction, a representative dermal papilla cell line

Wendy Filsell; Julie C. Little; Amanda J. Stones; Stewart P. Granger; Susan A. Bayley

1994-01-01

384

A chemical screen in diverse breast cancer cell lines reveals genetic enhancers and suppressors of sensitivity to PI3K isoform-selective inhibition.  

PubMed

The PI3K (phosphoinositide 3-kinase) pathway regulates cell proliferation, survival and migration and is consequently of great interest for targeted cancer therapy. Using a panel of small-molecule PI3K isoform-selective inhibitors in a diverse set of breast cancer cell lines, we have demonstrated that the biochemical and biological responses were highly variable and dependent on the genetic alterations present. p110alpha inhibitors were generally effective in inhibiting the phosphorylation of PKB (protein kinase B)/Akt and S6, two downstream components of PI3K signalling, in most cell lines examined. In contrast, p110beta-selective inhibitors only reduced PKB/Akt phosphorylation in PTEN (phosphatase and tensin homologue deleted on chromosome 10) mutant cell lines, and was associated with a lesser decrease in S6 phosphorylation. PI3K inhibitors reduced cell viability by causing cell-cycle arrest in the G(1) phase, with multi-targeted inhibitors causing the most potent effects. Cells expressing mutant Ras were resistant to the cell-cycle effects of PI3K inhibition, which could be reversed using inhibitors of Ras signalling pathways. Taken together, our data indicate that these compounds, alone or in suitable combinations, may be useful as breast cancer therapeutics, when used in appropriate genetic contexts. PMID:18498248

Torbett, Neil E; Luna-Moran, Antonio; Knight, Zachary A; Houk, Andrew; Moasser, Mark; Weiss, William; Shokat, Kevan M; Stokoe, David

2008-10-01

385

Synthesis and antitumor activity of ether glycerophospholipids bearing a carbamate moiety at the sn-2 position: selective sensitivity against prostate cancer cell lines.  

PubMed

Analogues of 1-O-hexadecyl-sn-3-glycerophosphonocholine (compounds 1-4) or sn-3-glycerophosphocholine (compound 5) bearing a carbamate or dicarbamate moiety at the sn-2 position were synthesized and evaluated for their antiproliferative activity against cancer cells derived from a variety of tissues. Although all of the compounds are antiproliferative, surprisingly the carbamates (1 and 2) are more effective against the hormone-independent cell lines DU145 and PC3 than toward other cancer cell lines we examined. This selectivity was not observed with the dicarbamates (3 and 4). Phosphocholine carbamate analogue 5 is as effective against the prostate cancer cell lines as the corresponding phosphonocholine analogue 1. Cell death induced by 2'-(trimethylammonio)ethyl 4-hexadecyloxy-3(R)-N-methylcarbamoyl-1-butanephosphonate (carbamate analogue 2) appeared to be mediated by apoptosis, as assessed by caspase activation and loss of mitochondrial membrane potential. The in vivo activity of 2 was evaluated in a murine prostate cancer xenograft model. Oral and intravenous administration showed that 2 is effective in inhibiting the growth of PC3 tumors in Rag2M mice. Our studies show that the glycerolipid carbamates reported herein represent a class of prostate-cancer-selective cytotoxic agents. PMID:20533503

Byun, Hoe-Sup; Bittman, Robert; Samadder, Pranati; Arthur, Gilbert

2010-07-01

386

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

Microsoft Academic Search

INTRODUCTION: Our goal was to generate xenograft mouse models of human breast cancer based on luciferase-expressing MDA-MB-231 tumor cells that would provide rapid mammary tumor growth; produce metastasis to clinically relevant tissues such as lymph nodes, lung, and bone; and permit sensitive in vivo detection of both primary and secondary tumor sites by bioluminescent imaging. METHOD: Two clonal cell sublines

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

2005-01-01

387

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

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.

2010-01-01

388

6-Aryl and Heterocycle Quinazoline Derivatives as Potent EGFR Inhibitors with Improved Activity toward Gefitinib-Sensitive and -Resistant Tumor Cell Lines.  

PubMed

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 IC50 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

Hamed, Mostafa M; Abou El Ella, Dalal A; Keeton, Adam B; Piazza, Gary A; Abadi, Ashraf H; Hartmann, Rolf W; Engel, Matthias

2013-07-11

389

Position- and time-sensitive coincident detection of fragments from the dissociative recombination of O2+ using a single hexanode delay-line detector  

NASA Astrophysics Data System (ADS)

This contribution describes the use of the RoentDek hexanode delay line detector to detect fragments from the dissociative recombination of O2+ in an experiment at the ion storage ring CRYRING, Manne Siegbahn Laboratory, Stockholm. In this experiment, the fragments have a maximum time- and position-separation of 20 ns and 40 mm, respectively. The position resolution obtained was 0.16 mm (FWHM) on the 67 mm diameter detector. The time resolution obtained from the time-of-arrival difference between the product fragments was about 1 ns. The detector system handles event rates as large as 30 kHz. Techniques for the calibration of the absolute position of particles on the detector are discussed.

Österdahl, F.; Rosén, S.; Bednarska, V.; Petrignani, A.; Hellberg, F.; Larsson, M.; van der Zande, W. J.

2005-01-01

390

Inhibition of the high-affinity glucose transporter GLUT 1 affects the sensitivity to glucose in a hamster-derived pancreatic beta cell line (HIT).  

PubMed

HIT is a hamster-derived beta-cell line which in contrast to normal beta cells that only express the high Km GLUT-2 glucose transporter, also expresses the low Km glucose transporter GLUT 1. In HIT cells the abnormal glucose transport mechanism is associated with a marked shift to the left of the glucose-induced insulin release dose-response curve. We have used this cell model to investigate whether changes in glucose transport affect the glucose-induced insulin release. HIT cells were first incubated with a concentration of cytochalasin B (0.4 mumol/l) that selectively inhibits the GLUT-1 but not the GLUT-2 transporter. The consequences of blocking glucose phosphorylation and insulin release were studied. Exposure to 0.4 mumol/l cytochalasin B for 1 h caused a selective loss of the low Km transport: the calculated Vmax of GLUT 1 was reduced from 1726 +/- 98 to 184 +/- 14 pmol.mg protein-1 5 min-1 (mean +/- SEM, n = 6, p < 0.005), while no major difference in the high Km (GLUT-2) transport was observed. In cytochalasin B exposed HIT cells the glucose phosphorylating activity (due to hexokinase and glucokinase) was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8270137

Rabuazzo, A M; Buscema, M; Vinci, C; Caltabiano, V; Anello, M; Vigneri, R; Purrello, F

1993-11-01

391

Differential sensitivity of melanoma cell lines with differing B-Raf mutational status to the new oncogenic B-Raf kinase inhibitor UI-152.  

PubMed

Activating mutations in B-Raf kinase are common in malignant melanoma, an aggressive tumor of neuroectodermal origin. In the present study, the antiproliferative effect of the new oncogenic B-Raf targeting drug UI-152 on two types of melanoma cell lines with differing B-Raf mutational status was examined, and the underlying mechanisms were investigated. In cellular assays, UI-152 displayed high selectivity for tumor cells bearing B-Raf(V600E), showing more than 1000-fold higher inhibition of their proliferation than wild-type B-Raf-bearing cells. As expected, UI-152 completely abolished MEK-ERK phosphorylation in A375P cells harboring B-Raf(V600E). In SK-MEL-2 cells expressing B-Raf(WT), UI-152 caused the paradoxical activation of the MAPK pathway but to a much lesser extent than that observed of other oncogenic B-Raf inhibitors. These data suggest that UI-152 may be a more ideal B-Raf inhibitor capable of preserving potency against oncogenic B-Raf while minimizing the paradoxical activation of MAPK signaling. In addition, we showed that UI-152 treatment of A375P cells simultaneously induced cellular autophagy and apoptosis. However, autophagy inhibition with 3-methyladenine and inhibition of apoptosis by overexpression of the X-linked inhibitor of apoptosis failed to rescue melanoma cells from UI-152-induced cell death, implying that apoptosis and autophagy may cooperate in the induction of cell death in UI-152-treated cells. Collectively, our data suggest that UI-152 may be an effective B-Raf inhibitor and a potential therapeutic strategy for B-Raf(WT) and Ras mutant melanoma. PMID:22425959

Kim, Yun-Ki; Ahn, Soon Kil; Lee, Michael

2012-03-13

392

The seminoma cell line TCam-2 is sensitive to HDAC inhibitor depsipeptide but tolerates various other chemotherapeutic drugs and loss of NANOG expression.  

PubMed

Seminomas and embryonal carcinomas (EC) are both type II germ cell tumor (GCT) entities and develop from the same precursor lesion (carcinoma-in situ, CIS). However, they show significant differences in growth behavior, differentiation potential, and gene expression. Although ECs are prone to differentiate into all three germ layers and give rise to the non-seminomatous GCT entities teratoma, choriocarcinoma, and yolk-sac tumor, differentiation of seminomas to these entities is only rarely observed. This might reflect the ability of seminomas to actively inhibit differentiation processes evoked by environmental cues. Also, it is not known why CIS gives rise to seminoma in some patients and to non-seminoma in the others. Here, we treated the seminoma-like cell line TCam-2 with the HDAC-inhibitor Depsipeptide, the global demethylating agent 5-aza-2'-deocycytidine, all-trans retinoic acid and the monaminooxidase inhibitor Tranylcipromine and also used knock down approaches to reduce expression of the pluripotency marker NANOG and/or the inhibitor of primordial germ cell differentiation TFAP2C. We found that TCam-2 cells induce apoptosis when treated with Depsipeptide (> 10 nM) but are resistant to treatments with 5-aza-2'-deocycytidine, all-trans retinoic acid and Tranylcipromine, highlighting Depsi as a treatment option for seminomas. We show that TCam-2 cells up-regulate endoderm- and throphectoderm-associated genes after down-regulation of NANOG expression; however, morphologically no indications of differentiation could be found. Instead, we observed up-regulation of OCT3/4 and SOX17 in TCam-2-NANOG knockdown and speculate that this compensates for the loss of the NANOG protein. Hence, NANOG is not a primary target gene responsible for the inhibition of differentiation in seminomas. PMID:21987446

Nettersheim, Daniel; Gillis, Ad; Biermann, Katharina; Looijenga, Leendert H J; Schorle, Hubert

2011-08-24

393

Targeting MAGE-C1/CT7 Expression Increases Cell Sensitivity to the Proteasome Inhibitor Bortezomib in Multiple Myeloma Cell Lines  

PubMed Central

The MAGE-C1/CT7 encodes a cancer/testis antigen (CTA), is located on the chromosomal region Xq26–27 and is highly polymorphic in humans. MAGE-C1/CT7 is frequently expressed in multiple myeloma (MM) that may be a potential target for immunotherapy in this still incurable disease. MAGEC1/CT7 expression is restricted to malignant plasma cells and it has been suggested that MAGE-C1/CT7 might play a pathogenic role in MM; however, the exact function this protein in the pathophysiology of MM is not yet understood. Our objectives were (1) to clarify the role of MAGE-C1/CT7 in the control of cellular proliferation and cell cycle in myeloma and (2) to evaluate the impact of silencing MAGE-C1/CT7 on myeloma cells treated with bortezomib. Myeloma cell line SKO-007 was transduced for stable expression of shRNA-MAGE-C1/CT7. Downregulation of MAGE-C1/CT7 was confirmed by real time quantitative PCR and western blot. Functional assays included cell proliferation, cell invasion, cell cycle analysis and apoptosis. Western blot showed a 70–80% decrease in MAGE-C1/CT7 protein expression in inhibited cells (shRNA-MAGE-C1/CT7) when compared with controls. Functional assays did not indicate a difference in cell proliferation and DNA synthesis when inhibited cells were compared with controls. However, we found a decreased percentage of cells in the G2/M phase of the cell cycle among inhibited cells, but not in the controls (p<0.05). When myeloma cells were treated with bortezomib, we observed a 48% reduction of cells in the G2/M phase among inhibited cells while controls showed 13% (empty vector) and 9% (ineffective shRNA) reduction, respectively (p<0.01). Furthermore, inhibited cells treated with bortezomib showed an increased percentage of apoptotic cells (Annexin V+/PI-) in comparison with bortezomib-treated controls (p<0.001). We found that MAGE-C1/CT7 protects SKO-007 cells against bortezomib-induced apoptosis. Therefore, we could speculate that MAGE-C1/CT7 gene therapy could be a strategy for future therapies in MM, in particular in combination with proteasome inhibitors.

de Carvalho, Fabricio; Costa, Erico T.; Camargo, Anamaria A.; Gregorio, Juliana C.; Masotti, Cibele; Andrade, Valeria C.C.; Strauss, Bryan E.; Caballero, Otavia L.; Atanackovic, Djordje; Colleoni, Gisele W.B.

2011-01-01

394

Ultra sensitive determination of limaprost, a prostaglandin E1 analogue, in human plasma using on-line two-dimensional reversed-phase liquid chromatography-tandem mass spectrometry.  

PubMed

A highly sensitive and selective method has been developed and validated to determine limaprost, a prostaglandin (PG) E(1) analogue, in human plasma by on-line two-dimensional reversed-phase liquid chromatography-tandem mass spectrometry (2D-LC/MS/MS) due to the lack of efficient methods to determine very low levels of limaprost in plasma. Limaprost and its deuterium derivatives, used as internal standard, were extracted by protein precipitation and following three-step solid phase extractions. After extraction procedure, samples were analyzed by on-line 2D-LC/MS/MS with electrospray ionization in negative mode. The 2D-LC system consists of Phenyl column at first dimension and ODS at second dimension with a trapping column placed between the separation columns. The linear dynamic range of this method was 0.1-10 pg/ml with 3 ml of plasma (r >0.9987). Acceptable precision and accuracy were obtained over the calibration curve ranges. The assay has been successfully used in analyses of human plasma samples to support clinical pharmacokinetics studies. PMID:17350904

Komaba, Junji; Masuda, Yoriko; Hashimoto, Yoshitaka; Nago, Sachiko; Takamoto, Mayumi; Shibakawa, Kimio; Nakade, Susumu; Miyata, Yasuyuki

2007-02-24

395

12-O-tetradecanoylphorbol-13-acetate-induced inhibition of gap junctional communication is differentially regulated in a transformation-sensitive Syrian hamster embryo cell line compared to early passage SHE cells.  

PubMed

The transformation-sensitive cell-line BPNi was more susceptible to 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inhibition of gap junctional intercellular communication (GJIC) than early passage Syrian hamster embryo (SHE) cells, while the potency of TPA to down-regulate EGF-binding was similar in the two cell types. The kinetics of TPA-induced inhibition of GJIC suggested that different mechanisms may operate at high and low TPA concentrations. The initial inhibition after exposure to high TPA concentrations was followed by a recovery of GJIC. The recovery was much more pronounced in SHE than in BPNi cells. This effect could not be explained by differences in down-regulation of protein kinase C. Removal of high TPA concentrations also resulted in a faster recovery of GJIC in SHE than in BPNi cells. In addition, although forskolin induced a similar protection against the inhibitory effect of TPA on GJIC, forskolin restored GJIC blocked by TPA much faster in SHE than in BPNi cells. Thus, BPNi cells are more sensitive to TPA induced inhibition of GJIC than SHE cells, and have reduced capability to recover from down-regulated GJIC as compared to SHE cells. PMID:8403209

Roseng, L E; Rivedal, E; Sanner, T

1993-09-01

396

Atypical multi-drug resistance (MDR): low sensitivity of a P-glycoprotein-expressing human T lymphoblastoid MDR cell line to classical P-glycoprotein-directed resistance-modulating agents.  

PubMed

Verapamil, cyclosporin A (CsA), the cyclosporin derivative SDZ PSC 833 and the novel cyclopeptolide SDZ 280-446 were tested for their capacity to chemosensitize a P-glycoprotein (Pgp)-expressing multi-drug resistant (MDR) variant of the CEM human T lymphoblastoid cell subline (CCRF ACTD 400+). That MDR-CEM cell subline had been previously selected for MDR by actinomycin D and displayed a very high resistance phenotype: 3700-fold for actinomycin D, 3900-fold for vincristine, 1200-fold for taxol, 1000-fold for daunomycin (DAU) and 400-fold for colchicine. Interestingly, these MDR-CEM cells displayed little chemosensitization by resistance-modulating agents (RMA) which presumably work by inhibiting Pgp function. These MDR-CEM cells displayed virtually no chemosensitization by 1 microM verapamil or 1 microgram/ml (about 0.8 microM) CsA, whereas their chemosensitization for different anti-cancer drugs (ACD) was rather stable (from 51- to 82-fold) with 1 microgram/ml (about 0.8 microM) SDZ 280-446, while being very unbalanced (from 5- to 38-fold) with 1 microgram/ml (about 0.8 microM) SDZ PSC 833. Exposure of the MDR-CEM cells to Pgp-directed RMAs, during their loading with DAU (DAU-loading phase), hardly restored DAU retention: SDZ 280-446 being as poorly active as SDZ PSC 833, and about only 3- and 4-fold more active than CsA and verapamil. In contrast, SDZ PSC 833 treatment of human MDR-KB and MDR-LoVo cell lines under the same conditions could restore most or all the DAU retention shown by the parental (Par) cells, in spite of their high level of resistance. By keeping the MDR-CEM cells in the presence of RMA throughout the experiment (both DAU-loading and DAU-efflux phases), a better DAU retention could be restored by the different RMAs used, their order of relative restoration activity being SDZ 280-446 3- to 4-fold > SDZ PSC 833 3- to 10-fold > CsA 2- to 4-fold > verapamil. Nevertheless, the level of DAU retention restored in the MDR-CEM cells reached a plateau at 50% of the Par-CEM cell level. Therefore, although the MDR-CEM cells expressed easily detectable membranous Pgp molecules and probably used them for DAU efflux, they displayed an additional efflux mechanism that was not sensitive to the Pgp inhibitors. PMID:7905300

Jachez, B; Loor, F

1993-12-01

397

Movie Lines  

NSDL National Science Digital Library

This algebra lesson from Illuminations involves using linear equations and graphs in a real world context. Students will graph a line based on data points, find the equation of the line, identify y-intercept and slope, and extrapolate data. The material is appropriate for grades 9-12 and should require 1 class period to complete.

2011-01-11

398

A plan for directional dark matter sensitivity in high-pressure xenon detectors through the addition of wavelength shifting gaseous molecules  

NASA Astrophysics Data System (ADS)

Xenon is an especially attractive candidate for both direct WIMP and 0??? decay searches. Although the current trend has exploited the liquid phase, the gas phase xenon offers remarkable performance advantages for: energy resolution, topology visualization, and discrimination between electron and nuclear recoils. The NEXT-100 experiment, now under construction in the Canfranc Underground Laboratory, Spain, will operate at ~ 15 bars with 100 kg of 136Xe for the 0??? decay search. We will describe recent results with small prototypes, indicating that NEXT-100 can provide about 0.5% FWHM energy resolution at the decay's Q value (2457.83 keV), as well as rejection of ?-rays with topological cuts. However, sensitivity goals for WIMP dark matter and 0??? decay searches indicate the probable need for ton-scale active masses. NEXT-100 provides the springboard to reach this scale with xenon gas. We describe a scenario for performing both searches in a single, high-pressure, ton-scale xenon gas detector, without significant compromise to either. In addition, even in a single ton-scale, high-pressure xenon gas TPC, an intrinsic sensitivity to the nuclear recoil direction may exist. This plausibly offers an advance of more than two orders of magnitude relative to current low-pressure TPC concepts. We argue that, in an era of deepening fiscal austerity, such a dual-purpose detector may be possible at acceptable cost, within the time frame of interest, and deserves our collective attention.

Gehman, V. M.; Goldschmidt, A.; Nygren, D.; Oliveira, C. A. B.; Renner, J.

2013-10-01

399

Poverty Lines  

NSDL National Science Digital Library

The World Bank has released the November 1997 issue of Poverty Lines, a newsletter that summarizes current research studies on poverty. The latest issue looks at how public works programs can help people who are poor.

1996-01-01

400

Light WIMP search in XMASS  

NASA Astrophysics Data System (ADS)

A search for light dark matter using low-threshold data from the single phase liquid xenon scintillation detector XMASS, has been conducted. Using the entire 835 kg inner volume as target, the analysis threshold can be lowered to 0.3 keVee (electron-equivalent) to search for light dark matter. With low-threshold data corresponding to a 5591.4 kg?day exposure of the detector and without discriminating between nuclear-recoil and electronic events, XMASS excludes part of the parameter space favored by other experiments.

Abe, K.; Hieda, K.; Hiraide, K.; Hirano, S.; Kishimoto, Y.; Kobayashi, K.; Moriyama, S.; Nakagawa, K.; Nakahata, M.; Ogawa, H.; Oka, N.; Sekiya, H.; Shinozaki, A.; Suzuki, Y.; Takeda, A.; Takachio, O.; Ueshima, K.; Umemoto, D.; Yamashita, M.; Yang, B. S.; Tasaka, S.; Liu, J.; Martens, K.; Hosokawa, K.; Miuchi, K.; Murata, A.; Onishi, Y.; Otsuka, Y.; Takeuchi, Y.; Kim, Y. H.; Lee, K. B.; Lee, M. K.; Lee, J. S.; Fukuda, Y.; Itow, Y.; Masuda, K.; Nishitani, Y.; Takiya, H.; Uchida, H.; Kim, N. Y.; Kim, Y. D.; Kusaba, F.; Motoki, D.; Nishijima, K.; Fujii, K.; Murayama, I.; Nakamura, S.

2013-02-01

401

Assembly Line  

NSDL National Science Digital Library

In this activity, learners work individually to assemble a product and then work in teams to design, construct, test, and redesign an assembly line process whose product must meet specific quality control criteria. Learners reflect and compare the two approaches. Note: Page 14 is not in the correct position. It should actually be between pages 2 and 3.

Ieee

2013-07-08

402

Cell lines  

US Patent & Trademark Office Database

Genomic instability in T-antigen expressing cells can be overcome by modifying the gene expressing T-antigen so that it lacks Bub1 binding. Stable cell lines can be produced by incorporation of the modified T-antigen gene, preferably together with the catalytic sub-unit of the telomerase construct.

2008-09-02