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Sample records for wimp line sensitivity

  1. Development of Bubble Chambers with Sensitivity to WIMPs

    SciTech Connect

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

    2005-05-01

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

  2. Development of Bubble Chambers with Sensitivity to WIMPs

    SciTech Connect

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

    2005-01-10

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

  3. XENON: A 1 tonne liquid Xenon Detector for a sensitive WIMP dark matter search

    NASA Astrophysics Data System (ADS)

    Oberlack, U.

    The current set of cosmological observations indicates a universe consisting of about 2/3 "dark energy" and 1/3 matter, of which90% is dark. Big bang nucleosyn- thesis and deuterium abundance measurements imply that most of the dark matter is non-baryonic. Dark matter also plays a central role in structure formation, and its microscopic properties have a significant impact on the spatial distribution of mass as traced by galaxies and clusters. Several lines of arguments indicate that dark matter consists of Weakly Interacting Massive Particles (WIMPs), the best-motivated exam- ple of which is the neutralino, the lightest supersymmetric particle. Direct detection offers the hope of studying the dark matter properties in detail, and shedding light on particle physics beyond the Standard Model. Understanding the nature of dark mat- ter is therefore highly significant from both the astrophysics and fundamental physics point of view. Current experiments are not yet sensitive enough by a factor of sev- eral 1000, to test the lowest SUSY predictions. Our approach to this challenge is XENON, a liquid Xenon experiment, based on an array of 10 self-shielded time pro- jection chambers of 100 kg fiducial mass each. The simultaneous measurement of ion- ization and scintillation signals produced by a WIMP interaction results in effective background discrimination (> 99.5%) down to a threshold of 4 keV. Event localiza- tion in 3D yields additional discrimination power. We describe this detector concept for a sensitive Dark Matter search in the context of other existing and planned experi- ments. Our target sensitivity of 4 10-10 pb is sufficient to probe the lowest predicted interaction rates for supersymmetric models.

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

    NASA Technical Reports Server (NTRS)

    Turner, Michael S.; Wilczek, Frank

    1989-01-01

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

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

    SciTech Connect

    Kamat, Sharmila

    2005-01-01

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

  6. Leptophilic effective WIMPs

    NASA Astrophysics Data System (ADS)

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

    2014-07-01

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

  7. Effective WIMPs

    NASA Astrophysics Data System (ADS)

    Hutchinson, Jeffrey Paul

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-06-01

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

  9. Sensitivity of sodium iodide cryogenic scintillation-phonon detectors to WIMP signals

    NASA Astrophysics Data System (ADS)

    Clark, M.; Nadeau, P.; Di Stefano, P. C. F.; Lanfranchi, J.-C.; Roth, S.; von Sivers, M.; Yavin, I.

    2016-05-01

    There is great interest in performing dark matter direct detection experiments using alkali halides such as NaI to test the DAMA/LIBRA claim. Cryogenic scintillation-phonon detectors measure both scintillation light and phonons to provide event-by-event discrimination between particles interacting with nuclei and particles interacting with electrons. An alkali halide scintillation-phonon detector could test the DAMA/LIBRA claim in a model-independent way using a similar material with added background discrimination. We present simulations of such detectors to determine their possible sensitivity to both annual modulation and particle interaction signals. We find that a 5 kg detector array could test the modulation reported by DAMA/LIBRA within 2 years using a likelihood-ratio test.

  10. Effective WIMPs

    NASA Astrophysics Data System (ADS)

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

    2014-01-01

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

  11. Vector WIMP miracle

    NASA Astrophysics Data System (ADS)

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

    2012-07-01

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

  12. Nonthermal 'WIMP miracle'

    SciTech Connect

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

    2009-10-15

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

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

    DOE Data Explorer

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

  14. Median recoil direction as a WIMP directional detection signal

    NASA Astrophysics Data System (ADS)

    Green, Anne M.; Morgan, Ben

    2010-03-01

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

  15. Median recoil direction as a WIMP directional detection signal

    SciTech Connect

    Green, Anne M.; Morgan, Ben

    2010-03-15

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

  16. WIMP physics with ensembles of direct-detection experiments

    NASA Astrophysics Data System (ADS)

    Peter, Annika H. G.; Gluscevic, Vera; Green, Anne M.; Kavanagh, Bradley J.; Lee, Samuel K.

    2014-12-01

    The search for weakly-interacting massive particle (WIMP) dark matter is multi-pronged. Ultimately, the WIMP-dark-matter picture will only be confirmed if different classes of experiments see consistent signals and infer the same WIMP properties. In this work, we review the ideas, methods, and status of direct-detection searches. We focus in particular on extracting WIMP physics (WIMP interactions and phase-space distribution) from direct-detection data in the early discovery days when multiple experiments see of order dozens to hundreds of events. To demonstrate the essential complementarity of different direct-detection experiments in this context, we create mock data intended to represent the data from the near-future Generation 2 experiments. We consider both conventional supersymmetry-inspired benchmark points (with spin-independent and -dependent elastic cross sections just below current limits), as well as benchmark points for other classes of models (inelastic and effective-operator paradigms). We also investigate the effect on parameter estimation of loosening or dropping the assumptions about the local WIMP phase-space distribution. We arrive at two main conclusions. Firstly, teasing out WIMP physics with experiments depends critically on having a wide set of detector target materials, spanning a large range of target nuclear masses and spin-dependent sensitivity. It is also highly desirable to obtain data from low-threshold experiments. Secondly, a general reconstruction of the local WIMP velocity distribution, which will only be achieved if there are multiple experiments using different target materials, is critical to obtaining a robust and unbiased estimate of the WIMP mass.

  17. NEWS: Nuclear Emulsions for WIMP Search

    NASA Astrophysics Data System (ADS)

    Di Marco, Natalia; NEWS Collaboration

    2016-05-01

    In the field of direct Dark Matter search a different and promising approach is the directionality: the observation of the incoming apparent direction of WIMPs would in fact provide a new and unambiguous signature. The NEWS project is a very innovative approach for a high sensitivity experiment aiming at the directional detection of WIMPs: the detector is based on a novel emulsion technology called NIT (Nano Imaging Trackers) acting both as target and tracking device. In this paper we illustrate the features of a NIT-based detector and the newly developed read-out systems allowing to reach a spatial resolution of the order of 10 nm. We present the background studies and the experimental design. Finally we report about the time schedule of the experiment and the expected sensitivity for DM searches.

  18. The fraternal WIMP miracle

    NASA Astrophysics Data System (ADS)

    Craig, Nathaniel; Katz, Andrey

    2015-10-01

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

  19. The fraternal WIMP miracle

    SciTech Connect

    Craig, Nathaniel; Katz, Andrey

    2015-10-27

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

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

    SciTech Connect

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

    2009-04-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-07-01

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

  2. Light WIMPs in the Sun: Constraints from helioseismology

    SciTech Connect

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

    2010-11-15

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

  3. Event rates for WIMP detection

    SciTech Connect

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

    2006-11-28

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

  4. NEWS: Nuclear emulsion WIMP search

    NASA Astrophysics Data System (ADS)

    Alexandrov, A.; Asada, T.; D'Ambrosio, N.; De Lellis, G.; Di Crescenzo, A.; Di Marco, N.; Furuya, S.; Gentile, V.; Hakamata, K.; Ishikawa, M.; Katsuragawa, T.; Kuwabara, K.; Machii, S.; Naka, T.; Pupilli, F.; Sirignano, C.; Tawara, Y.; Tioukov, V.; Umemoto, A.; Yoshimoto, M.

    2015-01-01

    The most convincing candidate as main constituent of the dark matter in the Universe consists of Weakly Interacting Massive Particles (WIMPs). WIMPs must be electrically neutral and interact with a very low cross-section ( σ<10^{-40} cm2) which makes them detectable in direct searches only through the observation of nuclear recoils induced by the WIMP rare scatterings. In the experiments carried out so far, recoiled nuclei are searched for as a signal over a background produced by Compton electrons and neutron scatterings. Signal found by some experiments have not been confirmed by other techniques. We propose an R&D program for a new experimental method able to observe the track of the scattered nucleus based on new developments in the nuclear emulsion technique. Nuclear emulsions would act both as the WIMP target and as the tracking detector able to reconstruct the direction of the recoiled nucleus. This unique characteristic would provide a new and unambiguous signature of the presence of the dark matter in our galaxy.

  5. Light WIMPs and Equivalent Neutrinos

    NASA Astrophysics Data System (ADS)

    Steigman, Gary; Nollett, Kenneth M.

    Very light WIMPs (χ), thermal relics that annihilate late in the early Universe, change the energy and entropy densities at BBN and at recombination. BBN, in combination with the CMB, can remove some of the degeneracies among light WIMPs and equivalent neutrinos, constraining the existence and properties of each. Depending on the nature of the light WIMP (Majorana or Dirac fermion, real or complex scalar) the joint BBN + CMB analyses set lower bounds to mχ in the range 0.5 - 5 MeV (mχ/me ≲1 - 10), and they identify best fit values for mχ in the range 5 - 10 MeV. The joint BBN + CMB analysis finds a best fit value for the number of equivalent neutrinos, ΔNν ≈ 0.65, nearly independent of the nature of the WIMP. In the absence of a light WIMP (mχ ≲20 MeV), Neff = 3.05(1 + ΔNν/3). In this case, there is excellent agreement between BBN and the CMB, but the joint fit reveals ΔNν = 0.40 ± 0.17, disfavoring standard big bang nucleosynthesis (SBBN) (ΔNν = 0) at ∼ 2.4 σ, as well as a sterile neutrino (ΔNν = 1) at ∼ 3.5 σ. The best BBN + CMB joint fit disfavors the absence of dark radiation (ΔNν = 0 at ∼ 95% confidence), while allowing for the presence of a sterile neutrino (ΔNν = 1 at ≲1 σ). For all cases considered here, the lithium problem persists. These results, presented at the TAUP 2013 Conference, are based on Nollett & Steigman [14].

  6. Direct WIMP searches with XENON100 and XENON1T

    NASA Astrophysics Data System (ADS)

    Alfredo Davide, Ferella

    2015-05-01

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

  7. A WIMP Dark Matter Detector Using MKIDs

    NASA Astrophysics Data System (ADS)

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

    2008-04-01

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

  8. Photon spectra from WIMP annihilation

    SciTech Connect

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

    2011-04-15

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

  9. WIMP detection and slow ion dynamics in carbon nanotube arrays

    NASA Astrophysics Data System (ADS)

    Cavoto, G.; Cirillo, E. N. M.; Cocina, F.; Ferretti, J.; Polosa, A. D.

    2016-06-01

    Large arrays of aligned carbon nanotubes (CNTs), open at one end, could be used as target material for the directional detection of weakly interacting dark matter particles (WIMPs). As a result of a WIMP elastic scattering on a CNT, a carbon ion might be injected in the body of the array and propagate through multiple collisions within the lattice. The ion may eventually emerge from the surface with open end CNTs, provided that its longitudinal momentum is large enough to compensate energy losses and its transverse momentum approaches the channeling conditions in a single CNT. Therefore, the angle formed between the WIMP wind apparent orientation and the direction of parallel carbon nanotube axes must be properly chosen. We focus on very low ion recoil kinetic energies, related to low mass WIMPs (≈ 11 GeV) where most of the existing experiments have low sensitivity. Relying on some exact results on two-dimensional lattices of circular obstacles, we study the low energy ion motion in the transverse plane with respect to CNT directions. New constraints are obtained on how to devise the CNT arrays to maximize the target channeling efficiency.

  10. WIMPs at the galactic center

    SciTech Connect

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

    2015-05-07

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

  11. WIMPs at the galactic center

    DOE PAGESBeta

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

    2015-05-07

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

  12. WIMPs at the galactic center

    SciTech Connect

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

    2015-05-07

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

  13. Sites of ozone sensitivity in diverse maize inbred lines

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  14. Soft collinear effective theory for heavy WIMP annihilation

    NASA Astrophysics Data System (ADS)

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

    2015-01-01

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

  15. WIMP abundance and lepton (flavour) asymmetry

    SciTech Connect

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

    2012-03-01

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

  16. Twin Higgs WIMP dark matter

    NASA Astrophysics Data System (ADS)

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

    2015-09-01

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

  17. Improved Detection Sensitivity of Line-Scanning Optical Coherence Microscopy

    PubMed Central

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

    2012-01-01

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

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

    SciTech Connect

    Agnese, R.

    2015-10-12

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

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

    DOE PAGESBeta

    Agnese, R.

    2015-10-12

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

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

    SciTech Connect

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

    2015-10-31

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

  1. Non-thermal WIMPs as dark radiation

    SciTech Connect

    Queiroz, Farinaldo S.

    2014-06-24

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

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

    SciTech Connect

    Collar, Juan

    2003-12-03

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

  3. Soft collinear effective theory for heavy WIMP annihilation

    DOE PAGESBeta

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

    2015-01-19

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

  4. Soft collinear effective theory for heavy WIMP annihilation

    SciTech Connect

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

    2015-01-19

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

  5. The CRESST-III low-mass WIMP detector

    NASA Astrophysics Data System (ADS)

    Strauss, R.; Angloher, G.; Bento, A.; Bucci, C.; Canonica, L.; Defay, X.; Erb, A.; von Feilitzsch, F.; Ferreiro Iachellini, N.; Gorla, P.; Gütlein, A.; Hauff, D.; Jochum, J.; Kiefer, M.; Kluck, H.; Kraus, H.; Lanfranchi, J. C.; Loebell, J.; Münster, A.; Pagliarone, C.; Petricca, F.; Potzel, W.; Pröbst, F.; Reindl, F.; Schäffner, K.; Schieck, J.; Schönert, S.; Seidel, W.; Stodolsky, L.; Strandhagen, C.; Tanzke, A.; Trinh Thi, H. H.; Türkoglu, C.; Ufflnger, M.; Ulrich, A.; Usherov, I.; Wawoczny, S.; Willers, M.; Wüstrich, M.; Zöller, A.

    2016-05-01

    The next generation direct dark matter experiment CRESST-III has a high potential to significantly increase the sensitivity to low-mass WIMPs (mx ≲10GeV/c2). We present the new CRESST detector module: it consists of a 24 g CaWO4 crystal operated as a phonon detector and a 20×20 mm2 silicon-on-sapphire light detector. The phonon energy threshold is lowered to ~100eV and a light detector resolution of typically 5eV is achieved. A fully-scintillating inner detector housing is realised which efficiently rejects events from surface-alpha decays. The CaWO4 sticks holding the target crystal are also operated as calorimeters to discriminate all possible artefacts related to the support structure. A projection for the sensitivity to spin-independent WIMP-nucleon scattering is given for the first phase of CRESST-III which will start beginning of 2016.

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

    PubMed Central

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

    1995-01-01

    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. Images Figure 2 PMID:7880730

  7. WIMP Dark Matter and the First Stars

    NASA Astrophysics Data System (ADS)

    Iocco, Fabio

    2010-11-01

    If weakly interacting massive particles (WIMPs) constitute the bulk of dark matter (DM), energy from the self-annihilation of these particles can affect Population III (Pop III) star formation via two mechanisms. Before the protostar forms, energy from DM annihilations can couple to primordial gas chemistry and slightly alter the properties of the cloud-without, however, inducing dramatic changes in the final mass of the star. Later, scattering between WIMPs and baryons within the protostar can in principle congregate enough DM for annihilations, rather than nuclear reactions, to support the star against gravity. In these proceedings I briefly summarize the state of the art of the field, as well the prospects for observing such stars.

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

    PubMed

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

    1989-07-01

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

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

    NASA Astrophysics Data System (ADS)

    Iguaz, F. J.; Garza, J. G.; Aznar, F.; Castel, J. F.; Cebrián, S.; Dafni, T.; García, J. A.; Irastorza, I. G.; Lagraba, A.; Luzón, G.; Peiró, A.

    2016-05-01

    Dark Matter experiments are recently focusing their detection techniques in low-mass WIMPs, which requires the use of light elements and low energy threshold. In this context, we describe the TREX-DM experiment, a low background Micromegas-based TPC for low-mass WIMP detection. Its main goal is the operation of an active detection mass ~0.3 kg, with an energy threshold below 0.4 keVee and fully built with previously selected radiopure materials. This work describes the commissioning of the actual setup situated in a laboratory on surface and the updates needed for a possible physics run at the Canfranc Underground Laboratory (LSC) in 2016. A preliminary background model of TREX-DM is also presented, based on a Geant4 simulation, the simulation of the detector’s response and two discrimination methods: a conservative muon/electron and one based on a neutron source. Based on this background model, TREX-DM could be competitive in the search for low-mass WIMPs. In particular it could be sensitive, e.g., to the low-mass WIMP interpretation of the DAMA/LIBRA and other hints in a conservative scenario.

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

    NASA Astrophysics Data System (ADS)

    Jeong, Manhee

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

  11. New class of biological detectors for WIMPs

    NASA Astrophysics Data System (ADS)

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

    2014-07-01

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

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

    SciTech Connect

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

    2009-03-15

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

  13. Output-sensitive 3D line integral convolution.

    PubMed

    Falk, Martin; Weiskopf, Daniel

    2008-01-01

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

  14. WIMP-Search Results from the Second CDMSlite Run

    SciTech Connect

    Agnese, R.

    2015-09-08

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

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

    NASA Astrophysics Data System (ADS)

    Gluscevic, Vera; Peter, Annika H. G.

    2014-09-01

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

  16. Magnetic-Field Sensitive Line Ratios in EUV and Soft X-ray Spectra

    NASA Technical Reports Server (NTRS)

    Beiersdorfer, P.; Scofield, J.; Brown, G. V.; Chen, H.; Trabert, E.; Lepson, J. K.

    2006-01-01

    We discovered a class of lines that are sensitive to the strength of the ambient magnetic field, and present a measurement of such a line in Ar IX near 49 A. Calculations show that the magnitude of field strengths that can be measured ranges from a few hundred gauss to several tens of kilogauss depending on the particular ion emitting the line.

  17. Sensitivity of bandpass filters using recirculating delay-line structures

    NASA Astrophysics Data System (ADS)

    Heyde, Eric C.

    1996-12-01

    Recirculating delay lines have value notably as sensors and optical signal processors. Most useful applications depend on a high-finesse response from a network. A proof that, with given response parameters, more complex systems can produce behavior that is more stable to the effects of nonidealities than a single recirculating loop is presented.

  18. Ionic liquids in enhancing the sensitivity of capillary electrophoresis: Off-line and on-line sample preconcentration techniques.

    PubMed

    El-Hady, Deia Abd; Albishri, Hassan M; Wätzig, Hermann

    2016-07-01

    The popularity of ionic liquids (ILs) has grown during the last decade in enhancing the sensitivity of CE through different off-line or on-line sample preconcentration techniques. Water-insoluble ILs were commonly used in IL-based liquid phase microextraction, in all its variants, as off-line sample preconcentration techniques combined with CE. Water-soluble ILs were rarely used in IL-based aqueous two phase system (IL-ATPS) as an off-line sample preconcentration approach combined with CE in spite of IL-ATPS predicted features such as more compatibility with CE sample injection due to its relatively low viscosity and more compatibility with CE running buffers avoid, in some cases, anion exchange precipitation. Therefore, the attentions for the key parameters affecting the performance of IL-ATPSs were generally presented and discussed. On-line CE preconcentration techniques containing IL-based surfactants at nonmicellar or micellar concentrations have become another interesting area to improve CE sensitivity and it is likely to remain a focus of the field in the endeavor because of their numerous to create rapid, simple and sensitive systems. In this article, significant contributions of ILs in enhancing the sensitivity of CE are described, and a specific overview of the relevant examples of their applications is also given. PMID:27067143

  19. BBN and the CMB constrain neutrino coupled light WIMPs

    NASA Astrophysics Data System (ADS)

    Nollett, Kenneth M.; Steigman, Gary

    2015-04-01

    In the presence of a light weakly interacting massive particle (WIMP) with mass mχ≲30 MeV , there are degeneracies among the nature of the WIMP (fermion or boson), its couplings to the standard model particles (to electrons, positrons, and photons, or only to neutrinos), its mass mχ, and the number of equivalent (additional) neutrinos, Δ Nν. These degeneracies cannot be broken by the cosmic microwave background (CMB) constraint on the effective number of neutrinos, Neff. However, since big bang nucleosynthesis (BBN) is also affected by the presence of a light WIMP and equivalent neutrinos, complementary BBN and CMB constraints can help to break some of these degeneracies. In a previous paper [K. M. Nollett and G. Steigman, Phys. Rev. D 89, 083508 (2014)] the combined BBN and Planck [P. A. R. Ade et al. (Planck Collaboration), Astron. Astrophys. 571, A16 (2014)] CMB constraints were used to explore the allowed ranges for mχ, Δ Nν, and Neff in the case where the light WIMPs annihilate electromagnetically (EM) to photons and/or e± pairs. In this paper the BBN predictions for the primordial abundances of deuterium and 4He (along with 3He and 7Li) in the presence of a light WIMP that only couples (annihilates) to neutrinos [either standard model (SM) only or both SM and equivalent] are calculated. Recent observational estimates of the relic abundances of D and 4He are used to limit the light WIMP mass, the number of equivalent neutrinos, the effective number of neutrinos, and the present Universe baryon density (ΩBh2 ). Allowing for a neutrino coupled light WIMP and Δ Nν equivalent neutrinos, the combined BBN and CMB data provide lower limits to the WIMP mass that depend very little on the nature of the WIMP (Majorana or Dirac fermion, real or complex scalar boson), with a best fit mχ≳35 MeV , equivalent to no light WIMP at all. The analysis here excludes all neutrino coupled WIMPs with masses below a few MeV, with specific limits varying from 4 to 9 Me

  20. Behavioral and color variations between rat lines developed for differential alcohol sensitivity.

    PubMed

    Sinclair, J D; Viitamaa, T; Hyytiä, P

    1987-01-01

    The AT and ANT rat lines, outbred for differential sensitivity to ethanol-induced motor impairment, also show a difference in their sober behavior. It is not manifested in an escapable-shock test or an amphetamine-stress test, but is shown as significantly more activity by the alcohol-insensitive ATs in a low-stress (33 degrees C) modification of the forced-swimming test. The correlation between alcohol sensitivity and swimming-test activity is, however, not significant in unselected Long Evans rats. Differences in coat color have also developed in the AT and ANT lines; it was possible to estimate whether these changes are independent of ethanol sensitivity with computer simulations. They showed, for example, that the probability of the observed loss of the agouti color in the ATs being by chance is about 0.53 and the probability is nearly 0.50 for there being a spurious line difference, i.e., unrelated to ethanol sensitivity, in which only line had lost the agouti allele. More generally, these and other simulations showed that permanently maintaining selected lines is not the optimal method for finding genetically-based factors related to ethanol sensitivity or other characteristics for which lines have been developed. Nor is either revitalization or replicate lines optimal. The best method apparently would be perpetual restarting of lines. PMID:3426714

  1. Detecting Dark Matter annihilation lines with Fermi

    SciTech Connect

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

    2009-05-15

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

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

    NASA Astrophysics Data System (ADS)

    Ylinen, Tomi

    2010-06-01

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

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

    SciTech Connect

    Ylinen, Tomi

    2010-06-23

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

  4. The moment of truth for WIMP dark matter.

    PubMed

    Bertone, Gianfranco

    2010-11-18

    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

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

    NASA Astrophysics Data System (ADS)

    Beltran, Berta; Picasso Collaboration

    2010-01-01

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

  6. Evaluation of neutron background in cryogenic Germanium target for WIMP direct detection when using reactor neutrino detector as neutron veto

    NASA Astrophysics Data System (ADS)

    Xu, Ye; Lan, Jieqin; Bai, Ying; Gao, Weiwei

    2016-09-01

    A direct WIMP (Weakly Interacting Massive Particle) detector with a neutron veto system is designed to better reject neutrons. An experimental configuration is studied in the present paper: 984 Ge modules are placed inside a reactor neutrino detector. In order to discriminate between nuclear and electron recoil, both ionization and heat signatures are measured using cryogenic germanium detectors in this detection. The neutrino detector is used as a neutron veto device. The neutron background for the experimental design has been estimated using the Geant4 simulation. The results show that the neutron background can decrease to O(0.01) events per year per tonne of high purity Germanium. We calculate the sensitivity to spin-independent WIMP-nucleon elastic scattering. An exposure of one tonne × year could reach a cross-section of about 2×10-11 pb.

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

    SciTech Connect

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

    2014-03-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1985-01-01

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

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

    SciTech Connect

    Colafrancesco, Sergio; Profumo, Stefano; Ullio, Piero

    2007-01-15

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

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

    NASA Astrophysics Data System (ADS)

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

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-05-01

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

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

    PubMed

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

    2015-06-01

    Combination chemotherapy with gemcitabine and cisplatin in patients with metastatic urothelial cancer of the bladder frequently results in the development of acquired drug resistance. Availability of cell culture models with acquired resistance could help to identify candidate treatments for an efficient second-line therapy. Six cisplatin- and six gemcitabine-resistant cell lines were established. Cell viability assays were performed to evaluate the sensitivity to 16 different chemotherapeutic substances. The activity of the drug transporter ATP-binding cassette transporter, subfamily B, member 1 (ABCB1, a critical mediator of multidrug resistance in cancer) was evaluated using fluorescent ABCB1 substrates. For functional assessment, cells overexpressing ABCB1 were generated by transduction with a lentiviral vector encoding for ABCB1, while zosuquidar was used for selective inhibition. In this study, 8 of 12 gemcitabine- or cisplatin-resistant cell lines were cross-resistant to carboplatin, 5 to pemetrexed, 4 to methotrexate, 3 to oxaliplatin, 5-fluorouracil, and paclitaxel, and 2 to cabazitaxel, larotaxel, docetaxel, topotecan, doxorubicin, and mitomycin c, and 1 of 12 cell lines was cross-resistant to vinflunine and vinblastine. In one cell line with acquired resistance to gemcitabine (TCC-SUP(r)GEMCI(20)), cross-resistance seemed to be mediated by ABCB1 expression. Our model identified the vinca alkaloids vinblastine and vinflunine, in Europe an already approved second-line therapeutic for metastatic bladder cancer, as the most effective compounds in urothelial cancer cells with acquired resistance to gemcitabine or cisplatin. These results demonstrate that this in vitro model can reproduce clinically relevant results and may be suitable to identify novel substances for the treatment of metastatic bladder cancer. PMID:26055179

  13. 3-Bromopyruvate induces necrotic cell death in sensitive melanoma cell lines

    SciTech Connect

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

    2010-05-28

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

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

    PubMed Central

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

    2012-01-01

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

  15. Improvement of polymer type EB resist sensitivity and line edge roughness

    NASA Astrophysics Data System (ADS)

    Otani, Makoto; Asada, Hironori; Tsunoda, Hosei; Kunitake, Masashi; Ishizaki, Takehiko; Miyagawa, Ryuji

    2011-05-01

    In order to improve sensitivity and line edge roughness (LER) for electron beam (EB) lithography, the positive-type polymer resists with various molecular weights and controlled dispersion were newly synthesized and examined. The synthesized resists have the same composition as ZEP520A (Nippon Zeon). With the low molecular and the narrow dispersion resist, improvements of both the sensitivity and LER are confirmed by obtaining the SEM images of line and space resist patterns exposed by EB writing system at an acceleration voltage of 100 kV. The polymer resist with molecular weight (Mw: 30k) and dispersion (1.4) exhibited 22 nm hp resolution, 20% improved LER and 15 % improved sensitivity compared with original ZEP520A.

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

    NASA Astrophysics Data System (ADS)

    Manungu Kiveni, Joseph

    2012-06-01

    During the last two decades, cosmology has become a precision observational science thanks (in part) to the incredible number of experiments performed to better understand the composition of the universe. The large amount of data accumulated strongly indicates that the bulk of the universe's matter is in the form of non-baryonic matter that does not interact electromagnetically. Combined evidence from the dynamics of galaxies and galaxy clusters confirms that most of the mass in the universe is not composed of any known form of matter. Measurements of the cosmic microwave background, big bang nucleosynthesis and many other experiments indicate that ˜80% of the matter in the universe is dark, non-relativistic and cold. The dark matter resides in the halos surrounding galaxies, galaxy clusters and other large-scale structures. Weakly Interacting Massive Particles (WIMPs) are well motivated class of dark matter candidates that arise naturally in supersymmetric extensions to the Standard Model of particles physics, and can be produced as non-relativistic thermal relics in the early universe with about the right density to account for the missing mass. The Cryogenic Dark Matter Search (CDMS) experiment seeks to directly detect the keV-scale energy deposited by WIMPs in the galactic halo when they scatter from nuclei in the crystalline detectors made of germanium and silicon. These detectors, called Z-sensitive Ionization and Phonon detectors (ZIPs) are operated at ˜ 45 mK and simultaneously measure the ionization and the (athermal) phonons produced by particle interactions. The ratio of ionization and phonon energies allows discrimination of a low rate of nuclear recoils (expected for WIMPs) from an overwhelming rate of electron recoils (expected for most backgrounds). Phonon-pulse shape and timing enables further suppression of lower-rate interactions at the detector surfaces. This dissertation describes the results of a WIMP search using CDMS II data sets

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

    PubMed Central

    2010-01-01

    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 μM. Among the sensitive cell lines, four were highly sensitive with IC50 values below 1 μM, and three were moderately sensitive with IC50 values between 1 and 10 μM. 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. PMID:20406486

  18. Optimizing Cryogenic Detectors for Low-Mass WIMP Searches

    NASA Astrophysics Data System (ADS)

    Arnaud, Q.; Billard, J.; Juillard, A.

    2016-07-01

    This paper describes the methodology and results from a study dedicated to the optimization of cryogenic detectors for low-mass WIMP searches. Considering a data-driven background model from the EDELWEISS-III experiment, and two analysis methods, namely profile likelihood and boosted decision tree, we indentify the main experimental constraints and performances that have to be improved. We found that there is a clear difference in how to optimize the detector setup whether focusing on WIMPs with masses below 5 GeV or above. Finally, in the case of a hundred-kg scale experiment, we discuss the requirements to probe most of the parameter space region delimited by the ultimate neutrino bound below 6 GeV.

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

    PubMed Central

    2013-01-01

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

  20. Can WIMP dark matter overcome the nightmare scenario?

    SciTech Connect

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

    2010-09-01

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

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

    PubMed

    O'Connell, J; Bennett, M W; Nally, K; O'Sullivan, G C; Collins, J K; Shanahan, F

    2000-12-01

    Homeostasis in the colonic epithelium is achieved by a continuous cycle of proliferation and apoptosis, in which imbalances are associated with disease. Inflammatory bowel disease (IBD) and colon cancer are associated with either excessive or insufficient apoptosis of colonic epithelial cells, respectively. By using two colonic epithelial cell lines, HT29 and SW620, we investigated how the epithelial cell's sensitivity to apoptosis was regulated by the proinflammatory cytokine interferon-gamma (IFN-gamma). We found that IFN-gamma sensitized HT29 cells, and to a lesser extent SW620, to diverse inducers of apoptosis of physiologic or therapeutic relevance to the colon. These apoptosis inducers included Fas (CD95/APO-1) ligand (FasL), short-chain fatty acids, and chemotherapeutic drugs. The extent of IFN-gamma-mediated apoptosis sensitization in these two cell lines correlated well with the degree of IFN-gamma-mediated upregulation of the proapoptotic protease caspase-1. Although IFN-gamma alone effectively sensitized HT29 cells to apoptosis, inclusion of the protein synthesis inhibitor cyclohexamide (CHX) during apoptotic challenge was necessary for maximal sensitization of SW620. The requirement of CHX to sensitize SW620 cells to apoptosis implies a need to inhibit translation of antiapoptotic proteins absent from HT29. In particular, the antiapoptotic protein Bcl-2 was strongly expressed in SW620 cells but absent from HT29. Our results indicate that IFN-gamma increases the sensitivity of colonic epithelial cells to diverse apoptotic stimuli in concert, via upregulation of caspase-1. Our findings implicate caspase-1 and Bcl-2 as important central points of control determining the general sensitivity of colonic epithelial cells to apoptosis. PMID:11056003

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

    PubMed Central

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

    2014-01-01

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

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

    SciTech Connect

    Manungu Kiveni, Joseph

    2012-12-01

    This dissertation describes the results of a WIMP search using CDMS II data sets accumulated at the Soudan Underground Laboratory in Minnesota. Results from the original analysis of these data were published in 2009; two events were observed in the signal region with an expected leakage of 0.9 events. Further investigation revealed an issue with the ionization-pulse reconstruction algorithm leading to a software upgrade and a subsequent reanalysis of the data. As part of the reanalysis, I performed an advanced discrimination technique to better distinguish (potential) signal events from backgrounds using a 5-dimensional chi-square method. This dataanalysis technique combines the event information recorded for each WIMP-search event to derive a backgrounddiscrimination parameter capable of reducing the expected background to less than one event, while maintaining high efficiency for signal events. Furthermore, optimizing the cut positions of this 5-dimensional chi-square parameter for the 14 viable germanium detectors yields an improved expected sensitivity to WIMP interactions relative to previous CDMS results. This dissertation describes my improved (and optimized) discrimination technique and the results obtained from a blind application to the reanalyzed CDMS II WIMP-search data.

  4. PICO-LON project for WIMPs search

    NASA Astrophysics Data System (ADS)

    Fushimi, K.-I.; Yasudai, K.; Kamedai, Y.; Ejiri, H.; Hazama, R.; Ichihara, K.; Imagawa, K.; Ito, H.; Koori, N.; Nakamura, H.; Nakayama, S.; Nomachi, M.; Shima, T.; Umehara, S.; Yoshida, S.

    2008-07-01

    Highly segmented inorganic crystal has been shown to have good performance for dark matter search. The energy resolution of ultra thin and large area NaI(T1) scintillator has been developed. The estimated sensitivity for spin-dependent excitation of 127I was discussed. The recent status of low background measurement at Oto Cosmo Observatory is reported

  5. Neutrino flavor ratios as diagnostic of solar WIMP annihilation

    NASA Astrophysics Data System (ADS)

    Lehnert, Ralf; Weiler, Thomas J.

    2008-06-01

    We consider the neutrino (and antineutrino) flavors arriving at the Earth for neutrinos produced in the annihilation of weakly interacting massive particles (WIMPs) in the sun’s core. Solar-matter effects on the flavor propagation of the resulting ≳GeV neutrinos are studied analytically within a density-matrix formalism. Matter effects, including mass-state level crossings, influence the flavor fluxes considerably. The exposition herein is somewhat pedagogical, in that it starts with adiabatic evolution of single flavors from the sun’s center, with θ13 set to zero, and progresses to fully realistic processing of the flavor ratios expected in WIMP decay, from the sun’s core to the Earth. In the fully realistic calculation, nonadiabatic level crossing is included, as are possible nonzero values for θ13 and the CP-violating phase δ. Because of resonance enhancement in matter, nonzero values of θ13 even smaller than a degree can noticeably affect flavor propagation. Both normal and inverted neutrino-mass hierarchies are considered. Our main conclusion is that measuring flavor ratios (in addition to energy spectra) of ≳GeV solar neutrinos can provide discrimination between WIMP models. In particular, we demonstrate the flavor differences at the Earth for neutrinos from the two main classes of WIMP final states, namely W+W- and 95%bb¯+5%τ+τ-. Conversely, if WIMP properties were to be learned from production in future accelerators, then the flavor ratios of ≳GeV solar neutrinos might be useful for inferring θ13 and the mass hierarchy. From the full calculations, we find (and prove) some general features: a flavor-democratic flux produced at the sun’s core arrives at the Earth still flavor democratic; for maximal θ32 but arbitrary θ21 and θ13, the replacement δ→π-δ leaves the νe flavor spectra unaltered but interchanges νμ and ντ spectra at the Earth; and, only for neutrinos in the inverted hierarchy and antineutrinos in the normal

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

    NASA Astrophysics Data System (ADS)

    Steigman, Gary; Nollett, Kenneth M.

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

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

    SciTech Connect

    Drees, Manuel; Shan, Chung-Lin

    2008-11-23

    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.

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

    NASA Astrophysics Data System (ADS)

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

    1992-06-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    1992-04-01

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

  11. Characterization of endocrine cell lines immortalized by a temperature-sensitive mutant SV40.

    PubMed

    Chen, C L; Simmen, R C; Chou, J Y

    1991-01-01

    An ideal in vitro model for the study of endocrine functions would be one in which cells could propagate in culture and express their specialized functions. Most endocrine studies to date have relied on primary cell culture or on the use of tumor cell lines. This report describes the characterization of three endocrine cell lines immortalized by transfecting endocrine cells with a temperature-sensitive mutant SV40 virus. Rabbit endometrium (HRE-H9), human placenta (SPA209-10) and rat pituitary (RP) cells were immortalized by SV40 virus, a temperature-sensitive (ts) mutant in the A gene, which encodes the large tumor antigen that is required for the maintenance of transformation. The transformed phenotype of the SV40 tsA mutant-immortalized cell line can be reversed simply by a shift in temperature. At the permissive temperature (34 degrees C), all three types of cells exhibited a transformed phenotype, which is characterized by high cell density growth and by the overgrowth of nontransformed cell layers. However, at the non-permissive temperature (40 degrees C) these cells reverted to a non-transformed phenotype as demonstrated by a marked decrease in the overgrowth of nontransformed layers and by the expression of differentiated functions. At the non-permissive temperature (40 degrees C), the endometrial cell line was capable of synthesizing beta-endorphin, and it exhibited hormonally regulated expression of the transfected hybrid uteroferrin gene construct. The human placenta cell line was capable of secreting GnRH upon stimulation by cAMP, forskolin, theophyllin, PGE, catecholamine and Ca++ channel stimulators. Moreover, the rat pituitary cell line was capable of synthesizing and secreting growth hormone (GH) which was stimulated by GHRH and cAMP. The advantage of the temperature-sensitive cell lines is that a single cell line is the source of both the normal and transformed states; thus, studies are internally controlled. These results demonstrate that ts

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

    PubMed

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

    2012-09-01

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

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

    PubMed

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

    2016-04-01

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

  14. Redox Signaling and Bioenergetics Influence Lung Cancer Cell Line Sensitivity to the Isoflavone ME-344.

    PubMed

    Manevich, Yefim; Reyes, Leticia; Britten, Carolyn D; Townsend, Danyelle M; Tew, Kenneth D

    2016-08-01

    ME-344 [(3R,4S)-3,4-bis(4-hydroxyphenyl)-8-methyl-3,4-dihydro-2H-chromen-7-ol] is a second-generation derivative natural product isoflavone presently under clinical development. ME-344 effects were compared in lung cancer cell lines that are either intrinsically sensitive or resistant to the drug and in primary immortalized human lung embryonic fibroblasts (IHLEF). Cytotoxicity at low micromolar concentrations occurred only in sensitive cell lines, causing redox stress, decreased mitochondrial ATP production, and subsequent disruption of mitochondrial function. In a dose-dependent manner the drug caused instantaneous and pronounced inhibition of oxygen consumption rates (OCR) in drug-sensitive cells (quantitatively significantly less in drug-resistant cells). This was consistent with targeting of mitochondria by ME-344, with specific effects on the respiratory chain (resistance correlated with higher glycolytic indexes). OCR inhibition did not occur in primary IHLEF. ME-344 increased extracellular acidification rates in drug-resistant cells (significantly less in drug-sensitive cells), implying that ME-344 targets mitochondrial proton pumps. Only in drug-sensitive cells did ME-344 dose-dependently increase the intracellular generation of reactive oxygen species and cause oxidation of total (mainly glutathione) and protein thiols and the concomitant immediate increases in NADPH levels. We conclude that ME-344 causes complex, redox-specific, and mitochondria-targeted effects in lung cancer cells, which differ in extent from normal cells, correlate with drug sensitivity, and provide indications of a beneficial in vitro therapeutic index. PMID:27255112

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

    PubMed Central

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

    2015-01-01

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

  16. FTIR Biospectroscopy Investigation on Cisplatin Cytotoxicity in Three Pairs of Sensitive and Resistant Cell Line.

    PubMed

    Farhadi, Ensieh; Kobarfard, Farzad; H Shirazi, Farshad

    2016-01-01

    Fourier Transformed Infrared Spectroscopy (FTIR) has extensively been used for biological applications. Cisplatin is one the most useful antineoplastic chemotherapy drugs for a variety of different human cancers. One of the clinical problems in its application, which would consequently affect the therapeutic outcome of its application, is the occurrence of resistance to this agent. In this project three different pairs of sensitive and resistant cell lines of human ovarian A2780 and its resistant pair of A2780-CP, human ovarian OV2008 and its resistant pair of C13, and finally human lung carcinoma of HTB56 and its resistant pair of HTB56-CP were grown in the laboratory under the standard procedure. Saline was exposed to control cells, whereas 1, 5 and 10 µg/mL of cisplatin was exposed to experimental cells, for 1 h. Cells were then collected and lyophilized from which spectra were taken. According to our results, we could not trigger a well-recognized cells biomolecular band at 1015 cm(-1), being modified after exposure to cisplatin in all cell lines. On the other hand, there was a clear dose-dependent increase in protein β-sheet structure related peaks shift in resistant cell lines after exposure to cisplatin. This would probably indicate an easier protein interaction site for cisplatin in the resistant cell lines, which would probably inhibit cisplatin from binding to DNA, as the cytotoxic target. As a conclusion, FTIR biospectroscopy has proven its potency to identify the interactions, as well as the false engagement cellular sites for cisplatin in sensitive and resistant cell lines. PMID:27610161

  17. FTIR Biospectroscopy Investigation on Cisplatin Cytotoxicity in Three Pairs of Sensitive and Resistant Cell Line

    PubMed Central

    Farhadi, Ensieh; Kobarfard, Farzad; H. Shirazi, Farshad

    2016-01-01

    Fourier Transformed Infrared Spectroscopy (FTIR) has extensively been used for biological applications. Cisplatin is one the most useful antineoplastic chemotherapy drugs for a variety of different human cancers. One of the clinical problems in its application, which would consequently affect the therapeutic outcome of its application, is the occurrence of resistance to this agent. In this project three different pairs of sensitive and resistant cell lines of human ovarian A2780 and its resistant pair of A2780-CP, human ovarian OV2008 and its resistant pair of C13, and finally human lung carcinoma of HTB56 and its resistant pair of HTB56-CP were grown in the laboratory under the standard procedure. Saline was exposed to control cells, whereas 1, 5 and 10 µg/mL of cisplatin was exposed to experimental cells, for 1 h. Cells were then collected and lyophilized from which spectra were taken. According to our results, we could not trigger a well-recognized cells biomolecular band at 1015 cm-1, being modified after exposure to cisplatin in all cell lines. On the other hand, there was a clear dose-dependent increase in protein β-sheet structure related peaks shift in resistant cell lines after exposure to cisplatin. This would probably indicate an easier protein interaction site for cisplatin in the resistant cell lines, which would probably inhibit cisplatin from binding to DNA, as the cytotoxic target. As a conclusion, FTIR biospectroscopy has proven its potency to identify the interactions, as well as the false engagement cellular sites for cisplatin in sensitive and resistant cell lines. PMID:27610161

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

    NASA Astrophysics Data System (ADS)

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

    2011-07-01

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

  19. In-line microfluidic integration of photonic crystal fibres as a highly sensitive refractometer.

    PubMed

    Wu, Chuang; Tse, Ming-Leung Vincent; Liu, Zhengyong; Guan, Bai-Ou; Zhang, A Ping; Lu, Chao; Tam, Hwa-Yaw

    2014-11-01

    Photonic crystal fibres appear to be an ideal platform for the realisation of novel optofluidic devices and sensors due to their waveguide nature and microstructured architecture. In this paper, we present the fabrication and characterisation of an in-line photonic crystal fibre microfluidic refractometer enabled by a C-shaped fibre. The C-shaped fibre spliced in-between the photonic crystal fibre and the single-mode fibre allows simultaneous in-line optical signal delivery and analyte fluid feeding. Through an arc discharge pre-treatment technique, we successfully achieve selective exploitation of only the central two channels of the photonic crystal fibre for microfluidic sensing. After constructing a Sagnac interferometer, a highly sensitive refractometer with a sensitivity of 8699 nm per RIU was achieved experimentally; this agrees very well with the theoretical value of 8675 nm per RIU. As a demonstration for label-free optical sensing application, the refractometer was used to measure the concentration of NaCl solution with a sensitivity of 15.08 nm/(1 wt%) and a detection limit of 2.3 × 10(-3) wt% (23 ppm). PMID:25142213

  20. Integrating Domain Specific Knowledge and Network Analysis to Predict Drug Sensitivity of Cancer Cell Lines.

    PubMed

    Kim, Sebo; Sundaresan, Varsha; Zhou, Lei; Kahveci, Tamer

    2016-01-01

    One of fundamental challenges in cancer studies is that varying molecular characteristics of different tumor types may lead to resistance to certain drugs. As a result, the same drug can lead to significantly different results in different types of cancer thus emphasizing the need for individualized medicine. Individual prediction of drug response has great potential to aid in improving the clinical outcome and reduce the financial costs associated with prescribing chemotherapy drugs to which the patient's tumor might be resistant. In this paper we develop a network based classifier (NBC) method for predicting sensitivity of cell lines to anticancer drugs from transcriptome data. In the literature, this strategy has been used for predicting cancer types. Here, we extend it to estimate sensitivity of cells from different tumor types to various anticancer drugs. Furthermore, we incorporate domain specific knowledge such as the use of apoptotic gene list and clinical dose information in our method to impart biological significance to the prediction. Our experimental results suggest that our network based classifier (NBC) method outperforms existing classifiers in estimating sensitivity of cell lines for different drugs. PMID:27607242

  1. Consistency of WIMP Dark Matter as radiative neutrino mass messenger

    NASA Astrophysics Data System (ADS)

    Merle, Alexander; Platscher, Moritz; Rojas, Nicolás; Valle, José W. F.; Vicente, Avelino

    2016-07-01

    The scotogenic scenario provides an attractive approach to both Dark Matter and neutrino mass generation, in which the same symmetry that stabilises Dark Matter also ensures the radiative seesaw origin of neutrino mass. However the simplest scenario may suffer from inconsistencies arising from the spontaneous breaking of the underlying ℤ 2 symmetry. Here we show that the singlet-triplet extension of the simplest model naturally avoids this problem due to the presence of scalar triplets neutral under the ℤ 2 which affect the evolution of the couplings in the scalar sector. The scenario offers good prospects for direct WIMP Dark Matter detection through the nuclear recoil method.

  2. The Magnetic Sensitivity of the Stokes I Profile of the 15260 Å Line of Mn I

    NASA Astrophysics Data System (ADS)

    Asensio Ramos, A.

    2009-01-01

    The near-IR line of Mn I at 15262.7 Å has recently been proposed as a new tool for diagnosing the magnetic field strength and magnetic energy density associated with unresolved magnetic structures, due to the enhanced sensitivity of the Stokes I profile. In this paper, the behavior of the line, focusing on the properties of the Stokes I profile, is analyzed in detail with the aid of state-of-the-art magneto-hydrodynamical simulations of the solar surface convection. The line is synthesized taking into account that the splitting and the strength of the Zeeman components have to be calculated under the framework of the Paschen-Back theory via the numerical diagonalization of the total Hamiltonian, including the hyperfine and Zeeman contributions. The peak ratio and separation of the blue and red lobes of the emergent Stokes I profile are shown to be correlated with the magnetic field strength when no smearing is taken into account, while the correlation slightly degrades when diffraction and stray-light contamination is accounted for. We also analyze the dependence of the first two line moments with the magnetic field, showing that the first and second moments can be used to trace the velocity and the magnetic field strength, respectively. This correlation is still maintained for ground-based observations.

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

    NASA Astrophysics Data System (ADS)

    Keitel, David; Prix, Reinhard

    2015-02-01

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

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

    SciTech Connect

    Emter, Roger; Ellis, Graham; Natsch, Andreas

    2010-06-15

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

  5. SABRE: WIMP modulation detection in the northern and southern hemisphere

    NASA Astrophysics Data System (ADS)

    Froborg, F.; SABRE Collaboration

    2016-05-01

    Measuring an annual modulation in a direct Dark Matter detection experiment is not only a proof of the existence of WIMPs but can also tell us more about their interaction with standard matter and maybe even their density and velocity in the halo. Such a modulation has been measured by the DAMA/LIBRA experiment in NaI(Tl) crystals. However, the interpretation as WIMP signal is controversial due to contradicting results by other experiments. The SABRE experiment aims to shed light on this controversy by detecting the annual modulation in the same target material as DAMA with twin detectors at LNGS in Italy and at SUPL in Australia. The two locations in the northern and southern hemisphere allow to verify if other seasonal effects or the site have an influence on the measurement, thus reducing systematic effects. This paper will give an overview on the experimental design, the current status of the proof of principle phase mainly devoted to high-purity crystal growing, and an outlook on future plans.

  6. High-Sensitivity Broadband Spectral Line Surveys of Star Forming Regions with the CSO

    NASA Astrophysics Data System (ADS)

    Weaver, Susanna L. Widicus; Sumner, Matthew C.; Rice, Frank; Zmuidzinas, Jonas; Blake, Geoffrey A.

    2009-06-01

    Spectral line surveys are powerful tools for astrochemistry because they circumvent the one-line-at-a-time approach that has historically hampered new molecule identification. Until recently, line surveys were typically motivated by the need to characterize the major components of interstellar clouds, i.e. the so-called ``interstellar weeds." Previously reported surveys therefore often do not provide the sensitivity levels required for identification of new molecules with weak spectral signatures. The goal of our recent observations with the Caltech Submillimeter Observatory (CSO) is to shift the focus of spectral line surveys away from the interstellar weeds and toward detection of new interstellar molecules. We have obtained broadband, high-sensitivity spectra toward several star forming regions with the new λ=1 mm receiver at the CSO. When used with the facility AOS's, this receiver affords 4 GHz of DSB spectral coverage for each LO setting. We have employed a stepped frequency-offset approach to allow for full spectral deconvolution. The noise temperature of this receiver is ˜100 K (SSB), resulting in spectral RMS levels that far surpass those reported in similar previous studies. Our initial observations targeted the Orion and Sagittarius B2(N-LMH) hot cores and a collection of Class 0 sources. We have now completed our coverage of these initial targets, and upcoming observing time has been allocated for similar surveys of the hot cores W51 e1/e2 and G34.3+0.2. We have fully deconvolved 28 GHz of spectra on Orion with RMS levels of T_A^*˜20 mK. Our coverage on Sgr was more limited, yielding ˜8 GHz of fully-deconvolved spectra to the same RMS level. In this talk, we will report on the data analysis for the Orion and Sgr observations, discuss our progress on line surveys of other star-forming regions, and discuss the implications of these results in the context of recent hot core astrochemical models.

  7. Experimental and theoretical evaluation of density sensitive N VII, Ar XIV and Fe XXII line ratios

    SciTech Connect

    Chen, H; Beiersdorfer, P; Heeter, L A; Liedahl, D A; Naranjo-Rivera, K L; Trabert, E; Gu, M F; Lepson, J K

    2004-01-09

    The line ratios of the 2p-3d transitions in the B-like spectra Ar XIV and Fe XXII have been measured using the electron beam ion traps at Livermore. Radiative-collisional model calculations show these line ratios to be sensitive to the electron density in the ranges ne = 10{sup 10} to 10{sup 12} cm{sup -3} and ne = 10{sup 13} to 10{sup 15} cm{sup -3}, respectively. In our experiment, the electron beam density of about 10{sup 11} cm{sup -3} was varied by about a factor of 5. Our data show a density effect for the line doublet in Ar XIV, and good agreement with theory is found. The relative intensity of the Fe XXII doublet shows good agreement with our predicted low density limit. The N VI K-shell spectrum was used to infer the actual electron density in the overlap region of ion cloud and electron beam, and systematic measurements and calculations of this spectrum are presented as well. The Ar XIV and Fe XXII spectra promise to be reliable density diagnostics for stellar coronae, complementing the K-shell diagnostics of helium-like ions.

  8. Differential effects of blueberry proanthocyanidins on androgen sensitive and insensitive human prostate cancer cell lines.

    PubMed

    Schmidt, Barbara M; Erdman, John W; Lila, Mary Ann

    2006-01-18

    Blueberries are rich in health-promoting polyphenolic compounds including proanthocyanidins. The purpose of this study was to determine if proanthocyanidin-rich fractions from both wild and cultivated blueberry fruit have the same inhibitory effects on the proliferation of LNCaP, an androgen-sensitive prostate cancer cell line, and DU145, a more aggressive androgen insensitive prostate cancer cell line. When 20 microg/ml of a wild blueberry proanthocyanidin fraction (fraction 5) was added to LNCaP media, growth was inhibited to 11% of control with an IC50 of 13.3 microg/ml. Two similar proanthocyanidin-rich fractions from cultivated blueberries (fractions 4 and 5) at the same concentration inhibited LNCaP growth to 57 and 26% of control with an IC50 of 22.7 and 5.8 microg/ml, respectively. In DU145 cells, the only fraction that significantly reduced growth compared to control was fraction 4 from cultivated blueberries with an IC50 value of 74.4 microg/ml, indicating only minor inhibitory activity. Differences in cell growth inhibition of LNCaP and DU145 cell lines by blueberry fractions rich in proanthocyanidins indicate that blueberry proanthocyanidins have an effect primarily on androgen-dependant growth of prostate cancer cells. Possible molecular mechanisms for growth inhibition are reviewed. PMID:16399225

  9. Method for Increasing Sensitivity of the Distance Protection on a 330 KV Double-Circuit Transmission Line

    NASA Astrophysics Data System (ADS)

    Brinkis, K.; Vanzovich, E.; Drozd, D.; Mutule, A.

    2010-01-01

    Possibilities of increasing the distance protection (DP) sensitivity are considered for a double-circuit transmission line connected to a substation busbar only with one circuit-breaker in each phase. The DP sensitivity can be increased on such a line using mutual connections of the phase wires along its whole length. The minimal (optimal) number of the connections is found by the proposed calculation method.

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

    NASA Astrophysics Data System (ADS)

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

    2015-07-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

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

  12. Gene and microRNA expression reveals sensitivity to paclitaxel in laryngeal cancer cell line

    PubMed Central

    Xu, Cheng-Zhi; Xie, Jin; Jin, Bin; Chen, Xin-Wei; Sun, Zhen-Feng; Wang, Bao-Xing; Dong, Pin

    2013-01-01

    Paclitaxel is a widely used chemotherapy drug for advanced laryngeal cancer patients. However, the fact that there are 20-40% of advanced laryngeal cancer patients do not response to paclitaxel makes it necessary to figure out potential biomarkers for paclitaxel sensitivity prediction. In this work, Hep2, a laryngeal cancer cell line, untreated or treated with lower dose of paclitaxel for 24 h, was applied to DNA microarray chips for gene and miR expression profile analysis. Expression of eight genes altered significantly following paclitaxel treatment, which was further validated by quantitative real-time PCR. Four up-regulated genes were ID2, BMP4, CCL4 and ACTG2, in which ID2 and BMP4 were implicated to be involved in several drugs sensitivity. While the down-regulated four genes, MAPK4, FASN, INSIG1 and SCD, were mainly linked to the endoplasmic reticulum and fatty acid biosynthesis, these two cell processes that are associated with drug sensitivity by increasing evidences. After paclitaxel treatment, expression of 49 miRs was significantly altered. Within these miRs, the most markedly expression-changed were miR-31-star, miR-1264, miR-3150b-5p and miR-210. While the miRs putatively modulated the mRNA expression of the most significantly expression-altered genes were miR-1264, miR-130a, miR-27b, miR-195, miR-1291, miR-214, miR-1277 and miR-1265, which were obtained by miR target prediction and miRNA target correlation. Collectively, our study might provide potential biomarkers for paclitaxel sensitivity prediction and drug resistance targets in laryngeal cancer patients. PMID:23826416

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

    PubMed Central

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

    2014-01-01

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

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

    SciTech Connect

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

    2006-01-04

    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.

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

    NASA Astrophysics Data System (ADS)

    McDonald, John

    2012-09-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

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

    SciTech Connect

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

    2005-09-01

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

  18. Polarization-sensitive optical coherence tomography system tolerant to fiber disturbances using a line camera.

    PubMed

    Marques, Manuel J; Rivet, Sylvain; Bradu, Adrian; Podoleanu, Adrian

    2015-08-15

    This Letter presents a spectral-domain, polarization-sensitive optical coherence tomography (PS-OCT) system, where the light collection from the two arms of the interferometer is performed exclusively using single-mode fibers and couplers, and the two orthogonal polarization components are sequentially detected by a single line camera. Retardance measurements can be affected by polarimetric effects because of fiber birefringence and diattenuation in fiber couplers. This configuration bypasses such issues by performing polarization selection before the collection fiber through the combination of a polarization rotator and a linear polarizer. Retardance calibration is achieved with a Berek compensator. Similar net retardance maps of a birefringent phantom are obtained for two different settings of induced fiber birefringence, effectively demonstrating the tolerance of the configuration to fiber-based disturbances. PMID:26274678

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

    SciTech Connect

    Tarun, Alvarado; Jecong, Julius; Saloma, Caesar

    2005-12-01

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

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

    NASA Astrophysics Data System (ADS)

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

    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.

  1. Establishment and characterization of a simian virus 40-transformed temperature-sensitive rat luteal cell line.

    PubMed

    Sugino, N; Zilberstein, M; Srivastava, R K; Telleria, C M; Nelson, S E; Risk, M; Chou, J Y; Gibori, G

    1998-04-01

    The primary culture of rat luteal cells and their long-term maintenance have been difficult. Low cellular yields have limited the possibility for the study of gene regulation in luteal cells. The goal of this study was to develop a cell line to serve as a model by which to study the expression and regulation of various genes specific to luteal cells. We attempted to develop a luteal cell line by transformation of large luteal cells through infection with a temperature-sensitive simian virus (SV-40 tsA209) mutant that has a temperature-sensitive mutation required for the maintenance of cell transformation. We report here the successful establishment of such a cell line, designated GG-CL cells. Large luteal cells were purified to homogeneity by flow cytometry from corpora lutea of day 14 pregnant rats, cultured for 24 h, and then infected with the SV-40 tsA209 mutant virus. Transformed cells were maintained at the permissive temperature (33 C) until colonies were identified. Several colonies of transformed cells were isolated and passaged. They multiplied at 33 C and formed multilayers. At the nonpermissive temperature (40 C), cells reverted to the normal differentiated phenotype similar to the primary luteal cells in culture. To determine whether GG-CL cells express the genes found in normal luteal cells, messenger RNA (mRNA) expression was examined by either Northern analysis or RT-PCR with primers specific to each mRNA. GG-CL cells were found to express receptors for interleukin-6 and glucocorticoid, as well as the newly discovered estrogen receptor-beta (ER-beta) and the orphan nuclear receptor nur 77. No receptors for ER-alpha, progesterone, LH, or PRL could be detected. This cell line also expressed 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD), but not cholesterol side-chain cleavage cytochrome P450 (P450scc), 3beta-hydroxysteroid dehydrogenase, or aromatase cytochrome P450 (P450arom). Although the cells did not express the PRL receptor, they did express

  2. PAMELA, DAMA, INTEGRAL and signatures of metastable excited WIMPs

    NASA Astrophysics Data System (ADS)

    Finkbeiner, Douglas P.; Slatyer, Tracy R.; Weiner, Neal; Yavin, Itay

    2009-09-01

    Models of dark matter with ~ GeV scale force mediators provide attractive explanations of many high energy anomalies, including PAMELA, ATIC, and the WMAP haze. At the same time, by exploiting the ~ MeV scale excited states that are automatically present in such theories, these models naturally explain the DAMA/LIBRA and INTEGRAL signals through the inelastic dark matter (iDM) and exciting dark matter (XDM) scenarios, respectively. Interestingly, with only weak kinetic mixing to hypercharge to mediate decays, the lifetime of excited states with δ < 2melectron is longer than the age of the universe. The fractional relic abundance of these excited states depends on the temperature of kinetic decoupling, but can be appreciable. There could easily be other mechanisms for rapid decay, but the consequences of such long-lived states are intriguing. We find that CDMS constrains the fractional relic population of ~ 100 keV states to be lsim 10-2, for a 1 TeV WIMP with σn = 10-40 cm2. Upcoming searches at CDMS, as well as xenon, silicon, and argon targets, can push this limit significantly lower. We also consider the possibility that the DAMA excitation occurs from a metastable state into the XDM state, which decays via e+e- emission, which allows lighter states to explain the INTEGRAL signal due to the small kinetic energies required. Such models yield dramatic signals from down-scattering, with spectra peaking at high energies, sometimes as high as ~ 1 MeV, well outside the usual search windows. Such signals would be visible at future Ar and Si experiments, and may be visible at Ge and Xe experiments, although γ-rays associated with nuclear excitations would complicate the signal for these heavier targets. We also consider other XDM models involving ~ 500 keV metastable states, and find they can allow lighter WIMPs to explain INTEGRAL as well.

  3. Decreased in vivo α2 adrenoceptor binding in the Flinders Sensitive Line rat model of depression.

    PubMed

    Landau, Anne M; Phan, Jenny-Ann; Iversen, Peter; Lillethorup, Thea P; Simonsen, Mette; Wegener, Gregers; Jakobsen, Steen; Doudet, Doris J

    2015-04-01

    Depression is a debilitating heterogeneous disorder and the underlying mechanisms remain elusive. Alterations in monoaminergic neurotransmission, including noradrenergic, have been implicated in the etiology of depression. Although depression is difficult to model in animals, the availability of animal models with face, predictive and construct validity permits more in-depth investigations resulting in a greater understanding of the disease. We investigated the role of noradrenaline (NA) and α2 adrenoceptors in vivo in a genetic model of depression, the Flinders Sensitive Line (FSL) rat. We determined baseline differences in NA receptor volume of distribution to α2 adrenoceptors in FSL, in comparison with two routinely used controls, Flinders Resistant Line (FRL) and Sprague-Dawley (SD) rats using positron emission tomography (PET) imaging and the carbon-11 labeled radioligand yohimbine. We demonstrate a 42-47% reduction in the binding of the tracer in the cortex, striatum, cerebellum, thalamus and pons of FSL rats compared to the two control groups. Our results suggest that the behavioral deficits expressed in the FSL depression model are associated with functional over-activity of the NA system. PMID:25576372

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

    PubMed

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

    2008-09-01

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

  5. Chicks from a high and low feather pecking line of laying hens differ in apomorphine sensitivity.

    PubMed

    van Hierden, Yvonne M; Koolhaas, Jaap M; Kost'ál, L'ubor; Výboh, Pavel; Sedlacková, Monika; Rajman, Marek; Juráni, Marian; Mechiel Korte, S

    2005-03-16

    Proactive rodents show a larger behavioral response to apomorphine (APO) than reactive copers, suggesting a more sensitive DA system in proactive individuals. Previously, chicks from a high feather pecking (HFP) and low feather pecking line (LFP) have been suggested to display a proactive and reactive coping strategy, respectively. Therefore, at approximately 4 weeks of age, the behavior of 48 LFP and 48 HFP chicks in response to an APO injection was studied using an open field. Another objective of the present study was to determine whether behavioral variation (in an open field) between HFP and LFP birds, after APO injection, is also reflected by variation of D(1) and D(2) receptor densities in the brain. Receptor binding capacities were assessed by measuring specific binding of tritiated D(1) and D(2) receptor ligands in different regions of the brain of control HFP and LFP chicks. In the present study, it is shown that indeed HFP chicks display a more enhanced behavioral response to acute APO treatment (0.5 mg/kg BW) than LFP birds in an open field. This difference was not reflected by variation of D(1) and D(2) receptor densities in the brain between both lines. PMID:15763586

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

    SciTech Connect

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

    2011-05-01

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

  7. Engineering an analog-sensitive CDK12 cell line using CRISPR/Cas.

    PubMed

    Bartkowiak, Bartlomiej; Yan, Christopher; Greenleaf, Arno L

    2015-09-01

    The RNA Polymerase II C-terminal domain (CTD) kinase CDK12 has been implicated as a tumor suppressor and regulator of DNA damage response genes. Although much has been learned about CDK12 and its activity, due to the lack of a specific inhibitor and the complications posed by long term RNAi depletion, much is still unknown about the particulars of CDK12 function. Therefore gaining a better understanding of CDK12's roles at the molecular level will be challenging without the development of additional tools. In order to address these issues we have used the CRISPR/Cas gene engineering system to create a mammalian cell line in which the only functional copy of CDK12 is selectively inhibitable by a cell-permeable adenine analog (analog-sensitive CDK12). Inhibition of CDK12 results in a perturbation of the phosphorylation patterns on the CTD and an arrest in cellular proliferation. This cell line should serve as a powerful tool for future studies. PMID:26189575

  8. Regulation of ionic conductances and gene expression by hypoxia in an oxygen sensitive cell line.

    PubMed

    Millhorn, D E; Conforti, L; Beitner-Johnson, D; Zhu, W; Raymond, R; Filisko, T; Kobayashi, S; Peng, M; Genter, M B

    1996-01-01

    We have shown that the PC12 cell line is an excellent model system for investigations of the molecular and cellular processes involved in O2-chemosensitivity. We have identified an O2-sensitive K channel in this cell line that mediates membrane depolarization, an increase in intracellular free Ca2+, and dopamine release during hypoxia. We also presented evidence which shows that expression of the gene for tyrosine hydroxylase, the rate-limiting enzyme in dopamine biosynthesis, is stimulated by reduced O2 tension in PC12 and type I carotid body cells. In addition, we have successfully identified the DNA sequences and trans-acting protein factors that regulate transcription of the TH gene during hypoxia. The mechanisms by which a reduction in O2 tension is transduced into alter cell function including increased gene expression remain unknown. Unpublished results from our laboratory show that the increased TH gene expression during hypoxia does not require activation of the cAMP-PKA signal transduction pathway. We propose that the increase in intracellular free Ca2+ that occurs as a result of membrane depolarization might play an important role. Preliminary findings from our laboratory show that blockade of the voltage operated Ca2+ channel or chelation of intracellular Ca2+ prevent full activation of the TH gene during hypoxia. PMID:9030290

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

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

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

  10. Sensitivity analysis of oxygen absorption lines in the 1.26-1.27 micron spectral band

    NASA Astrophysics Data System (ADS)

    Edwards, W. C.; Prasad, N.; Browell, E. V.

    2009-12-01

    In the Decadal Survey prepared by the National Research Council (Reference: Earth Science and Applications from Space: National Imperatives for the Next Decade and Beyond), the ASCENDS mission (Active Sensing of CO2 Emissions over Nights, Days and Seasons), requires simultaneous laser remote sensing of CO2 and O2 in order to convert CO2 atmospheric concentrations to mixing ratios. As the mission is envisioned, the CO2 mixing ratio needs to be measured to a precision of 0.5 percent of background or better (slightly less than 2 ppm) at 100-km horizontal length scale overland and at 200-km scale over open oceans. While the O2 measurement could be made at 0.765 µm (the oxygen A band), the absorption cross section is substantially higher and the scattering is lower in the 1.26-1.27 µm wavelength band, and as such it is anticipated that better accuracies could be accomplished. Hence, NASA Langley Research Center is developing oxygen lidar technology in the 1.26-1.27 micron band for surface pressure measurements. One or more wavelengths for differential absorption lidar operation have to be carefully chosen to eliminate ambient influences on them. The model optical depth calculation is very sensitive to knowledge of the transmitted wavelengths and to the choice of Voigt input parameters. Uncertainties in atmospheric profiles of temperature, pressure and relative humidity can cause ~0.5 % errors in model optical depths. In order to select candidate wavelengths in the 1.26 micron spectral band, wavelength uncertainties due to temperature and pressure have to be determined. Uncertainties at line center and offset wavelengths have to be known precisely to reduce uncertainties in oxygen concentration measurements from airborne and space based platforms. In this paper, based on HITRAN database and absorption line measurements, we evaluate systematic relative errors and their sources of pressure shift and atmospheric temperature influences for selected O2 lines suitable for

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

    PubMed Central

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

    2009-01-01

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

  12. A rapid and sensitive fluorometric microassay for determining cell mediated cytotoxicity to adherent growing cell lines.

    PubMed

    Krüger-Krasagakes, S; Garbe, C; Kossman, P; Orfanos, C E

    1992-11-25

    In order to measure cell mediated cytotoxicity to adherent growing cell lines in vitro more rapidly and conveniently, a fluorometric microassay was developed and results were compared with those obtained by the 51Cr release assay. The fluorometric method is based on the hydrolysis of the fluorochrome 4-methylumbelliferyl heptanoate (MUH) by intracellular esterases of viable cells. Melanoma cell monolayers were incubated with lymphokine activated killer (LAK) cells for 4 h at various effector: target (E:T) cell ratios (E:T = 16, 8, 4, 2:1). Thereafter surviving adherent melanoma cells were stained with MUH for 30 min and fluorescence was measured directly in a 96 well plate reader. For the calculation of LAK cell cytotoxicity fluorescence values were corrected for the number of nonspecifically detached tumor cells during the washes and the number of nonspecifically adherent LAK cells. Using identical target and effector cell preparations both assays showed a nearly proportional increase of percentage cytotoxicity with rising numbers of lymphocytes. Compared with the 51Cr release assay, however, higher cytotoxicity values were obtained with the fluorometric MUH microassay: 57% with MUH versus 26% with 51Cr and 39% versus 14% for cell lines StML-11 and SKMel-28, respectively (E:T ratio = 16:1). The higher cytotoxicity rates obtained with the fluorometric MUH microassay were not due to the additional 30 min staining with MUH or due to nonspecific hydrolysis of MUH by extracellular esterases released from damaged cells, as could be shown by a series of experiments. In conclusion, a simple and rapid fluorometric microassay has been developed showing reliable reproducibility and a higher sensitivity compared with the 51Cr release assay for the determination of cellular cytotoxicity to adherent growing cell lines, avoiding hazardous radioactive labels. PMID:1431156

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

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

    2009-03-01

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

  15. Reconstructing WIMP properties through an interplay of signal measurements in direct detection, Fermi-LAT, and CTA searches for dark matter

    NASA Astrophysics Data System (ADS)

    Roszkowski, Leszek; Sessolo, Enrico Maria; Trojanowski, Sebastian; Williams, Andrew J.

    2016-08-01

    We examine the projected ability to reconstruct the mass, scattering, and annihilation cross section of dark matter in the new generation of large underground detectors, XENON-1T, SuperCDMS, and DarkSide-G2, in combination with diffuse gamma radiation from expected 15 years of data from Fermi-LAT observation of 46 local spiral dwarf galaxies and projected CTA sensitivity to a signal from the Galactic Center. To this end we consider several benchmark points spanning a wide range of WIMP mass, different annihilation final states, and large enough event rates to warrant detection in one or more experiments. As previously shown, below some 100 GeV only direct detection experiments will in principle be able to reconstruct WIMP mass well. This may, in case a signal at Fermi-LAT is also detected, additionally help restricting σv and the allowed decay branching rates. In the intermediate range between some 100 GeV and up a few hundred GeV, direct and indirect detection experiments can be used in complementarity to ameliorate the respective determinations, which in individual experiments can at best be rather poor, thus making the WIMP reconstruction in this mass range very challenging. At large WIMP mass, ~ 1 TeV, CTA will have the ability to reconstruct mass, annihilation cross section, and the allowed decay branching rates to very good precision for the τ+τ‑ or purely leptonic final state, good for the W+W‑ case, and rather poor for bbar b. A substantial improvement can potentially be achieved by reducing the systematic uncertainties, increasing exposure, or by an additional measurement at Fermi-LAT that would help reconstruct the annihilation cross section and the allowed branching fractions to different final states.

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

    PubMed

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

    1999-08-20

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

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

    PubMed Central

    Ye, Anna A.; Maresca, Thomas J.

    2016-01-01

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

  18. Comparative evaluation of cisplatin and carboplatin sensitivity in endometrial adenocarcinoma cell lines.

    PubMed Central

    Rantanen, V.; Grénman, S.; Kulmala, J.; Grénman, R.

    1994-01-01

    Platinum analogues are frequently used in the treatment of advanced or recurrent endometrial cancer. To study the sensitivity of endometrial cancer to cisplatin and carboplatin, we tested two long-established (RL95-2, KLE) and six new cell lines (UM-EC-1, UM-EC-2, UM-EC-3, UT-EC-2A, UT-EC-2B, UT-EC-3) using the 96-well-plate clonogenic assay. This assay has proven to be suitable for testing chemosensitivity of both adenocarcinoma and squamous cell carcinoma. The chemosensitivity was expressed as an IC50 value, the drug concentration causing 50% inhibition of clonogenic survival. IC50 values were obtained from dose-response curves after fitting the data by the linear quadratic equation, F = exp[-(alpha D + beta D2)]. The IC50 values of the two platinum derivatives varied considerably. The values for cisplatin varied between 0.022 microgram ml-1 and 0.56 microgram ml-1 and the corresponding values for carboplatin were 0.096-1.20 microgram ml-1. The range of the ratios between carboplatin IC50 and cisplatin IC50, from 1.5:1 to 4.4:1, was rather narrow. However, no constant ratio between carboplatin IC50 and cisplatin IC50 could be detected. The equivalent doses with regard to efficacy of these two platinum analogues remain to be determined. PMID:8123477

  19. Sensitivity of the curve-to-growth technique utilized in rocket experiments to determine the line shape of solar He I resonance lines

    NASA Technical Reports Server (NTRS)

    Wu, C. Y. R.; Ogawa, H. S.

    1986-01-01

    The sensitivity of the curve-of-growth (COG) technique utilized in rocket measurements to determine the line profiles of the solar He I resonance emissions is theoretically examined with attention to the possibility of determining the line core shape using this technique. The line at 584.334 A is chosen as an illustration. Various possible source functions of the solar line have been assumed in the computation of the integrated transmitted intensity. A recent observational data set obtained by the present researchers is used as the constraint of the computation. It is confirmed that the COG technique can indeed provide a good measurement of the solar line width. However, to obtain detailed knowledge of the solar profile at line center and in the core region, (1) it is necessary to be able to carry out relative solar flux measurements with a 1-percent or better precision, and (2) it must be possible to measure the He gas pressure in the absorption cell to lower than 0.1 mtorr. While these numbers apply specifically to the present geometry, the results are readily scaled to other COG measurements using other experimental parameters.

  20. Molecular and Physiological Responses to Water Deficit in Drought-Tolerant and Drought-Sensitive Lines of Sunflower1

    PubMed Central

    Cellier, Françoise; Conéjéro, Geneviève; Breitler, Jean-Christophe; Casse, Francine

    1998-01-01

    To investigate correlations between phenotypic adaptation to water limitation and drought-induced gene expression, we have studied a model system consisting of a drought-tolerant line (R1) and a drought-sensitive line (S1) of sunflowers (Helianthus annuus L.) subjected to progressive drought. R1 tolerance is characterized by the maintenance of shoot cellular turgor. Drought-induced genes (HaElip1, HaDhn1, and HaDhn2) were previously identified in the tolerant line. The accumulation of the corresponding transcripts was compared as a function of soil and leaf water status in R1 and S1 plants during progressive drought. In leaves of R1 plants the accumulation of HaDhn1 and HaDhn2 transcripts, but not HaElip1 transcripts, was correlated with the drought-adaptive response. Drought-induced abscisic acid (ABA) concentration was not associated with the varietal difference in drought tolerance. Stomata of both lines displayed similar sensitivity to ABA. ABA-induced accumulation of HaDhn2 transcripts was higher in the tolerant than in the sensitive genotype. HaDhn1 transcripts were similarly accumulated in the tolerant and in the sensitive plants in response to ABA, suggesting that additional factors involved in drought regulation of HaDhn1 expression might exist in tolerant plants. PMID:9499218

  1. Cell-Line Selectivity Improves the Predictive Power of Pharmacogenomic Analyses and Helps Identify NADPH as Biomarker for Ferroptosis Sensitivity.

    PubMed

    Shimada, Kenichi; Hayano, Miki; Pagano, Nen C; Stockwell, Brent R

    2016-02-18

    Precision medicine in oncology requires not only identification of cancer-associated mutations but also effective drugs for each cancer genotype, which is still a largely unsolved problem. One approach for the latter challenge has been large-scale testing of small molecules in genetically characterized cell lines. We hypothesized that compounds with high cell-line-selective lethality exhibited consistent results across such pharmacogenomic studies. We analyzed the compound sensitivity data of 6,259 lethal compounds from the NCI-60 project. A total of 2,565 cell-line-selective lethal compounds were identified and grouped into 18 clusters based on their median growth inhibitory GI50 profiles across the 60 cell lines, which were shown to represent distinct mechanisms of action. Further transcriptome analysis revealed a biomarker, NADPH abundance, for predicting sensitivity to ferroptosis-inducing compounds, which we experimentally validated. In summary, incorporating cell-line-selectivity filters improves the predictive power of pharmacogenomic analyses and enables discovery of biomarkers that predict the sensitivity of cells to specific cell death inducers. PMID:26853626

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

    PubMed

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

    2010-08-16

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

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

    SciTech Connect

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

    2011-09-16

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

  4. Chemical sensitization and regulation of TRAIL-induced apoptosis in a panel of B-lymphocytic leukaemia cell lines.

    PubMed

    Kang, Jian; Kisenge, Rodrick R; Toyoda, Hidemi; Tanaka, Shigeki; Bu, Jun; Azuma, Eiichi; Komada, Yoshihiro

    2003-12-01

    Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) effectively kills tumour cells but not normal cells. We investigated TRAIL sensitivity and the TRAIL-induced apoptosis signalling pathway in a panel of B-lymphocytic leukaemia cell lines. Depending upon TRAIL sensitivity, leukaemia cells could be divided into three groups: highly sensitive, moderately sensitive and resistant. TRAIL receptor-2 (DR5) plays an important role in transducing apoptosis signals. DR5 was internalized into the cytoplasm where it recruited FAS-associated death domain protein (FADD) under TRAIL stimulation in both sensitive and resistant cells. However, the active form of caspase-8 was recruited to FADD and only sensitive cells showed increased caspase-8 activity upon TRAIL stimulation. The caspase-8 specific inhibitor, Z-IETD, impaired caspase-8 activation and completely abrogated TRAIL-induced apoptosis. These results suggest that TRAIL resistance in B-lymphocytic leukaemia cells is due to negative regulation at the level of caspase-8 activation and that caspase-8 activation is an indispensable process in TRAIL-induced apoptosis. However, FADD-like interleukin-1 beta-converting enzyme inhibitory protein (c-FLIPL) was similarly expressed and down-regulated after TRAIL stimulation in both sensitive and resistant cells. Interestingly, in some cell lines, TRAIL sensitivity and caspase-8 activity was enhanced or restored with the treatment of cycloheximide (CHX). In addition, X-linked inhibitor of apoptosis (XIAP) levels decreased significantly and rapidly following treatment with CHX. Down-regulation of XIAP may be responsible for enhancement or restoration of TRAIL sensitivity after CHX treatment in B-lymphocytic leukaemia cells. PMID:14632785

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

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

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

  6. Effective sensitization of temozolomide by ABT-888 is lost with development of TMZ resistance in glioblastoma xenograft lines

    PubMed Central

    Clarke, Michelle J.; Mulligan, Evan A.; Grogan, Patrick T.; Mladek, Ann C.; Carlson, Brett L.; Schroeder, Mark A.; Curtin, Nicola J.; Lou, Zhenkun; Decker, Paul A.; Wu, Wenting; Plummer, E. Ruth; Sarkaria, Jann N.

    2009-01-01

    Resistance to temozolomide (TMZ) and radiotherapy (RT) is a major problem for patients with GBM but may be overcome using the PARP-inhibitor ABT-888. Using two primary GBM xenografts, the efficacy of ABT-888 combined with RT and/or TMZ was evaluated. Treatment with ABT-888 combined with TMZ resulted in significant survival prolongation (GBM12: 55.1%, p=0.005; GBM22: 54.4%, p=0.043). ABT-888 had no effect with RT alone, but significantly enhanced survival in GBM12 when combined with concurrent RT/TMZ. With multi-cycle therapy, ABT-888 further extended the survival benefit of TMZ in the inherently sensitive GBM12 and GBM22 xenograft lines. However, after in vivo selection for TMZ resistance, the derivative GBM12TMZ and GBM22TMZ lines were no longer sensitized by ABT-888 in combination with TMZ, and a similar lack of efficacy was observed in two other TMZ resistant tumor lines. Thus, the sensitizing effects of ABT-888 were limited to tumor lines that had not been previously exposed to TMZ, and these results suggest that patients with newly diagnosed GBM may be more likely to respond to combined TMZ/PARP inhibitor therapy than patients with recurrent disease. PMID:19174557

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

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2014-03-15

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

  10. EDELWEISS-III experiment: Status and first low WIMP mass results

    NASA Astrophysics Data System (ADS)

    Scorza, Silvia; EDELWEISS Collaboration

    2016-05-01

    The EDELWEISS-III collaboration is operating an experiment for the direct detection of Weakly Interacting Massive Particle (WIMPs) dark matter in the low radioactivity environment of the Modane Underground Laboratory. It consists of 24 advanced high-purity germanium detectors operating at 18 mK in a dilution refrigerator in order to identify rare nuclear recoils induced by elastic scattering of WIMPs from our Galactic halo. The current EDELWEISS-III program, including improvements of the background, data-acquisition and the current installation will be detailed. Sources of background along with the rejection techniques will be discussed. Detector performances and a first low WIMP mass (Boosted Decision Tree) BDT- based analysis of data acquired in a long-term campaign will be presented as well.

  11. Detection of WIMP-like dark matter in some extensions of the Standard Model

    NASA Astrophysics Data System (ADS)

    Goudelis, Andreas

    2011-06-01

    One of the most popular classes of candidates for dark matter are Weakly Interacting Massive Particles (WIMPs), i.e. particles possessing masses and couplings falling roughly within the electroweak scale. Apart from offering a natural mechanism for explaining dark matter, WIMPs also provide us with a hope that they could be detected through their non-gravitational interactions. In such an eventuality, we shall certainly get closer to the goal of identifying the true nature of dark matter. After introducing some formalism and elements of theory, we study the phenomenology of WIMP-type dark matter both in a model-independent manner as well as in the framework of specific models, focusing on the prospects for detection in running or oncoming direct and indirect detection experiments.

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

    SciTech Connect

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

    1999-10-01

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

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

    SciTech Connect

    Conrad, J.; Cohen-Tanugi, J.

    2015-12-15

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

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

    SciTech Connect

    Baer, Howard

    2014-01-01

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

  15. 750 GeV dark pion: Cousin of a dark G -parity odd WIMP

    NASA Astrophysics Data System (ADS)

    Bai, Yang; Berger, Joshua; Lu, Ran

    2016-04-01

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

  16. 47 CFR 69.713 - Common line, traffic-sensitive, and tandem-switched transport services.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

  17. 47 CFR 69.713 - Common line, traffic-sensitive, and tandem-switched transport services.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

  18. 47 CFR 69.713 - Common line, traffic-sensitive, and tandem-switched transport services.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  19. 47 CFR 69.713 - Common line, traffic-sensitive, and tandem-switched transport services.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  20. 47 CFR 69.713 - Common line, traffic-sensitive, and tandem-switched transport services.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  1. Synovial sarcoma cell lines showed reduced DNA repair activity and sensitivity to a PARP inhibitor.

    PubMed

    Yamasaki, Hiroyuki; Miyamoto, Mamiko; Yamamoto, Yuki; Kondo, Tadashi; Watanabe, Toshiki; Ohta, Tsutomu

    2016-08-01

    Synovial sarcoma is a soft-tissue sarcoma and a rare type of cancer. Unfortunately, effective chemotherapies for synovial sarcomas have not been established. In this report, we show that synovial sarcoma cell lines have reduced repair activity for DNA damage induced by ionizing radiation (IR) and a topoisomerase II inhibitor (etoposide). We also observed reduced recruitment of RAD51 homologue (S. cerevisiae; RAD51) at sites of double-strand breaks (DSBs) in synovial sarcoma cell lines that had been exposed to IR. These findings showed that synovial sarcoma cell lines are defective in homologous recombination (HR) repair. Furthermore, we found that a poly-(ADP-ribose) polymerase (PARP) inhibitor (AZD2281; olaparib) effectively reduced the growth of synovial sarcoma cell lines in the presence of an alkylating agent (temozolomide). Our findings offer evidence that treatment combining a PARP inhibitor and an alkylating agent could have therapeutic benefits in the treatment of synovial sarcoma. PMID:27353471

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2000-01-01

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

  4. Lines

    ERIC Educational Resources Information Center

    Mires, Peter B.

    2006-01-01

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

  5. Sensitivity of locally recurrent rat mammary tumour cell lines to syngeneic polymorphonuclear cell, macrophage and natural killer cell cytolysis.

    PubMed

    Aeed, P A; Welch, D R

    1988-12-01

    Using a recently developed model for studying the biology of locally recurrent (LR) mammary tumours in the 13762NF rat mammary adenocarcinoma system, we examined the sensitivity to polymorphonuclear cell, macrophage and natural killer cell cytolysis. The parental MTF7(T20) cell line; the 'primary' tumours which arose following subcutaneous inoculation into the mammary fat pad, sc1 and sc3; and the local recurrences (following surgical excision) LR1 and LR1a from sc1, and LR3 from sc3 were all cells generally resistant to specific PMN cytolysis. LPS-activated macrophages caused 25.1%, 38.7% and 58.8% specific cytolysis in MTF7, sc1 and LR1 cells, respectively at E:T of 20:1 and 72 h co-incubation. LR1a, sc3 and LR3 lysis ranged from 0-4.4% under the same conditions. Non-activated macrophages did not lyse any of the cell lines. Locally recurrent and 'primary' tumour cell lines were also not lysed by naive NK cells (range 0.5-4.0% cytolysis). NK cells activated with bropirimine, a potent immunomodulator currently being studied in clinical trials, and/or interleukin-2 were mildly more effective at killing LR cells. Our results show that locally recurrent tumours exhibit heterogeneous sensitivities and are different from 'primary' tumour cells in sensitivities to immune cell killing, but they are not necessarily more or less sensitive. Results with bropirimine-activated or IL-2-activated NK cells emphasize that nonspecific activation is insufficient to eliminate all tumour subpopulations. PMID:3224080

  6. 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...

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

    NASA Astrophysics Data System (ADS)

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

    2005-09-01

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

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

    NASA Astrophysics Data System (ADS)

    Rao, Gottipaty N.; Karpf, Andreas

    2011-05-01

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

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

    NASA Astrophysics Data System (ADS)

    McDonald, John

    2011-11-01

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

  10. Detector Simulation and WIMP Search Analysis for the Cryogenic Dark Matter Search Experiment

    SciTech Connect

    McCarthy, Kevin

    2013-06-01

    Astrophysical and cosmological measurements on the scales of galaxies, galaxy clusters, and the universe indicate that 85% of the matter in the universe is composed of dark matter, made up of non-baryonic particles that interact with cross-sections on the weak scale or lower. Hypothetical Weakly Interacting Massive Particles, or WIMPs, represent a potential solution to the dark matter problem, and naturally arise in certain Standard Model extensions. The Cryogenic Dark Matter Search (CDMS) collaboration aims to detect the scattering of WIMP particles from nuclei in terrestrial detectors. Germanium and silicon particle detectors are deployed in the Soudan Underground Laboratory in Minnesota. These detectors are instrumented with phonon and ionization sensors, which allows for discrimination against electromagnetic backgrounds, which strike the detector at rates orders of magnitude higher than the expected WIMP signal. This dissertation presents the development of numerical models of the physics of the CDMS detectors, implemented in a computational package collectively known as the CDMS Detector Monte Carlo (DMC). After substantial validation of the models against data, the DMC is used to investigate potential backgrounds to the next iteration of the CDMS experiment, known as SuperCDMS. Finally, an investigation of using the DMC in a reverse Monte Carlo analysis of WIMP search data is presented.

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

    SciTech Connect

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

    2015-06-12

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

  12. Status and Prospects of the EDELWEISS-III Direct WIMP Search Experiment

    NASA Astrophysics Data System (ADS)

    Juillard, A.

    2016-08-01

    EDELWEISS-III is a direct dark matter search experiment, running 800 g heat-and-ionization cryogenic germanium detectors equipped with Full InterDigitized electrodes (FID) for the rejection of near-surface events. We report a preliminary analysis for a subset of the data (35 kg\\cdot days) as well as future prospects for low-mass WIMPs seach.

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

    NASA Astrophysics Data System (ADS)

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

    2003-06-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

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

  15. ET-59DEVELOPMENT AND CHARACTERIZATION OF A MEK1 INHIBITOR (AZD6244) SENSITIVE CHILDHOOD ASTROCYTOMA CELL LINE

    PubMed Central

    Studebaker, Adam; Bid, Hemant; Phelps, Doris; Houghton, Peter

    2014-01-01

    We previously characterized the development and reversal of acquired resistance to the MEK1 inhibitor AZD6244 in an in vivo model of childhood astrocytoma. The BT-40 astrocytoma xenograft model expresses mutated BRAFV600E and is highly sensitive to AZD6244, but acquires resistance, which can be overcome with the addition of the STAT3 inhibitor LLL12. The purpose of this current study was to establish and characterize a cell line derived from the xenograft model as well as develop an orthotopic mouse model. Sensitivity to AZD6244 and LLL12, expression-profiling assessment of MEK signature and compensatory pathways, and cytokine levels were assessed in the newly developed BT-40 cell line. The BT-40 cell line exhibited sensitivity to AZD6244 and LLL12 with IC50 values of 350nM and 1 µM, respectively. Combination treatment was additive. Treatment with AZD6244 inhibited p-Erk and the mTOR downstream signaling molecule p-S6, while p-Akt, p-STAT3, p-4E-BP1 increased. Kinase expression arrays performed on cells treated with AZD6244 showed a decrease in IL-1α, G-CSF, and IL-6 and an increase in CXCL10. The decrease in IL-6 was restored to baseline levels with the addition of LLL12. Interestingly, the JAK2 inhibitor AZD1480 failed to restore the IL-6 levels. The IL-6 results observed in the expression arrays were confirmed by ELISA. The BT-40 cell line, along with a cell line stably expressing luciferase (BT-40Luc), were implanted into the caudate putamen using stereotaxic guidance. The BT-40Luc cells exhibited exponential growth over time as evaluated with bioluminescent imaging. In conclusion, a cell line derived from a previously described in vivo model of childhood astrocytoma was developed that closely recapitulated our original findings in the xenograft model following treatment with the MEK1 inhibitor AZD6244. Furthermore, an orthotopic model of these cells was developed, which will allow us to characterize response to established and novel therapeutic agents

  16. Striatal transcriptome analysis of a congenic mouse line (chromosome 11: 50-60Mb) exhibiting reduced methamphetamine sensitivity.

    PubMed

    Yazdani, Neema; Shen, Ying; Johnson, W Evan; Bryant, Camron D

    2016-06-01

    Addiction to psychostimulants such as Methamphetamine (MA) is a significant public health issue in the United States and currently, there are no FDA approved pharmacological interventions. Previously, using short term-selected mouse lines for high and low MA sensitivity that were derived from an F2 cross between C57BL/6J (B6) and DBA/2J (D2) strains, we identified a quantitative trait locus (QTL) on chromosome (chr) 11 that influenced sensitivity to MA-induced locomotor activity (D2 < B6). Using interval-specific murine congenic lines containing various D2 allelic segments on a B6 background, we fine mapped the QTL to a 206 kb critical interval on chromosome 11. To investigate the neurobiological mechanism by which this QTL decreases MA sensitivity, we conducted transcriptome analysis in a 10 Mb congenic mouse (chromosome 11: 50-60 Mb) on whole-striatum brain tissue punches compared to wild-type B6 littermate controls [1]. The data from this study can be found in the NCBI Gene Expression Omnibus (GSE66366). PMID:27222804

  17. Comparison of the sensitivity of three lung derived cell lines to metals from combustion derived particulate matter.

    PubMed

    Riley, Mark R; Boesewetter, Dianne E; Turner, Rachael A; Kim, Aana M; Collier, Jayne M; Hamilton, Amy

    2005-04-01

    While the effects of inhalation of combustion-derived particulate matter have received extensive study, there remains no reliable means to rapidly quantify inhalation toxicity outside of a laboratory setting. Cell-based biosensors provide a potential solution, but few comparisons have been made of the sensitivity of various cell lines to the wide range of inhalation health hazards that are likely to be encountered. This work compares the response of three immortalized lung cell lines (A549 human epithelia, RLE-6TN rat type II epithelia, and NR8383 rat alveolar macrophages) to metals commonly present in combustion-derived particulate matter. Quantifications of the cell response involved measurement of inhibition of cell culture metabolism (mitochondrial succinate dehydrogenase activity) and cell death (release of lactate dehydrogenase). While these three cell types generally ranked metals in ED50 values similarly (Vsensitive to metals by nearly an order of magnitude in metal concentration, followed by RLE-6TN rat epithelia, then A549 human cells. This comparison of the sensitivity of three cell types provides a basis for selection of cell types for use in cell-based biosensors. PMID:15713548

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

    PubMed Central

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

    2016-01-01

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

  19. A high sensitive two-line detector with large dynamic range for intravenous coronary angiography

    NASA Astrophysics Data System (ADS)

    Lohmann, M.; Besch, H. J.; Dix, W.-R.; Dünger, O.; Jung, M.; Menk, R. H.; Reime, B.; Schildwächter, L.

    1998-12-01

    The medical community is highly interested in methods for non-invasive imaging of coronary arteries. One method under development is dichromography. This method allows imaging of small fast moving objects like the coronary arteries including distal parts and sidebranches after intravenous injection of contrast material. Two images with monochromatic X-rays at energies just below and above the K-edge of iodine at 33.17 keV are simultaneously taken. After logarithmic subtraction coronary arteries down to 0.7 mm diameter with extremely low iodine concentrations of 10 mg/ml become visible. At the Hamburger Synchrotronstrahlungslabor HASYLAB at DESY in Hamburg, Germany the system NIKOS was developed for dichromography. In this system the detector is one of the main components. This two-line detector is an ionization chamber for the two energies. The two gaps are separated by the drift cathode. A Frisch-grid for shielding the ions in a distance of 3 mm defines the conversion room. The 336 anode strips per line with a length of 56 mm in the direction of the beam are connected to the frontend electronics. The parameters of the current version of the detector in one setting are: noise equivalent of 7.6 photons, dynamic range of 300 000 : 1, readout time for the two lines (672 pixels) 0.18 ms.

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

    SciTech Connect

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

    1983-07-01

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

  1. Isolation and characterization of a UV-sensitive hypermutable aphidicolin-resistant Chinese hamster cell line

    SciTech Connect

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

    1981-01-01

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

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

    PubMed Central

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

    2014-01-01

    For devices such as bio-/chemical sensors in microfluidic systems, flow fluctuations result in noise in the sensor output. Here, we demonstrate in-line monitoring of flow fluctuations with a cantilever-like sensor integrated in a microfluidic channel. The cantilevers are fabricated in different materials (SU-8 and SiN) and with different thicknesses. The integration of arrays of holes with different hole size and number of holes allows the modification of device sensitivity, theoretical detection limit and measurement range. For an average flow in the microliter range, the cantilever deflection is directly proportional to the flow rate fluctuations in the microfluidic channel. The SiN cantilevers show a detection limit below 1 nL/min and the thinnest SU-8 cantilevers a detection limit below 5 nL/min. Finally, the sensor is applied for in-line monitoring of flow fluctuations generated by external pumps connected to the microfluidic system. PMID:24366179

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

    PubMed Central

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

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2006-12-01

    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.

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

    Our brains readily decode facial movements and changes in social attention, reflected in earlier and larger N170 event-related potentials (ERPs) to viewing gaze aversions vs. direct gaze in real faces (Puce et al., 2000). In contrast, gaze aversions in line-drawn faces do not produce these N170 differences (Rossi et al., 2014), suggesting that physical stimulus properties or experimental context may drive these effects. Here we investigated the role of stimulus-induced context on neurophysiological responses to dynamic gaze. Sixteen healthy adults viewed line-drawn and real faces, with dynamic eye aversion and direct gaze transitions, and control stimuli (scrambled arrays and checkerboards) while continuous electroencephalographic (EEG) activity was recorded. EEG data from 2 temporo-occipital clusters of 9 electrodes in each hemisphere where N170 activity is known to be maximal were selected for analysis. N170 peak amplitude and latency, and temporal dynamics from Event-Related Spectral Perturbations (ERSPs) were measured in 16 healthy subjects. Real faces generated larger N170s for averted vs. direct gaze motion, however, N170s to real and direct gaze were as large as those to respective controls. N170 amplitude did not differ across line-drawn gaze changes. Overall, bilateral mean gamma power changes for faces relative to control stimuli occurred between 150–350 ms, potentially reflecting signal detection of facial motion. Our data indicate that experimental context does not drive N170 differences to viewed gaze changes. Low-level stimulus properties, such as the high sclera/iris contrast change in real eyes likely drive the N170 changes to viewed aversive movements. PMID:25914636

  7. A sensitive mutation screening method supporting cell line development for biotherapeutics.

    PubMed

    Valisheva, Ildana; Harris, Reed J; Zhu-Shimoni, Judith

    2016-07-15

    Random genetic mutations, which can occur during cell line development, can lead to sequence variants that comprise pharmaceutical product quality generated by recombinant technology. Mutation screening can minimize the probability of selecting clones harboring sequence variants. Here we report a polymerase chain reaction (PCR)-based mutation screening approach using high-resolution melting (HRM) analysis combined with a mutation enrichment step using limiting dilution to detect low-level mutations at 0.5%. The method allows unknown mutation discovery regardless of its location in a transgene as well as independent of its position in an HRM fragment, ranging from approximately 200 to 300 bp in size. PMID:27108188

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

  9. Thioridazine Sensitizes Esophageal Carcinoma Cell Lines to Radiotherapy-Induced Apoptosis In Vitro and In Vivo

    PubMed Central

    Li, Hongxia; Juan, Li; Xia, Leiming; Wang, Yi; Bao, Yangyi; Sun, Guoping

    2016-01-01

    Background Radiotherapy is one of the primary treatments for esophageal squamous cell carcinoma (ESCC). Identification of novel radio-sensitizing agents will improve the therapeutic outcome of radiotherapy. This study aimed to determine the radio-sensitizing effect of the antipsychotic agent thioridazine in ESCC and explored the underlying mechanisms. Material/Methods ECA-109 and TE-1 ESCC cells were treated with thioridazine and radiotherapy alone and in combination. Cell survival was measured by MTT assay. Cell cycle and apoptosis were monitored by flow cytometry. Western blot analysis was used to analyze the expression of phospho-PI3K, phosphor-AKT, phospho-mTOR, Caspase-3, Caspase-9, Bax, Bcl-2, Bal-xl, Bak, and p53. The xenograft mouse model was used to study the in vivo anticancer effect of thioridazine and irradiation. Results Combined treatment with thioridazine and irradiation significantly reduced viability of ESCC cells compared with thioridazine or irradiation treatment alone. Thioridazine and irradiation treatment induced G0/G1 phases cell cycle arrest through down-regulation of CDK4 and cyclinD1. In addition, thioridazine and irradiation treatment induced apoptosis through up-regulation of cleaved capase-3 and 9, as well as an increase in the expression of Bax and Bak and a decrease in the expression of Bcl-2 and Bcl-xl. Furthermore, thioridazine and irradiation treatment inhibited the PI3K-AKT-mTOR pathway and up-regulated the expression of p53. In xenograft mice, thioridazine and irradiation reduced ESCC tumor growth. Conclusions Thioridazine sensitizes ESCC cells to radiotherapy. Thioridazine may play a role in ESCC radiation therapy as a promising radiosensitizer. PMID:27453171

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

    PubMed

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

    2012-01-01

    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. PMID:23145051

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

    NASA Technical Reports Server (NTRS)

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

    1988-01-01

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

  12. PKC activation sensitizes basal-like breast cancer cell lines to Smac mimetics

    PubMed Central

    Cornmark, L; Holmgren, C; Masoumi, K; Larsson, C

    2016-01-01

    There is a need for novel strategies to initiate cancer cell death. One approach is the use of Smac mimetics, which antagonize inhibitor of apoptosis proteins (IAPs). Recent studies have shown that combinations of Smac mimetics such as LBW242 or LCL161 in combination with chemotherapeutic agents increase cancer cell death. Here we show that the protein kinase C (PKC) activator TPA together with the Smac mimetic LBW242 induces cell death in two basal breast cancer cell lines (MDA-MB-468 and BT-549) that are resistant to Smac mimetic as single agent. Ten other LBW242-insensitive cancer cell lines were not influenced by the TPA+LBW242 combination. The TPA+LBW242 effect was suppressed by the PKC inhibitor GF109203X, indicating dependence on PKC enzymatic activity. The PKC effect was mediated via increased synthesis and release of TNFα, which can induce death in the presence of Smac mimetics. The cell death, coinciding with caspase-3 cleavage, was suppressed by caspase inhibition and preceded by the association of RIP1 with caspase-8, as seen in complex II formation. Smac mimetics, but not TPA, induced the non-canonical NF-κB pathway in both MDA-MB-231 and MDA-MB-468 cells. Blocking the canonical NF-κB pathway suppressed TPA induction of TNFα in MDA-MB-468 cells whereas isolated downregulation of either the canonical or non-canonical pathways did not abolish the Smac mimetic induction of the NF-κB driven genes TNFα and BIRC3 in MDA-MB-231 cells although the absolute levels were suppressed. A combined downregulation of the canonical and non-canonical pathways further suppressed TNFα levels and inhibited Smac mimetic-mediated cell death. Our data suggest that in certain basal breast cancer cell lines co-treatment of TPA with a Smac mimetic induces cell death highlighting the potential of using these pathways as molecular targets for basal-like breast cancers. PMID:27551497

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

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

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

  14. Vectorized polarization-sensitive model of non-line-of-sight multiple-scatter propagation.

    PubMed

    Yin, Hongwei; Jia, Honghui; Zhang, Hailiang; Wang, Xiaofeng; Chang, Shengli; Yang, Juncai

    2011-10-01

    The existing Monte-Carlo-based non-line-of-sight (NLOS) multiple-scatter propagation model is extended to include polarization and also vectorized to improve the simulation speed by about 500 times. This model is validated by the noncoplanar single-scatter model; the results show a perfect match. Numerical examples for various polarization setups are obtained, and results show that the single-scatter and multiple-scatter signals are all polarization dependent. Therefore, NLOS polarized UV communication with a high data rate is achievable--the polarizing information is coded by a time-dependent polarizer, influenced by the atmospheric channel, and decoded according to the distribution characteristics of the scattered signals after the time-independent analyzers. PMID:21979512

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

    PubMed Central

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

    2015-01-01

    Mycoplasma are a frequent and occult contaminant of cell cultures, whereby these prokaryotic organisms can modify many aspects of cell physiology, rendering experiments that are conducted with such contaminated cells problematic. Chronic Mycoplasma contamination in human monocytic cells lines has been associated with suppressed Toll-like receptor (TLR) function. In contrast, we show here that components derived from a Mycoplasma hyorhinis-infected cell line can activate innate immunity in non-infected primary immune cells. Release of pro-inflammatory cytokines such as IL-6 by dendritic cells in response to Mycoplasma hyorhinis-infected cell components was critically dependent on the adapter protein MyD88 but only partially on TLR2. Unlike canonical TLR2 signaling that is triggered in response to the detection of Mycoplasma infection, innate immune activation by components of Mycoplasma-infected cells was inhibited by chloroquine treatment and sensitive to protease treatment. We further show that in plasmacytoid dendritic cells, soluble factors from Mycoplasma hyorhinis-infected cells induce the production of large amounts of IFN-α. We conclude that Mycoplasma hyorhinis-infected cell lines release protein factors that can potently activate co-cultured innate immune cells via a previously unrecognized mechanism, thus limiting the validity of such co-culture experiments. PMID:26565413

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

    PubMed

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

    2015-01-01

    Mycoplasma are a frequent and occult contaminant of cell cultures, whereby these prokaryotic organisms can modify many aspects of cell physiology, rendering experiments that are conducted with such contaminated cells problematic. Chronic Mycoplasma contamination in human monocytic cells lines has been associated with suppressed Toll-like receptor (TLR) function. In contrast, we show here that components derived from a Mycoplasma hyorhinis-infected cell line can activate innate immunity in non-infected primary immune cells. Release of pro-inflammatory cytokines such as IL-6 by dendritic cells in response to Mycoplasma hyorhinis-infected cell components was critically dependent on the adapter protein MyD88 but only partially on TLR2. Unlike canonical TLR2 signaling that is triggered in response to the detection of Mycoplasma infection, innate immune activation by components of Mycoplasma-infected cells was inhibited by chloroquine treatment and sensitive to protease treatment. We further show that in plasmacytoid dendritic cells, soluble factors from Mycoplasma hyorhinis-infected cells induce the production of large amounts of IFN-α. We conclude that Mycoplasma hyorhinis-infected cell lines release protein factors that can potently activate co-cultured innate immune cells via a previously unrecognized mechanism, thus limiting the validity of such co-culture experiments. PMID:26565413

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

    PubMed Central

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

    2015-01-01

    Evidence that culture modulates on-line neural responses to the emotional meanings encoded by vocal and facial expressions was demonstrated recently in a study comparing English North Americans and Chinese (Liu et al., 2015). Here, we compared how individuals from these two cultures passively respond to emotional cues from faces and voices using an Oddball task. Participants viewed in-group emotional faces, with or without simultaneous vocal expressions, while performing a face-irrelevant visual task as the EEG was recorded. A significantly larger visual Mismatch Negativity (vMMN) was observed for Chinese vs. English participants when faces were accompanied by voices, suggesting that Chinese were influenced to a larger extent by task-irrelevant vocal cues. These data highlight further differences in how adults from East Asian vs. Western cultures process socio-emotional cues, arguing that distinct cultural practices in communication (e.g., display rules) shape neurocognitive activity associated with the early perception and integration of multi-sensory emotional cues. PMID:26074808

  18. A Study of Nuclear Recoils in Liquid Argon Time Projection Chamber for the Direct Detection of WIMP Dark Matter

    SciTech Connect

    Cao, Huajie

    2014-11-01

    Robust results of WIMP direct detection experiments depend on rm understandings of nuclear recoils in the detector media. This thesis documents the most comprehensive study to date on nuclear recoils in liquid argon - a strong candidate for the next generation multi-ton scale WIMP detectors. This study investigates both the energy partition from nuclear recoil energy to secondary modes (scintillation and ionization) and the pulse shape characteristics of scintillation from nuclear recoils.

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

    PubMed Central

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

    2014-01-01

    Drought stress is a major factor that contributes to disease susceptibility and yield loss in agricultural crops. To identify drought responsive proteins and explore metabolic pathways involved in maize tolerance to drought stress, two maize lines (B73 and Lo964) with contrasting drought sensitivity were examined. The treatments of drought and well water were applied at 14 days after pollination (DAP), and protein profiles were investigated in developing kernels (35 DAP) using iTRAQ (isobaric tags for relative and absolute quantitation). Proteomic analysis showed that 70 and 36 proteins were significantly altered in their expression under drought treatments in B73 and Lo964, respectively. The numbers and levels of differentially expressed proteins were generally higher in the sensitive genotype, B73, implying an increased sensitivity to drought given the function of the observed differentially expressed proteins, such as redox homeostasis, cell rescue/defense, hormone regulation and protein biosynthesis and degradation. Lo964 possessed a more stable status with fewer differentially expressed proteins. However, B73 seems to rapidly initiate signaling pathways in response to drought through adjusting diverse defense pathways. These changes in protein expression allow for the production of a drought stress-responsive network in maize kernels. PMID:25334062

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

    PubMed

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

    2014-01-01

    Drought stress is a major factor that contributes to disease susceptibility and yield loss in agricultural crops. To identify drought responsive proteins and explore metabolic pathways involved in maize tolerance to drought stress, two maize lines (B73 and Lo964) with contrasting drought sensitivity were examined. The treatments of drought and well water were applied at 14 days after pollination (DAP), and protein profiles were investigated in developing kernels (35 DAP) using iTRAQ (isobaric tags for relative and absolute quantitation). Proteomic analysis showed that 70 and 36 proteins were significantly altered in their expression under drought treatments in B73 and Lo964, respectively. The numbers and levels of differentially expressed proteins were generally higher in the sensitive genotype, B73, implying an increased sensitivity to drought given the function of the observed differentially expressed proteins, such as redox homeostasis, cell rescue/defense, hormone regulation and protein biosynthesis and degradation. Lo964 possessed a more stable status with fewer differentially expressed proteins. However, B73 seems to rapidly initiate signaling pathways in response to drought through adjusting diverse defense pathways. These changes in protein expression allow for the production of a drought stress-responsive network in maize kernels. PMID:25334062

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

    PubMed

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

    2016-06-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

    In the progress of allergic and irritant contact dermatitis, chemicals that cause the generation of reactive oxygen species trigger a heat shock response in keratinocytes. In this study, an optical sensor cell line based on cultured human keratinocytes (HaCaT cells) expressing green fluorescent protein (GFP) under the control of the stress-inducible HSP70B' promoter were constructed. Exposure of HaCaT sensor cells to 25 μM cadmium, a model substance for oxidative stress induction, provoked a 1.7-fold increase in total glutathione and a ∼300-fold induction of transcript level of the gene coding for heat shock protein HSP70B'. An extract of Arnica montana flowers resulted in a strong induction of the HSP70B' gene and a pronounced decrease of total glutathione in keratinocytes. The HSP70B' promoter-based sensor cells conveniently detected cadmium-induced stress using GFP fluorescence as read-out with a limit of detection of 6 μM cadmium. In addition the sensor cells responded to exposure of cells to A. montana extract with induction of GFP fluorescence. Thus, the HaCaT sensor cells provide a means for the automated detection of the compromised redox status of keratinocytes as an early indicator of the development of human skin disorders and could be applied for the prediction of skin irritation in more complex in vitro 3D human skin models and in the development of micro-total analysis systems (μTAS) that may be utilized in dermatology, toxicology, pharmacology and drug screenings. PMID:24967604

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

    PubMed

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

    2014-01-01

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

  6. Enhanced sensitivity to irinotecan by Cdk1 inhibition in the p53-deficient HT29 human colon cancer cell line.

    PubMed

    Abal, Miguel; Bras-Goncalves, Rui; Judde, Jean-Gabriel; Fsihi, Hafida; De Cremoux, Patricia; Louvard, Daniel; Magdelenat, Henri; Robine, Sylvie; Poupon, Marie-France

    2004-03-01

    Mutations in the tumor-suppressor gene p53 have been associated with advanced colorectal cancer (CRC). Irinotecan (CPT-11), a DNA topoisomerase 1 inhibitor, has been recently incorporated to the adjuvant therapy. Since the DNA-damage checkpoint depends on p53 activation, the status of p53 might critically influence the response to CPT-11. We analysed the sensitivity to CPT-11 in the human colon cancer cell line HT29 (mut p53) and its wild-type (wt)-p53 stably transfected subclone HT29-A4. Cell-cycle analysis in synchronised cells demonstrated the activation of transfected wt-p53 and a p21(WAF1/CIP1)-dependent cell-cycle blockage in the S phase. Activated wt-p53 increased apoptosis and enhanced sensitivity to CPT-11. In p53-deficient cells, cDNA-macroarray analysis and western blotting showed an accumulation of the cyclin-dependent kinase (cdk)1/cyclin B complex. Subsequent p53-independent activation of the cdk-inhibitor (cdk-I) p21(WAF1/CIP1) prevented cell-cycle progression. Cdk1 induction was exploited in vivo to improve the sensitivity to CPT-11 by additional treatment with the cdk-I CYC-202. We demonstrate a gain of sensitivity to CPT-11 in a p53-mutated colon cancer model either by restoring wild-type p53 function or by sequential treatment with cdk-Is. Considering that mutations in p53 are among the most common genetic alterations in CRC, a therapeutic approach specifically targeting p53-deficient tumors could greatly improve the treatment outcomes. PMID:15001986

  7. ErbB-3 mediates phosphoinositide 3-kinase activity in gefitinib-sensitive non-small cell lung cancer cell lines

    PubMed Central

    Engelman, Jeffrey A.; Jänne, Pasi A.; Mermel, Craig; Pearlberg, Joseph; Mukohara, Toru; Fleet, Christina; Cichowski, Karen; Johnson, Bruce E.; Cantley, Lewis C.

    2005-01-01

    Therapies that target the EGF receptor (EGFR), such as gefitinib (IRESSA), are effective in a subset of patients with advanced non-small cell lung cancer (NSCLC). The differences in intracellular signaling networks between gefitinib-sensitive and -resistant NSCLCs remain poorly understood. In this study, we observe that gefitinib reduces phospho-Akt levels only in NSCLC cell lines in which it inhibits growth. To elucidate the mechanism underlying this observation, we compared immunoprecipitates of phosphoinositide 3-kinase (PI3K) between gefitinib-sensitive and -resistant NSCLC cell lines. We observe that PI3K associates with ErbB-3 exclusively in gefitinib-sensitive NSCLC cell lines. Gefitinib dissociates this complex, thereby linking EGFR inhibition to decreased Akt activity. In contrast, gefitinib-resistant cells do not use ErbB-3 to activate the PI3K/Akt pathway. In fact, abundant ErbB-3 expression is detected only in gefitinib-sensitive NSCLC cell lines. Two gefitinib-sensitive NSCLC cell lines with endogenous distinct activating EGFR mutations (L858R and Del747-749), frequently observed in NSCLC patients who respond to gefitinib, also use ErbB-3 to couple to PI3K. Down-regulation of ErbB-3 by means of short hairpin RNA leads to decreased phospho-Akt levels in the gefitinib-sensitive NSCLC cell lines, Calu-3 (WT EGFR) and H3255 (L858R EGFR), but has no effect on Akt activation in the gefitinib-resistant cell lines, A549 and H522. We conclude that ErbB-3 is used to couple EGFR to the PI3K/Akt pathway in gefitinib-sensitive NSCLC cell lines harboring WT and mutant EGFRs. PMID:15731348

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

    PubMed

    Nicholas, Andrea C; Seiden, Lewis S

    2003-04-01

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

  9. DarkSide-50 WIMP search results with low radioactivity argon

    NASA Astrophysics Data System (ADS)

    Xiang, Xin; DarkSide Collaboration

    2016-03-01

    Located at the Laboratori Nazionali del Gran Sasso, DarkSide-50 is the first physics detector of the DarkSide dark matter search program. The experiment features a dual-phase Time Projection Chamber as the WIMP detector, surrounded by an organic liquid-scintillator neutron veto and a water-Cherenkov muon detector. We report the results from the first use of low radioactivity argon extracted from underground sources in a dark matter search. We have determined that underground argon is depleted in 39Ar by a factor (1 . 4 +/- 0 . 2) ×103 relative to atmospheric argon whose 39Ar activity is 1 bq/kg. The underground argon is also found to contain (2 . 05 +/- 0 . 13) mBq/kg of 85Kr. We find no evidence for dark matter in the form of WIMPs in 70.9 live-days of data with a fiducial mass of (36 . 9 +/- 0 . 6) kg. When combined with our preceding search with an atmospheric argon target, we set a 90 % C.L. upper limit on the WIMP-nucleon spin-independent cross section of 2 . 0 ×10-44 cm2 (8 . 6 ×10-44 cm2, 8 . 0 ×10-43 cm2) for a WIMP mass of 100 GeV/c2 (1 TeV/c2, 10 TeV/c2). DS-50 will continue dark matter search with the underground argon target for a total of 3 years. See also the DS-50 presentations by E. Edkins and G. Koh.

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

    SciTech Connect

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

    2015-08-25

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

  11. WIMPs Search by Exclusive Measurements with Thin Multilayer NaI(Tl) Scintillators (PICO-LON)

    NASA Astrophysics Data System (ADS)

    Fushimi, K.; Kawasuso, H.; Yasuda, K.; Kameda, Y.; Koori, N.; Nakayama, S.; Ichihara, K.; Nomachi, M.; Umehara, S.; Hazama, R.; Yoshida, S.; Ejiri, H.; Imagawa, K.; Ito, H.

    2007-08-01

    The WIMPs search project PICO-LON has been started with multilayer thin NaI(Tl) crystals. The thin (0.05cm) and wide area (5cm × 5cm) NaI(Tl) crystals was successfully developed. The performances of thin NaI(Tl) scintillator was measured and they showed good energy resolution (20% at 60keV) and good position resolution (20% in 5cm × 5cm wider area).

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

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

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

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

    PubMed

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

    2011-10-28

    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

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

    SciTech Connect

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

    2013-10-01

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

  15. Energy partition and distribution of excited species in direction-sensitive detectors for WIMP searches

    NASA Astrophysics Data System (ADS)

    Hitachi, A.

    2013-12-01

    The Bragg-like curve for compounds is introduced for directional detection of galactic dark matter. The slow ion collisions are discussed in relation to direct dark matter searches. The Coulomb effect and the threshold effect in stopping power theory are examined. Ionization via molecular orbit (MO) is suggested for an additional contribution to the electronic stopping power at very slow energy.

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

    SciTech Connect

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

    2015-03-15

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

  17. Variation in Drug Sensitivity of Malignant Mesothelioma Cell Lines with Substantial Effects of Selenite and Bortezomib, Highlights Need for Individualized Therapy

    PubMed Central

    Szulkin, Adam; Nilsonne, Gustav; Mundt, Filip; Wasik, Agata M.; Souri, Pega; Hjerpe, Anders; Dobra, Katalin

    2013-01-01

    Background Malignant mesothelioma cells have an epithelioid or sarcomatoid morphology, both of which may be present in the same tumor. The sarcomatoid phenotype is associated with worse prognosis and heterogeneity of mesothelioma cells may contribute to therapy resistance, which is often seen in mesothelioma. This study aimed to investigate differences in sensitivity between mesothelioma cell lines to anti-cancer drugs. We studied two novel drugs, selenite and bortezomib and compared their effect to four conventional drugs. We also investigated the immunoreactivity of potential predictive markers for drug sensitivity; Pgp, MRP-1, ERCC1, RRM1, TS, xCT and proteasome 20S subunit. Materials and methods We treated six mesothelioma cell lines with selenite, bortezomib, carboplatin, pemetrexed, doxorubicin or gemcitabine as single agents and in combinations. Viability was measured after 24 and 48 hours. Immunocytochemistry was used to detect predictive markers. Results As a single agent, selenite was effective on four out of six cell lines, and in combination with bortezomib yielded the greatest response in the studied mesothelioma cell lines. Cells with an epithelioid phenotype were generally more sensitive to the different drugs than the sarcomatoid cells. Extensive S-phase arrest was seen in pemetrexed-sensitive cell lines. MRP-1 predicted sensitivity of cell lines to treatment with carboplatin and xCT predicted pemetrexed effect. Conclusions The observed heterogeneity in sensitivity of mesothelioma cell lines with different morphology highlights the need for more individualized therapy, requiring development of methods to predict drug sensitivity of individual tumors. Selenite and bortezomib showed a superior effect compared to conventional drugs, motivating clinical testing of these agents as future treatment regime components for patients with malignant mesothelioma. PMID:23840376

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

    PubMed

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

    2012-11-01

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

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

    PubMed

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

    2015-12-01

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

  20. Biophysical characterization of MDR breast cancer cell lines reveals the cytoplasm is critical in determining drug sensitivity.

    PubMed

    Coley, Helen M; Labeed, Fatima H; Thomas, Hilary; Hughes, Michael P

    2007-04-01

    Dielectrophoresis (DEP) was used to examine a panel of MCF-7 cell lines comprising parental MCF-7 cells and MDR derivatives: MCF-7TaxR (paclitaxel-resistant, P-glycoprotein (P-gp) positive), MCF-7DoxR (doxorubicin-resistant MRP2 positive) plus MCF-7MDR1 (MDR1 transfected, P-gp positive). MCF-7DoxR and MCF-7MDR1 were broadly cross-resistant to natural product anticancer agents, whereas MCF-7TaxR cells were not, contrary to P-gp expression. Whilst DEP revealed modest membrane changes in MDR sub-lines, we saw significant changes in their cytoplasmic conductivity: MCF-7TaxRsensitivity is associated with low ionic conductance (reduced cellular trafficking and ion transport) and substantial anthracycline accumulation. For classical MDR i.e. MCF-7MDR1, we saw the reverse picture. Thus, the drug resistance phenotypes of this panel of MCF-7 lines can be delineated by assessment of cytoplasmic biophysical properties using DEP. PMID:17270349

  1. Female Flinders Sensitive Line rats show estrous cycle-independent depression-like behavior and altered tryptophan metabolism.

    PubMed

    Eskelund, Amanda; Budac, David P; Sanchez, Connie; Elfving, Betina; Wegener, Gregers

    2016-08-01

    Clinical studies suggest a link between depression and dysfunctional tryptophan (TRP) metabolism. Even though depression is twice as prevalent in women as men, the impact of the estrous cycle on TRP metabolism is not well-understood. Here we investigated 13 kynurenine and serotonin metabolites in female Flinders Sensitive Line (FSL) rats, a genetic rat model of depression. FSL rats and controls (Flinders Resistant Line rats), 12-20weeks old, were subject to the forced swim test (FST), a commonly used measure of depression-like behavior. Open field was used to evaluate locomotor ability and agoraphobia. Subsequently, plasma and hemispheres were collected and analyzed for their content of TRP metabolites using liquid chromatography-tandem mass spectrometry. Vaginal saline lavages were obtained daily for ⩾2 cycles. To estimate the effects of sex and FST we included plasma from unhandled, naïve male FSL and FRL rats. Female FSL rats showed a depression-like phenotype with increased immobility in the FST, not confounded by anxiety. In the brain, 3-hydroxykynurenine was increased whereas anthranilate and 5-hydroxytryptophan were decreased. In plasma, anthranilate and quinolinate levels were lower in FSL rats compared to the control line, independent of sex and FST. The estrous cycle neither impacted behavior nor TRP metabolite levels in the FSL rat. In conclusion, the female FSL rat is an interesting preclinical model of depression with altered TRP metabolism, independent of the estrous cycle. The status of the pathway in brain was not reflected in the plasma, which may indicate that an inherent local, cerebral regulation of TRP metabolism occurs. PMID:27210075

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

    PubMed

    Zhao, Xiao-Qing; Zhang, Zhi-Qi

    2009-11-15

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

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

    PubMed Central

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

    2016-01-01

    Purpose This study evaluates whether gene signatures for chemosensitivity for irinotecan and 5-fluorouracil (5-FU) derived from in vitro grown cancer cell lines can predict clinical sensitivity to these drugs. Methods To test if an irinotecan signature and a SN-38 signature could identify patients who benefitted from the addition of irinotecan to 5-FU, we used gene expression profiles based on cell lines and clinical tumor material. These profiles were applied to expression data obtained from pretreatment formalin fixed paraffin embedded (FFPE) tumor tissue from 636 stage III colon cancer patients enrolled in the PETACC-3 prospective randomized clinical trial. A 5-FU profile developed similarly was assessed by comparing the PETACC-3 cohort with a cohort of 359 stage II colon cancer patients who underwent surgery but received no adjuvant therapy. Results There was no statistically significant association between the irinotecan or SN-38 profiles and benefit from irinotecan. The 5-FU sensitivity profile showed a statistically significant association with relapse free survival (RFS) (hazard ratio (HR) = 0.54 (0.41–0.71), p<1e-05) and overall survival (HR = 0.47 (0.34–0.63), p<1e-06) in the PETACC-3 subpopulation. The effect of the 5-FU profile remained significant in a multivariable Cox Proportional Hazards model, adjusting for several relevant clinicopathological parameters. No statistically significant effect of the 5-FU profile was observed in the untreated cohort of 359 patients (relapse free survival, p = 0.671). Conclusion The irinotecan predictor had no predictive value. The 5-FU predictor was prognostic in stage III patients in PETACC-3 but not in stage II patients with no adjuvant therapy. This suggests a potential predictive ability of the 5-FU sensitivity profile to identify colon cancer patients who may benefit from 5-FU, however, any biomarker predicting benefit for adjuvant 5-FU must be rigorously evaluated in independent cohorts. Given differences

  4. A search for WIMP dark matter using the first five-tower run of the Cryogenic Dark Matter Search

    NASA Astrophysics Data System (ADS)

    Filippini, Jeffrey Peter

    In recent decades astronomers and physicists have accumulated a vast array of evidence that the bulk of the universe's matter is in some non-baryonic form that remains undetected by electromagnetic means. This "dark matter" resides in diffuse halos surrounding galaxies and other cosmic structures. Particle theorists have proposed a wide array of candidates for its nature. One particularly promising class of candidates are Weakly Interacting Massive Particles (WIMPs): quanta with masses of order 100 GeV/c 2 and interactions characteristic of the weak nuclear force. The Cryogenic Dark Matter Search (CDMS) experiment seeks to directly detect the rare elastic interactions of galactic WIMPs with terrestrial nuclei. To this end, CDMS operates an array of crystalline Ge and Si particle detectors in Soudan Underground Laboratory in northern Minnesota. These crystals are operated at millikelvin temperatures and instrumented to measure the ionization and athermal phonons generated by each particle interaction. This combination provides a powerful two-fold discrimination against the interactions of particles generated by radioactive decay and cosmogenic showers. This dissertation describes the commissioning, analysis, and results of the first WIMP-search data runs of the CDMS experiment with its full complement of 5 "Towers" of detectors. These data represent a substantial increase in target mass and exposure over previous CDMS results. The results of this work place the most stringent limits yet set upon the WIMP-nucleon spin-independent cross section for WIMP masses above ~ 44 GeV/c 2 , as well as setting competitive limits on spin-dependent WIMP-nucleon interactions. This work also outlines the larger context of this and other probes of the WIMP theory of dark matter, as well as some current development efforts toward a larger cryogenic experiment.

  5. Sensitivity of aerosol-induced effects on numerically simulated squall lines to the vertical distribution of aerosols

    NASA Astrophysics Data System (ADS)

    Lebo, Z. J.

    2013-12-01

    The sensitivity of aerosol-induced enhancement of convective strength and precipitation to the vertical distribution is analyzed in the context of numerically simulated squall lines. Recent investigations have hypothesized and demonstrated that an increase in an aerosol loading may lead to enhanced vertical updrafts and potentially more precipitation in a variety of deep convective systems. One of the generally accepted hypotheses for such an enhancement in convective strength suggests that the predominant effect of an increase in aerosol loading is related to enhanced latent heat release in the mid to upper levels of the convective cores. This enhancement has been attributed to an increase in supercooled liquid water that tends to exist in clouds formed in more polluted environments and it is suggested that this water is lofted from below the freezing level to the mixed-phase region of the cloud where the latent heating effects are maximized. However, deep convective cores are quite strong and so a reduction in cloud droplet size due to enhanced aerosol number concentration (which reduces the terminal fall speed) ought to have a negligible effect on the trajectory of the droplets (since the updraft velocity is much larger than the terminal fall speed). Thus, it should be expected that low-level aerosol pollution would have little to no effect on latent heating rates aloft since the droplets will end up in the mixed-phase region regardless of size. Moreover, more recent investigations have shown that aerosol perturbations, especially in squall lines, can lead to less intense cold pools and thus a more optimal state according to RKW theory. Numerical simulations of idealized squall lines are performed to specifically analyze the sensitivity of the aforementioned effects to the vertical distribution of aerosols. The simulations suggest that low-level air tends to either be detrained at the bottom of the convective cores or remains in the convective cores throughout

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

    PubMed

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

    2014-03-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

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

  8. Adipocytokine signaling is altered in flinders sensitive line rats, and adiponectin correlates in humans with some symptoms of depression

    PubMed Central

    Wilhelm, Clare J.; Choi, Dongseok; Huckans, Marilyn; Manthe, Laura; Loftis, Jennifer M.

    2015-01-01

    Major depression is a complex multi-factorial disorder with a lifetime diagnosis of nearly 1 out of 6. We used the Flinders Sensitive Line (FSL) of rats, a model of depression, and the parent Sprague–Dawley (SD) rats to identify genes, gene ontology categories and pathways associated with depression. Depression-like behavior was verified in the FSL line by forced swim testing, with FSL animals exhibiting greater immobility compared to SD rats. RNA samples from the hippocampus were isolated from a group of experimentally naïve FSL and SD rats for microarray analysis. Microarray analysis yielded a total of 361 genes that were differentially regulated between FSL and SD rats, with catechol-O-methyltransferase (COMT) being the most up-regulated. The genes that were differentially regulated between FSL and SD rats were subjected to bioinformatic analysis using the Database for Annotation, Visualization and Integrated Discovery (DAVID), which yielded several gene ontology categories that were overrepresented. Subsequent pathway analysis indicated dysregulation of the adipocytokine signaling pathway. To test the translational impact of this pathway, metabolic factors and psychiatric symptoms were evaluated in a sample of human research participants. Results from our human subjects indicated that anxiety and a subset of depressive symptoms were correlated with adiponectin levels (but not leptin levels). Our results and those of others suggest that disruption of the adipocytokine signaling pathway may be a critical component of the depressive-like behaviors observed in the FSL rats and may also be an important indicator of depressive and anxiety symptoms in humans. PMID:23153628

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

    PubMed Central

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

    2015-01-01

    Background Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in tumor cells, but when used alone, it is not effective in the treatment of TRAIL-resistant tumors. Some studies have shown that gefitinib interacts with recombinant mutant human TRAIL (rmhTRAIL) to induce high levels of apoptosis in gefitinib-responsive bladder cancer cell lines; however, the molecular mechanisms underlying the anticancer effects are not fully understood. Several reports have shown that the death receptor 5 (DR5) plays an important role in sensitizing cancer cells to apoptosis induced by TRAIL. Therefore, we investigated the effects of the combination of drugs and the expression of the DR5 to analyze the growth of a gefitinib-responsive non-small cell lung cancer cell line PC9, which was treated with rmhTRAIL and gefitinib individually or in combination. Methods Human PC9 non-small cell lung cancer cells harboring an epidermal growth factor receptor mutation were used as a model for the identification of the therapeutic effects of gefitinib alone or in combination with rmhTRAIL, and cytotoxicity was assessed by MTT assays. Cell cycle and apoptosis were investigated using flow cytometry. Moreover, the effects of drugs on DR5, BAX, FLIP, and cleaved-caspase3 proteins expressions were analyzed using Western blot analyses. Finally, quantitative polymerase chain reaction analysis was carried out to assess whether rmhTRAIL and gefitinib modulate the expression of genes related to drug activity. Results Gefitinib and rmhTRAIL synergistically interact to inhibit cell proliferation, and apoptosis assessment demonstrated that associations of drug increased the apoptotic index. rmhTRAIL when used alone downregulated DR5 and upregulated BAX, FLIP, and cleaved-caspase3 proteins expressions. However, results obtained in Western blot analyses demonstrated that the combined treatment-induced cell apoptosis was achieved involving upregulated DR5, cleaved-caspase3, and

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

    SciTech Connect

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

    2007-01-01

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

  11. Defining ploidy-specific thresholds in array comparative genomic hybridization to improve the sensitivity of detection of single copy alterations in cell lines.

    PubMed

    Ng, Grace; Huang, Jingxiang; Roberts, Ian; Coleman, Nicholas

    2006-09-01

    Array comparative genomic hybridization (CGH) is being widely used to screen for recurrent genomic copy number alterations in neoplasms, with imbalances typically detected through the application of gain and loss thresholds. Review of array CGH publications for the year 2005 showed that a wide range of thresholds are used. However, the effect of sample ploidy on the sensitivity of these thresholds for single copy alterations (SCAs) has not been evaluated. Here, we describe a method to evaluate the detection accuracy of thresholds for detecting SCAs in cell line array CGH data. By applying a hidden Markov model-based method, we segmented array CGH data from well-karyotyped cell lines and generated ploidy-specific sensitivity-specificity plots, from which we identified optimum thresholds relevant to sample ploidy. We demonstrate that commonly used nonploidy-specific thresholds are suboptimal in their ability to call SCAs, particularly when applied to hypertriploid or tetraploid cell lines. We conclude that the use of ploidy-specific thresholds improves the sensitivity of thres-hold-based array CGH for detecting SCAs in cell lines. Because polyploidy is a common feature of cancer cells, the application of ploidy-specific thresholds to cell lines (and potentially to clinical samples) may improve the detection sensitivity of SCAs of biological significance. PMID:16931585

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

    SciTech Connect

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

    1984-01-01

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

  13. Increased sensitivity to glucose starvation correlates with downregulation of glycogen phosphorylase isoform PYGB in tumor cell lines resistant to 2-deoxy-d-glucose

    PubMed Central

    Philips, Katherine B.; Kurtoglu, Metin; Leung, Howard J.; Liu, Huaping; Gao, Ningguo; Lehrman, Mark A.; Murray, Timothy G.

    2015-01-01

    Background As tumors evolve, they upregulate glucose metabolism while also encountering intermittent periods of glucose deprivation. Here, we investigate mechanisms by which pancreatic cancer cells respond to therapeutic (2-deoxy-d-glucose, 2-DG) and physiologic (glucose starvation, GS) forms of glucose restriction. Methods From a tumor cell line (1420) that is unusually sensitive to 2-DG under normoxia, low (14DG2)- and high (14DG5)-dose resistant cell lines were selected and used to probe the metabolic pathways involved with their response to different forms of glucose deprivation. Results Muted induction of the unfolded protein response was found to correlate with resistance to 2-DG. Additionally, 14DG2 displayed reduced 2-DG uptake, while 14DG5 was cross-resistant to tunicamycin, suggesting it has enhanced ability to manage glycosylation defects. Conversely, 2-DG-resistant cell lines were more sensitive than their parental cell line to GS, which coincided with lowered levels of glycogen phosphorylase (PYGB) and reduced breakdown of glycogen to glucose in the 2-DG-resistant cell lines. Moreover, by inhibiting PYGB in the parental cell line, sensitivity to GS was increased. Conclusions Overall, the data demonstrate that the manner in which glucose is restricted in tumor cells, i.e., therapeutic or physiologic, leads to differential biological responses involving distinct glucose metabolic pathways. Moreover, in evolving tumors where glucose restriction occurs, the identification of PYGB as a metabolic target may have clinical application. PMID:24292700

  14. Model sensitivity of ice flux over the grounding line to present-day climatic forcing and geothermal flux

    NASA Astrophysics Data System (ADS)

    Kleiner, Thomas; Humbert, Angelika

    2016-04-01

    Large uncertainties remain in the current and future contribution to sea level change from Antarctica from observations and numerical flow modelling. Within the SeaRISE project atmospheric, oceanic, and subglacial forcing scenarios were applied to different ice-sheet models to assess Antarctic ice sheet sensitivity over a 500 year timescale. The scenario results have been compared to the individual state of each model at the end of its spin-up. It has been shown, that the model results highly depend on the chosen climate forcing and spin-up strategy. Here we use the Parallel Ice Sheet Model (PISM) to perform spin-up simulations across different data sets for present-day boundary conditions for the Antarctic Ice Sheet (surface temperature, surface mass balance and geothermal flux). The utilized spin-up methods include free evolving and geometry constrained simulations. Here we present our analysis of the ice flux over the grounding line for each set-up and compare the fluxes from large drainage basin units with estimates derived from remote sensing.

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

    SciTech Connect

    Wai, Larry; /SLAC

    2007-02-05

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

  16. The SuperCDMS Soudan high threshold WIMP search and the planned SuperCDMS SNOLAB experiment

    NASA Astrophysics Data System (ADS)

    Calkins, R.; SuperCDMS collaboration

    2016-05-01

    There is ample evidence that visible matter cannot account for a large component of the mass in the universe. Weakly Interacting Massive Particles (WIMPs) are one popular hypothesis to account for the missing mass. The Super Cryogenic Dark Matter Search (SuperCDMS) experiment is designed to directly detect WIMPs through interactions with a nucleus in a target crystal. The SuperCDMS detectors are instrumented with phonon and charge sensors, enabling excellent rejection of electron-recoil backgrounds. Approximately 3000 kg-days of exposure have been collected with the SuperCDMS Soudan experiment. We will describe the search for WIMPs with masses between 10-100 GeV and work towards the SuperCDMS SNOLAB experiment.

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

    SciTech Connect

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

    2010-08-01

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

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

    PubMed

    Dickson, J A; Oswald, B E

    1976-09-01

    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 and anaerobic glycolysis of the cells were studied at normal pHi (pH 7-0-7-4) or at low pHi (pH 6-2-6-6) and at 38 degrees C or 42 degrees C over 6 h in Warburg manometers; the ability of the cells to replicate in culture was examined after 3 h or 6 h incubation in the flasks. The relationship between pHi and extracellular pH (pHe) depended upon the buffer system used and the exact pH in question; no assumption regarding pHi based only on pHe measurement could be made. At 38 degrees C and low pHi, the Pasteur effect became negative due to a relatively greater inhibition of anaerobic than aerobic glycolysis. Respiration was unaffected and cell replicative ability unimpaired. At 42 degrees C and normal pHi, respiration was totally inhibited after 4 h and the Pasteur effect was decreased, in this case due to a compensatory increase in aerobic glycolysis without alteration in anaerobic CO2 production. Low pHi in the presence of hyperthermia enabled cell respiration to continue at a reduced level with no further change in glycolysis. There was delayed cell replication after 3 h at 42 degrees C and inability to multiply following 6 h hyperthermia: low pHi did not influence these results. It is concluded that with these cancer cells, pHi values maintained in the region of 1-0 pH unit below normal for 6 h had no deleterious effect on the cells. No sensitizing effect of the low pHi for the destructive effect of hyperthermia on the cells was observed. PMID:9969

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

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

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

    PubMed Central

    Hindle, Allyson G.; Martin, Sandra L.

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

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

    2012-03-01

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

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

    SciTech Connect

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

    2013-08-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2009-11-01

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

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

    PubMed Central

    Hershfinkel, Michal; Gheber, Larisa

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-07-01

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

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

    SciTech Connect

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

    2013-07-01

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

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

    PubMed Central

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

    2015-01-01

    Ecdysteroids, analogs of the insect molting hormone, are known for their various mild, nonhormonal bioactivities in mammals. Previously, we reported that less-polar ecdysteroids can modulate the doxorubicin resistance of a multidrug resistant (MDR) mouse lymphoma cell line expressing the human ABCB1 transporter. Here, we describe the ability of 20-hydroxyecdysone (1) and its mono- (2) and diacetonide (3) derivatives to sensitize various MDR and non-MDR cancer cell lines towards doxorubicin, paclitaxel, vincristine, or cisplatin. Drug IC50 values with or without ecdysteroid were determined by MTT assay. Compound 3 significantly sensitized all cell lines to each chemotherapeutic except for cisplatin, whose activity was decreased. In order to overcome solubility and stability issues for the future in vivo administration of compound 3, liposomal formulations were developed. By means of their combination index values obtained via checkerboard microplate method, a formulation showed superior activity to that of compound 3 alone. Because ecdysteroids act also on non-ABCB1 expressing (sensitive) cell lines, our results demonstrate that they do not or not exclusively exert their adjuvant anticancer activity as ABCB1 inhibitors, but other mechanisms must be involved, and they opened the way towards their in vivo bioactivity testing against various cancer xenografts. PMID:26075272

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

    SciTech Connect

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

    2012-11-15

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

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

    PubMed Central

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

    1996-01-01

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

  11. In-line phase-sensitive amplification of QPSK signal using multiple quasi-phase matched LiNbO₃ waveguide.

    PubMed

    Asobe, Masaki; Umeki, Takeshi; Takenouchi, Hirokazu; Miyamoto, Yutaka

    2014-11-01

    Phase-sensitive amplifiers (PSA) using periodically poled (PPLN) LiNbO₃ waveguides are promising as low-noise optical amplifiers. However, it is difficult to realize in-line operation for multi-level phase modulated signals using a PPLN based PSA with the conventional configuration. In this paper, we report a PPLN based in-line PSA that can regenerate quadrature phase shift keying (QPSK) signals. Multi-stage frequency mixing in a multiple quasi-phase matched LiNbO₃waveguide allows carrier phase recovery from a QPSK signal. Non-degenerate parametric amplification enables the phase-sensitive amplification of a QPSK signal. Amplitude and phase regeneration is examined utilizing gain saturation and phase squeezing capability. PMID:25401814

  12. Tests of WIMP Dark Matter Candidates with Direct Dark Matter Detection Experiments

    NASA Astrophysics Data System (ADS)

    Georgescu, Andreea Irina

    We reexamine the current direct dark matter (DM) detection data for several types of DM candidates, both assuming the Standard Halo Model (SHM) and in a halo-independent manner. We consider the potential signals for light WIMPs that have appeared in three direct detection searches: DAMA, CDMS-II-Si, and CoGeNT, and we analyze their compatibility with the null results of other direct detection experiments. We first consider light WIMPs with exothermic scattering with nuclei (exoDM). Exothermic interactions favor light targets, thus reducing the importance of upper limits derived from Xe targets, the most restrictive of which is at present the LUX limit. In our SHM analysis the CDMS-II-Si and CoGeNT regions become allowed by these bounds, however the SuperCDMS limit rejects both regions for exoDM with isospin-conserving couplings. An isospin-violating coupling of the exoDM, in particular one with a neutron to proton coupling ratio of -0.8 (which we call "Ge-phobic"), maximally reduces the DM coupling to Ge and allows the CDMS-II-Si region to become compatible with all upper bounds. This is also clearly shown in our halo-independent analysis. Next, we extend and correct a recently proposed maximum-likelihood halo-independent method to analyze unbinned direct DM detection data. Instead of the recoil energy as an independent variable, we use the minimum speed a DM particle must have to impart a given recoil energy to a nucleus. This has the advantage of allowing us to apply the method to any type of target composition and interaction, e.g. with general momentum and velocity dependence, and with elastic or inelastic scattering. We prove the method and provide a rigorous statistical interpretation of the results. As first applications, we find that for dark matter particles with elastic spin-independent interactions and neutron to proton coupling ratio ƒn/ƒp = --0.7 ("Xe-phobic", which reduces maximally the coupling to Xe), the WIMP interpretation of the signal observed

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

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

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

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

    PubMed Central

    2012-01-01

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

  15. BRCA1-deficient breast cancer cell lines are resistant to MEK inhibitors and show distinct sensitivities to 6-thioguanine

    PubMed Central

    Gu, Yuexi; Helenius, Mikko; Väänänen, Kristiina; Bulanova, Daria; Saarela, Jani; Sokolenko, Anna; Martens, John; Imyanitov, Evgeny; Kuznetsov, Sergey

    2016-01-01

    Germ-line or somatic inactivation of BRCA1 is a defining feature for a portion of human breast cancers. Here we evaluated the anti-proliferative activity of 198 FDA-approved and experimental drugs against four BRCA1-mutant (HCC1937, MDA-MB-436, SUM1315MO2, and SUM149PT) and four BRCA1-wild-type (MDA-MB-231, SUM229PE, MCF10A, and MCF7) breast cancer cell lines. We found that all BRCA1-mutant cell lines were insensitive to inhibitors of mitogen-activated protein kinase kinase 1 and 2 (MEK1/2) Selumetinib and Pimasertib in contrast to BRCA1-wildtype control cell lines. However, unexpectedly, only two BRCA1-mutant cell lines, HCC1937 and MDA-MB-436, were hypersensitive to a nucleotide analogue 6-thioguanine (6-TG). SUM149PT cells readily formed radiation-induced RAD51-positive nuclear foci indicating a functional homologous recombination, which may explain their resistance to 6-TG. However, the reason underlying 6-TG resistance of SUM1315MO2 cells remains unclear. Our data reveal a remarkable heterogeneity among BRCA1-mutant cell lines and provide a reference for future studies. PMID:27313062

  16. BRCA1-deficient breast cancer cell lines are resistant to MEK inhibitors and show distinct sensitivities to 6-thioguanine.

    PubMed

    Gu, Yuexi; Helenius, Mikko; Väänänen, Kristiina; Bulanova, Daria; Saarela, Jani; Sokolenko, Anna; Martens, John; Imyanitov, Evgeny; Kuznetsov, Sergey

    2016-01-01

    Germ-line or somatic inactivation of BRCA1 is a defining feature for a portion of human breast cancers. Here we evaluated the anti-proliferative activity of 198 FDA-approved and experimental drugs against four BRCA1-mutant (HCC1937, MDA-MB-436, SUM1315MO2, and SUM149PT) and four BRCA1-wild-type (MDA-MB-231, SUM229PE, MCF10A, and MCF7) breast cancer cell lines. We found that all BRCA1-mutant cell lines were insensitive to inhibitors of mitogen-activated protein kinase kinase 1 and 2 (MEK1/2) Selumetinib and Pimasertib in contrast to BRCA1-wildtype control cell lines. However, unexpectedly, only two BRCA1-mutant cell lines, HCC1937 and MDA-MB-436, were hypersensitive to a nucleotide analogue 6-thioguanine (6-TG). SUM149PT cells readily formed radiation-induced RAD51-positive nuclear foci indicating a functional homologous recombination, which may explain their resistance to 6-TG. However, the reason underlying 6-TG resistance of SUM1315MO2 cells remains unclear. Our data reveal a remarkable heterogeneity among BRCA1-mutant cell lines and provide a reference for future studies. PMID:27313062

  17. Anti-oestrogen resistant human breast cancer cell lines are more sensitive towards treatment with the vitamin D analogue EB1089 than parent MCF-7 cells

    PubMed Central

    Larsen, S S; Heiberg, I; Lykkesfeldt, A E

    2001-01-01

    Most breast cancer patients treated with anti-oestrogens will eventually develop resistance towards treatment. Therefore it is important to find new therapeutic agents effective for treatment of patients relapsing on anti-oestrogen. The vitamin D analogue EB1089 (SeocalcitolTM) is a promising new agent for treatment of breast cancer patients with advanced disease, and in this study we show that two different anti-oestrogen-resistant human breast cancer cell lines are more sensitive towards treatment with EB1089, than the parent MCF-7 cell line. The two resistant cell lines both express a lower content of the anti-apoptotic protein Bcl-2, and we suggest that this may explain the higher sensitivity towards EB1089. The importance of Bcl-2 for response to EB1089 is supported by our observation that oestradiol abrogates the effect of EB1089 in cell lines which increase Bcl-2 in response to oestradiol treatment. Overall these results indicate that treatment with SeocalcitolTMmay prove effective when patients become refractory to anti-oestrogen therapy, and that Bcl-2 may be used as a predictive marker. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11237391

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

    PubMed Central

    Kimpton, J; Emerman, M

    1992-01-01

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

  19. Single-detector polarization-sensitive optical frequency domain imaging using high-speed intra A-line polarization modulation

    PubMed Central

    Oh, W. Y.; Vakoc, B. J.; Yun, S. H.; Tearney, G. J.; Bouma, B. E.

    2009-01-01

    We demonstrate a novel high-speed polarization-sensitive optical frequency domain imaging system employing high-speed polarization modulation. Rapid and continuous polarization modulation of light prior to illumination of the sample is accomplished by shifting the frequency of one polarization eigenstate by an amount equal to one quarter of the digitization sampling frequency. This approach enables polarization-sensitive imaging with a single detection channel and overcomes artifacts that may arise from temporal variations of the birefringence in fiber-optic imaging probes and spatial variation of birefringence in the sample. PMID:18552948

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

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

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

  1. Multidrug resistance-associated protein gene overexpression and reduced drug sensitivity of topoisomerase II in a human breast carcinoma MCF7 cell line selected for etoposide resistance.

    PubMed

    Schneider, E; Horton, J K; Yang, C H; Nakagawa, M; Cowan, K H

    1994-01-01

    A human breast cancer cell line (MCF7/WT) was selected for resistance to etoposide (VP-16) by stepwise exposure to 2-fold increasing concentrations of this agent. The resulting cell line (MCF7/VP) was 28-, 21-, and 9-fold resistant to VP-16, VM-26, and doxorubicin, respectively. MCF7/VP cells also exhibited low-level cross-resistance to 4'-(9-acridinylamino)-methanesulfon-m-anisidide, mitoxantrone, and vincristine and no cross-resistance to genistein and camptothecin. Furthermore, these cells were collaterally sensitive to the alkylating agents melphalan and chlorambucil. DNA topoisomerase II levels were similar in both wild-type MCF7/WT and drug-resistant MCF7/VP cells. In contrast, topoisomerase II from MCF7/VP cells appeared to be 7-fold less sensitive to drug-induced cleavable complex formation in whole cells and 3-fold less sensitive in nuclear extracts than topoisomerase II from MCF7/WT cells. Although this suggested that the resistant cells may contain a qualitatively altered topoisomerase II, no mutations were detected in either the ATP-binding nor the putative breakage/resealing regions of either DNA topoisomerase II alpha or II beta. In addition, the steady-state intracellular VP-16 concentration was reduced by 2-fold in the resistant cells, in the absence of detectable mdr1/P-gp expression and without any change in drug efflux. In contrast, expression of the gene encoding the MRP was increased at least 10-fold in resistant MCF7/VP cells as compared to sensitive MCF7/WT cells. These results suggest that resistance to epipodophyllotoxins in MCF7/VP cells is multifactorial, involving a reduction in intracellular drug concentration, possibly as a consequence of MRP overexpression, and an altered DNA topoisomerase II drug sensitivity. PMID:7903202

  2. Effects of cis-unsaturated fatty acids on doxorubicin sensitivity in P388/DOX resistant and P388 parental cell lines.

    PubMed

    Liu, Q Y; Tan, B K

    2000-01-01

    It has been reported that several cis-unsaturated fatty acids (c-UFAs) could increase doxorubicin (DOX) accumulation in cancer cells and hence elevate its cytotoxicity. However, some researchers showed that c-UFA pretreatment did not affect its cytotoxicity in special cell lines. It is possible that the different results occurred due to different cellular characteristics. We hypothesized that c-UFA treatment might modulate the activities of some antioxidant enzymes to affect the resistance of cells to DOX. In the present study, we examined how c-UFA pretreatment affected DOX cytotoxicity on mouse leukemia cell line, P388, and its resistant subline, P388/DOX, which we found to have significantly higher glutathione peroxidase (GPx) activity as well as P-glycoprotein (p-gp) overexpression. We chose two c-UFAs, gamma-linolenic acid (GLA) (18:3n-6) and docosahexaenoic acid (DHA) (22:6n-3). Cytotoxicity was measured by MTT (3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and trypan blue exclusion assays. DOX accumulation and p-gp expression were measured by flow cytometry. The activities of catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST), and GPx were determined for both cell lines with and without treatment with GLA or DHA. Significant DOX accumulation occurred in both cell lines with GLA or DHA pretreatment, but without any change in p-gp expression in either cell line. Sensitivity to DOX cytotoxicity was improved by GLA or DHA pretreatment in P388/DOX in which only SOD activity was significantly increased, but not in the parental cell line P388 in which both SOD and CAT were significantly increased by the pretreatment. However, combined pretreatment of GLA or DHA with antioxidants, pyrrolidinedithiocarbamate (PDTC) or Vitamin C, could sensitize not only P388/DOX but also P388 cells to DOX. We conclude that the effects of c-UFA pretreatment on the sensitivity of cancer cells to DOX not only depend on the change in drug

  3. Limits on spin-independent couplings of WIMP dark matter with a p-type point-contact germanium detector.

    PubMed

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

    2013-06-28

    We report new limits on a spin-independent weakly interacting massive particle (WIMP)-nucleon interaction cross section using 39.5 kg days of data taken with a p-type point-contact germanium detector of 840 g fiducial mass at the Kuo-Sheng Reactor Neutrino Laboratory. Crucial to this study is the understanding of the selection procedures and, in particular, the bulk-surface events differentiation at the sub-keV range. The signal-retaining and background-rejecting efficiencies were measured with calibration gamma sources and a novel n-type point-contact germanium detector. Part of the parameter space in the cross section versus WIMP-mass implied by various experiments is probed and excluded. PMID:23848861

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

    PubMed Central

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

    2016-01-01

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

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

    SciTech Connect

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

    2015-02-23

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-02-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-02-01

    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.

  8. Evidence for an Inducible Repair-Recombination System in the Female Germ Line of Drosophila Melanogaster. II. Differential Sensitivity to Gamma Rays

    PubMed Central

    Laurencon, A.; Bregliano, J. C.

    1995-01-01

    In a previous paper, we reported that the reactivity level, which regulates the frequency of transposition of I factor, a LINE element-like retrotransposon, is enhanced by the same agents that induce the SOS response in Escherichia coli. In this report, we describe experimental evidence that, for identical genotypes, the reactivity levels correlate with the sensitivity of oogenesis to gamma rays, measured by the number of eggs laid and by frequency of dominant lethals. This strongly supports the hypothesis that the reactivity level is one manifestation of an inducible DNA repair system taking place in the female germ line of Drosophila melanogaster. The implications of this finding for the understanding of the regulation of I factor are discussed and some other possible biological roles of this system are outlined. PMID:8647394

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

    PubMed

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

    2015-09-22

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

  10. 3-methyladenine-DNA-glycosylase and O6-alkyl guanine-DNA-alkyltransferase activities and sensitivity to alkylating agents in human cancer cell lines.

    PubMed Central

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

    1996-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

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

    2014-11-21

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

  13. Expression of microRNA-30a-5p in drug-resistant and drug-sensitive ovarian cancer cell lines

    PubMed Central

    Liu, Jin; Wu, Xiaohua; Liu, Hongmei; Liang, Yijuan; Gao, Xinping; Cai, Zhihui; Wang, Weiming; Zhang, Hui

    2016-01-01

    The present study aimed to explore the expression of microRNA (miRNA or miR) in drug-resistant and drug-sensitive ovarian cancer cell lines, and to seek the potential therapeutic target of ovarian cancer drug-resistant mechanism in order to improve drug resistance by altering miRNA levels. The drug-resistant characteristics of SKOV3/DDP, SKOV3, COC1/DDP and COC1 cell lines were studied. The miRNAs that were differentially expressed between cisplatin-resistant cells and its parental cells in ovarian cancer were screened with a miRNA chip. The effect of miRNAs was detected, and their drug-resistant mechanism was investigated by transfection and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide methods. Among the expression screening of miRNAs, 41 mRNAs, including Homo sapiens (hsa)-miR-30a-5p and hsa-miR-34c-5p, were highly expressed in the drug-resistant cells, whereas 44 miRNAs, including hsa-miR-96-5p and hsa-miR-200c-3p, were lowly expressed. The expression levels of hsa-miR-30a-5p in two types of ovarian cancer chemotherapy-resistant cell lines were significantly higher than those in chemotherapy-sensitive cell lines, which was associated with ovarian cancer chemotherapy resistance. In conclusion, high expression of miRNA-30a-5p was able to promote cell growth and colony forming ability, and enhance cell migration and invasion. Thus, miRNA-30a-5p is expected to become a meaningful novel target for ovarian cancer resistant treatment. PMID:27602140

  14. 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)

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

    2013-11-01

    The absorption spectrum of water vapor in “natural” isotopic abundance has been recorded by high sensitivity Continuous Wave Cavity Ring Down Spectroscopy (CW-CRDS) between 5852 and 6607 cm-1. The investigated region covers the 1.5 μm transparency window of major importance for atmospheric applications. The achieved sensitivity of the recordings varies from αmin ∼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. Five thousand seven hundred and twenty seven lines were assigned to 6379 transitions of six water isotopologues (H216O, H218O, H217O, HD16O, HD18O and HD17O). The first detection of lines due to HD17O in “natural” water (relative abundance on the order of 1.1×10-7) illustrates the sensitivity of the recordings. Most of the 1842 newly reported transitions belong to the main isotopologue (1022 transitions) and to the HD16O isotopologue (684 transitions). Sixty-three levels are newly determined and 22 are corrected by more than 0.015 cm-1 compared to those recommended by the water IUPAC task group. Overall, a list of 6589 transitions was constructed for the studied region. The present CRDS line list complemented with 210 strong transitions from the literature is believed to be the most complete empirical list of the region. The obtained results are critically compared to recent IUPAC task group compilations. Overall the agreement between variational and measured intensities is very satisfactory. We nevertheless point out a number of important disagreements for some lines of the highly excited bending bands, mainly 4ν2 of H216O.

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

    PubMed

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

    2012-08-01

    Since the 7th amendment to the EU cosmetics directive foresees a complete ban on animal testing, alternative in vitro methods have been established to evaluate the sensitizing potential of small molecular weight compounds. To find out whether these novel in vitro assays are also capable to predict the sensitizing potential of small molecular weight drugs, model compounds such as beta-lactams and sulfonamides - which are the most frequent cause of adverse drug reactions - were co-incubated with THP-1, MUTZ-LC, or primary monocyte-derived dendritic cells for 48 h and subsequent expression of selected marker genes (IL-8, IL-1β, CES1, NQO1, GCLM, PIR and TRIM16) was studied by real time PCR. Benzylpenicillin and phenoxymethylpenicillin were recognized as sensitizing compounds because they are capable to induce the mRNA expression of these genes in moDCs and, except for IL-8, in THP-1 cells but not in MUTZ-LC. Ampicillin stimulated the expression of some marker genes in moDCs and THP-1 cells. SMX did not affect the expression of these genes in THP-1, however, in moDCs, at least PIR was enhanced and there was an increase of the release of IL-8. These data reveal that novel in vitro DC based assays might play a role in the evaluation of the allergenic potential of novel drug compounds, but these systems seem to lack the ability to detect the sensitizing potential of prohaptens that require metabolic activation prior to sensitization and moDCs seem to be superior with regard to the sensitivity compared with THP-1 and MUTZ-3 cell lines. PMID:22609641

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2015-07-01

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

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

    NASA Astrophysics Data System (ADS)

    Wang, Lu; Mei, Dongming

    2014-03-01

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

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

    NASA Technical Reports Server (NTRS)

    Tao, W.-K.; Simpson, J.; Sui, C.-H.; Ferrier, B.; Lang, S.; Scala, J.; Chou, M.-D.; Pickering, K.

    1993-01-01

    A 2D time-dependent and nonhydrostatic numerical cloud model is presently used to estimate the heating, moisture, and water budgets in the convective and stratiform regions for both a tropical and a midlatitude squall line. The model encompasses a parameterized, three-class ice phase microphysical scheme and longwave radiative transfer process. It is noted that the convective region plays an important role in the generation of stratiform rainfall for both cases. While a midlevel minimum in the moisture profile for the tropical case is due to vertical eddy transport in the convective region, the contribution to the heating budget by the cloud-scale fluxes is minor; by contrast, the vertical eddy heat-flux is relatively important for the midlatitude case due to the stronger vertical velocities present in the convective cells.

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

    PubMed Central

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

    2014-01-01

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

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

    SciTech Connect

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

    2012-08-01

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

  3. The Effectiveness and Safety of Fluoroquinolone-Containing Regimen as a First-Line Treatment for Drug-Sensitive Pulmonary Tuberculosis: A Systematic Review and Meta-Analysis

    PubMed Central

    Lee, Hyun Woo; Lee, Jung Kyu; Kim, Eunyoung; Yim, Jae-Joon; Lee, Chang-Hoon

    2016-01-01

    Background Fluoroquinolone is recommended as a pivotal antituberculous agent for treating multi-drug-resistant pulmonary tuberculosis. However, its effectiveness as first-line treatment remains controversial. The present study was conducted to validate the fluoroquinolone-containing regimen for drug-sensitive pulmonary tuberculosis. Methods We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials until June 5, 2015. Randomized controlled trials (RCTs) that compared antituberculous regimens containing fluoroquinolone with the standard regimen were included. Results Eleven RCTs that included 6,334 patients were selected. Fluoroquinolone-containing regimens had a higher rate of sputum culture conversion at 2 months of treatment (M-H fixed odds ratio [OR], 1.36; 95% confidence interval [CI], 1.20–1.54). However, the outcomes were less favorable (M-H fixed OR, 0.69; 95% CI, 0.59–0.82) and the associated total adverse events were more frequent (M-H fixed OR, 1.84; 95% CI, 1.46–2.31) in the fluoroquinolone-containing regimen group, without a significant heterogeneity according to treatment duration. Treatment with the fluoroquinolone-containing regimen for 4 months showed a higher relapse rate. Conclusions Despite a higher culture conversion rate at 2 months of treatment, the fluoroquinolone-containing regimen had limitations, including less favorable outcomes and more adverse events, as the first-line therapy for drug-sensitive pulmonary tuberculosis. PMID:27455053

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

    PubMed

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

    2015-07-01

    Staphylococcus aureus (S. aureus) is an important human pathogen that causes several diseases ranging from superficial skin infections to life-threatening diseases. Here, a method combining positive dielectrophoresis (pDEP) driven on-line enrichment and aptamer-fluorescent silica nanoparticle label has been developed for the rapid and sensitive detection of S. aureus in microfluidic channels. An aptamer, having high affinity to S. aureus, is used as the molecular recognition tool and immobilized onto chloropropyl functionalized fluorescent silica nanoparticles through a click chemistry approach to obtain S. aureus aptamer-nanoparticle bioconjugates (Apt(S.aureus)/FNPs). The pDEP driven on-line enrichment technology was used for accumulating the Apt(S.aureus)/FNP labeled S. aureus. After incubating with S. aureus, the mixture of Apt(S.aureus)/FNP labeled S. aureus and Apt(S.aureus)/FNPs was directly introduced into the pDEP-based microfluidic system. By applying an AC voltage in a pDEP frequency region, the Apt(S.aureus)/FNP labelled S. aureus moved to the electrodes and accumulated in the electrode gap, while the free Apt(S.aureus)/FNPs flowed away. The signal that came from the Apt(S.aureus)/FNP labelled S. aureus in the focused detection areas was then detected. Profiting from the specificity of aptamer, signal amplification of FNP label and pDEP on-line enrichment, this assay can detect as low as 93 and 270 cfu mL(-1)S. aureus in deionized water and spiked water samples, respectively, with higher sensitivities than our previously reported Apt(S.aureus)/FNP based flow cytometry. Moreover, without the need for separation and washing steps usually required for FNP label involved bioassays, the total assay time including sample pretreatment was within 2 h. PMID:25963028

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

    PubMed

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

    1999-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  8. AS sensitivity study of the mesoscale characteristics of squall-line systems to environmental conditions: Implication of anvil cirrus parameterization

    SciTech Connect

    Chin, H.-N.S.

    1996-04-01

    Cloud-radiation feedback has been identified as the single most important effect limiting general circulation models (GCMs) to further progress in climate change research, and regarded as major uncertainties in estimating the impact of increasing concentrations of green house gases on climate simulations. Therefore, it is crucially important to further understand the physical processes involved in order to improve the representation of cloud processes in GCMs. To this end, a cloud resolving model with enhanced model physics was used to study the impact of microphysics, long-and shortwave radiation on mediated and tropical mesoscale convective systems (MCSs). The objective of this work is to parameters the large- scale effects of an important sub-GCM-grid-scale process associated with the titling structure of MCSs. The objective of this work is to parameters the large-scale effects of an important sub- GCM-grid- scale process associated with the titling structure of MCSs. To this end, our primary interest focuses on MCSs in an environment with substantial wind shear, such as squall-line systems, since they have longer lifetimes and wider coverage to affect the earth- atmosphere radiation budget and climate.

  9. GSH, GSH-related enzymes and GS-X pump in relation to sensitivity of human tumor cell lines to chlorambucil and adriamycin.

    PubMed

    Zhang, K; Yang, E B; Wong, K P; Mack, P

    1999-05-01

    Glutathione (GSH) contents and activities of glutathione S-transferase (GST), glutathione reductase (GSH-RD), glutathione peroxidase (GSHpx) and glutathione conjugate export pump (GS-X pump) were determined in eight human tumor cell lines with different sensitivities to adriamycin and chlorambucil. Correlations between sensitivities of the human tumor cells to adriamycin and chlorambucil and the glutathione related factors were analyzed statistically. Sensitivities of the human tumor cells to chlorambucil were found to be correlated to all the glutathione related factors tested (r=0.68-0.88). IC50 values of adriamycin were also positively correlated to GSH contents and activities of GSH-RD, GSHpx and GS-X pump with r values ranging from 0.66 to 0.77 but not to GST activity (r=0.25). Chang liver cells with highest GSH content and highest activities of GST, GSH-RD, GSHpx and GS-X pump were most resistant to both adriamycin and chlorambucil. These data suggested that glutathione related factors may work as an overall detoxification system participating in the detoxification of anticancer drugs such as adriamycin and chlorambucil, and to be involved in cellular resistance to these drugs. PMID:10200335

  10. Sensitive NADH detection in a tumorigenic cell line using a nano-biosensor based on the organic complex formation.

    PubMed

    Akhtar, Mahmood H; Mir, Tanveer A; Gurudatt, N G; Chung, Saeromi; Shim, Yoon-Bo

    2016-11-15

    A robust amperometric sensor for β-nicotinamide adenine dinucleotide (NADH) detection was developed through the organic complex formation with ethylenediaminetetraacetic acid (EDTA) bonded on the polyethylenimine (PEI)/activated graphene oxide (AGO) layer. The EDTA immobilized sensor probe (GCE/AGO/PEI-EDTA) revealed a catalytic property towards NADH oxidation that allows for the highly sensitive electrochemical detection of NADH at a low oxidation potential. Surface characterization demonstrated that the negatively charged AGO acted as nanofillers in the positively charged PEI matrix through the charge interaction. The immobilization of EDTA on the polymer layer provided more surface area for NADH to interact with through the enhanced chemical interlocking between them. We observed the strong interaction between NADH and EDTA on the AGO/PEI layer using a quartz crystal microbalance (QCM), X-ray photoelectron spectroscopy (XPS), and the calculation of the minimized energy for complex formation. The dynamic range of NADH was determined to be between 0.05μM and 500μM with a detection limit (LD) of 20.0±1.1nM. The reliability of the developed sensor for biomedical applications was examined by detecting NADH in tumorigenic lung epithelial cells using the standard addition method. PMID:27209575

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  15. High sensitivity cavity ring down spectroscopy of N2O near 1.22 μm: (II) 14N216O line intensity modeling and global fit of 14N218O line positions

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

    In a recent work (Karlovets et al., 2016 [1]), we reported the measurement and rovibrational assignments of more than 3300 transitions belonging to 64 bands of five nitrous oxide isotopologues (14N216O, 14N15N16O, 15N14N16O, 14N218O and 14N217O) in the high sensitivity CRDS spectrum recorded in the 7915-8334 cm-1 spectral range. The assignments were performed by comparison with predictions of the effective Hamiltonian models developed for each isotopologue. In the present paper, the large amount of measurements from our previous work mentioned above and literature are gathered to refine the modeling of the nitrous oxide spectrum in two ways: (i) improvement of the intensity modeling for the principal isotopologue, 14N216O, near 8000 cm-1 from a new fit of the relevant effective dipole moment parameters, (ii) global modeling of 14N218O line positions from a new fit of the parameters of the global effective Hamiltonian using an exhaustive input dataset collected in the literature in the 12-8231 cm-1 region. The fitted set of 81 parameters allowed reproducing near 5800 measured line positions with an RMS deviation of 0.0016 cm-1. The dimensionless weighted standard deviation of the fit is 1.22. As an illustration of the improvement of the predictive capabilities of the obtained effective Hamiltonian, two new 14N218O bands could be assigned in the CRDS spectrum in the 7915-8334 cm-1 spectral range. A line list at 296 K has been generated in the 0-10,700 cm-1 range for 14N218O in natural abundance with a 10-30 cm/molecule intensity cutoff.

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

    SciTech Connect

    Attota, Ravikiran Dixson, Ronald G.

    2014-07-28

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

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

    PubMed

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

    2015-01-01

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

  18. Synthesis of 17β-N-arylcarbamoylandrost-4-en-3-one derivatives and their anti-proliferative effect on human androgen-sensitive LNCaP cell line.

    PubMed

    Cortés-Benítez, Francisco; Cabeza, Marisa; Ramírez-Apan, María Teresa; Alvarez-Manrique, Berenice; Bratoeff, Eugene

    2016-10-01

    In this study, we report the synthesis and anti-proliferative effect of a set of eight androst-4-ene-3-one derivatives with different arylcarbamoyl groups at C-17. The novel compounds were prepared from commercially available 3β-hydroxy-5-pregnen-20-one and evaluated against the androgen-sensitive human prostate adenocarcinoma LNCaP cell line. The cancerous cells were exposed to 50 μM of each compound and the proliferating agent testosterone (T) or dihydrotestosterone (DHT). The most potent compounds from this assay were further tested against the androgen-insensitive PC3 cell line. We also demonstrate the activity of these compounds on rat peripheral blood mononuclear cells for comparison. Both 17β-N-[3,5-bis(trifluoromethyl)phenylcarbamoyl]androst-4-ene-3-one (6f) and 17β-N-(1,3-thiazol-2-ylcarbamoyl)androst-4-ene-3-one (6g) exhibited a higher growth inhibitory effect than commercially available drugs finasteride, flutamide and ketoconazole on LNCaP cells in the presence and absence of androgens. In addition, 6f and 6g demonstrated high potency on PC3 cells suggesting an androgen-independent anti-proliferative effect. Moreover, the novel compounds showed a small effect on rat mononuclear cells, an indication of low toxicity. PMID:27423983

  19. Differential expression of postsynaptic NMDA and AMPA receptor subunits in the hippocampus and prefrontal cortex of the flinders sensitive line rat model of depression.

    PubMed

    Treccani, Giulia; Gaarn du Jardin, Kristian; Wegener, Gregers; Müller, Heidi Kaastrup

    2016-11-01

    Glutamatergic abnormalities have recently been implicated in the pathophysiology of depression, and the ionotropic glutamate receptors in particular have been suggested as possible underlying molecular determinants. The Flinders Sensitive Line (FSL) rats constitute a validated model of depression with dysfunctional regulation of glutamate transmission relatively to their control strain Flinders Resistant Line (FRL). To gain insight into how signaling through glutamate receptors may be altered in the FSL rats, we investigated the expression and phosphorylation of AMPA and NMDA receptor subunits in an enriched postsynaptic fraction of the hippocampus and prefrontal cortex. Compared to the hippocampal postsynaptic fractions of FRL rats, FSL rats exhibited decreased and increased levels of the NMDA receptor subunits GluN2A and GluN2B, respectively, causing a lower ratio of GluN2A/GluN2B. The GluA2/GluA3 AMPA receptor subunit ratio was significantly decreased while the expression of the individual GluA1, GluA2, and GluA3 subunits were unaltered including phosphorylation levels of GluA1 at S831 and S845. There were no changes in the prefrontal cortex. These results support altered expression of postsynaptic glutamate receptors in the hippocampus of FSL rats, which may contribute to the depressive-like phenotype of these rats. PMID:27262028

  20. ELF magnetic fields tuned to ion parametric resonance conditions do not affect TEA-sensitive voltage-dependent outward K(+) currents in a human neural cell line.

    PubMed

    Gavoçi, Entelë; Zironi, Isabella; Remondini, Daniel; Virelli, Angela; Castellani, Gastone; Del Re, Brunella; Giorgi, Gianfranco; Aicardi, Giorgio; Bersani, Ferdinando

    2013-12-01

    Despite the experimental evidence of significant biological effects of extremely low frequency (ELF) magnetic fields (MFs), the underlying mechanisms are still unclear. Among the few mechanisms proposed, of particular interest is the so called "ion parametric resonance (IPR)" hypothesis, frequently referred to as theoretical support for medical applications. We studied the effect of different combinations of static (DC) and alternating (AC) ELF MFs tuned on resonance conditions for potassium (K(+)) on TEA-sensitive voltage-dependent outward K(+) currents in the human neuroblastoma BE(2)C cell line. Currents through the cell membrane were measured by whole-cell patch clamp before, during, and after exposure to MF. No significant changes in K(+) current density were found. This study does not confirm the IPR hypothesis at the level of TEA-sensitive voltage-dependent outward K(+) currents in our experimental conditions. However, this is not a direct disprove of the hypothesis, which should be investigated on other ion channels and at single channel levels also. PMID:23900932

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

    PubMed

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

    2015-07-01

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

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

    SciTech Connect

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

    2005-07-01

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

  3. Differentiation-associated toxin receptor modulation, cytokine production, and sensitivity to Shiga-like toxins in human monocytes and monocytic cell lines.

    PubMed Central

    Ramegowda, B; Tesh, V L

    1996-01-01

    Infections with Shiga toxin-producing Shigella dysenteriae type 1 or Shiga-like toxin (SLT)-producing Escherichia coli cause bloody diarrhea and are associated with an increased risk of acute renal failure and severe neurological complications. Histopathological examination of human and animal tissues suggests that the target cells for toxin action are vascular endothelial cells. Proinflammatory cytokines regulate endothelial cell membrane expression of the glycolipid globotriaosylceramide (Gb(3)) which serves as the toxin receptor, suggesting that the host response to the toxins or other bacterial products may contribute to pathogenesis by regulating target cell sensitivity to the toxins. We examined the effects of purified SLTs on human peripheral blood monocytes (PBMn) and two monocytic cell lines. Undifferentiated THP-1 cells were sensitive to SLTs. Treatment of the cells with a number of differentiation factors resulted in increased toxin resistance which was associated with decreased toxin receptor expression. U-937 cells, irrespective of maturation state, and PBMn were resistant to the toxins. U-937 cells expressed low levels of GB(3), and toxin receptor expression was not altered during differentiation. Treatment of monocytic cells with tumor necrosis factor alpha (TNF-alpha) did not markedly increase sensitivity or alter toxin receptor expression. Undifferentiated monocytic cells failed to synthesize TNF and interleukin 1beta when treated with sublethal concentrations of SLT type I (SLT-I), whereas cells treated with 12-0-tetradecanoylphorbol-13-acetate acquired the ability to produce cytokines when stimulated with SLT-I. When stimulated with SLT-I, U-937 cells produced lower levels of TNF than PBMn and THP-1 cells did. PMID:8606075

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

    PubMed

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

    2016-04-01

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

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

    PubMed

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

    2007-02-01

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

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

    PubMed

    Hindmarsh, Richard C A

    2006-07-15

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

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

    SciTech Connect

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

    2011-01-14

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

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

    NASA Astrophysics Data System (ADS)

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

    2010-12-01

    The National Research Council’s (NRC) Decadal Survey (DS) of Earth Science and Applications from Space has identified the Active Sensing of CO2 Emissions over Nights, Days, and Seasons (ASCENDS) as an important atmospheric science mission. The CO2 mixing ratio needs to be measured to a precision of 0.5 percent of background or better (slightly less than 2 ppm) at 100-km horizontal resolution overland and 200-km resolution over oceans. To meet this goal, the ASCENDS mission requires simultaneous laser remote sensing of CO2 and O2 in order to convert CO2 column number densities to average column CO2 mixing ratios (XCO2). As such, the CO2 column number density and the O2 column number density will be utilized to derive the average XCO2 column. NASA Langley Research Center, working with its partners, is developing O2 lidar technology in the 1.26-1.27-μm band for surface pressure measurements. To obtain XCO2 with LAS technique the simultaneous measurement of the CO2 column number density, the O2 column number density for converting the CO2 column number density to XCO2 and the total path length of the measurement are required. The O2 LAS operating at 1.26 μm will be used to convert CO2 number density to mixing ratio. The 1.26-μm spectral band was chosen due to architectural advantage from wavelengths being close to 1.57-μm CO2 LAS column measurements and the favorable spectroscopic characteristics of the O2 absorption line parameters. Furthermore, the surface and atmospheric scattering characteristics from aerosols and thin clouds are nearly the same as for 1.26-μm O2 measurements and the 1.57-μm CO2 measurements. One or more "on-line" wavelengths in the 1.26-μm O2 absorption band have to be carefully chosen to eliminate ambient influences on them when used in conjunction with the integrated path differential absorption (IPDA) technique. The O2 model optical depth calculation is very sensitive to knowledge of the transmitted wavelengths and to the choice of

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2013-04-01

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

  11. Quantitative analysis of the effect of tubulin isotype expression on sensitivity of cancer cell lines to a set of novel colchicine derivatives

    PubMed Central

    2010-01-01

    Background A maximum entropy approach is proposed to predict the cytotoxic effects of a panel of colchicine derivatives in several human cancer cell lines. Data was obtained from cytotoxicity assays performed with 21 drug molecules from the same family of colchicine compounds and correlate these results with independent tubulin isoform expression measurements for several cancer cell lines. The maximum entropy method is then used in conjunction with computed relative binding energy values for each of the drug molecules against tubulin isotypes to which these compounds bind with different affinities. Results We have found by using our analysis that αβI and αβIII tubulin isoforms are the most important isoforms in establishing predictive response of cancer cell sensitivity to colchicine derivatives. However, since αβI tubulin is widely distributed in the human body, targeting it would lead to severe adverse side effects. Consequently, we have identified tubulin isotype αβIII as the most important molecular target for inhibition of microtubule polymerization and hence cancer cell cytotoxicity. Tubulin isotypes αβI and αβII are concluded to be secondary targets. Conclusions The benefit of being able to correlate expression levels of specific tubulin isotypes and the resultant cell death effect is that it will enable us to better understand the origin of drug resistance and hence design optimal structures for the elimination of cancer cells. The conclusion of the study described herein identifies tubulin isotype αβIII as a target for optimized chemotherapy drug design. PMID:20509970

  12. 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

    Hascup, Kevin N; Hascup, Erin R; Stephens, Michelle L; Glaser, Paul EA; Yoshitake, Takashi; Mathé, Aleksander A; Gerhardt, Greg A; Kehr, Jan

    2011-01-01

    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 μm) 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. PMID:21525860

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-01-01

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

  16. Highly sensitive chiral analysis of amino acids by in-line single drop microextraction and capillary electrophoresis with laser-induced fluorescence detection.

    PubMed

    Liang, Guodong; Choi, Kihwan; Badjah Hadj Ahmed, Ahmed Yacine; ALOthman, Zeid A; Chung, Doo Soo

    2010-09-10

    A highly sensitive method for chiral analysis of amino acids by in-line single drop microextraction (SDME) and chiral capillary electrophoresis (CE) with laser-induced fluorescence (LIF) detection was developed. In SDME, a drop of a basic aqueous acceptor phase covered with a thin organic layer was formed at the tip of a capillary by simple combination of sample-handling sequences of a CE apparatus. Then fluorescein isothiocyanate (FITC)-derivatized amino acids in an acidic donor solution were enriched into the drop through the organic layer. The enriched enantiomers were then resolved using a dual chiral selector of β-cyclodextrin (β-CD) and sodium taurodeoxycholate (STC). Here, in addition to serving as a labeling reagent providing high fluorescence signal, hydrophobic FITC was primarily used as a modifier aiding the extraction of zwitterionic amino acids by blocking the amino groups and increasing the hydrophobicity, yielding 220 times increase in extraction efficiency. Several hundred-fold enrichments were achieved with 10 min SDME, yielding LODs of 30-60 pM and enabling direct analysis of d-AAs in a 99% enantiomeric excess mixture. In view of no additional modification of the existing commercial CE instrument, this method without stirring can be easily realized using known operations. When a microstirrer was customized to the CE instrument several thousand-fold enrichments could be obtained with LODs in the low picomolar range of 1-3 pM. PMID:20850587

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

    PubMed

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

    2011-11-01

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

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

    NASA Astrophysics Data System (ADS)

    Trummer, Brian J.

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

  19. Screening for (anti)androgenic properties using a standard operation protocol based on the human stably transfected androgen sensitive PALM cell line. First steps towards validation.

    PubMed

    Freyberger, A; Witters, H; Weimer, M; Lofink, W; Berckmans, P; Ahr, H-J

    2010-08-01

    Despite more than a decade of research in the field of endocrine active compounds targeting the androgen receptor (AR), and although suitable cell lines can be obtained, no validated human stably transfected androgen sensitive transactivation assay is available. Bayer Schering Pharma (BSP) and the Flemish Institute for Technological Research (VITO), partners within the EU-sponsored 6th framework project ReProTect, made first steps towards such a validation. A standard operation protocol (SOP) developed at BSP based on the androgen sensitive PALM cell line was transferred to VITO and its performance and transferability were thoroughly studied. The investigation followed a generic protocol prepared for all reporter gene assays evaluated within ReProTect, and in both laboratories at least three independent experiments were performed. The highest concentration to be tested was limited to 10 microM, if needed. A few compounds, 17alpha-methyltestosterone (17alpha-MT), vinclozolin and linuron, were studied using a real world scenario, i.e., assuming that their interaction with the AR was not known: A prescreening for agonism and true, competitive antagonism was used to select conditions such as the appropriate mode of action, and the working range excluding cytotoxicity for the final screening. All other compounds were tested according to the generic protocol: Compounds screened for agonism were the reference androgen 17alpha-methyldihydrotestosterone (MDHT), levonorgestrel, norethynodrel, progesterone, o,p'-DDT, and dibutylphthalate (DBP), while compounds screened for antagonism were the reference anti-androgen flutamide, prochloraz, o,p'-DDT, progesterone, norethynodrel, and DBP. Cytotoxicity was assessed in parallel as lactate dehydrogenase release. The prescreen classified 17alpha-MT as androgenic, vinclozolin and linuron as anti-androgenic and compounds were tested accordingly. In the absence of cytotoxicity, appropriate androgenic properties of reference and test

  20. AGN-2979, an inhibitor of tryptophan hydroxylase activation, does not affect serotonin synthesis in Flinders Sensitive Line rats, a rat model of depression, but produces a significant effect in Flinders Resistant Line rats

    PubMed Central

    Kanemaru, Kazuya; Nishi, Kyoko; Diksic, Mirko

    2009-01-01

    The neurotransmitter, serotonin, is involved in several brain functions, including both normal, physiological functions, and pathophysiological functions. Alterations in any of the normal parameters of serotonergic neurotransmission can produce several different psychiatric disorders, including major depression. In many instances, brain neurochemical variables are not able to be studied properly in humans, thus making the use of good animal models extremely valuable. One of these animal models is the Flinders Sensitive Line (FSL) of rats, which has face, predictive and constructive validities in relation to human depression. The objective of this study was to quantify the effect of the tryptophan hydroxylase (TPH) activation inhibitor, AGN-2979, on the FSL rats (rats with depression-like behaviour), and compare it to the effect on the Flinders Resistant Line (FRL) of rats used as the control rats. The effect was evaluated by measuring changes in regional serotonin synthesis in the vehicle treated rats (FSL-VEH and FRL-VEH) relative to those measured in the AGN-2979 treated rats (FSL-AGN and FRL-AGN). Regional serotonin synthesis was measured autoradiographically in more than thirty brain regions. The measurements were performed using α-[14C]methyl-L-tryptophan as the tracer. The results indicate that AGN-2979 did not produce a significant reduction of TPH activity in the AGN-2979 group relative to the vehicle group (a reduction would have been observed if there had been an activation of TPH by the experimental set up) in the FSL rats. On the other hand, there was a highly significant reduction of synthesis in the FRL rats treated by AGN-2979, relative to the vehicle group. Together, the results demonstrate that in the FSL rats, AGN-2979 does not affect serotonin synthesis. This suggests that there was no activation of TPH in the FSL rats during the experimental procedure, but such activation did occur in the FRL rats. Because of this finding, it could be

  1. New Results from the Search for Low-Mass Weakly Interacting Massive Particles with the CDMS Low Ionization Threshold Experiment [WIMP-Search Results from the Second CDMSlite Run

    DOE PAGESBeta

    Agnese, R.

    2016-02-01

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

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

    PubMed

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

    1995-09-01

    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 an animal model of depression, and presents new information. FSL rats exhibited exaggerated immobility in the forced swim test which is counteracted by the tricyclic antidepressants imipramine and desipramine and the serotonin reuptake blocker sertraline; the low immobility exhibited by the FRL rats is generally unaffected by these compounds. In contrast to these "therapeutic" effects of well recognized antidepressants, lithium and bright light treatment did not alter the exaggerated immobility of FSL rats. Novel data indicated that neither FSL nor FRL rats exhibited alterations in swim test immobility following chronic administration of the psychomotor stimulant amphetamine (2 mg/kg) and the anticholinergic scopolamine (2 mg/kg), which typically reduce immobility after acute administration. However, it was found that the calcium channel blockers verapamil (5 and 15 mg/kg) and nicardipine (10 mg/kg) did reduce the exaggerated immobility in FSL rats following chronic administration, suggesting that these compounds need to be evaluated further in humans. Previous studies have indicated no differences between FSL and FRL rats evaluated in the elevated plus maze, either at baseline or after the administration of diazepam, suggesting that the FSL rat may not differ from controls in anxiety-related behavior. Another recently published study showed that the FSL rat also did not differ from normal Sprague-Dawley rats in startle tests, indicating that the FSL rats do not exhibit behaviors shown in animal models of schizophrenia. These findings confirm the utility of FSL rats as an animal

  3. The role of bioreductive activation of doxorubicin in cytotoxic activity against leukaemia HL60-sensitive cell line and its multidrug-resistant sublines

    PubMed Central

    Kostrzewa-Nowak, D; Paine, M J I; Wolf, C R; Tarasiuk, J

    2005-01-01

    Clinical usefulness of doxorubicin (DOX) is limited by the occurrence of multidrug resistance (MDR) associated with the presence of membrane transporters (e.g. P-glycoprotein, MRP1) responsible for the active efflux of drugs out of resistant cells. Doxorubicin is a well-known bioreductive antitumour drug. Its ability to undergo a one-electron reduction by cellular oxidoreductases is related to the formation of an unstable semiquionone radical and followed by the production of reactive oxygen species. There is an increasing body of evidence that the activation of bioreductive drugs could result in the alkylation or crosslinking binding of DNA and lead to the significant increase in the cytotoxic activity against tumour cells. The aim of this study was to examine the role of reductive activation of DOX by the human liver NADPH cytochrome P450 reductase (CPR) in increasing its cytotoxic activity especially in regard to MDR tumour cells. It has been evidenced that, upon CPR catalysis, DOX underwent only the redox cycling (at low NADPH concentration) or a multistage chemical transformation (at high NADPH concentration). It was also found, using superoxide dismutase (SOD), that the first stage undergoing reductive activation according to the mechanism of the redox cycling had the key importance for the metabolic conversion of DOX. In the second part of this work, the ability of DOX to inhibit the growth of human promyelocytic-sensitive leukaemia HL60 cell line as well as its MDR sublines exhibiting two different phenotypes of MDR related to the overexpression of P-glycoprotein (HL60/VINC) or MRP1 (HL60/DOX) was studied in the presence of exogenously added CPR. Our assays showed that the presence of CPR catalysing only the redox cycling of DOX had no effect in increasing its cytotoxicity against sensitive and MDR tumour cells. In contrast, an important increase in cytotoxic activity of DOX after its reductive conversion by CPR was observed against HL60 as well as HL60

  4. Arctic land hydrothermal sensitivity under warming: Idealized off-line evaluation of a physical terrestrial scheme in a global climate model

    NASA Astrophysics Data System (ADS)

    Saito, Kazuyuki

    2008-11-01

    A series of idealized one-dimensional off-line sensitivity experiments for the Arctic hydroclimate under a transitional warming environment were conducted to investigate the impact of different internal mechanisms and external forcing (excessive water input) in a physical terrestrial scheme, Minimal Advanced Treatments of Surface Interaction and Runoff (MATSIRO), used in a global climate model. The scheme has freeze/thaw processes and was run with the column depth greater than 50 m. The inclusion of the top organic layers and the physically based parameterization of soil hydrothermal properties led to a realistic seasonal amplitude of a subsurface thermal regime and mitigated the warming and deepening of the maximum active layer thickness (ALT). After a 6-K warming over 100 years, ALT increases by 67% (from 9.6 to 16 cm) with the top organic layers and increases by more than a factor of 2 for the default mineral layers (122% from 45 cm to 1.0 m). With the more realistic thermal property profile, the physically based parameterizations projected ALT after the 100-year warming to be about a half of what the original parameterization did (2.0 against 3.5 m). Finer soil layer thickness near the surface had impacts on the near-surface wetness and the energy and water exchange between the atmosphere and also showed greater tolerance to the misconfiguration of porosity profile, whose global-scale distribution is poorly known for global climate model applications. With much wetter forcing, water infiltration kept the soil close to the saturation, degradation of the frozen state proceeded faster, and the adaptation back to a drier condition occurred on a decadal time scale.

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

    PubMed Central

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

    2015-01-01

    Further elaborating the mechanism of antidepressants, beyond modulation of monoaminergic neurotransmission, this study sought to elucidate the mechanism of amitriptyline-induced production of glial cell line-derived neurotrophic factor (GDNF) in astroglial cells. Previous studies demonstrated that an amitriptyline-evoked matrix metalloproteinase (MMP)/FGF receptor (FGFR)/FGFR substrate 2α (FRS2α)/ERK cascade is crucial for GDNF production, but how amitriptyline triggers this cascade remains unknown. MMP is activated by intracellular mediators such as G proteins, and this study sought to clarify the involvement of G protein signaling in amitriptyline-evoked GDNF production in rat C6 astroglial cells (C6 cells), primary cultured rat astrocytes, and normal human astrocytes. Amitriptyline-evoked GDNF mRNA expression and release were inhibited by pertussis toxin (PTX), a Gαi/o inhibitor, but not by NF449, a Gαs inhibitor, or YM-254890, a Gαq inhibitor. The activation of the GDNF production cascade (FGFR/FRS2α/ERK) was also inhibited by PTX. Deletion of Gαο1 and Gαi3 by RNAi demonstrated that these G proteins play important roles in amitriptyline signaling. G protein activation was directly analyzed by electrical impedance-based biosensors (CellKeyTM assay), using a label-free (without use of fluorescent proteins/probes or radioisotopes) and real time approach. Amitriptyline increased impedance, indicating Gαi/o activation that was suppressed by PTX treatment. The impedance evoked by amitriptyline was not affected by inhibitors of the GDNF production cascade. Furthermore, FGF2 treatment did not elicit any effect on impedance, indicating that amitriptyline targets PTX-sensitive Gαi/o upstream of the MMP/FGFR/FRS2α/ERK cascade. These results suggest novel targeting for the development of antidepressants. PMID:25869129

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

    PubMed

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

    2016-03-01

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

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

    NASA Astrophysics Data System (ADS)

    Okumura, Akihiko

    2015-09-01

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

  8. A high-fat diet exacerbates depressive-like behavior in the Flinders Sensitive Line (FSL) rat, a genetic model of depression.

    PubMed

    Abildgaard, Anders; Solskov, Lasse; Volke, Vallo; Harvey, Brian H; Lund, Sten; Wegener, Gregers

    2011-06-01

    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

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

    PubMed

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

    2015-05-29

    Further elaborating the mechanism of antidepressants, beyond modulation of monoaminergic neurotransmission, this study sought to elucidate the mechanism of amitriptyline-induced production of glial cell line-derived neurotrophic factor (GDNF) in astroglial cells. Previous studies demonstrated that an amitriptyline-evoked matrix metalloproteinase (MMP)/FGF receptor (FGFR)/FGFR substrate 2α (FRS2α)/ERK cascade is crucial for GDNF production, but how amitriptyline triggers this cascade remains unknown. MMP is activated by intracellular mediators such as G proteins, and this study sought to clarify the involvement of G protein signaling in amitriptyline-evoked GDNF production in rat C6 astroglial cells (C6 cells), primary cultured rat astrocytes, and normal human astrocytes. Amitriptyline-evoked GDNF mRNA expression and release were inhibited by pertussis toxin (PTX), a Gα(i/o) inhibitor, but not by NF449, a Gα(s) inhibitor, or YM-254890, a Gαq inhibitor. The activation of the GDNF production cascade (FGFR/FRS2α/ERK) was also inhibited by PTX. Deletion of Gα(ο1) and Gα(i3) by RNAi demonstrated that these G proteins play important roles in amitriptyline signaling. G protein activation was directly analyzed by electrical impedance-based biosensors (CellKey(TM) assay), using a label-free (without use of fluorescent proteins/probes or radioisotopes) and real time approach. Amitriptyline increased impedance, indicating Gα(i/o) activation that was suppressed by PTX treatment. The impedance evoked by amitriptyline was not affected by inhibitors of the GDNF production cascade. Furthermore, FGF2 treatment did not elicit any effect on impedance, indicating that amitriptyline targets PTX-sensitive Gα(i/o) upstream of the MMP/FGFR/FRS2α/ERK cascade. These results suggest novel targeting for the development of antidepressants. PMID:25869129

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

    PubMed

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

    2016-05-01

    Neuroblastoma is the most commonly extra-cranial solid tumor of childhood frequently diagnosed. The nervous system-specific metabolite N-acetylaspartate (NAA) is synthesized from aspartate and acetyl-CoA in neurons, it is among the most abundant metabolites present in the central nervous system (CNS) and appears to be involved in many CNS disorders. The functional significance of the high NAA concentration in the brain remains uncertain, but it confers to NAA a unique clinical significance exploited in magnetic resonance spectroscopy. In the current study, we show that treatment of SH-SY5Y neuroblastoma-derived cell line with sub-cytotoxic physiological concentrations of NAA inhibits cell growth. This effect is partly due to enhanced apoptosis, shown by decrease of the anti-apoptotic factors survivin and Bcl-xL, and partly to arrest of the cell-cycle progression, linked to enhanced expression of the cyclin-inhibitors p53, p21Cip1/Waf1 and p27Kip1. Moreover, NAA-treated SH-SY5Y cells exhibited morphological changes accompanied with increase of the neurogenic markers TH and MAP2 and down-regulation of the pluripotency markers OCT4 and CXCR4/CD184. Finally, NAA-pre-treated SH-SY5Y cells resulted more sensitive to the cytotoxic effect of the chemotherapeutic drugs Cisplatin and 5-fluorouracil.To our knowledge, this is the first study demonstrating the neuronal differentiating effects of NAA in neuroblastoma cells. NAA may be a potential preconditioning or adjuvant compound in chemotherapeutic treatment. PMID:27036033

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

    NASA Astrophysics Data System (ADS)

    Trummer, Brian J.

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

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

    SciTech Connect

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

    2009-05-15

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

  13. In vitro cross-resistance and collateral sensitivity in seven resistant small-cell lung cancer cell lines: preclinical identification of suitable drug partners to taxotere, taxol, topotecan and gemcitabin.

    PubMed Central

    Jensen, P. B.; Holm, B.; Sorensen, M.; Christensen, I. J.; Sehested, M.

    1997-01-01

    The acquisition of drug-resistant tumour cells is the main problem in the medical treatment of a range of malignant diseases. In recent years, three new classes of anti-cancer agents, each with a novel mechanism of action, have been brought forward to clinical trials. These are the topoisomerase I (topo I) poisons topotecan and irinotecan, which are both camptothecin derivatives, the taxane tubulin stabilizers taxol and taxotere and, finally, the antimetabolite gemcitabin, which is active in solid tumours. The process of optimizing their use in a combination with established agents is very complex, with numerous possible drug and schedule regimens. We describe here how a broad panel of drug-resistant small-cell lung cancer (SCLC) cell lines can be used as a model of tumour heterogeneity to aid in the selection of non-cross-resistant regimens. We have selected low-fold (3-10x) drug-resistant sublines from a classic (NCI-H69) and a variant (OC-NYH) SCLC cell line. The resistant cell lines include two sublines with different phenotypes towards alkylating agents (H69/BCNU and NYH/CIS), two sublines with different phenotypes against topo I poisons (NYH/CAM and NYH/TPT) and three multidrug resistant (MDR) sublines (H69/DAU, NYH/VM, and H69/VP) with combinations of mdr1 and MRP overexpression as well as topoisomerase II (topo II) down-regulation or mutation. Sensitivity to 20 established and new agents was measured in a standardized clonogenic assay. Resistance was highly drug specific. Thus, none of the cell lines was resistant to all drugs. In fact, all resistant cell lines exhibited patterns of collateral sensitivity to various different classes of drugs. The most intriguing pattern was collateral sensitivity to gemcitabin in two cell lines and to ara-C in five drug-resistant cell lines, i.e. in all lines except the lines resistant to topo I poisons. Next, all sensitivity patterns in the nine cell lines were compared by correlation analysis. A high correlation

  14. Genetic selection for resistance to mycoplasmal pneumonia of swine (MPS) in the Landrace line influences the expression of soluble factors in blood after MPS vaccine sensitization.

    PubMed

    Shimazu, Tomoyuki; Borjigin, Liushiqi; Katayama, Yuki; Li, Meihua; Satoh, Takumi; Watanabe, Kouichi; Kitazawa, Haruki; Roh, Sang-gun; Aso, Hisashi; Kazuo, Katoh; Suda, Yoshihito; Sakuma, Akiko; Nakajo, Mituru; Suzuki, Keiichi

    2014-04-01

    We recently developed a Landrace line that is resistant to mycoplasmal pneumonia of swine (MPS) infection by genetic selection for five generations, and we reported that the immunophenotype of this line is different from that of the non-selected line in terms of changes in peripheral blood leukocyte population after MPS vaccination. This study followed up previous findings demonstrating changes in soluble factors in blood, namely, hormones, Mycoplasma hyopneumoniae-specific immunoglobulin G (IgG), and cytokines. These two lines were injected with MPS vaccine on days -7 and 0 after blood sampling on those days, and blood samples were collected on days -14, -7, 0, 2, 7 and 14. We found changes in the levels of many hormones and cytokines in both lines. However, we found that only growth hormone (GH) and interferon (IFN)-γ levels were statistically different between these two lines. GH concentration was reduced (day 0) and IFN-γ concentration was increased (day 14) in the MPS-selected line compared with the non-selected line, despite unchanged IFN-γ messenger RNA expression in blood cells. Although detailed mechanisms underlying these phenotypes remain unsolved, these traits would be useful to improve MPS resistance in pig production and provide an insight into MPS infection. PMID:24329865

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

    NASA Astrophysics Data System (ADS)

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

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

  16. IL-27 Promotes Proliferation of Human Leukemic Cell Lines Through the MAPK/ERK Signaling Pathway and Suppresses Sensitivity to Chemotherapeutic Drugs

    PubMed Central

    Dilger, Paula; Bird, Chris; Wadhwa, Meenu

    2016-01-01

    IL-27 is a pleiotropic cytokine of the IL-6/IL-12 family with diverse biological functions. Previous in vivo studies have suggested the antitumor activities of IL-27 in animal models, whereas clinical observations indicate the link of IL-27 in tumor progression. IL-27 has recently been shown to cause inhibition of proliferation on primary leukemic cells from pediatric patients, but information on its role in human leukemic cell lines is limited. In the present study, we investigated the ability of IL-27 to regulate cell growth and survival of various human leukemic cell lines. Our results showed that in human leukemic cell lines coexpressing both IL-27R chains, IL-27Rα and gp130, IL-27 did not inhibit cell growth, but caused dose-dependent proliferation of the acute myeloid leukemic cell line, OCI-AML5, and the erythroleukemic cell lines, TF-1, UT-7, and UT-7/EPO. Consistent with this, IL-27 promoted cell survival and reduced TNF-α-induced apoptosis of the leukemic cell lines. IL-27 also decreased the responsiveness of the leukemic cells to chemotherapeutic drugs, cytarabine and daunorubicin. We observed that IL-27 induced the activation of STAT1/3 and ERK1/2 in the leukemic cells. Growth stimulation by IL-27 was suppressed by the specific MEK inhibitor, U0126, indicating that IL-27-induced cell proliferation is mainly mediated through the activation of the MAPK/ERK signaling pathway. The present study is the first demonstration of the proliferative and antichemotherapeutic properties of IL-27 in human leukemic cell lines, suggesting that IL-27 can play an unfavorable role in tumor growth and can be an important determinant in the chemoresponsiveness of certain subtypes of human leukemia. PMID:27119567

  17. IL-27 Promotes Proliferation of Human Leukemic Cell Lines Through the MAPK/ERK Signaling Pathway and Suppresses Sensitivity to Chemotherapeutic Drugs.

    PubMed

    Jia, Haiyan; Dilger, Paula; Bird, Chris; Wadhwa, Meenu

    2016-05-01

    IL-27 is a pleiotropic cytokine of the IL-6/IL-12 family with diverse biological functions. Previous in vivo studies have suggested the antitumor activities of IL-27 in animal models, whereas clinical observations indicate the link of IL-27 in tumor progression. IL-27 has recently been shown to cause inhibition of proliferation on primary leukemic cells from pediatric patients, but information on its role in human leukemic cell lines is limited. In the present study, we investigated the ability of IL-27 to regulate cell growth and survival of various human leukemic cell lines. Our results showed that in human leukemic cell lines coexpressing both IL-27R chains, IL-27Rα and gp130, IL-27 did not inhibit cell growth, but caused dose-dependent proliferation of the acute myeloid leukemic cell line, OCI-AML5, and the erythroleukemic cell lines, TF-1, UT-7, and UT-7/EPO. Consistent with this, IL-27 promoted cell survival and reduced TNF-α-induced apoptosis of the leukemic cell lines. IL-27 also decreased the responsiveness of the leukemic cells to chemotherapeutic drugs, cytarabine and daunorubicin. We observed that IL-27 induced the activation of STAT1/3 and ERK1/2 in the leukemic cells. Growth stimulation by IL-27 was suppressed by the specific MEK inhibitor, U0126, indicating that IL-27-induced cell proliferation is mainly mediated through the activation of the MAPK/ERK signaling pathway. The present study is the first demonstration of the proliferative and antichemotherapeutic properties of IL-27 in human leukemic cell lines, suggesting that IL-27 can play an unfavorable role in tumor growth and can be an important determinant in the chemoresponsiveness of certain subtypes of human leukemia. PMID:27119567

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

    PubMed

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

    1984-12-01

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

  19. Silicon photonic crystal microarrays for high throughput label-free detection of lung cancer cell line lysates with sensitivity and specificity

    NASA Astrophysics Data System (ADS)

    Chakravarty, Swapnajit; Lai, Wei-Cheng; Zou, Yi; Gemmill, Robert M.; Chen, Ray T.

    2013-03-01

    Detection of biomolecules on microarrays based on label-free on-chip optical biosensors is very attractive since this format avoids complex chemistries caused by steric hindrance of labels. Application areas include the detection of cancers and allergens, and food-borne pathogens to name a few. We have demonstrated photonic crystal microcavity biosensors with high sensitivity down to 1pM concentrations (67pg/ml). High sensitivities were achieved by slow light engineering which reduced the radiation loss and increased the stored energy in the photonic crystal microcavity resonance mode. Resonances with high quality factor Q~26,760 in liquid ambient, coupled with larger optical mode volumes allowed enhanced interaction with the analyte biomolecules which resulted in sensitivities down to 10 cells per micro-liter to lung cancer cell lysates. The specificity of detection was ensured by multiplexed detections from multiple photonic crystal microcavities arrayed on the arms of a multimode interference power splitter. Specific binding interactions and control experiments were performed simultaneously at the same instant of time with the same 60 microliter sample volume. Specificity is further ensured by sandwich assay methods in the multiplexed experiment. Sandwich assay based amplification increased the sensitivity further resulting in the detection of lung cancer cell lysates down to concentrations of 2 cells per micro-liter. The miniaturization enabled by photonic crystal biosensors coupled with waveguide interconnected layout thus offers the potential of high throughput proteomics with high sensitivity and specificity.

  20. Experimental Concept for a Precision Measurement of Nuclear Recoil Ionization Yields for Low Mass WIMP Searches

    NASA Astrophysics Data System (ADS)

    Saab, T.; Figueroa-Feliciano, E.

    2016-07-01

    Understanding the response of dark matter detectors at the lowest recoil energies is important for correctly interpreting data from current experiments or predicting the sensitivity of future experiments to low mass weakly interacting massive particles. In particular, the ionization yield is essential for determining the correct recoil energy of candidate nuclear recoil events; however, few measurements in cryogenic crystals exist below 1 keV. Using the voltage-assisted calorimetric ionization detection technique with a mono-energetic neutron source, we show that it is possible to determine the ionization yield in cryogenic crystals down to an energy to 100 eV. This measurement will also determine the statistics of ionization production at these low energies.

  1. Bosonic super-WIMPs as keV-scale dark matter

    SciTech Connect

    Pospelov, Maxim; Ritz, Adam; Voloshin, Mikhail

    2008-12-01

    We consider models of light superweakly interacting cold dark matter, with O(10-100) keV mass, focusing on bosonic candidates such as pseudoscalars and vectors. We analyze the cosmological abundance, the {gamma} background created by particle decays, the impact on stellar processes due to cooling, and the direct-detection capabilities in order to identify classes of models that pass all the constraints. In certain models, variants of photoelectric (or axioelectric) absorption of dark matter in direct-detection experiments can provide a sensitivity to the superweak couplings to the standard model which is superior to all existing indirect constraints. In all models studied, the annual modulation of the direct-detection signal is at the currently unobservable level of O(10{sup -5})

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

    PubMed

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

    2015-10-01

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

  3. Blockade of Hedgehog Signaling Synergistically Increases Sensitivity to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-Small-Cell Lung Cancer Cell Lines

    PubMed Central

    Bai, Xiao-Yan; Zhang, Xu-Chao; Yang, Su-Qing; An, She-Juan; Chen, Zhi-Hong; Su, Jian; Xie, Zhi; Gou, Lan-Ying; Wu, Yi-Long

    2016-01-01

    Aberrant activation of the hedgehog (Hh) signaling pathway has been implicated in the epithelial-to-mesenchymal transition (EMT) and cancer stem-like cell (CSC) maintenance; both processes can result in tumor progression and treatment resistance in several types of human cancer. Hh cooperates with the epidermal growth factor receptor (EGFR) signaling pathway in embryogenesis. We found that the Hh signaling pathway was silenced in EGFR-TKI-sensitive non-small-cell lung cancer (NSCLC) cells, while it was inappropriately activated in EGFR-TKI-resistant NSCLC cells, accompanied by EMT induction and ABCG2 overexpression. Upregulation of Hh signaling through extrinsic SHH exposure downregulated E-cadherin expression and elevated Snail and ABCG2 expression, resulting in gefitinib tolerance (P < 0.001) in EGFR-TKI-sensitive cells. Blockade of the Hh signaling pathway using the SMO antagonist SANT-1 restored E-cadherin expression and downregulate Snail and ABCG2 in EGFR-TKI-resistant cells. A combination of SANT-1 and gefitinib markedly inhibited tumorigenesis and proliferation in EGFR-TKI-resistant cells (P < 0.001). These findings indicate that hyperactivity of Hh signaling resulted in EGFR-TKI resistance, by EMT introduction and ABCG2 upregulation, and blockade of Hh signaling synergistically increased sensitivity to EGFR-TKIs in primary and secondary resistant NSCLC cells. E-cadherin expression may be a potential biomarker of the suitability of the combined application of an Hh inhibitor and EGFR-TKIs in EGFR-TKI-resistant NSCLCs. PMID:26943330

  4. Neisseria gonorrhoeae in a London sexually transmitted infection clinic not fully sensitive to quinolones: are isolates imported and how effective is ciprofloxacin as a first-line therapy?

    PubMed

    Ivens, D; Martin, I; Ison, C

    2000-12-01

    Our objectives were to determine the prevalence of Neisseria gonorrhoeae not fully sensitive to ciprofloxacin from a sexually transmitted infection (STI) clinic in London and where the isolates were acquired from. Data of antibiotic sensitivities of N. gonorrhoeae from 292 patients were reviewed over a 6-month period at St Mary's Genitourinary Medicine (GUM) Clinic, London. Isolates which exhibited reduced susceptibility (minimum inhibitory concentration [MIC] 0.03-0.12 mg/l) and high level resistance (MIC>0.12 mg/l) to ciprofloxacin represented 10% and 1.3% of the total respectively. All patients infected with a high level resistant isolate to ciprofloxacin had had a recent sexual partner from abroad but 18 of the 28 patients infected with a reduced susceptibility isolate denied recent travel. None of the 20 patients with a non-sensitive isolate who re-attended for post treatment cultures had persistant gonococcal infection. From this study we concluded that although N. gonorrhoeae resistant to ciprofloxacin was rare and probably always acquired abroad, isolates exhibiting reduced susceptibility were more common and were mainly as a result of infection from the UK. A stat dose of ciprofloxacin 500 mg and doxycycline 100 mg twice a day for one week was effective treatment. PMID:11138910

  5. Blockade of Hedgehog Signaling Synergistically Increases Sensitivity to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-Small-Cell Lung Cancer Cell Lines.

    PubMed

    Bai, Xiao-Yan; Zhang, Xu-Chao; Yang, Su-Qing; An, She-Juan; Chen, Zhi-Hong; Su, Jian; Xie, Zhi; Gou, Lan-Ying; Wu, Yi-Long

    2016-01-01

    Aberrant activation of the hedgehog (Hh) signaling pathway has been implicated in the epithelial-to-mesenchymal transition (EMT) and cancer stem-like cell (CSC) maintenance; both processes can result in tumor progression and treatment resistance in several types of human cancer. Hh cooperates with the epidermal growth factor receptor (EGFR) signaling pathway in embryogenesis. We found that the Hh signaling pathway was silenced in EGFR-TKI-sensitive non-small-cell lung cancer (NSCLC) cells, while it was inappropriately activated in EGFR-TKI-resistant NSCLC cells, accompanied by EMT induction and ABCG2 overexpression. Upregulation of Hh signaling through extrinsic SHH exposure downregulated E-cadherin expression and elevated Snail and ABCG2 expression, resulting in gefitinib tolerance (P < 0.001) in EGFR-TKI-sensitive cells. Blockade of the Hh signaling pathway using the SMO antagonist SANT-1 restored E-cadherin expression and downregulate Snail and ABCG2 in EGFR-TKI-resistant cells. A combination of SANT-1 and gefitinib markedly inhibited tumorigenesis and proliferation in EGFR-TKI-resistant cells (P < 0.001). These findings indicate that hyperactivity of Hh signaling resulted in EGFR-TKI resistance, by EMT introduction and ABCG2 upregulation, and blockade of Hh signaling synergistically increased sensitivity to EGFR-TKIs in primary and secondary resistant NSCLC cells. E-cadherin expression may be a potential biomarker of the suitability of the combined application of an Hh inhibitor and EGFR-TKIs in EGFR-TKI-resistant NSCLCs. PMID:26943330

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

    PubMed

    Roussel, M J; Lanotte, M

    2001-10-29

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

  7. Increased sensitivity of HPV-positive head and neck cancer cell lines to x-irradiation ± Cisplatin due to decreased expression of E6 and E7 oncoproteins and enhanced apoptosis

    PubMed Central

    Ziemann, Frank; Arenz, Andrea; Preising, Stefanie; Wittekindt, Claus; Klussmann, Jens P; Engenhart-Cabillic, Rita; Wittig, Andrea

    2015-01-01

    Squamous cell carcinoma of the head and neck region (HNSCC), which is related to an infection with human papilloma virus (HPV), responds better to simultaneous radio-chemotherapy with Cisplatin based regimens than HPV-negative tumors. The underlying molecular mechanisms for this clinical observation are not fully understood. Therefore, the response of four HPV-positive (HPV+) (UM-SCC-47, UM-SCC-104, 93-VU-147T, UPCI:SCC152) and four HPV-negative (HPV-) (UD-SCC-1, UM-SCC-6, UM-SCC-11b, UT-SCC-33) HNSCC cell lines to x-irradiation ± Cisplatin incubation in terms of clonogenic survival, cell cycle progression, protein expression (cyclin A2, cyclin E2, E6, E7, p53) and induction of apoptosis, was investigated. HPV+ cells were more radio- and chemosensitive and were more effectively sensitized to x-irradiation by simultaneous Cisplatin incubation than HPV- cell lines. HPV+ cell lines revealed an increased and prolonged G2/M arrest after irradiation, whereas Cisplatin induced a blockage of cells in S phase. In comparison to irradiation only, addition of Cisplatin significantly enhanced apoptosis especially in HPV+ cell lines. While irradiation alone increased the amount of HPV E6 and E7 proteins, both were down-regulated by Cisplatin incubation either alone or in combination with x-rays, which however did not increase the expression of endogenous p53. Our results demonstrate that cell cycle deregulation together with downregulation of HPV E6 and E7 proteins facilitating apoptosis after Cisplatin incubation promote the enhanced sensitivity of HPV+ HNSCC cells to simultaneous radio-chemotherapy. Combined effects of irradiation and Cisplatin appear to be relevant in mediating the enhanced therapeutic response of HPV-related HNSCC and are indicative of the benefit of combined modality approaches in future treatment optimization strategies. PMID:26045983

  8. CpG-ODN 7909 increases radiation sensitivity of radiation-resistant human lung adenocarcinoma cell line by overexpression of Toll-like receptor 9.

    PubMed

    Yan, Li; Xu, Guoxiong; Qiao, Tiankui; Chen, Wei; Yuan, Sujuan; Li, Xuan

    2013-09-01

    Radioresistance is one of the main reasons for the failure of radiotherapy in lung cancer. The aim of this study was to establish a radiation-resistant lung cancer cell line, to evaluate whether CpG oligodeoxyribonucleotide (CpG-ODN) 7909 could increase its radiosensitivity and to explore the relevant mechanisms. The radioresistant cell line, referred to as R-A549, was generated by reduplicative fractionated irradiation from the human lung adenocarcinoma cell line A549. The radioresistance of R-A549 cells were confirmed by the Cell Counting Kit-8 (CCK-8), cell viability assay, and clonogenic assay. Cell growth kinetics, morphological feature, and radiosensitivity were compared between the original A549 cells and R-A549 cells treated with or without CpG-ODN 7909 or radiation. To further explore the potential mechanisms of radiosensitivity, the cell cycle distributions and the expression of Toll-like receptor 9 (TLR-9) were examined by Western blot and flow cytometry. The R-A549 cell line was generated and its radioresistance was further confirmed. CpG-ODN 7909 was found to increase much more radiosensitivity of R-A549 cells under combined treatments with CpG-ODN 7909 and radiation compared with its control group without any treatments. They presented their respective D0 1.33 ± 0.20 Gy versus 1.76 ± 0.25 Gy with N 3.44 ± 1.01 versus 4.96 ± 0.32. Further, there was a larger cell population of R-A549 cells under combined treatment in the G2/M phase compared with the control group after treatment with CpG-ODN7909 or radiation alone at 24 and 48 hour. The expression level of TLR-9 in R-A549 cells was found higher than in A549 cells. These results suggested that CpG-ODN 7909 increased the radiosensitivity of R-A549 cells, which might be mediated via the upregulated TLR-9 and prolonged cell cycle arrest in the G2/M phase compared with A549 cells. PMID:23705865

  9. The local dark matter phase-space density and impact on WIMP direct detection

    SciTech Connect

    Catena, Riccardo; Ullio, Piero E-mail: ullio@sissa.it

    2012-05-01

    We present a new determination of the local dark matter phase-space density. This result is obtained implementing, in the limit of isotropic velocity distribution and spherical symmetry, Eddington's inversion formula, which links univocally the dark matter distribution function to the density profile, and applying, within a Bayesian framework, a Markov Chain Monte Carlo algorithm to sample mass models for the Milky Way against a broad and variegated sample of dynamical constraints. We consider three possible choices for the dark matter density profile, namely the Einasto, NFW and Burkert profiles, finding that the velocity dispersion, which characterizes the width in the distribution, tends to be larger for the Burkert case, while the escape velocity depends very weakly on the profile, with the mean value we obtain being in very good agreement with estimates from stellar kinematics. The derived dark matter phase-space densities differ significantly — most dramatically in the high velocity tails — from the model usually taken as a reference in dark matter detection studies, a Maxwell-Boltzmann distribution with velocity dispersion fixed in terms of the local circular velocity and with a sharp truncation at a given value of the escape velocity. We discuss the impact of astrophysical uncertainties on dark matter scattering rates and direct detection exclusion limits, considering a few sample cases and showing that the most sensitive ones are those for light dark matter particles and for particles scattering inelastically. As a general trend, regardless of the assumed profile, when adopting a self-consistent phase-space density, we find that rates are larger, and hence exclusion limits stronger, than with the standard Maxwell-Boltzmann approximation. Tools for applying our result on the local dark matter phase-space density to other dark matter candidates or experimental setups are provided.

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

    SciTech Connect

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

    2013-11-15

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

  11. [The Mechanisms of Orientation Sensitivity of Human Vision System. Part II: Neural Patterns of Early Processing of Information about Line Orientation].

    PubMed

    Mikhailova, E S; Gerasimenko, N Yu; Krylova, M A; Izyurov, I V; Slavutskaya, A V

    2015-01-01

    The high density EEG was registered in 41 healthy subjects (20 males, 21 females) in the cardinal (horizontal and vertical) and oblique (45 and 135 deg) line orientation identification task. The analysis of the adaptive amplitude maximum (4 ms averaging) of P1 and N1 evoked potentials in the symmetrical occipital, parietal and inferior temporal areas and dipole source modelling showed the anisotropy of cortical responses in the 80-150 ms interval. The amplitude is higher on the oblique orientations as comparison with cardinal ones. The temporal and regional features of cortical answers were discovered. The earlier selective response (~90 ms latency) is registered.in the parietal areas, while the later (~145 ms latency) is found in the occipital ones. We discovered a number of sex-related differences in the early stages of line orientation detection. In males, the amplitude of components is higher; they have broader area of localisation of their dipole sources: in addition to the occipital and parietal regions, cortex of the temporal regions is involved. Theobtained data are discussed in the context of the idea of effective neural coding (Barlow, 1959) and the features of spatial information processing in the visual system of males and females. PMID:26237944

  12. The Stream algorithm: computationally efficient ridge-regression via Bayesian model averaging, and applications to pharmacogenomic prediction of cancer cell line sensitivity.

    PubMed

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

    2014-01-01

    Computational efficiency is important for learning algorithms operating in the "large p, small n" setting. In computational biology, the analysis of data sets containing tens of thousands of features ("large p"), but only a few hundred samples ("small n"), is nowadays routine, and regularized regression approaches such as ridge-regression, lasso, and elastic-net are popular choices. In this paper we propose a novel and highly efficient Bayesian inference method for fitting ridge-regression. Our method is fully analytical, and bypasses the need for expensive tuning parameter optimization, via cross-validation, by employing Bayesian model averaging over the grid of tuning parameters. Additional computational efficiency is achieved by adopting the singular value decomposition reparametrization of the ridge-regression model, replacing computationally expensive inversions of large p × p matrices by efficient inversions of small and diagonal n × n matrices. We show in simulation studies and in the analysis of two large cancer cell line data panels that our algorithm achieves slightly better predictive performance than cross-validated ridge-regression while requiring only a fraction of the computation time. Furthermore, in comparisons based on the cell line data sets, our algorithm systematically out-performs the lasso in both predictive performance and computation time, and shows equivalent predictive performance, but considerably smaller computation time, than the elastic-net. PMID:24297531

  13. VeroNectin-4 is a highly sensitive cell line that can be used for the isolation and titration of Peste des Petits Ruminants virus.

    PubMed

    Fakri, F; Elarkam, A; Daouam, S; Tadlaoui, K; Fassi-Fihri, O; Richardson, C D; Elharrak, M

    2016-02-01

    Peste des Petits Ruminants virus (PPRV) is a member of the Morbillivirus subgroup of the family Paramyxoviridae, and is one of the most contagious diseases of small ruminants throughout Africa and the rest of the world. Different cell lines have previously been used to isolate PPRV but with limited success. Thus, to improve the isolation of Morbilliviruses, human, canine, and goat homologues of the lymphocyte receptor signaling lymphocyte activation molecule (SLAM) have been introduced into cells that can support virus replication. However, the amino acid sequence of SLAM varies between species, and often requires adaptation of a particular virus to different versions of the receptor. The protein sequence of Nectin-4 is highly conserved between different mammals, which eliminate the need for receptor adaptation by the virus. Cell lines expressing Nectin-4 have previously been used to propagate measles and canine distemper viruses. In this study, we compared infections in Vero cells expressing canine SLAM (VeroDogSLAM) to those in Vero cells expressing Nectin-4 (VeroNectin-4), following inoculations with wild-type strains of PPRV. Virus isolation using VeroNectin-4 cells was successful with 23% of swabbed samples obtained from live infected animals, and was 89% effective using post-mortem tissues of infected sheep. By contrast, only 4.5% efficiency was observed from swab samples and 67% efficiency was obtained in virus isolation from post-mortem tissues using VeroDogSLAM cells. The average incubation period for virus recovery from post-mortem tissues was 3.4 days using VeroNectin-4 cells, compared with 5.5 days when using VeroDogSLAM cells. The virus titers of PPRV obtained from VeroNectin-4 cells were also higher than those derived from VeroDogSLAM cells. A comparison of the growth kinetics for PPRV in the two cell lines confirmed the superiority of VeroNectin-4 cells for PPR diagnostic purposes and vaccine virus titration. PMID:26615804

  14. Noscapine Increases the Sensitivity of Drug-Resistant Ovarian Cancer Cell Line SKOV3/DDP to Cisplatin by Regulating Cell Cycle and Activating Apoptotic Pathways.

    PubMed

    Shen, Wei; Liang, Bingfeng; Yin, Jie; Li, Xiurong; Cheng, Jianxin

    2015-05-01

    Cisplatin is a first-line chemotherapy drug against ovarian cancer. However, its strong toxic side effects and the development of cisplatin resistance in human cancer cells seriously influence the effects of chemotherapy and quality of life in patients. Noscapine (Nos), a non-toxic benzylisoquinoline alkaloid extracted from opium, has been recently reported to have anti-cancer activity, but the mechanism of that effect has not been clearly established. In the present study, we investigated cytotoxicity of Nos in combination with cisplatin (DDP) in drug-resistant human ovarian cancer cell line SKOV3/DDP in vitro and in vivo null mice xenograft model. Cell proliferation was measured by MTT assay, flow cytometry was used to analyze cell cycle and apoptosis, protein expression of several apoptotic factors was investigated by flow cytometry and immunohistochemical method, and their mRNA expression levels were determined by real-time PCR. In vitro experiments showed that Nos significantly inhibited proliferation of SKOV3/DDP cells. DDP/Nos-combined treatment notably enhanced DDP-induced inhibition of cell proliferation and increased the pro-apoptotic effect of DDP in SKOV3/DDP cells. DDP/Nos administration increased the proportion of G2/M cells, reduced both protein and mRNA expression of anti-apoptotic factors XIAP, surviving and NF-kB, and augmented protein and mRNA levels of pro-apoptotic caspase-3. In vivo experiments revealed that Nos/DDP treatment increased the apoptotic rate of xenograft tumors in null mice. Tumor volume decreased from 1.733 ± 0.155 g in mice treated with DDP alone to 1.191 ± 0.106 g in animals treated with Nos/DDP. These observations suggest that Nos increases the anti-cancer activity of DDP against the drug-resistant ovarian cancer cell line SKOV3/DDP by modulating the cell cycle and activating apoptotic pathways. The study provides a new chemotherapy strategy for the treatment of DDP-resistant human ovarian cancer. PMID:25510462

  15. A new sensitive indicator cell line reveals cross-transactivation of the viral LTR by gorilla and chimpanzee simian foamy viruses.

    PubMed

    Lambert, Caroline; Rua, Réjane; Gessain, Antoine; Buseyne, Florence

    2016-09-01

    The majority of currently identified simian foamy virus (SFV)-infected Cameroonian and Gabonese individuals harbor SFV from the gorilla lineage. We constructed an indicator cell line for the quantification of gorilla SFVs, in which the U3 sequence of a gorilla SFV directs the expression of the β-galactosidase protein. The gorilla foamy virus activated β-galactosidase (GFAB) cells efficiently quantified two zoonotic primary gorilla isolates and SFVs from three chimpanzee subspecies. Primary gorilla SFVs replicated more slowly and at lower levels than primary chimpanzee SFVs. Analysis of previously described motifs of Tas proteins and U3 LTRs involved in viral gene synthesis revealed conservation of such motifs in Tas proteins from gorilla and chimpanzee SFVs, but little sequence homology in the LTR regions previously shown to interact with viral and cellular factors. PMID:27348053

  16. Strong sensitivity of x-ray emission lines following charge exchange between highly charged ions and H (1 s ) in weakly screened media

    NASA Astrophysics Data System (ADS)

    Cariatore, N. D.; Otranto, S.

    2015-11-01

    We use the classical trajectory Monte Carlo method to analyze charge exchange processes between fully stripped projectiles with H (1 s ) in a screened environment at impact energies in the range 18 eV/amu to 10 keV/amu. For Fe+26 projectiles, (n ,l )-state selective charge exchange and line emission cross sections are presented for Debye screening lengths from 15 a.u. up to the unscreened case limit. At low-impact energies, a strong dependence of the hardness ratio on the Debye screening length is found. We show that such strong dependence also evidences itself for Ne+10,P+15,Ar+18, and Kr+36 projectiles. Clear indications of this dependence are noticeable in the photonic spectra even for large screening lengths (˜100 a.u.).

  17. Human B-cell lymphoma cell lines are highly sensitive to apoptosis induced by all-trans retinoic acid and interferon-gamma.

    PubMed

    Niitsu, Nozomi; Higashihara, Masaaki; Honma, Yoshio

    2002-08-01

    When cells were incubated in the presence of both interferon-gamma (IFN-gamma) and all-trans retinoic acid (ATRA), the concentration of IFN-gamma required to induce apoptosis of B-cell lymphoma cells was much lower than that required for myeloid or erythroid cell lines. The concentration of IFN-gamma that effectively inhibited the proliferation of BALM-3 cells was 1/40 of that required for BALM-1 cells. STAT-1 phosphorylation, IRF-1 mRNA and protein expression and RAR-beta expression were enhanced to a greater degree in BALM-3 cells treated with IFN-gamma and ATRA than in BALM-1 cells treated with IFN-gamma and ATRA, suggesting that these IFN-gamma related genes were involved in the induction of apoptosis of BALM-3 cells. PMID:12191570

  18. A Recombinant Human Pluripotent Stem Cell Line Stably Expressing Halide-Sensitive YFP-I152L for GABAAR and GlyR-Targeted High-Throughput Drug Screening and Toxicity Testing

    PubMed Central

    Kuenzel, Katharina; Friedrich, Oliver; Gilbert, Daniel F.

    2016-01-01

    GABAARs and GlyRs are considered attractive drug targets for therapeutic intervention and are also increasingly recognized in the context of in vitro neurotoxicity (NT) and developmental neurotoxicity (DNT) testing. However, systematic human-specific GABAAR and GlyR-targeted drug screening and toxicity testing is hampered due to lack of appropriate in vitro models that express native GABAARs and GlyRs. We have established a human pluripotent stem cell line (NT2) stably expressing YFP-I152L, a halide-sensitive variant of yellow fluorescent protein (YFP), allowing for fluorescence-based functional analysis of chloride channels. Upon stimulation with retinoic acid, NT2 cells undergo neuronal differentiation and allow pharmacological and toxicological evaluation of native GABAARs and GlyRs at different stages of brain maturation. We applied the cell line in concentration-response experiments with the neurotransmitters GABA and glycine as well as with the drugs strychnine, picrotoxin, fipronil, lindane, bicuculline, and zinc and demonstrate that the established in vitro model is applicable to GABAAR and GlyR-targeted pharmacological and toxicological profiling. We quantified the proportion of GABAAR and GlyR-sensitive cells, respectively, and identified percentages of approximately 20% each within the overall populations, rendering the cells a suitable model for systematic in vitro GABAAR and GlyR-targeted screening in the context of drug development and NT/DNT testing. PMID:27445687

  19. A Recombinant Human Pluripotent Stem Cell Line Stably Expressing Halide-Sensitive YFP-I152L for GABAAR and GlyR-Targeted High-Throughput Drug Screening and Toxicity Testing.

    PubMed

    Kuenzel, Katharina; Friedrich, Oliver; Gilbert, Daniel F

    2016-01-01

    GABAARs and GlyRs are considered attractive drug targets for therapeutic intervention and are also increasingly recognized in the context of in vitro neurotoxicity (NT) and developmental neurotoxicity (DNT) testing. However, systematic human-specific GABAAR and GlyR-targeted drug screening and toxicity testing is hampered due to lack of appropriate in vitro models that express native GABAARs and GlyRs. We have established a human pluripotent stem cell line (NT2) stably expressing YFP-I152L, a halide-sensitive variant of yellow fluorescent protein (YFP), allowing for fluorescence-based functional analysis of chloride channels. Upon stimulation with retinoic acid, NT2 cells undergo neuronal differentiation and allow pharmacological and toxicological evaluation of native GABAARs and GlyRs at different stages of brain maturation. We applied the cell line in concentration-response experiments with the neurotransmitters GABA and glycine as well as with the drugs strychnine, picrotoxin, fipronil, lindane, bicuculline, and zinc and demonstrate that the established in vitro model is applicable to GABAAR and GlyR-targeted pharmacological and toxicological profiling. We quantified the proportion of GABAAR and GlyR-sensitive cells, respectively, and identified percentages of approximately 20% each within the overall populations, rendering the cells a suitable model for systematic in vitro GABAAR and GlyR-targeted screening in the context of drug development and NT/DNT testing. PMID:27445687

  20. In-Line Separation by Capillary Electrophoresis Prior to Analysis by Top-Down Mass Spectrometry Enables Sensitive Characterization of Protein Complexes

    PubMed Central

    2015-01-01

    Intact protein analysis via top-down mass spectrometry (MS) provides a bird’s eye view over the protein complexes and complex protein mixtures with the unique capability of characterizing protein variants, splice isoforms, and combinatorial post-translational modifications (PTMs). Here we applied capillary electrophoresis (CE) through a sheathless CE–electrospray ionization interface coupled to an LTQ Velos Orbitrap Elite mass spectrometer to analyze the Dam1 complex from Saccharomyces cerevisiae. We achieved a 100-fold increase in sensitivity compared to a reversed-phase liquid chromatography coupled MS analysis of recombinant Dam1 complex with a total loading of 2.5 ng (12 amol). N-terminal processing forms of individual subunits of the Dam1 complex were observed as well as their phosphorylation stoichiometry upon Mps1p kinase treatment. PMID:25382489

  1. High-sensitivity HLA class I peptidome analysis enables a precise definition of peptide motifs and the identification of peptides from cell lines and patients' sera.

    PubMed

    Ritz, Danilo; Gloger, Andreas; Weide, Benjamin; Garbe, Claus; Neri, Dario; Fugmann, Tim

    2016-05-01

    The characterization of peptides bound to human leukocyte antigen (HLA) class I is of fundamental importance for understanding CD8+ T cell-driven immunological processes and for the development of immunomodulatory therapeutic strategies. However, until now, the mass spectrometric analysis of HLA-bound peptides has typically required billions of cells, still resulting in relatively few high-confidence peptide identifications. Capitalizing on the recent developments in mass spectrometry and bioinformatics, we have implemented a methodology for the efficient recovery of acid-eluted HLA peptides after purification with the pan-reactive antibody W6/32 and have identified a total of 27 862 unique peptides with high confidence (1% false discovery rate) from five human cancer cell lines. More than 93% of the identified peptides were eight to 11 amino acids in length and contained signatures that were in excellent agreement with published HLA binding motifs. Furthermore, by purifying soluble HLA class I complexes (sHLA) from sera of melanoma patients, up to 972 high-confidence peptides could be identified, including melanoma-associated antigens already described in the literature. Knowledge of the HLA class I peptidome should facilitate multiplex tetramer technology-based characterization of T cells, and allow the development of patient selection, stratification and immunomodulatory therapeutic strategies. PMID:26992070

  2. On-line coupling of ionic liquid-based single-drop microextraction with capillary electrophoresis for sensitive detection of phenols.

    PubMed

    Wang, Qing; Qiu, Hongdeng; Li, Jing; Liu, Xia; Jiang, Shengxiang

    2010-08-13

    An ionic liquid-based single-drop microextraction (IL-SDME) procedure using IL as an extractant on-line coupled to capillary electrophoresis (CE) is proposed. The method is capable of quantifying trace amounts of phenols in environmental water samples. For the SDME of three phenols, a 2.40 nL IL microdrop was exposed for 10 min to the aqueous sample and then was directly injected into the capillary column for analysis. Extraction parameters such as the extraction time, the IL single-drop volume, pH of the sample solution, ionic strength, volume of the sample solution and the extraction temperature were systematically investigated. Detection limits to three phenols were less than 0.05 microg mL(-1), and their calibration curves were all linear (R(2) > or = 0.9994) in the range from 0.05 to 50 microg mL(-1). And enrichment factors for three phenols were 156, 107 and 257 without agitation, respectively. This method was then utilized to analyze two real environmental samples from Yellow River and tap water, obtaining satisfactory results. Compared with the usual SDME for CE, IL-SDME-CE is a simple, low-cost, fast and environmentally friendly preconcentration technique. PMID:20621300

  3. Suppression of telomere-binding protein TPP1 resulted in telomere dysfunction and enhanced radiation sensitivity in telomerase-negative osteosarcoma cell line

    SciTech Connect

    Qiang, Weiguang; Wu, Qinqin; Zhou, Fuxiang; Xie, Conghua; Wu, Changping; Zhou, Yunfeng

    2014-03-07

    Highlights: • Down-regulation of TPP1 shortened telomere length in telomerase-negative cells. • Down-regulation of TPP1 induced cell apoptosis in telomerase-negative cells. • Down-regulation of TPP1 increased radiosensitivity in telomerase-negative cells. - Abstract: Mammalian telomeres are protected by the shelterin complex that contains the six core proteins POT1, TPP1, TIN2, TRF1, TRF2 and RAP1. TPP1, formerly known as TINT1, PTOP, and PIP1, is a key factor that regulates telomerase recruitment and activity. In addition to this, TPP1 is required to mediate the shelterin assembly and stabilize telomere. Previous work has found that TPP1 expression was elevated in radioresistant cells and that overexpression of TPP1 led to radioresistance and telomere lengthening in telomerase-positive cells. However, the exact effects and mechanism of TPP1 on radiosensitivity are yet to be precisely defined in the ALT cells. Here we report on the phenotypes of the conditional deletion of TPP1 from the human osteosarcoma U2OS cells using ALT pathway to extend the telomeres.TPP1 deletion resulted in telomere shortening, increased apoptosis and radiation sensitivity enhancement. Together, our findings show that TPP1 plays a vital role in telomere maintenance and protection and establish an intimate relationship between TPP1, telomere and cellular response to ionizing radiation, but likely has the specific mechanism yet to be defined.

  4. The seminoma cell line TCam-2 is sensitive to HDAC inhibitor depsipeptide but tolerates various other chemotherapeutic drugs and loss of NANOG expression.

    PubMed

    Nettersheim, Daniel; Gillis, Ad; Biermann, Katharina; Looijenga, Leendert H J; Schorle, Hubert

    2011-12-01

    Seminomas and embryonal carcinomas (EC) are both type II germ cell tumor (GCT) entities and develop from the same precursor lesion (carcinoma-in situ, CIS). However, they show significant differences in growth behavior, differentiation potential, and gene expression. Although ECs are prone to differentiate into all three germ layers and give rise to the non-seminomatous GCT entities teratoma, choriocarcinoma, and yolk-sac tumor, differentiation of seminomas to these entities is only rarely observed. This might reflect the ability of seminomas to actively inhibit differentiation processes evoked by environmental cues. Also, it is not known why CIS gives rise to seminoma in some patients and to non-seminoma in the others. Here, we treated the seminoma-like cell line TCam-2 with the HDAC-inhibitor Depsipeptide, the global demethylating agent 5-aza-2'-deocycytidine, all-trans retinoic acid and the monaminooxidase inhibitor Tranylcipromine and also used knock down approaches to reduce expression of the pluripotency marker NANOG and/or the inhibitor of primordial germ cell differentiation TFAP2C. We found that TCam-2 cells induce apoptosis when treated with Depsipeptide (> 10 nM) but are resistant to treatments with 5-aza-2'-deocycytidine, all-trans retinoic acid and Tranylcipromine, highlighting Depsi as a treatment option for seminomas. We show that TCam-2 cells up-regulate endoderm- and throphectoderm-associated genes after down-regulation of NANOG expression; however, morphologically no indications of differentiation could be found. Instead, we observed up-regulation of OCT3/4 and SOX17 in TCam-2-NANOG knockdown and speculate that this compensates for the loss of the NANOG protein. Hence, NANOG is not a primary target gene responsible for the inhibition of differentiation in seminomas. PMID:21987446

  5. A sensitive and selective on-line amperometric sulfite biosensor using sulfite oxidase immobilized on a magnetite-gold-folate nanocomposite modified carbon-paste electrode.

    PubMed

    Sroysee, Wongduan; Ponlakhet, Kitayanan; Chairam, Sanoe; Jarujamrus, Purim; Amatatongchai, Maliwan

    2016-08-15

    We describe a novel amperometric sulfite biosensor, comprising a carbon-paste electrode (Fe3O4@Au-Cys-FA/CPE) modified with immobilized sulfite oxidase (SOx) on a gold-coated magnetite nanoparticle core, encased within a conjugated folic acid (FA) cysteine (Cys) shell. The biosensor electrode was fabricated using a polydimethylsiloxane (PDMS) and mineral oil mixture as binder, which also enhances the physical stability and sensitivity of the electrode. The developed biosensor displays good electrocatalytic activity toward oxidation of H2O2, which occurs by an enzymatic reaction between SOx and sulfite. The Fe3O4@Au-Cys-FA electrode exhibits good electrocatalytic activity, and has good retention of chemisorbed SOx on the electrode because of its large surface area. Sulfite was quantified using amperometric measurements from the Fe3O4@Au-Cys-FA/CPE biosensor, and using an in-house assembled flow cell at +0.35V (vs. Ag/AgCl), with a phosphate buffer carrier (0.10M, pH 7.0) at a flow rate of 0.8mLmin(-1). The system detects sulfite over the range 0.1-200mgL(-1) (r(2)=0.998), with a detection limit of 10µgL(-1) (3σ of blank). The system exhibits acceptable precision (%R.S.D.=3.1%), rapid sample throughput (109samplesh(-1)), and good stability (2w). The developed biosensor shows satisfactory tolerance to potential interferences, such as sugars, anions, ascorbic acid, and ethanol. We applied the developed method to the determination of sulfite content in wines and pickled food extracts, and our results are in good agreement with those obtained by the standard iodometric method. PMID:27260448

  6. Test battery with the human cell line activation test, direct peptide reactivity assay and DEREK based on a 139 chemical data set for predicting skin sensitizing potential and potency of chemicals.

    PubMed

    Takenouchi, Osamu; Fukui, Shiho; Okamoto, Kenji; Kurotani, Satoru; Imai, Noriyasu; Fujishiro, Miyuki; Kyotani, Daiki; Kato, Yoshinao; Kasahara, Toshihiko; Fujita, Masaharu; Toyoda, Akemi; Sekiya, Daisuke; Watanabe, Shinichi; Seto, Hirokazu; Hirota, Morihiko; Ashikaga, Takao; Miyazawa, Masaaki

    2015-11-01

    To develop a testing strategy incorporating the human cell line activation test (h-CLAT), direct peptide reactivity assay (DPRA) and DEREK, we created an expanded data set of 139 chemicals (102 sensitizers and 37 non-sensitizers) by combining the existing data set of 101 chemicals through the collaborative projects of Japan Cosmetic Industry Association. Of the additional 38 chemicals, 15 chemicals with relatively low water solubility (log Kow > 3.5) were selected to clarify the limitation of testing strategies regarding the lipophilic chemicals. Predictivities of the h-CLAT, DPRA and DEREK, and the combinations thereof were evaluated by comparison to results of the local lymph node assay. When evaluating 139 chemicals using combinations of three methods based on integrated testing strategy (ITS) concept (ITS-based test battery) and a sequential testing strategy (STS) weighing the predictive performance of the h-CLAT and DPRA, overall similar predictivities were found as before on the 101 chemical data set. An analysis of false negative chemicals suggested a major limitation of our strategies was the testing of low water-soluble chemicals. When excluded the negative results for chemicals with log Kow > 3.5, the sensitivity and accuracy of ITS improved to 97% (91 of 94 chemicals) and 89% (114 of 128). Likewise, the sensitivity and accuracy of STS to 98% (92 of 94) and 85% (111 of 129). Moreover, the ITS and STS also showed good correlation with local lymph node assay on three potency classifications, yielding accuracies of 74% (ITS) and 73% (STS). Thus, the inclusion of log Kow in analysis could give both strategies a higher predictive performance. PMID:25820183

  7. Sensitive determination of aspirin and its metabolites in plasma by LC-UV using on-line solid-phase extraction with methylcellulose-immobilized anion-exchange restricted access media.

    PubMed

    Yamamoto, Eiichi; Takakuwa, Susumu; Kato, Takashi; Asakawa, Naoki

    2007-02-01

    We describe a sensitive determination of aspirin (ASA) and its three metabolites (salicylic acid [SA], 2,3-dihydroxybenzoic acid [2,3-DHBA], and 2,5-dihydroxybenzoic acid [gentisic acid (GA)]) in rat plasma. Analysis was carried out by on-line solid-phase extraction (SPE) using a methylcellulose-immobilized-strong anion-exchanger (MC-SAX), followed by liquid chromatography (LC) coupled with UV detection. The lower limits of quantitation for ASA and SA were 60 ng/mL in 100 microL of plasma, respectively. This method was validated with respect to intra- and inter-day precision, accuracy, and linearity up to concentrations of 20,000 ng/mL for ASA, SA, 2,3-DHBA and gentisic acid, respectively. The method was successfully applied to an analysis of the pharmacokinetics of ASA and SA in rats. PMID:16959551

  8. The physics of background discrimination in liquid xenon, and first results from Xenon10 in the hunt for WIMP dark matter

    NASA Astrophysics Data System (ADS)

    Dahl, Carl Eric

    2009-06-01

    The WIMP limit set by the Xenon10 experiment in 2007 signals a new era in direct detection of dark matter, with several large-scale liquid target detectors now under construction. A major challenge in these detectors will be to understand backgrounds at the level necessary to claim a positive WIMP signal. In liquid xenon, these backgrounds are dominated by electron recoils, which may be distinguished from the WIMP signal (nuclear recoils) by their higher charge-to-light ratio. During the construction and operation of Xenon10, the prototype detector Xed probed the physics of this discrimination. Particle interactions in liquid xenon both ionize and excite xenon atoms, giving charge and scintillation signals, respectively. Some fraction of ions recombine, reducing the charge signal and creating additional scintillation. The charge-to-light ratio, determined by the initial exciton-ion ratio and the ion recombination fraction, provides the basis for discrimination between electron and nuclear recoils. Intrinsic fluctuations in the recombination fraction limit discrimination. Changes in recombination induce an exact anti-correlation between charge and light, and when calibrated this anti-correlation distinguishes recombination fluctuations from uncorrelated fluctuations in the measured signals. We determine the mean recombination and recombination fluctuations as a function of energy and applied field for electron and nuclear recoils, finding that recombination fluctuations are already the limiting factor for discrimination above ~12 keVr (nuclear recoil energy). Below 12 keVr statistical fluctuations in the number of scintillation photons counted dominate, and we project a x6 improvement in background rejection with a x2 increase in light collection efficiency. We also build a simple recombination model that successfully reproduces the mean recombination in electron and nuclear recoils, including the surprising reversal of the expected trend for recombination with

  9. Cytotoxic, apoptotic, and sensitization properties of ent-kaurane-type diterpenoids from Croton tonkinensis Gagnep on human liver cancer HepG2 and Hep3b cell lines.

    PubMed

    Pham, Minh Quan; Iscache, Anne Laure; Pham, Quoc Long; Gairin, Jean Edouard

    2016-04-01

    Human hepatocellular carcinoma (HCC) is the most common type of liver cancer, the second most common cause of death from cancer worldwide. A very poor prognosis and a lack of effective treatments make liver cancer a major public health problem, notably in less developed regions, particularly in eastern Asia. This fully justifies the search of new molecules and therapeutic strategies against HCC. Ent-kaurane diterpenoids are natural compounds displaying a broad spectrum of potential therapeutic effects including anticancer activity. In this study, we analyzed the pharmacological properties of a family of ent-kaurane diterpenoids from Croton tonkinensis Gagnep in human HepG2 and Hep3b cell lines, used as cellular reference models for in vitro evaluation of new molecules active on HCC. A structure-related cytotoxicity was observed against both HCC cell lines, enlighting the role of the 16-en-15-one skeleton of ent-kaurane diterpenoids. Cytotoxicity was closely correlated to apoptosis, evidenced by concentration-dependent subG1 cell accumulation, and increased annexin V expression. In addition, subtoxic concentration of ent-kaurane diterpenoid dramatically enhanced the sensitivity of HCC cells to doxorubicin. All together, our data bring strong support to the potential interest of ent-kaurane diterpenoids, alone or in combination with a cytotoxic agent, in cancer and more precisely against HCC. PMID:26713517

  10. An enhanced and sensitive autocrine stimulation by transforming growth factor-alpha is acquired in the brain metastatic variant of a human non-small-cell lung cancer cell line.

    PubMed

    Fang, K

    1996-12-01

    Transforming growth factor-alpha (TGF-alpha)-mediated autocrine regulation in human non-small-cell lung cancer (NSCLC) cells NCI-H226 and its brain metastatic variant H226Br were compared. An enhanced TGF-alpha-induced dose-dependent mitogenic responsiveness in H226Br cells was observed. Neutralising antibody that binds TGF-alpha inhibits H226Br cell growth more effectively than NCI-H226 cell growth. Binding assay with 125I-labelled epidermal growth factor (EGF) revealed that H226Br has two types of EGF receptors (EGFRs), whereas the parental cell line, NCI-H226, has only one. H226Br cells contain twice as many EGFRs as H226 cells, as proved by Scatchard analysis and immune kinase assay. Northern analysis indicated that there is more EGFR transcript in H226Br than in NCI-H226, indicating a transcriptional EGFR gene elevation during metastasis progression. The level of accumulated immunoactive TGF-alpha is lower in the conditioned medium of H226Br than in that of NCI-H226. demonstrating down-regulation of TGF-alpha transcript. The accumulated data suggest an elevated and sensitive autocrine modulation by TGF-alpha and EGFR in immortalising the brain metastatic variant cells that were derived from a human NSCLC squamous cell line. PMID:8956792

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

    PubMed

    Padilla-Sánchez, Juan Antonio; Haug, Line Småstuen

    2016-05-01

    A fast and sensitive method for simultaneous determination of 18 traditional and 6 alternative per- and polyfluoroalkyl substances (PFASs) using solid-liquid extraction (SLE), off-line clean-up using activated carbon and on-line solid phase extraction-ultrahigh performance liquid chromatography-time-of-flight-mass spectrometry (on-line SPE-UHPLC-TOF-MS) was developed. The extraction efficiency was studied and recoveries in range the 58-114% were obtained. Extraction and injection volumes were also optimized to 2mL and 400μL, respectively. The method was validated by spiking dust from a vacuum cleaner bag that had been found to contain low levels of the PFASs in focus. Low method detection limits (MDLs) and method quantification limits (MQLs) in the range 0.008-0.846ngg(-1) and 0.027-2.820ngg(-1) were obtained, respectively. For most of the PFASs, the accuracies were between 70 and 125% in the range from 2 to100ngg(-1) dust. Intra-day and inter-day precisions were in general well below 30%. Analysis of a Standard Reference Material (SRM 2585) showed high accordance with results obtained by other laboratories. Finally, the method was applied to seven indoor dust samples, and PFAS concentrations in the range 0.02-132ngg(-1) were found. The highest median concentrations were observed for some of the alternative PFASs, such as 6:2-diPAP (25ngg(-1)), 8:2-diPAP (49ngg(-1)), and PFOPA (23ngg(-1)), illustrating the importance of inclusion of new PFASs in the analytical methods. PMID:27062722

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

    PubMed

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

    2016-04-01

    A high throughput, high-sensitivity procedure, involving simultaneous microwave-assisted extraction (MAS) and unsaponifiable extraction, followed by on-line liquid chromatography (LC)-gas chromatography (GC), has been optimised for rapid and efficient extraction and analytical determination of mineral oil saturated hydrocarbons (MOSH) and mineral oil aromatic hydrocarbons (MOAH) in cereal-based products of different composition. MAS has the advantage of eliminating fat before LC-GC analysis, allowing an increase in the amount of sample extract injected, and hence in sensitivity. The proposed method gave practically quantitative recoveries and good repeatability. Among the different cereal-based products analysed (dry semolina and egg pasta, bread, biscuits, and cakes), egg pasta packed in direct contact with recycled paperboard had on average the highest total MOSH level (15.9 mg kg(-1)), followed by cakes (10.4 mg kg(-1)) and bread (7.5 mg kg(-1)). About 50% of the pasta and bread samples and 20% of the biscuits and cake samples had detectable MOAH amounts. The highest concentrations were found in an egg pasta in direct contact with recycled paperboard (3.6 mg kg(-1)) and in a milk bread (3.6 mg kg(-1)). PMID:26593464

  13. Characterization of Nuclear Recoils in High Pressure Xenon Gas: Towards a Simultaneous Search for WIMP Dark Matter and Neutrinoless Double Beta Decay

    DOE PAGESBeta

    Renner, J.; Gehman, V. M.; Goldschmidt, A.; Oliveira, C. A.B.; Nygren, D.

    2015-03-24

    Xenon has recently been the medium of choice in several large scale detectors searching for WIMP dark matter and neutrinoless double beta decay. Though present-day large scale experiments use liquid xenon, the gas phase offers advantages favorable to both types of searches such as improved intrinsic energy resolution and fewer fluctuations in the partition of deposited energy between scintillation and ionization channels. We recently constructed a high pressure xenon gas TPC as a prototype for the NEXT (Neutrino Experiment with a Xenon TPC) neutrinoless double beta decay experiment and have demonstrated the feasibility of 0.5% FWHM energy resolution at themore » 136Xe double beta Q-value with 3-D tracking capabilities. We now present results from this prototype on the simultaneous observation of scintillation and ionization produced by nuclear recoils at approximately 14 bar pressure. The recoils were produced by neutrons of approximately 2-6 MeV emitted from a radioisotope plutonium-beryllium source, and primary scintillation (S1) and electroluminescent photons produced by ionization (S2) were observed. We discuss the potential of gaseous xenon to distinguish between electron and nuclear recoils through the ratio of these two signals S2/S1. From these results combined with the possibility of using columnar recombination to sense nuclear recoil directionality at high pressures we envision a dual-purpose, ton-scale gaseous xenon detector capable of a combined search for WIMP dark matter and neutrinoless double beta decay. This work has been performed within the context of the NEXT collaboration.« less

  14. Characterization of Nuclear Recoils in High Pressure Xenon Gas: Towards a Simultaneous Search for WIMP Dark Matter and Neutrinoless Double Beta Decay

    NASA Astrophysics Data System (ADS)

    Renner, J.; Gehman, V. M.; Goldschmidt, A.; Oliveira, C. A. B.; Nygren, D.

    Xenon has recently been the medium of choice in several large scale detectors searching for WIMP dark matter and neutrinoless double beta decay. Though present-day large scale experiments use liquid xenon, the gas phase o_ers advantages favorable to both types of searches such as improved intrinsic energy resolution and fewer fluctuations in the partition of deposited energy between scintillation and ionization channels. We recently constructed a high pressure xenon gas TPC as a prototype for the NEXT (Neutrino Experiment with a Xenon TPC) neutrinoless double beta decay experiment and have demonstrated the feasibility of 0.5% FWHM energy resolution at the 136Xe double beta Q-value with 3-D tracking capabilities. We now present results from this prototype on the simultaneous observation of scintillation and ionization produced by nuclear recoils at approximately 14 bar pressure. The recoils were produced by neutrons of approximately 2-6 MeV emitted from a radioisotope plutonium-beryllium source, and primary scintillation (S1) and electroluminescent photons produced by ionization (S2) were observed. We discuss the potential of gaseous xenon to distinguish between electron and nuclear recoils through the ratio of these two signals S2/S1. From these results combined with the possibility of using columnar recombination to sense nuclear recoil directionality at high pressures we envision a dual-purpose, ton-scale gaseous xenon detector capable of a combined search for WIMP dark matter and neutrinoless double beta decay. This work has been performed within the context of the NEXT collaboration.

  15. Characterization of Nuclear Recoils in High Pressure Xenon Gas: Towards a Simultaneous Search for WIMP Dark Matter and Neutrinoless Double Beta Decay

    SciTech Connect

    Renner, J.; Gehman, V. M.; Goldschmidt, A.; Oliveira, C. A.B.; Nygren, D.

    2015-03-24

    Xenon has recently been the medium of choice in several large scale detectors searching for WIMP dark matter and neutrinoless double beta decay. Though present-day large scale experiments use liquid xenon, the gas phase offers advantages favorable to both types of searches such as improved intrinsic energy resolution and fewer fluctuations in the partition of deposited energy between scintillation and ionization channels. We recently constructed a high pressure xenon gas TPC as a prototype for the NEXT (Neutrino Experiment with a Xenon TPC) neutrinoless double beta decay experiment and have demonstrated the feasibility of 0.5% FWHM energy resolution at the 136Xe double beta Q-value with 3-D tracking capabilities. We now present results from this prototype on the simultaneous observation of scintillation and ionization produced by nuclear recoils at approximately 14 bar pressure. The recoils were produced by neutrons of approximately 2-6 MeV emitted from a radioisotope plutonium-beryllium source, and primary scintillation (S1) and electroluminescent photons produced by ionization (S2) were observed. We discuss the potential of gaseous xenon to distinguish between electron and nuclear recoils through the ratio of these two signals S2/S1. From these results combined with the possibility of using columnar recombination to sense nuclear recoil directionality at high pressures we envision a dual-purpose, ton-scale gaseous xenon detector capable of a combined search for WIMP dark matter and neutrinoless double beta decay. This work has been performed within the context of the NEXT collaboration.

  16. Endogenous gamma-aminobutyric acid (GABA)(A) receptor active neurosteroids and the sedative/hypnotic action of gamma-hydroxybutyric acid (GHB): a study in GHB-S (sensitive) and GHB-R (resistant) rat lines.

    PubMed

    Barbaccia, Maria Luisa; Carai, Mauro A M; Colombo, Giancarlo; Lobina, Carla; Purdy, Robert H; Gessa, Gian Luigi

    2005-07-01

    In the rat brain, gamma-hydroxybutyric-acid (GHB) increases the concentrations of 3alpha-hydroxy,5alpha-pregnan-20-one (allopregnanolone, 3alpha,5alpha-THP) and 3alpha,21-dihydroxy,5alpha-pregnan-20-one (allotetrahydrodeoxycorticosterone/3alpha,5alphaTHDOC), two neurosteroids acting as positive allosteric modulators of gamma-aminobutyric acid (GABA)(A) receptors. This study was aimed at assessing whether neurosteroids play a role in GHB-induced loss of righting reflex (LORR). Basal and GHB-stimulated brain concentrations of endogenous 3alpha,5alpha-THP and 3alpha,5alpha-THDOC were analyzed in two rat lines, GHB-sensitive (GHB-S) and GHB-resistant (GHB-R), selectively bred for opposite sensitivity to GHB-induced sedation/hypnosis. Basal neurosteroid concentrations were similar in brain cortex of the two rat lines. However, in male GHB-S rats, administration of GHB (1000 mg/kg, i.p., 30 min) increased brain cortical concentrations of 3alpha,5alpha-THP and 3alpha,5alpha-THDOC 7- and 2.5-fold, respectively, whilst male GHB-R animals displayed only a 4- and 2-fold increase, respectively. In GHB-S rats this increase lasted up to 90 min and declined 180 min following GHB administration, a time course that matches LORR onset and duration. In contrast, in GHB-R rats, which failed to show GHB-induced LORR, brain cortical 3alpha,5alpha-THP and 3alpha,5alpha-THDOC had returned to control values within 90 min. At onset of LORR, a similar increase in brain cortical levels of 3alpha,5alpha-THP and 3alpha,5alpha-THDOC (2-3-fold) was observed in GHB-S female rats and in the few female GHB-R rats that lost the righting reflex after GHB administration, but not in female GHB-R rats failing to show LORR. Sub-hypnotic doses (7.5 and 12.5 mg/kg, i.p.) of pregnanolone, administered 10 min before GHB, dose-dependently facilitated the expression of GHB-induced LORR in GHB-R male rats. These results suggest that the GHB-induced increases of brain 3alpha,5alpha-THP and 3alpha,5alpha

  17. Cell Lines

    PubMed Central

    Cherbas, Lucy; Gong, Lei

    2014-01-01

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

  18. Loss of CDKN2A expression is a frequent event in primary invasive melanoma and correlates with sensitivity to the CDK4/6 inhibitor PD0332991 in melanoma cell lines.

    PubMed

    Young, Richard J; Waldeck, Kelly; Martin, Claire; Foo, Jung H; Cameron, Donald P; Kirby, Laura; Do, Hongdo; Mitchell, Catherine; Cullinane, Carleen; Liu, Wendy; Fox, Stephen B; Dutton-Regester, Ken; Hayward, Nicholas K; Jene, Nicholas; Dobrovic, Alexander; Pearson, Richard B; Christensen, James G; Randolph, Sophia; McArthur, Grant A; Sheppard, Karen E

    2014-07-01

    We have investigated the potential for the p16-cyclin D-CDK4/6-retinoblastoma protein pathway to be exploited as a therapeutic target in melanoma. In a cohort of 143 patients with primary invasive melanoma, we used fluorescence in situ hybridization to detect gene copy number variations (CNVs) in CDK4, CCND1, and CDKN2A and immunohistochemistry to determine protein expression. CNVs were common in melanoma, with gain of CDK4 or CCND1 in 37 and 18% of cases, respectively, and hemizygous or homozygous loss of CDKN2A in 56%. Three-quarters of all patients demonstrated a CNV in at least one of the three genes. The combination of CCND1 gain with either a gain of CDK4 and/or loss of CDKN2A was associated with poorer melanoma-specific survival. In 47 melanoma cell lines homozygous loss, methylation or mutation of CDKN2A gene or loss of protein (p16(INK) (4A) ) predicted sensitivity to the CDK4/6 inhibitor PD0332991, while RB1 loss predicted resistance. PMID:24495407

  19. Sensitive determination of polycyclic aromatic hydrocarbons in water samples using monolithic capillary solid-phase extraction and on-line thermal desorption prior to gas chromatography-mass spectrometry.

    PubMed

    Galán-Cano, Francisco; Bernabé-Zafón, Virginia; Lucena, Rafael; Cárdenas, Soledad; Herrero-Martínez, José Manuel; Ramis-Ramos, Guillermo; Valcárcel, Miguel

    2011-04-01

    A methacrylate-based monolithic capillary column has been evaluated for the preconcentration of polycyclic aromatic hydrocarbons (PAHs) from environmental water samples. For this purpose, the monolyte was in situ synthesized in a 6cm×0.32mm id fused-silica capillary. The microextraction unit was fitted to a micro-HPLC pump to pass 10mL of sample. The isolated pollutants were eluted by means of 10μL of methanol, the organic phase being directly collected in a specific interface that can be fitted to the injection port of the gas chromatograph without modification. The interface allows the on-line thermal desorption of the PAHs, avoiding the dilution and providing enough sensitivity to reach the legal limits established for these pollutants in the matrices selected. The limits of detection achieved for 10mL of water ranged between 2.8ng/L (indeno(1,2,3-cd)pyrene) and 11.5ng/L (acenaphthene) with acceptable precision (between 4.5 and 18.2% RSD). The method was applied to the determination of the selected PAHs in tap, river waters and sewage, being fluoranthene and pyrene detected in all of them at concentrations lower than the legal limits established for these compounds in the matrices assayed. PMID:21377161

  20. Measure Lines

    ERIC Educational Resources Information Center

    Crissman, Sally

    2011-01-01

    One tool for enhancing students' work with data in the science classroom is the measure line. As a coteacher and curriculum developer for The Inquiry Project, the author has seen how measure lines--a number line in which the numbers refer to units of measure--help students not only represent data but also analyze it in ways that generate…

  1. Effects of the environmental estrogens bisphenol A, o,p'-DDT, p-tert-octylphenol and coumestrol on apoptosis induction, cell proliferation and the expression of estrogen sensitive molecular parameters in the human breast cancer cell line MCF-7.

    PubMed

    Diel, Patrick; Olff, Sabine; Schmidt, Simone; Michna, Horst

    2002-01-01

    In the presented study, we have analysed effects of the environmental estrogens bisphenol A (BPA), p-tert-octylphenol (OCT), o,p'-DDT (DDT) and coumestrol (COU) on cell proliferation, apoptosis induction, progesterone receptor (PR) and androgen receptor (AR) mRNA expression and ER alpha protein expression in comparison to estradiol (E2) and the selective ER modulator (SERM) raloxifene (RAL) and the pure antiestrogen faslodex (ICI 182780) in the human breast cancer cell line MCF-7. A dose dependent analysis of the cell cycle distribution of MCF-7 cells after administration of OCT, DDT and COU revealed a significant induction of cell proliferation and reduced rate of apoptosis. Maximum induction of cell proliferation and the lowest rate of apoptosis could be observed at a dose of 10(-6)M. Interestingly, administration of BPA reduces the rate of apoptosis, but does not enhance proliferation at any dose analysed. PR mRNA expression in MCF-7 cells was up regulated after administration of COU and DDT, whereas treatment with BPA and OCT did not effect PR mRNA expression. AR mRNA expression was down regulated by COU, but not effected by BPA, DDT and OCT. The expression of ER alpha protein in the breast cancer cells was slightly down regulated by COU and DDT, but unaffected by BPA and OCT. In summary and in comparison to the effects observed after administration of E2, RAL and ICI our data indicate that none of the analysed compounds exhibit properties comparable to RAL and ICI. COU and DDT exhibit properties which are very similar to E2. Administration of BPA and OCT did not effect any of the estrogen sensitive molecular parameters analysed. Nevertheless OCT is a very potent stimulator of cell proliferation in MCF-7 cells. Surprisingly, BPA is not able to induce the proliferation of MCF-7 breast cancer cells, but turns out to be a very potent inhibitor of apoptosis. For this reason and in agreement to the effects of BPA on the molecular parameters analysed, we conclude

  2. Circumstellar radio molecular lines

    NASA Technical Reports Server (NTRS)

    NGUYEN-QUANG-RIEU

    1987-01-01

    Radio molecular lines appear to be useful probes into the stellar environment. Silicon oxide masers provide information on the physical conditions in the immediate vicinity of the stellar photosphere. Valuable information on the physics operating in the envelope of IRC + 10216 was recently obtained by high sensitivity observations and detailed theoretical analyses. Infrared speckle interferometry in the molecular lines and in the continuum is helpful in the investigation of the inner region of the envelope. These techniques are discussed in terms of late-type star mass loss.

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

    NASA Astrophysics Data System (ADS)

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

    2015-09-01

    Collider, direct and indirect searches for dark matter have typically little or no sensitivity to weakly interacting massive particles (WIMPs) with masses above a few TeV. This rather unexplored regime can however be probed through the search for distinctive gamma-ray spectral features produced by the annihilation of WIMPs at very high energies. Here we present a dedicated search for gamma-ray boxes—sharp spectral features that cannot be mimicked by astrophysical sources—with the upcoming Cherenkov Telescope Array (CTA). Using realistic projections for the instrument performance and detailed background modelling, a profile likelihood analysis is implemented to derive the expected upper limits and sensitivity reach after 100 h of observations towards a 2°×2° region around the Galactic centre. Our results show that CTA will be able to probe gamma-ray boxes down to annihilation cross sections of 10-27-10-26 cm3/s up to tens of TeV. We also identify a number of concrete particle physics models providing thermal dark matter candidates that can be used as target benchmarks in future search campaigns. This constitutes a golden opportunity for CTA to either discover or rule out multi-TeV thermal dark matter in a corner of parameter space where all other experimental efforts are basically insensitive.

  4. Sensitive skin.

    PubMed

    Misery, L; Loser, K; Ständer, S

    2016-02-01

    Sensitive skin is a clinical condition defined by the self-reported facial presence of different sensory perceptions, including tightness, stinging, burning, tingling, pain and pruritus. Sensitive skin may occur in individuals with normal skin, with skin barrier disturbance, or as a part of the symptoms associated with facial dermatoses such as rosacea, atopic dermatitis and psoriasis. Although experimental studies are still pending, the symptoms of sensitive skin suggest the involvement of cutaneous nerve fibres and neuronal, as well as epidermal, thermochannels. Many individuals with sensitive skin report worsening symptoms due to environmental factors. It is thought that this might be attributed to the thermochannel TRPV1, as it typically responds to exogenous, endogenous, physical and chemical stimuli. Barrier disruptions and immune mechanisms may also be involved. This review summarizes current knowledge on the epidemiology, potential mechanisms, clinics and therapy of sensitive skin. PMID:26805416

  5. Climate Sensitivity

    SciTech Connect

    Lindzen, Richard

    2011-11-09

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

  6. Gluten Sensitivity

    MedlinePlus

    Gluten is a protein found in wheat, rye, and barley. It is found mainly in foods but ... products like medicines, vitamins, and supplements. People with gluten sensitivity have problems with gluten. It is different ...

  7. Gluten Sensitivity

    MedlinePlus

    ... have problems with gluten. It is different from celiac disease, an immune disease in which people can't ... the symptoms of gluten sensitivity are similar to celiac disease. They include tiredness and stomachaches. It can cause ...

  8. Diatomic predissociation line widths

    NASA Technical Reports Server (NTRS)

    Child, M. S.

    1973-01-01

    Predissociation by rotation and curve crossing in diatomic molecules is discussed. The pattern of predissociation line widths is seen as providing a highly sensitive yardstick for the determination of unknown potential curves. In addition, the computation of such a pattern for given potential curves is considered a matter of routine, unless the predissociation happens to occur from an adiabatic potential curve. Analytic formulas are used to provide physical insight into the details of the predissociation pattern, to the extent that a direct inversion procedure is developed for determination of the repulsive potential curves for Type 1 predissociations.

  9. Interaction of doxorubicin with the subcellular structures of the sensitive and Bcl-xL-overexpressing MCF-7 cell line: confocal and low-energy-loss transmission electron microscopy.

    PubMed

    Mhawi, A Amir

    2009-10-01

    The present investigation was directed to examine the interaction of the anti-cancer agent doxorubicin (DOX) with the subcellular compartments of the drug sensitive and Bcl-xL-overexpressing (Bcl-xL) MCF-7 cells using confocal and low-energy-loss transmission electron microscopy (LELTEM). Intracellular detection of DOX with LELTEM was carried out without specific antibodies or heavy metal stains but via the electron-induced molecular orbital excitation of the drug. Cells were incubated with 10 microM DOX for 1 min, 1, 24, and 48 h and then examined live by confocal microscope and as very thin sections in an electron microscope equipped with an energy filter having an energy resolution of 1eV. Ultrastructural localization of DOX, obtained from pairs of images taken at energy losses of 3+/-1 and 10+/-1eV, were analyzed and correlated with the confocal observations. When the sensitive and Bcl-xL cells were examined under the confocal microscope after 1 min, DOX uptake could not be detected in the nuclei nor in the cytoplasm whereas LELTEM observation revealed that at this stage of incubation the drug has already been incorporated by both cell types and that the nuclear membrane, nucleolus, and mitochondria of the Bcl-xL cells were temporally less DOX-responsive as compared to the sensitive cells. As the incubation time increased, nuclear membranes and nucleoli of both cell types appeared equally sensitive to DOX, nonetheless, mitochondria of the Bcl-xL cells remained invulnerable to DOX for 24h. The results point to LELTEM feasibility to better characterize yet unresolved cellular events caused by DOX and suggest a transitory role for Bcl-xL overexpression in protecting the cellular compartments from DOX invasion. PMID:19502069

  10. Evaluation of TPGS-modified thermo-sensitive Pluronic PF127 hydrogel as a potential carrier to reverse the resistance of P-gp-overexpressing SMMC-7721 cell lines.

    PubMed

    Gao, Lei; Wang, Xiaoqing; Ma, Jianli; Hao, Daifeng; Wei, Pei; Zhou, Liang; Liu, Guiyang

    2016-04-01

    In the present studies locally injectable docetaxel nanocrystals loaded d-alpha tocopheryl polyethylene glycol 1000 succinate-modified Pluronic F127 (DOC-NCs-TPGS-PF127) thermo-sensitive hydrogels were prepared to reverse drug resistance of P-glycoprotein (P-gp)-overexpressing human liver cancer SMMC-7721 tumors. Firstly, DOC nanosuspensions with mean particle size of 196nm were prepared and dispersed into series of mixed solutions containing PF127 and TPGS of different ratios to obtain DOC-NCs-TPGS-PF127 hydrogels. DOC NCs, exhibiting a uniform distribution and very good physical stability during three sol-gel cycles in the hydrogel network, did not influence the gelation temperature. Swelling-dependent release pattern was found for DOC NCs from hydrogels and release profiles could be well fitted by the Peppas equation. MTT test showed that hydrogels containing 0% or 0.1% TPGS had no cytotoxicity against L929 fibroblasts. Both DOC solution and DOC-NCs-TPGS-PF127 hydrogels exhibited obvious cytotoxicity against sensitive SMMC-7721 cells. When resistant SMMC7721 cells were treated, DOC-NCs-TPGS-PF127 hydrogels showed significantly higher cytotoxicity compared with DOC solution and hydrogels containing no TPGS (DOC-NCs-PF127), with markedly lower IC50 and resistant index (RI). After intratumoral injection in SMMC-7721/RT tumor xenograft Balb/c mice model, DOC-NCs-TPGS-PF127 hydrogels exhibited about 5-fold increase and 1.8-fold increase in the inhibition rate of tumor growth compared with intravenous and intratumoral injection of DOC solution, respectively. It could be concluded that TPGS-modified PF127 thermo-sensitive hydrogel was an excellent locally injectable carrier to reverse P-gp overexpression associated multi-drug resistance. PMID:26764117

  11. High Voltage Lines: Hazard at a Distance.

    ERIC Educational Resources Information Center

    Marino, Andrew A.; Becker, Robert O.

    1978-01-01

    It appears that a variety of biological organisms, including man, are sensitive to both long and short-term exposure to the extra low frequency electric and magnetic fields produced by high voltage lines. (BB)

  12. Sensitive determination of a pharmaceutical compound and its metabolites in human plasma by ultra-high performance liquid chromatography-tandem mass spectrometry with on-line solid-phase extraction.

    PubMed

    Heinig, K; Wirz, T; Bucheli, F; Monin, V; Gloge, A

    2011-03-25

    This paper describes the determination of a drug candidate and two metabolites in human plasma by column-switching LC-MS/MS after protein precipitation. Starting from a standard method with a quantitation limit of 0.5 ng/mL, a highly sensitive assay was developed, employing UHPLC separation and detection on an API 5000 mass spectrometer. The injected plasma equivalent was increased from 6 to 20 μL; conventional column trapping for compound enrichment and removal of matrix constituents was combined with high-pressure analytical separation using small particle columns to improve resolution and signal-to-noise ratio. Quantitation limits were thus lowered to between 5 and 20 pg/mL, offering the possibility to provide bioanalytical support for microdosing studies in humans. Excellent assay quality and robustness were achieved by both methods. PMID:21051172

  13. Gluten Sensitivity.

    PubMed

    Catassi, Carlo

    2015-01-01

    Non-celiac gluten sensitivity (NCGS) is a syndrome characterized by intestinal and extraintestinal symptoms related to the ingestion of gluten-containing food in subjects who are not affected by either celiac disease (CD) or wheat allergy (WA). The prevalence of NCGS is not clearly defined yet. Indirect evidence suggests that NCGS is slightly more common than CD, the latter affecting around 1% of the general population. NCGS has been mostly described in adults, particularly in females in the age group of 30-50 years; however, pediatric case series have also been reported. Since NCGS may be transient, gluten tolerance needs to be reassessed over time in patients with NCGS. NCGS is characterized by symptoms that usually occur soon after gluten ingestion, disappear with gluten withdrawal, and relapse following gluten challenge within hours/days. The 'classical' presentation of NCGS is a combination of irritable bowel syndrome-like symptoms, including abdominal pain, bloating, bowel habit abnormalities (either diarrhea or constipation), and systemic manifestations such as 'foggy mind', headache, fatigue, joint and muscle pain, leg or arm numbness, dermatitis (eczema or skin rash), depression, and anemia. In recent years, several studies explored the relationship between the ingestion of gluten-containing food and the appearance of neurological and psychiatric disorders/symptoms like ataxia, peripheral neuropathy, schizophrenia, autism, depression, anxiety, and hallucinations (so-called gluten psychosis). The diagnosis of NCGS should be considered in patients with persistent intestinal and/or extraintestinal complaints showing a normal result of the CD and WA serological markers on a gluten-containing diet, usually reporting worsening of symptoms after eating gluten-rich food. NCGS should not be an exclusion diagnosis only. Unfortunately, no biomarker is sensitive and specific enough for diagnostic purposes; therefore, the diagnosis of NCGS is currently based on

  14. Central line infections - hospitals

    MedlinePlus

    ... infection; CVC - infection; Central venous device - infection; Infection control - central line infection; Nosocomial infection - central line infection; Hospital acquired infection - central line infection; Patient safety - central ...

  15. Differential Gene Expression Profiles of Radioresistant Non-Small-Cell Lung Cancer Cell Lines Established by Fractionated Irradiation: Tumor Protein p53-Inducible Protein 3 Confers Sensitivity to Ionizing Radiation

    SciTech Connect

    Lee, Young Sook; Oh, Jung-Hwa; Yoon, Seokjoo; Kwon, Myung-Sang

    2010-07-01

    Purpose: Despite the widespread use of radiotherapy as a local and regional modality for the treatment of cancer, some non-small-cell lung cancers commonly develop resistance to radiation. We thus sought to clarify the molecular mechanisms underlying resistance to radiation. Methods and Materials: We established the radioresistant cell line H460R from radiosensitive parental H460 cells. To identify the radioresistance-related genes, we performed microarray analysis and selected several candidate genes. Results: Clonogenic and MTT assays showed that H460R was 10-fold more resistant to radiation than H460. Microarray analysis indicated that the expression levels of 1,463 genes were altered more than 1.5-fold in H460R compared with parental H460. To evaluate the putative functional role, we selected one interesting gene tumor protein p53-inducible protein 3 (TP53I3), because that this gene was significantly downregulated in radioresistant H460R cells and that it was predicted to link p53-dependent cell death signaling. Interestingly, messenger ribonucleic acid expression of TP53I3 differed in X-ray-irradiated H460 and H460R cells, and overexpression of TP53I3 significantly affected the cellular radiosensitivity of H460R cells. Conclusions: These results show that H460R may be useful in searching for candidate genes that are responsible for radioresistance and elucidating the molecular mechanism of radioresistance.

  16. Stochastic resonance in visual sensitivity.

    PubMed

    Kundu, Ajanta; Sarkar, Sandip

    2015-04-01

    It is well known from psychophysical studies that stochastic resonance, in its simplest threshold paradigm, can be used as a tool to measure the detection sensitivity to fine details in noise contaminated stimuli. In the present manuscript, we report simulation studies conducted in the similar threshold paradigm of stochastic resonance. We have estimated the contrast sensitivity in detecting noisy sine-wave stimuli, with varying area and spatial frequency, as a function of noise strength. In all the cases, the measured sensitivity attained a peak at intermediate noise strength, which indicate the occurrence of stochastic resonance. The peak sensitivity exhibited a strong dependence on area and spatial frequency of the stimulus. We show that the peak contrast sensitivity varies with spatial frequency in a nonmonotonic fashion and the qualitative nature of the sensitivity variation is in good agreement with human contrast sensitivity function. We also demonstrate that the peak sensitivity first increases and then saturates with increasing area, and this result is in line with the results of psychophysical experiments. Additionally, we also show that critical area, denoting the saturation of contrast sensitivity, decreases with spatial frequency and the associated maximum contrast sensitivity varies with spatial frequency in a manner that is consistent with the results of psychophysical experiments. In all the studies, the sensitivities were elevated via a nonlinear filtering operation called stochastic resonance. Because of this nonlinear effect, it was not guaranteed that the sensitivities, estimated at each frequency, would be in agreement with the corresponding results of psychophysical experiments; on the contrary, close agreements were observed between our results and the findings of psychophysical investigations. These observations indicate the utility of stochastic resonance in human vision and suggest that this paradigm can be useful in psychophysical studies

  17. Tuberculin sensitivity.

    PubMed

    Eason, R J

    1987-06-01

    A prospective study of tuberculin sensitivity has been conducted among 3610 subjects under 20 years old in the Solomon Islands, Western Province. Mantoux positivity (greater than or equal to mm induration after 5 TU) fell from 81% during the 6 months following birth BCG vaccination to 13% for children aged 1-8 years of age among whom it was not significantly higher than the rate of 9% noted for unvaccinated subjects. Birth BCG does not, therefore, hinder the diagnostic usefulness of tuberculin testing for such children. For the study population as a whole, BCG-induced Mantoux positivity was restricted to induration under 15 mm diameter. Stronger responses were considered specific for tuberculin infection and indicated a prevalence rate that rose from 2% to 16% with age. Accelerated BCG reactions recorded among 45% of 162 tuberculin non-reactors under 8 years old indicated that the waning of tuberculin responsiveness at this time could not be equated with loss of clinical protection against tuberculosis. PMID:2441657

  18. Magnetic Splitting of Molecular Lines in Sunspot

    NASA Astrophysics Data System (ADS)

    Berdyugina, S. V.; Frutiger, C.; Solanki, S. K.

    A study of molecular lines in sunspots is of particular interest because of their high temperature and pressure sensitivity. Many of them are also magnetically sensitive, but this was not yet widely investigated. With high-resolution, high signal-to-noise Fourier spectroscopy in four Stokes parameters now available, the use of molecular lines for studying the structure of sunspots brings real gains. One is the extension of spot models, including magnetic field, up to layers, where atomic lines suffer from NLTE effects but molecules can still be treated in the LTE approximation. Equally important is the fact that since molecular lines are extremely temperature sensitive they can be used to probe the thermal and magnetic structure of the coolest parts of sunspots. We present calculations of splitting and the Stokes parameters for a number of molecular lines in the visible and near-infrared regions. Our first selections are the green system of MgH A2Π-X2σ and the TiO triplet α, γ' and γ systems as the most studied band systems in the sunspot spectrum. The calculations involve different regimes of the molecular Zeeman effect, up to the complete Paschen-Back effect for individual lines. We look for molecular lines which can be used along with atomic lines to derive magnetic, thermal and dynamic properties of the umbra.

  19. Gravitational-wave sensitivity curves

    NASA Astrophysics Data System (ADS)

    Moore, C. J.; Cole, R. H.; Berry, C. P. L.

    2015-01-01

    There are several common conventions in use by the gravitational-wave community to describe the amplitude of sources and the sensitivity of detectors. These are frequently confused. We outline the merits of and differences between the various quantities used for parameterizing noise curves and characterizing gravitational-wave amplitudes. We conclude by producing plots that consistently compare different detectors. Similar figures can be generated on-line for general use at http://rhcole.com/apps/GWplotter.

  20. Dark Matter Searches With GLAST

    SciTech Connect

    Wai, Lawrence; Nuss, E.

    2007-02-05

    Indirect detection of particle dark matter relies upon pair annihilation of Weakly Interaction Massive Particles (WIMPs), which is complementary to the well known techniques of direct detection (WIMP-nucleus scattering) and collider production (WIMP pair production). Pair annihilation of WIMPs results in the production of gamma-rays, neutrinos, and anti-matter. Of the various experiments sensitive to indirect detection of dark matter, the Gamma-ray Large Area Space Telescope (GLAST) may play the most crucial role in the next few years. After launch in late 2007, The GLAST Large Area Telescope (LAT) will survey the gamma-ray sky in the energy range of 20MeV-300GeV. By eliminating charged particle background above 100 MeV, GLAST may be sensitive to as yet to be observed Milky Way dark matter subhalos, as well as WIMP pair annihilation spectral lines from the Milky Way halo. Discovery of gamma-ray signals from dark matter in the Milky Way would not only demonstrate the particle nature of dark matter; it would also open a new observational window on galactic dark matter substructure. Location of new dark matter sources by GLAST would dramatically alter the experimental landscape; ground based gamma ray telescopes could follow up on the new GLAST sources with precision measurements of the WIMP pair annihilation spectrum.

  1. Electric Field Lines

    NASA Astrophysics Data System (ADS)

    Arribas, E.; Gallardo, C.; Molina, M.; Sanjosé, V.

    We present the computer program called LINES which is able to calculate and visualize the electric field lines due to seven different discrete configurations of electric point charges. Also we show two examples of the graphic screens generated by LINES.

  2. Sensitivity analysis of hydrodynamic stability operators

    NASA Technical Reports Server (NTRS)

    Schmid, Peter J.; Henningson, Dan S.; Khorrami, Mehdi R.; Malik, Mujeeb R.

    1992-01-01

    The eigenvalue sensitivity for hydrodynamic stability operators is investigated. Classical matrix perturbation techniques as well as the concept of epsilon-pseudoeigenvalues are applied to show that parts of the spectrum are highly sensitive to small perturbations. Applications are drawn from incompressible plane Couette, trailing line vortex flow and compressible Blasius boundary layer flow. Parametric studies indicate a monotonically increasing effect of the Reynolds number on the sensitivity. The phenomenon of eigenvalue sensitivity is due to the non-normality of the operators and their discrete matrix analogs and may be associated with large transient growth of the corresponding initial value problem.

  3. Small pinning points increase grounding-line sensitivity

    NASA Astrophysics Data System (ADS)

    Favier, Lionel; Pattyn, Frank; Berger, Sophie; Drews, Reinhard

    2016-04-01

    Initialising prognostic simulations of outlet glaciers relies on geometry and surface velocity, from which data assimilation methods rectify poorly known parameters such as ice stiffness or basal slipperiness. Stemming from the contact between ice shelves and submarine topographic highs, pinning points impact both ice velocity and stiffness but, wherever they are small enough, they can easily be overlooked by satellite observations. Here, we use the ice-sheet model BISICLES to investigate the future ice dynamical behaviour of two neighbouring outlet glaciers in Dronning Maud Land, i.e., Hansenbreen and West Raghnild glacier. The latter is buttressed by a previously uncharted pinning point at the ice shelf front while both are separated by an ice promontory. We also reconstruct ice velocity and geometry fields including the pinning point, which is absent from Antarctic-wide datasets, from data collected on site. The model is initialised with three combinations of ice geometry and stiffness, (i) with or (ii) without the pinning point influence in the assimilation procedure, and (iii) being a variant of (i) but starting with unpinning. We explore two sub-ice shelf melting scenarios of three amplitudes, and two weertmann-type sliding law exponents for each initialisation. The results show the future unstable retreat of Hansenbreen, moderately affected by unpinning. However, ignoring the pinning point in data assimilation overstiffens the ice shelf and highly decreases the timing of the retreat. This study stresses the need of accurate bathymetry and ice velocity, as the current datasets that disregard pinning points tend to stabilise marine sectors of the East Antarctic ice sheet, hence affecting sea-level rise predictions.

  4. Sensitivity Analysis in Engineering

    NASA Technical Reports Server (NTRS)

    Adelman, Howard M. (Compiler); Haftka, Raphael T. (Compiler)

    1987-01-01

    The symposium proceedings presented focused primarily on sensitivity analysis of structural response. However, the first session, entitled, General and Multidisciplinary Sensitivity, focused on areas such as physics, chemistry, controls, and aerodynamics. The other four sessions were concerned with the sensitivity of structural systems modeled by finite elements. Session 2 dealt with Static Sensitivity Analysis and Applications; Session 3 with Eigenproblem Sensitivity Methods; Session 4 with Transient Sensitivity Analysis; and Session 5 with Shape Sensitivity Analysis.

  5. Ringberg15: Earth's Climate Sensitivities

    NASA Technical Reports Server (NTRS)

    Stevens, Bjorn; Abe-Ouchi, Ayako; Bony, Sandrine; Hegerl, Gabi; Schmidt, Gavin; Sherwood, Steven; Webb, Mark

    2015-01-01

    To assess gaps in understanding of Earth's climate sensitivities a workshop was organised under the auspices of the WCRP (World Climate Research Programme) Grand Science Challenge on Clouds, Circulation and Climate Sensitivity (Ringberg15). The workshop took place in March 2015 and gathered together over thirty experts from around the world for one week. Attendees each gave short presentations and participated in moderated discussions of specific questions related to understanding Earth's climate sensitivities. Most of the time was focused on understanding of the equilibrium climate sensitivity, defined as the equilibrium near-surface warming associated with a doubling of atmospheric carbon dioxide. The workshop produced nine recommendations, many of them focusing on specific research avenues that could be exploited to advance understanding of climate sensitivity. Many of these dealt, in one fashion or another, with the need to more sharply focus research on identifying and testing story lines for a high (larger than 4 degrees Kelvin) or low (less than 2 degrees Kelvin) equilibrium climate sensitivity. Additionally, a subset of model intercomparison projects (CFMIP (Cloud Feedback Model Intercomparison Project), PMIP (Palaeoclimate Modelling Intercomparison Project), PDRMIP (Precipitation Driver and Response Model Intercomparison Project), RFMIP (Radiative Forcing Model Intercomparison Project) and VolMIP (Volcanic Forcings Model Intercomparison Project)) that have been proposed for inclusion within CMIP were identified as being central to resolving important issues raised at the workshop; for this reason modelling groups were strongly encouraged to participate in these projects. Finally the workshop participants encouraged the WCRP to initiate and support an assessment process lead by the Grand Science Challenge on Clouds, Circulation and Climate Sensitivity on the topic of Earth's Climate Sensitivities, culminating in a report that will be published in 2019

  6. Abstract Line Designs

    ERIC Educational Resources Information Center

    Nevinskas, Nancy

    2011-01-01

    In this article, the author describes a unit on the exploration of line. The unit was composed of two individual line lessons. In the first lesson, students were introduced to line as an element of design. They were asked to describe different types of lines, and look for them in art reproductions. The second lesson in the unit involved painting…

  7. The Language of Lines.

    ERIC Educational Resources Information Center

    Breig-Allen, Cheryl; Hill, Janet; Geismar-Ryan, Lori; Cadwell, Louise Boyd

    1998-01-01

    Describes a project about lines in the environment used with 2- and 3-year olds and based on the Reggio Emilia approach. Activities included making tracks with riding toys, drawing lines on papers, seeing cloud lines, and making lines with yarn and Cuisenaire rods. Shows how young children's observations and ongoing discoveries can uncover their…

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

    PubMed Central

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

    2015-01-01

    A previous genome-wide screening analysis identified a panel of genes that sensitize the human non-small-cell lung carcinoma cell line NCI-H1155 to taxol. However, whether the identified genes sensitize other cancer cells to taxol has not been examined. Here, we silenced the taxol-sensitizer genes identified (acrbp, atp6v0d2, fgd4, hs6st2, psma6, and tubgcp2) in nine other cancer cell types (including lung, cervical, ovarian, and hepatocellular carcinoma cell lines) that showed reduced cell viability in the presence of a sub-lethal concentration of taxol. Surprisingly, none of the genes studied increased sensitivity to taxol in the tested panel of cell lines. As observed in H1155 cells, SKOV3 cells displayed induction of five of the six genes studied in response to a cell killing dose of taxol. The other cell types were much less responsive to taxol. Notably, four of the five inducible taxol-sensitizer genes tested (acrbp, atp6v0d2, psma6, and tubgcp2) were upregulated in a taxol-resistant ovarian cancer cell line. These results indicate that the previously identified taxol-sensitizer loci are not conserved genetic targets involved in inhibiting cell proliferation in response to taxol. Our findings also suggest that regulation of taxol-sensitizer genes by taxol may be critical for acquired cell resistance to the drug. PMID:26086592

  9. Light sensitivity in a vertebrate mechanoreceptor?

    PubMed Central

    Baker, Gary E.; de Grip, Willem J.; Turton, Michael; Wagner, Hans-Joachim; Foster, Russell G.; Douglas, Ron H.

    2015-01-01

    ABSTRACT Using immunohistochemistry and western blot analysis, we demonstrate that melanopsin is localised in cells around the central pore of lateral line neuromasts in the African clawed frog, Xenopus laevis. Since melanopsin is a known photoreceptor pigment with diverse functions in vertebrates, we suggest that the lateral line of Xenopus laevis, which is primarily a mechanoreceptor, might also be light sensitive. Potential functions of such photosensitivity are discussed, including its role in mediating locomotor responses following dermal illumination. PMID:26206352

  10. Development of the PEFP's beam line BPM

    NASA Astrophysics Data System (ADS)

    Ryu, Jin-Yeong; Kwon, Hyeok-Jung; Jang, Ji-Ho; Kim, Han-Sung; Seol, Kyung-Tae; Cho, Yong-Sub

    2013-01-01

    The Proton Engineering Frontier Project (PEFP) has 20-MeV and 100-MeV beam lines to supply proton beams to users. A stripline-type Beam Position Monitor (BPM) was designed and fabricated in order to measure the beam's position in the beam line. The RF properties of the BPM were measured and compared with the simulation. After the sensitivity of the BPM at a test stand had been obtained, we performed a beam test in a test beam line of the PEFP 20-MeV proton linac.

  11. Reconnection of vorticity lines and magnetic lines

    NASA Technical Reports Server (NTRS)

    Greene, John M.

    1993-01-01

    Magnetic field and fluid vorticity share many features. First, as divergence-free vector fields they are conveniently visualized in terms of their field lines, curves that are everywhere tangent to the field. The lines indicate direction and their density indicates field strength. The question arises of the extent to which the evolution of the fields can be treated in terms of the evolution of their field lines. Newcomb (1958) derived the general conditions on the evolution of vector fields that permit the identification of field lines from one instant to the next. The equations of evolution of the vorticity field and the magnetic field fall within Newcomb's analysis. The dynamics of the flows differ between these two systems, so that geometrically similar phenomena happen in different ways in the two systems. In this paper the geometrical similarities are emphasized. Reconnection will be defined here as evolution in which it is not possible to preserve the global identification of some field lines. There is a close relation between reconnection and the topology of the vector field lines. Nontrivial topology occurs where the field has null points or there are field lines that are closed loops.

  12. Nuclear reactor overflow line

    DOEpatents

    Severson, Wayne J.

    1976-01-01

    The overflow line for the reactor vessel of a liquid-metal-cooled nuclear reactor includes means for establishing and maintaining a continuous bleed flow of coolant amounting to 5 to 10% of the total coolant flow through the overflow line to prevent thermal shock to the overflow line when the reactor is restarted following a trip. Preferably a tube is disposed concentrically just inside the overflow line extending from a point just inside the reactor vessel to an overflow tank and a suction line is provided opening into the body of liquid metal in the reactor vessel and into the annulus between the overflow line and the inner tube.

  13. Peripheral arterial line - infants

    MedlinePlus

    PAL - infants; Art line - infants ... an "art line." This article addresses PALs in babies. Why is a PAL used? Doctors and nurses use a PAL to watch your baby's blood pressure. A PAL can also be use ...

  14. How Sensitively Timed Are Sensitive Periods?

    ERIC Educational Resources Information Center

    Zener, Rita Schaefer

    2003-01-01

    Reviews Maria Montessori's view of sensitive periods and examines the kinds of help needed from adults: an open mind, specific help from a prepared learning environment, and challenges presented at the right time. Stresses the universality of sensitive periods and their connection to brain development. Focuses on the unconscious nature and…

  15. Gamma ray lines from dark matter annihilation

    SciTech Connect

    Giudice, G.F.

    1989-08-01

    If direct annihilation of dark matter particles into a pair of photons occurs in the galactic halo, a narrow {gamma}-ray line can be discovered at future {gamma}-ray detectors sensitive to the GeV region. The signals predicted by different dark matter candidates are analyzed. 16 refs., 3 figs.

  16. Easy Observation of Infrared Spectral Lines

    ERIC Educational Resources Information Center

    Cortel, Adolf

    2012-01-01

    The spectra of some chemical elements display intense infrared (IR) lines that can be used more effectively than the ones in the visible region for identification purposes. A simple setup, based on the IR sensitivity of a handycam in nightshot mode, is described to record the visible as well as the IR spectra from decorative bulbs or salts on the…

  17. Gamma ray line astronomy

    NASA Technical Reports Server (NTRS)

    Ramaty, R.

    1984-01-01

    The interpretations and implications of the astrophysical observations of gamma-ray lines are reviewed. At the Galactic Center e(+)-e(-) pairs from a compact object produce an annihilation line that shows no redshift, indicating an annihilation site far removed from this object. In the jets of SS433, gamma-ray lines are produced by inelastic excitations, probably in dust grains, although line emission from fusion reactions has also been considered. Observations of diffuse galactic line emission reveal recently synthesized radioactive aluminum in the interstellar medium. In gamma-ray bursts, redshifted pair annihilation lines are consistent with a neutron star origin for the bursts. In solar flares, gamma-ray line emission reveals the prompt acceleration of protons and nuclei, in close association with the flare energy release mechanism.

  18. Unveiling the nature of dark matter with high redshift 21 cm line experiments

    SciTech Connect

    Evoli, C.; Mesinger, A.; Ferrara, A. E-mail: andrei.mesinger@sns.it

    2014-11-01

    Observations of the redshifted 21 cm line from neutral hydrogen will open a new window on the early Universe. By influencing the thermal and ionization history of the intergalactic medium (IGM), annihilating dark matter (DM) can leave a detectable imprint in the 21 cm signal. Building on the publicly available 21cmFAST code, we compute the 21 cm signal for a 10 GeV WIMP DM candidate. The most pronounced role of DM annihilations is in heating the IGM earlier and more uniformly than astrophysical sources of X-rays. This leaves several unambiguous, qualitative signatures in the redshift evolution of the large-scale (k ≅ 0.1 Mpc{sup -1}) 21 cm power amplitude: (i) the local maximum (peak) associated with IGM heating can be lower than the other maxima; (ii) the heating peak can occur while the IGM is in emission against the cosmic microwave background (CMB); (iii) there can be a dramatic drop in power (a global minimum) corresponding to the epoch when the IGM temperature is comparable to the CMB temperature. These signatures are robust to astrophysical uncertainties, and will be easily detectable with second generation interferometers. We also briefly show that decaying warm dark matter has a negligible role in heating the IGM.

  19. Pharmacogenomic agreement between two cancer cell line data sets.

    PubMed

    2015-12-01

    Large cancer cell line collections broadly capture the genomic diversity of human cancers and provide valuable insight into anti-cancer drug response. Here we show substantial agreement and biological consilience between drug sensitivity measurements and their associated genomic predictors from two publicly available large-scale pharmacogenomics resources: The Cancer Cell Line Encyclopedia and the Genomics of Drug Sensitivity in Cancer databases. PMID:26570998

  20. Pressure Sensitive Paints

    NASA Technical Reports Server (NTRS)

    Liu, Tianshu; Bencic, T.; Sullivan, J. P.

    1999-01-01

    This article reviews new advances and applications of pressure sensitive paints in aerodynamic testing. Emphasis is placed on important technical aspects of pressure sensitive paint including instrumentation, data processing, and uncertainty analysis.

  1. Dynamical compactness and sensitivity

    NASA Astrophysics Data System (ADS)

    Huang, Wen; Khilko, Danylo; Kolyada, Sergiĭ; Zhang, Guohua

    2016-05-01

    To link the Auslander point dynamics property with topological transitivity, in this paper we introduce dynamically compact systems as a new concept of a chaotic dynamical system (X , T) given by a compact metric space X and a continuous surjective self-map T : X → X. Observe that each weakly mixing system is transitive compact, and we show that any transitive compact M-system is weakly mixing. Then we discuss the relationships between it and other several stronger forms of sensitivity. We prove that any transitive compact system is Li-Yorke sensitive and furthermore multi-sensitive if it is not proximal, and that any multi-sensitive system has positive topological sequence entropy. Moreover, we show that multi-sensitivity is equivalent to both thick sensitivity and thickly syndetic sensitivity for M-systems. We also give a quantitative analysis for multi-sensitivity of a dynamical system.

  2. Difference in Membrane Repair Capacity Between Cancer Cell Lines and a Normal Cell Line.

    PubMed

    Frandsen, Stine Krog; McNeil, Anna K; Novak, Ivana; McNeil, Paul L; Gehl, Julie

    2016-08-01

    Electroporation-based treatments and other therapies that permeabilize the plasma membrane have been shown to be more devastating to malignant cells than to normal cells. In this study, we asked if a difference in repair capacity could explain this observed difference in sensitivity. Membrane repair was investigated by disrupting the plasma membrane using laser followed by monitoring fluorescent dye entry over time in seven cancer cell lines, an immortalized cell line, and a normal primary cell line. The kinetics of repair in living cells can be directly recorded using this technique, providing a sensitive index of repair capacity. The normal primary cell line of all tested cell lines exhibited the slowest rate of dye entry after laser disruption and lowest level of dye uptake. Significantly, more rapid dye uptake and a higher total level of dye uptake occurred in six of the seven tested cancer cell lines (p < 0.05) as well as the immortalized cell line (p < 0.001). This difference in sensitivity was also observed when a viability assay was performed one day after plasma membrane permeabilization by electroporation. Viability in the primary normal cell line (98 % viable cells) was higher than in the three tested cancer cell lines (81-88 % viable cells). These data suggest more effective membrane repair in normal, primary cells and supplement previous explanations why electroporation-based therapies and other therapies permeabilizing the plasma membrane are more effective on malignant cells compared to normal cells in cancer treatment. PMID:27312328

  3. High energy beam lines

    NASA Astrophysics Data System (ADS)

    Marchetto, M.; Laxdal, R. E.

    2014-01-01

    The ISAC post accelerator comprises an RFQ, DTL and SC-linac. The high energy beam lines connect the linear accelerators as well as deliver the accelerated beams to two different experimental areas. The medium energy beam transport (MEBT) line connects the RFQ to the DTL. The high energy beam transport (HEBT) line connects the DTL to the ISAC-I experimental stations (DRAGON, TUDA-I, GPS). The DTL to superconducting beam (DSB) transport line connects the ISAC-I and ISAC-II linacs. The superconducting energy beam transport (SEBT) line connects the SC linac to the ISAC-II experimental station (TUDA-II, HERACLES, TIGRESS, EMMA and GPS). All these lines have the function of transporting and matching the beams to the downstream sections by manipulating the transverse and longitudinal phase space. They also contain diagnostic devices to measure the beam properties.

  4. Series Transmission Line Transformer

    DOEpatents

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

    2004-06-29

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

  5. Zebrafish Sensitivity to Botulinum Neurotoxins.

    PubMed

    Chatla, Kamalakar; Gaunt, Patricia S; Petrie-Hanson, Lora; Ford, Lorelei; Hanson, Larry A

    2016-01-01

    Botulinum neurotoxins (BoNT) are the most potent known toxins. The mouse LD50 assay is the gold standard for testing BoNT potency, but is not sensitive enough to detect the extremely low levels of neurotoxin that may be present in the serum of sensitive animal species that are showing the effects of BoNT toxicity, such as channel catfish affected by visceral toxicosis of catfish. Since zebrafish are an important animal model for diverse biomedical and basic research, they are readily available and have defined genetic lines that facilitate reproducibility. This makes them attractive for use as an alternative bioassay organism. The utility of zebrafish as a bioassay model organism for BoNT was investigated. The 96 h median immobilizing doses of BoNT/A, BoNT/C, BoNT/E, and BoNT/F for adult male Tübingen strain zebrafish (0.32 g mean weight) at 25 °C were 16.31, 124.6, 4.7, and 0.61 picograms (pg)/fish, respectively. These findings support the use of the zebrafish-based bioassays for evaluating the presence of BoNT/A, BoNT/E, and BoNT/F. Evaluating the basis of the relatively high resistance of zebrafish to BoNT/C and the extreme sensitivity to BoNT/F may reveal unique functional patterns to the action of these neurotoxins. PMID:27153088

  6. Zebrafish Sensitivity to Botulinum Neurotoxins

    PubMed Central

    Chatla, Kamalakar; Gaunt, Patricia S.; Petrie-Hanson, Lora; Ford, Lorelei; Hanson, Larry A.

    2016-01-01

    Botulinum neurotoxins (BoNT) are the most potent known toxins. The mouse LD50 assay is the gold standard for testing BoNT potency, but is not sensitive enough to detect the extremely low levels of neurotoxin that may be present in the serum of sensitive animal species that are showing the effects of BoNT toxicity, such as channel catfish affected by visceral toxicosis of catfish. Since zebrafish are an important animal model for diverse biomedical and basic research, they are readily available and have defined genetic lines that facilitate reproducibility. This makes them attractive for use as an alternative bioassay organism. The utility of zebrafish as a bioassay model organism for BoNT was investigated. The 96 h median immobilizing doses of BoNT/A, BoNT/C, BoNT/E, and BoNT/F for adult male Tübingen strain zebrafish (0.32 g mean weight) at 25 °C were 16.31, 124.6, 4.7, and 0.61 picograms (pg)/fish, respectively. These findings support the use of the zebrafish-based bioassays for evaluating the presence of BoNT/A, BoNT/E, and BoNT/F. Evaluating the basis of the relatively high resistance of zebrafish to BoNT/C and the extreme sensitivity to BoNT/F may reveal unique functional patterns to the action of these neurotoxins. PMID:27153088

  7. Sensitivity Test Analysis

    Energy Science and Technology Software Center (ESTSC)

    1992-02-20

    SENSIT,MUSIG,COMSEN is a set of three related programs for sensitivity test analysis. SENSIT conducts sensitivity tests. These tests are also known as threshold tests, LD50 tests, gap tests, drop weight tests, etc. SENSIT interactively instructs the experimenter on the proper level at which to stress the next specimen, based on the results of previous responses. MUSIG analyzes the results of a sensitivity test to determine the mean and standard deviation of the underlying population bymore » computing maximum likelihood estimates of these parameters. MUSIG also computes likelihood ratio joint confidence regions and individual confidence intervals. COMSEN compares the results of two sensitivity tests to see if the underlying populations are significantly different. COMSEN provides an unbiased method of distinguishing between statistical variation of the estimates of the parameters of the population and true population difference.« less

  8. Birds on power lines

    NASA Astrophysics Data System (ADS)

    Arnaldo Redinz, José

    2014-07-01

    Why can a bird safely rest on a high-voltage power line? We discuss three effects that can lead to the development of voltages and currents in the bird's body. To explain the absence of electric shocks, we give numerical estimates of these voltages and currents obtained from the standard solution for the voltage along a two-wire transmission line.

  9. Structuring a service line.

    PubMed

    Zablocki, E

    1997-05-01

    In 1993, Community Hospitals Indianapolis created 10 service lines--each unique to the needs of the patients it serves. Two service line leaders talk about the factors critical to successful restructuring, the working relationships established, and the importance of clear communication to ensure understanding and get buy-in to the process. PMID:10167712

  10. Tangent Lines without Calculus

    ERIC Educational Resources Information Center

    Rabin, Jeffrey M.

    2008-01-01

    This article presents a problem that can help high school students develop the concept of instantaneous velocity and connect it with the slope of a tangent line to the graph of position versus time. It also gives a method for determining the tangent line to the graph of a polynomial function at any point without using calculus. (Contains 1 figure.)

  11. Transmission Line Security Monitor

    SciTech Connect

    2011-01-01

    The Transmission Line Security Monitor is a multi-sensor monitor that mounts directly on high-voltage transmission lines to detect, characterize and communicate terrorist activity, human tampering and threatening conditions around support towers. For more information about INL's critical infrastructure protection research, visit http://www.facebook.com/idahonationallaboratory.

  12. Transmission Line Security Monitor

    ScienceCinema

    None

    2013-05-28

    The Transmission Line Security Monitor is a multi-sensor monitor that mounts directly on high-voltage transmission lines to detect, characterize and communicate terrorist activity, human tampering and threatening conditions around support towers. For more information about INL's critical infrastructure protection research, visit http://www.facebook.com/idahonationallaboratory.

  13. Airborne Fraunhofer Line Discriminator

    NASA Technical Reports Server (NTRS)

    Gabriel, F. C.; Markle, D. A.

    1969-01-01

    Airborne Fraunhofer Line Discriminator enables prospecting for fluorescent materials, hydrography with fluorescent dyes, and plant studies based on fluorescence of chlorophyll. Optical unit design is the coincidence of Fraunhofer lines in the solar spectrum occurring at the characteristic wavelengths of some fluorescent materials.

  14. Database of emission lines

    NASA Astrophysics Data System (ADS)

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

    1998-11-01

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

  15. CRIRES spectroscopy and empirical line-by-line identification of FeH molecular absorption in an M dwarf

    NASA Astrophysics Data System (ADS)

    Wende, S.; Reiners, A.; Seifahrt, A.; Bernath, P. F.

    2010-11-01

    sensitive or very temperature sensitive lines, which can be used to investigate M-type stars. Data were taken at ESO Telescopes under the program 79.D-0357(A).Full Table 4 and FeH atlas are only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/viz-bin/qcat?J/A+A/523/A58

  16. White paper: Chemical sensitivity: history and phenomenology.

    PubMed

    Miller, C S

    1994-01-01

    Nearly everyone has heard something about chemical sensitivity, either from personal experience with someone who has the condition or from the media. The television series Northern Exposure recently featured a chemically sensitive attorney who lived in a geodesic dome in Alaska, and L.A. Law depicted the struggles of a Persian Gulf veteran with chemical sensitivities who lost his case against the Veterans Administration, but may appeal later in the season. Television news programs and the printed media have showcased patients living spartan existences in remote areas or in aluminum foil-lined rooms. Our views of the illness no doubt are colored by our own personal experiences of it. While some discount or make jokes about chemical sensitivity or these patients, physicians who have seen a number of them are discovering that many appear to be credible individuals with prior good work records who say they became ill following an identifiable exposure to chemicals. PMID:7778099

  17. On-line surfactant monitoring

    SciTech Connect

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

    1995-04-01

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

  18. Plasma Line in the Ionosphere

    NASA Astrophysics Data System (ADS)

    Rosenmary, M.; Sulzer, M. P.

    2014-12-01

    New Plasma Line Observations from the Arecibo Radar show the exact timings of the Arecibo's conjugate sunrise as well as the local sunrise. Using the shadow height of the Earth's radius extend 175 km, we have predicted the time at which local sunrise effects propagate downward with time. These predictions agree within a minute of the observed effects. We can observe the apparent conjugate sunrise with equivalent sensitivity. We are currently comparing the data with predictions from various locations of Arecibo's conjugate point. We have compared our results with the standard tilted dipole configuration and seen a 25 minute discrepancy. Now we are investigating if the delay can be accounted for using research from Laura Waldrop's paper "Photoelectron impact excitation of OI 8446 A emission observed from Arecibo Observatory.

  19. Linear Polarization Measurements of Chromospheric Emission Lines

    NASA Technical Reports Server (NTRS)

    Sheeley, N. R., Jr.; Keller, C. U.

    2003-01-01

    We have used the Zurich Imaging Stokes Polarimeter (ZIMPOL I) with the McMath-Pierce 1.5 m main telescope on Kitt Peak to obtain linear polarization measurements of the off-limb chromosphere with a sensitivity better than 1 x 10(exp -5). We found that the off-disk observations require a combination of good seeing (to show the emission lines) and a clean heliostat (to avoid contamination by scattered light from the Sun's disk). When these conditions were met, we obtained the following principal results: 1. Sometimes self-reversed emission lines of neutral and singly ionized metals showed linear polarization caused by the transverse Zeeman effect or by instrumental cross talk from the longitudinal Zeeman effect in chromospheric magnetic fields. Otherwise, these lines tended to depolarize the scattered continuum radiation by amounts that ranged up to 0.2%. 2. Lines previously known to show scattering polarization just inside the limb (such as the Na I lambda5889 D2 and the He I lambda5876 D3 lines) showed even more polarization above the Sun's limb, with values approaching 0.7%. 3. The O I triplet at lambda7772, lambda7774, and lambda7775 showed a range of polarizations. The lambda7775 line, whose maximum intrinsic polarizability, P(sub max), is less than 1%, revealed mainly Zeeman contributions from chromospheric magnetic fields. However, the more sensitive lambda7772 (P(sub max) = 19%) and lambda7774 (P(sub max) = 29%) lines had relatively strong scattering polarizations of approximately 0.3% in addition to their Zeeman polarizations. At times of good seeing, the polarization spectra resolve into fine structures that seem to be chromospheric spicules.

  20. Coherent soliton communication lines

    SciTech Connect

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

    2014-11-15

    The data transmission in coherent fiber-optical communication lines using solitons with a variable phase is studied. It is shown that nonlinear coherent structures (solitons) can be applied for effective signal transmission over a long distance using amplitude and optical-phase keying of information. The optimum ratio of the pulse width to the bit slot at which the spectral efficiency (transmitted bits per second and hertz) is maximal is determined. It is shown that soliton fiber-optical communication lines can ensure data transmission at a higher spectral efficiency as compared to traditional communication lines and at a high signal-to-noise ratio.

  1. Flow line sampler

    DOEpatents

    Nicholls, Colin I.

    1992-07-14

    An on-line product sampling apparatus and method for measuring product samples from a product stream (12) in a flow line (14) having a sampling aperture (11), includes a sampling tube (18) for containing product samples removed from flow line (14). A piston (22) removes product samples from the product stream (12) through the sampling aperture (11) and returns samples to product stream (12). A sensor (20) communicates with sample tube (18), and senses physical properties of samples while the samples are within sample tube (18). In one embodiment, sensor (20) comprises a hydrogen transient nuclear magnetic resonance sensor for measuring physical properties of hydrogen molecules.

  2. Flash Mob Project Creates Awareness of Environmental Sensitivities: Making "Multiple Chemical Sensitivity" a Household Name

    ERIC Educational Resources Information Center

    Smith, Melva Gail

    2011-01-01

    Having severe Asthma and trying to maintain a social life isn't easy, but when one adds the disability of Multiple Chemical Sensitivity (MCS) to the combination, the challenges become even tougher. As a dancer with both Asthma and MCS, the author was forced to give up the sport for 15 years before finding a group of line dancers that were…

  3. Emission line spectropolarimetry and circumstellar structures

    NASA Astrophysics Data System (ADS)

    Vink, Jorick S.

    2015-10-01

    We discuss the role of linear emission-line polarimetry in a wide set of stellar environments, involving the accretion disks around young pre-main sequence stars, to the aspherical outflows from O stars, luminous blue variables and Wolf-Rayet stars, just prior to explosion as a supernova or a gamma-ray burst. We predict subtle QU line signatures, such as single/double QU loops for un/disrupted disks. Whilst there is plenty of evidence for single QU loops, suggesting the presence of disrupted disks around young stars, current sensitivity (with S/N of order 1000) is typically not sufficient to allow for quantitative 3D Monte Carlo modeling. However, the detection of our predicted signatures is expected to become feasible with the massive improvement in sensitivity of extremely large mirrors.

  4. Neutral line chaos and phase space structure

    NASA Technical Reports Server (NTRS)

    Burkhart, Grant R.; Speiser, Theodore W.; Martin, Richard F., Jr.; Dusenbery, Paul B.

    1991-01-01

    Phase space structure and chaos near a neutral line are studied with numerical surface-of-section (SOS) techniques and analytic methods. Results are presented for a linear neutral line model with zero crosstail electric field. It was found that particle motion can be divided into three regimes dependening on the value of the conserved canonical momentum, Py, and the conserved Hamiltonian, h. The phase space structure, using Poincare SOS plots, is highly sensitive to bn = Bn/B0 variations, but not to h variations. It is verified that the slow motion preserves the action, Jz, as evaluated by Sonnerup (1971), when the period of the fast motion is smaller than the time scale of the slow motion. Results show that the phase space structure and particle chaos depend sensitively upon Py and bn, but are independent of h.

  5. Fabrics Protect Sensitive Skin from UV Rays

    NASA Technical Reports Server (NTRS)

    2009-01-01

    Late Johnson Space Center engineer Dr. Robert Dotts headed a team to develop cool suits for children suffering from life-threatening sun sensitivities. Dotts hoped to develop ultraviolet-blocking technology in a fabric that -- unlike in a bulky space suit -- could remain comfortable, light, and breathable in the sun and heat. The team worked with SPF 4 US LLC (SPF) of Madison, Wisconsin to design ultraviolet-blocking cool suits, which protect sun-sensitive patients and enable them to experience life outdoors safely. Using knowledge gained during the NASA collaboration, SPF created an entire line of ultraviolet-blocking apparel.

  6. Lunar magnetic permeability studies and magnetometer sensitivity

    NASA Technical Reports Server (NTRS)

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

    1977-01-01

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

  7. Climate Sensitivity in the Geologic Past

    NASA Astrophysics Data System (ADS)

    Royer, Dana L.

    2016-06-01

    The response of temperature to CO2 change (climate sensitivity) in the geologic past may help inform future climate predictions. Proxies for CO2 and temperature generally imply high climate sensitivities: ≥3 K per CO2 doubling during ice-free times (fast-feedback sensitivity) and ≥6 K during times with land ice (Earth-system sensitivity). Climate models commonly underpredict the magnitude of climate change and have fast-feedback sensitivities close to 3 K. A better characterization of feedbacks in warm worlds raises climate sensitivity to values more in line with proxies and produces climate simulations that better fit geologic evidence. As CO2 builds in our atmosphere, we should expect both slow (e.g., land ice) and fast (e.g., vegetation, clouds) feedbacks to elevate the long-term temperature response over that predicted from the canonical fast-feedback value of 3 K. Because temperatures will not decline for centuries to millennia, climate sensitivities that integrate slower processes have relevance for current climate policy.

  8. Nonthermal WIMPs and primordial black holes

    NASA Astrophysics Data System (ADS)

    Georg, Julian; Şengör, Gizem; Watson, Scott

    2016-06-01

    Nonthermal histories for the early universe have received notable attention as they are a rich source of phenomenology, while also being well motivated by top-down approaches to beyond the Standard Model physics. The early (pre-big bang nucleosynthesis) matter phase in these models leads to enhanced growth of density perturbations on sub-Hubble scales. Here, we consider whether primordial black hole formation associated with the enhanced growth is in conflict with existing observations. Such constraints depend on the tilt of the primordial power spectrum, and we find that nonthermal histories are tightly constrained in the case of a significantly blue spectrum. Alternatively, if dark matter is taken to be of nonthermal origin, we can restrict the primordial power spectrum on scales inaccessible to cosmic microwave background and large scale structure observations. We establish constraints for a wide range of scalar masses (reheat temperatures) with the most stringent bounds resulting from the formation of 1015 g black holes. These black holes would be evaporating today and are constrained by FERMI observations. We also consider whether the breakdown of the coherence of the scalar oscillations on subhorizon scales can lead to a Jean's pressure preventing black hole formation and relaxing our constraints. Our main conclusion is that primordial black hole constraints, combined with existing constraints on nonthermal weakly interacting massive particles, favor a primordial spectrum closer to scale invariance or a red tilted spectrum.

  9. Measurement of Deflection Line on Bridges

    NASA Astrophysics Data System (ADS)

    Urban, Rudolf; Štroner, Martin

    2013-12-01

    Prestressed concrete bridges are very sensitive to the increase in long-term deflections. Reliable forecasts of deflections of bridge structures during construction and durability are crucial for achieving good durability. The main results of measurements are the changes of the deflection line of the bridge structures, which places special demands on the measurement procedure. Results from measurements are very useful for the improvement of mathematical prediction methods of behaviour of long span prestressed concrete structures.

  10. Strain monitoring averts line failure in Rockies

    SciTech Connect

    Miller, B.; Bukovansky, M.

    1987-08-10

    The case history of a landslide in the U.S. Rocky Mountains shows that the potential for pipeline monitoring in geologically sensitive areas, those subject to landslides and subsidence, for example. A properly installed monitoring system monitored by the pipeline operator, Western Gas Supply Co. (West Gas), Denver, provided an early warning of increasing line strains. The problem was complicated by rugged topography which is described here. Stability analysis was the key technique utilized in the process.

  11. Power line detection system

    DOEpatents

    Latorre, Victor R.; Watwood, Donald B.

    1994-01-01

    A short-range, radio frequency (RF) transmitting-receiving system that provides both visual and audio warnings to the pilot of a helicopter or light aircraft of an up-coming power transmission line complex. Small, milliwatt-level narrowband transmitters, powered by the transmission line itself, are installed on top of selected transmission line support towers or within existing warning balls, and provide a continuous RF signal to approaching aircraft. The on-board receiver can be either a separate unit or a portion of the existing avionics, and can also share an existing antenna with another airborne system. Upon receipt of a warning signal, the receiver will trigger a visual and an audio alarm to alert the pilot to the potential power line hazard.

  12. Power line detection system

    DOEpatents

    Latorre, V.R.; Watwood, D.B.

    1994-09-27

    A short-range, radio frequency (RF) transmitting-receiving system that provides both visual and audio warnings to the pilot of a helicopter or light aircraft of an up-coming power transmission line complex. Small, milliwatt-level narrowband transmitters, powered by the transmission line itself, are installed on top of selected transmission line support towers or within existing warning balls, and provide a continuous RF signal to approaching aircraft. The on-board receiver can be either a separate unit or a portion of the existing avionics, and can also share an existing antenna with another airborne system. Upon receipt of a warning signal, the receiver will trigger a visual and an audio alarm to alert the pilot to the potential power line hazard. 4 figs.

  13. Line, Shape, Color.

    ERIC Educational Resources Information Center

    Greenman, Geri

    2002-01-01

    Describes an art project used with beginning high school art students that teaches them about continuous line drawing. Explains that the students create portraits of themselves, or another student, using glue, black construction paper, and chalk. (CMK)

  14. IRIS Spectrum Line Plot

    NASA Video Gallery

    This video shows a line plot of the spectrum. The spectra here are shown for various locations on the Sun. The changes in the movie are caused by differing physical conditions in the locations. Cre...

  15. Central line infections - hospitals

    MedlinePlus

    ... risk is higher if you: Are in the intensive care unit (ICU) Have a weakened immune system or serious ... unless you have washed your hands. Tell your nurse if your central line: Gets dirty Is coming ...

  16. Veterans Crisis Line

    MedlinePlus

    ... also access and download the Veterans Crisis Line Branding Guidelines for guidance on how to consistently apply ... Program ADMINISTRATION Veterans Health Administration Veterans Benefits Administration National Cemetery Administration U.S. Department of Veterans Affairs | 810 ...

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

    ERIC Educational Resources Information Center

    Saraç, Seda; Karakelle, Sema

    2012-01-01

    The study investigates the interrelationships between different on-line and off-line measures for assessing metacognition. The participants were 47 fifth grade elementary students. Metacognition was assessed through two off-line and two on-line measures. The off-line measures consisted of a teacher rating scale and a self-report questionnaire. The…

  18. PORTION OF A LINE (AT LEFT) AND B LINE (AT ...

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

    PORTION OF A LINE (AT LEFT) AND B LINE (AT RIGHT) ON GENTLE TERRACE SLOPE. A LINE POLE 75A (LEFT FOREGROUND) HAS ORIGINAL GLASS PIN-TYPE INSULATORS AND INTACT COMMUNICATION LINE CROSS ARM. VIEW TO WEST-SOUTHWEST. - Mystic Lake Hydroelectric Facility, Electric Transmission A Line, Along West Rosebud Creek, Fishtail, Stillwater County, MT

  19. Mentoring Emotionally Sensitive Individuals.

    ERIC Educational Resources Information Center

    Shaughnessy, Michael F.; Self, Elizabeth

    Mentoring individuals who are gifted, talented, and creative, but somewhat emotionally sensitive is a challenging and provocative arena. Several reasons individuals experience heightened sensitivity include: lack of nurturing, abuse, alcoholism in the family, low self-esteem, unrealistic parental expectations, and parental pressure to achieve.…

  20. Are Psychopaths Morally Sensitive?

    ERIC Educational Resources Information Center

    Maxwell, Bruce; Le Sage, Leonie

    2009-01-01

    Philosophical and psychological opinion is divided over whether moral sensitivity, understood as the ability to pick out a situation's morally salient features, necessarily involves emotional engagement. This paper seeks to offer insight into this question. It reasons that if moral sensitivity does draw significantly on affective capacities of…

  1. Tuned cavity magnetometer sensitivity.

    SciTech Connect

    Okandan, Murat; Schwindt, Peter

    2009-09-01

    We have developed a high sensitivity (sensitivity levels.

  2. Nasca Lines, Peru

    NASA Technical Reports Server (NTRS)

    2001-01-01

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

    The U.S. science team is located at NASA's Jet Propulsion Laboratory, Pasadena, Calif. The Terra mission is part of NASA's Science Mission Directorate.

  3. Line Lengths and Starch Scores.

    ERIC Educational Resources Information Center

    Moriarty, Sandra E.

    1986-01-01

    Investigates readability of different line lengths in advertising body copy, hypothesizing a normal curve with lower scores for shorter and longer lines, and scores above the mean for lines in the middle of the distribution. Finds support for lower scores for short lines and some evidence of two optimum line lengths rather than one. (SKC)

  4. [Contrast sensitivity in glaucoma].

    PubMed

    Bartos, D

    1989-05-01

    Author reports on results of the contrast sensitivity examinations using the Cambridge low-contrast lattice test supplied by Clement Clarke International LTD, in patients with open-angle glaucoma and ocular hypertension. In glaucoma patients there was observed statistically significant decrease of the contrast sensitivity. In patients with ocular hypertension decrease of the contrast sensitivity was in patients affected by corresponding changes of the visual field and of the optical disc. The main advantages of the Cambridge low-contrast lattice test were simplicity, rapidity and precision of its performance. PMID:2743444

  5. Method for rapid isolation of sensitive mutants

    DOEpatents

    Freyer, James P.

    1997-01-01

    Sensitive mammalian cell mutants are rapidly isolated using flow cytometry. A first population of clonal spheroids is established to contain both normal and mutant cells. The population may be naturally occurring or may arise from mutagenized cells. The first population is then flow sorted by size to obtain a second population of clonal spheroids of a first uniform size. The second population is then exposed to a DNA-damaging agent that is being investigated. The exposed second population is placed in a growth medium to form a third population of clonal spheroids comprising spheroids of increased size from the mammalian cells that are resistant to the DNA-damaging agent and spheroids of substantially the first uniform size formed from the mammalian cells that are sensitive to the DNA-damaging agent. The third population is not flow sorted to differentiate the spheroids formed from resistant mammalian cells from spheroids formed from sensitive mammalian cells. The spheroids formed from sensitive mammalian cells are now treated to recover viable sensitive cells from which a sensitive cell line can be cloned.

  6. Method for rapid isolation of sensitive mutants

    DOEpatents

    Freyer, J.P.

    1997-07-29

    Sensitive mammalian cell mutants are rapidly isolated using flow cytometry. A first population of clonal spheroids is established to contain both normal and mutant cells. The population may be naturally occurring or may arise from mutagenized cells. The first population is then flow sorted by size to obtain a second population of clonal spheroids of a first uniform size. The second population is then exposed to a DNA-damaging agent that is being investigated. The exposed second population is placed in a growth medium to form a third population of clonal spheroids comprising spheroids of increased size from the mammalian cells that are resistant to the DNA-damaging agent and spheroids of substantially the first uniform size formed from the mammalian cells that are sensitive to the DNA-damaging agent. The third population is not flow sorted to differentiate the spheroids formed from resistant mammalian cells from spheroids formed from sensitive mammalian cells. The spheroids formed from sensitive mammalian cells are now treated to recover viable sensitive cells from which a sensitive cell line can be cloned. 15 figs.

  7. Blasted Cell Line Names

    PubMed Central

    Wang, Jing; Byers, Lauren A.; Yordy, John S.; Liu, Wenbin; Shen, Li; Baggerly, Keith A.; Giri, Uma; Myers, Jeffrey N.; Ang, K. Kian; Story, Michael D.; Girard, Luc; Minna, John D.; Heymach, John V.; Coombes, Kevin R.

    2010-01-01

    Background: While trying to integrate multiple data sets collected by different researchers, we noticed that the sample names were frequently entered inconsistently. Most of the variations appeared to involve punctuation, white space, or their absence, at the juncture between alphabetic and numeric portions of the cell line name. Results: Reasoning that the variant names could be described in terms of mutations or deletions of character strings, we implemented a simple version of the Needleman-Wunsch global sequence alignment algorithm and applied it to the cell line names. All correct matches were found by this procedure. Incorrect matches only occured when a cell line was present in one data set but not in the other. The raw match scores tended to be substantially worse for the incorrect matches. Conclusions: A simple application of the Needleman-Wunsch global sequence alignment algorithm provides a useful first pass at matching sample names from different data sets. PMID:21082038

  8. Sensitivity of photoacoustic microscopy

    PubMed Central

    Yao, Junjie; Wang, Lihong V.

    2014-01-01

    Building on its high spatial resolution, deep penetration depth and excellent image contrast, 3D photoacoustic microscopy (PAM) has grown tremendously since its first publication in 2005. Integrating optical excitation and acoustic detection, PAM has broken through both the optical diffusion and optical diffraction limits. PAM has 100% relative sensitivity to optical absorption (i.e., a given percentage change in the optical absorption coefficient yields the same percentage change in the photoacoustic amplitude), and its ultimate detection sensitivity is limited only by thermal noise. Focusing on the engineering aspects of PAM, this Review discusses the detection sensitivity of PAM, compares the detection efficiency of different PAM designs, and summarizes the imaging performance of various endogenous and exogenous contrast agents. It then describes representative PAM applications with high detection sensitivity, and outlines paths to further improvement. PMID:25302158

  9. Constrained sensitivity theory

    SciTech Connect

    Greenspan, E.; Williams, M.L.

    1980-01-01

    In sensitivity and uncertainty analysis of to-be-built reactors it is customary to use k-reset sensitivity functions - accounting for the combined effects of the change (or uncertainty) in the input data and of the alteration in some design variable applied to maintain criticality. Critical reactors are usually subjected to several constraints, such as power peaking factor and breeding ratio constraints, in addition to the criticality constraint. Perturbation theory formulations which can account, simultaneously, for several constraints both in critical reactors and in source driven systems (such as radiation shields and blankets of fusion devices) are presented. All the sensitivity and uncertainty analyses of source driven systems carried out so far used unconstrained sensitivity functions despite the fact that such systems can be also subjected to a variety of constraints.

  10. Contact sensitization in children.

    PubMed

    Manzini, B M; Ferdani, G; Simonetti, V; Donini, M; Seidenari, S

    1998-01-01

    Our study concerns contact sensitization in children, the frequency of which is still debated in the literature, even though specific reports are increasing. During a 7 year period (1988-1994) 670 patients, 6 months to 12 years of age, were patch tested with the European standard series, integrated with 24 haptens, at the same concentrations as for adults. We observed positive results in 42% of our patients. Thimerosal, nickel sulfate, Kathon CG, fragrance mix, neomycin, wool alcohols, and ammoniated mercury induced most of the positive responses. The highest sensitization rate was found in children from 0 to 3 years of age. Comments on main positive haptens are reported. Seventy-seven percent of our sensitized patients were atopics, suggesting that atopy represents a predisposing factor for contact hypersensitivity. Patch testing represents a useful diagnostic procedure for the definition of childhood eczematous dermatitis and for the identification of agents inducing contact sensitization which is frequently associated with atopic dermatitis. PMID:9496796

  11. Absolute sensitivity calibration of extreme ultraviolet photoresists

    SciTech Connect

    Jones, Juanita; Naulleau, Patrick P.; Gullikson, Eric M.; Aquila, Andrew; George, Simi; Niakoula, Dimitra

    2008-05-16

    One of the major challenges facing the commercialization of extreme ultraviolet (EUV) lithography remains simultaneously achieving resist sensitivity, line-edge roughness, and resolution requirement. Sensitivity is of particular concern owing to its direct impact on source power requirements. Most current EUV exposure tools have been calibrated against a resist standard with the actual calibration of the standard resist dating back to EUV exposures at Sandia National Laboratories in the mid 1990s. Here they report on an independent sensitivity calibration of two baseline resists from the SEMATECH Berkeley MET tool performed at the Advanced Light Source Calibrations and Standards beamline. The results show the baseline resists to be approximately 1.9 times faster than previously thought based on calibration against the long standing resist standard.

  12. LISA Telescope Sensitivity Analysis

    NASA Technical Reports Server (NTRS)

    Waluschka, Eugene; Krebs, Carolyn (Technical Monitor)

    2001-01-01

    The results of a LISA telescope sensitivity analysis will be presented, The emphasis will be on the outgoing beam of the Dall-Kirkham' telescope and its far field phase patterns. The computed sensitivity analysis will include motions of the secondary with respect to the primary, changes in shape of the primary and secondary, effect of aberrations of the input laser beam and the effect the telescope thin film coatings on polarization. An end-to-end optical model will also be discussed.

  13. Argon I Lines Produced in a Hollow Cathode Source, 332 nm to 5865 nm

    PubMed Central

    Whaling, W.; Anderson, W. H. C.; Carle, M. T.; Brault, J. W.; Zarem, H. A.

    2002-01-01

    We report precision measurements by Fourier transform spectroscopy of the vacuum wavenumber, line width, and relative signal strength of 928 lines in the Ar I spectrum. Wavelength in air and classification of the transition are supplied for each line. A comparison of our results with other precision measurements illustrates the sensitivity of Ar I wavelengths to conditions in the light source.

  14. A study of eigenvalue sensitivity for hydrodynamic stability operators

    NASA Technical Reports Server (NTRS)

    Schmid, Peter J.; Henningson, Dan S.; Khorrami, Mehdi R.; Malik, Mujeeb R.

    1993-01-01

    The eigenvalue sensitivity for hydrodynamic stability operators is investigated. Classical matrix perturbation techniques as well as the concept of epsilon-pseudospectra are applied to show that parts of the spectrum are highly sensitive to small perturbations. Applications are drawn from incompressible plane Couette flow, trailing line vortex flow, and compressible Blasius boundary-layer flow. Parameter studies indicate a monotonically increasing effect of the Reynolds number on the sensitivity. The phenomenon of eigenvalue sensitivity is due to the nonnormality of the operators and their discrete matrix analogs and may be associated with large transient growth of the corresponding initial value problem.

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

    NASA Technical Reports Server (NTRS)

    Whiting, E. E.

    1994-01-01

    This program predicts the spectra resulting from electronic transitions of diatomic molecules and atoms in local thermodynamic equilibrium. The program produces a spectrum by accounting for the contribution of each rotational and atomic line considered. The integrated intensity of each line is distributed in the spectrum by an approximate Voigt profile. The program can produce spectra for optically thin gases or for cases where simultaneous emission and absorption occurs. In addition, the program can compute the spectrum resulting from the absorption of incident radiation by a column of cold gas or the high-temperature, self-absorbed emission spectrum from a nonisothermal gas. The computed spectrum can be output directly or combined with a slit function and sensitivity calibration to predict the output of a grating spectrograph or a fixed wavelength radiometer. Specifically, the program has the capability to include the following features in any computations: (1) Parallel transitions, in which spin splitting and lambda doubling are ignored (ignoring spin splitting and/or lambda doubling means that the total multiple strength is assumed to reside in a single "effective" line), (2) Perpendicular transitions, in which spin splitting and lambda doubling are ignored, (3) Sigma Pi transitions, in which lambda doubling is ignored, (4) Atomic lines, (5) Option to terminate rotational line calculations when the molecule dissociates due to rotation, (6) Option to include the alternation of line intensities for homonuclear molecules, (7) Use of an approximate Voigt profile for the line shape, and (8) Radiative energy transport in a nonisothermal gas. The output options available in the program are: (1) Tabulation of the spontaneous emission spectrum (i.e., optically thin spectrum) for a 1.0 cm path length, (2) Tabulation of the "true" spectrum, which incorporates spontaneous emission, induced emission, absorption, and externally incident radiation through the equation of

  16. Absorption line CW EPR using an amplitude modulated longitudinal field.

    PubMed

    Fedin, Matvey; Gromov, Igor; Schweiger, Arthur

    2004-11-01

    In standard continuous wave electron paramagnetic resonance (CW-EPR) experiments, the first derivative of absorption lines is detected. This type of a line shape is caused by the magnetic field modulation and is usually an undesired feature, since the sensitivity of CW-EPR drastically decreases with increasing linewidth. A new approach is introduced, which allows for the measurement of absorption line EPR spectra in systems with broad inhomogeneous lines. The method makes use of multiple-photon transitions that are induced in spin systems when a transverse microwave and a longitudinal radio frequency field are simultaneously applied. The absorption lines are obtained by using amplitude modulation of the radio frequency field and slight saturation of the spectral lines. The basics of the new approach are discussed and experimental examples are given. PMID:15504685

  17. Personalized chemotherapy profiling using cancer cell lines from selectable mice

    PubMed Central

    Kamiyama, Hirohiko; Rauenzahn, Sherri; Shim, Joong Sup; Karikari, Collins A.; Feldmann, Georg; Hua, Li; Kamiyama, Mihoko; Schuler, F. William; Lin, Ming-Tseh; Beaty, Robert M.; Karanam, Balasubramanyam; Liang, Hong; Mullendore, Michael E.; Mo, Guanglan; Hidalgo, Manuel; Jaffee, Elizabeth; Hruban, Ralph H.; Jinnah, H. A.; Roden, Richard B. S.; Jimeno, Antonio; Liu, Jun O.; Maitra, Anirban; Eshleman, James R.

    2013-01-01

    Purpose High-throughput chemosensitivity testing of low-passage cancer cell lines can be used to prioritize agents for personalized chemotherapy. However, generating cell lines from primary cancers is difficult, because contaminating stromal cells overgrow the malignant cells. Experimental Design We produced a series of hypoxanthine phosphoribosyl transferase (hprt)-null immunodeficient mice. During growth of human cancers in these mice, hprt-null murine stromal cells replace their human counterparts. Results Pancreatic and ovarian cancers explanted from these mice were grown in selection media to produce pure human cancer cell lines. We screened one cell line with a 3,131-drug panel and identified seventy-seven FDA approved drugs with activity, including two novel drugs to which the cell line was uniquely sensitive. Xenografts of this carcinoma were selectively responsive to both drugs. Conclusion Chemotherapy can be personalized using patient-specific cell lines derived in biochemically selectable mice. PMID:23340293

  18. Microwave spectral line listing

    NASA Technical Reports Server (NTRS)

    White, W. F., Jr.

    1975-01-01

    The frequency, intensity, and identification of 9615 spectral lines belonging to 75 molecules are tabulated in order of increasing frequency. Measurements for all 75 molecules were made in the frequency range from 26500 to 40000 MHz by a computer controlled spectrometer. Measurements were also made in the 18000 to 26500 MHz range for some of the molecules.

  19. Straight Line Graphs

    ERIC Educational Resources Information Center

    Krueger, Tom

    2010-01-01

    In this article, the author shares one effective lesson idea on straight line graphs that he applied in his lower ability Y9 class. The author wanted something interesting for his class to do, something that was fun and engaging with direct feedback, and something that worked because someone else had tried it before. In a word, the author admits…

  20. Cracks and Lines

    NASA Technical Reports Server (NTRS)

    2004-01-01

    6 June 2004 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) picture shows an odd area of the south polar region that has sets of fine, nearly parallel lines running from the northeast (upper right) toward southwest (lower left) and a darker, wider set of cracks with a major trend running almost perpendicular to the finer lines. The appearance of these features is enhanced by seasonal frost. Dark areas have no frost, bright areas still have frozen carbon dioxide ice. In summer, the ice would be gone and the cracks and lines less obvious when viewed from orbit. Although unknown, wind might be responsible for forming the fine set of lines, and perhaps freeze-thaw cycles of ground ice or structural deformation would have contributed to formation of the wider cracks. The image is located near 85.0oS, 324.0oW, and covers an area about 1.5 km (nearly 1 mi) across. The scene is illuminated by sunlight from the upper left.

  1. Control line sealing connection

    SciTech Connect

    Tohill, H.O.

    1984-07-10

    A sealing connection for the passage of a fluid control line through adjoining members is claimed. The connection comprises a metallic tubular sealing element provided with tapered end portions, each end having internal frusto-conical surfaces and external frusto-conical surfaces in coaxial alignment with the bore through the element. The external frusto-conical surfaceas provide metal-to-metal sealing with aligned frusto-conical seating surfaces in opposed pockets formed in aligned portions of the control line at their respective openings at the adjoining surfaces of the adjoined member. The tubular sealing element is subjected to axial compression between the frusto-conical pocket seating surfaces when the adjoined members are bolted tightly together which results in deformation of its tapered end portions to provide metal-to-metal sealing with the adjoined members which is effective to seal against both internal and external fluid pressurization of the control line and without internally obstructing or restricting the control line. Secondary sealing is provided by elastomeric O-ring seals mounted in circumferential annular grooves formed in the exterior of the tubular sealing element.

  2. Building with a Line

    ERIC Educational Resources Information Center

    Hubbert, Beth

    2011-01-01

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

  3. The Front Line.

    ERIC Educational Resources Information Center

    Unks, Gerald

    1979-01-01

    The author draws an analogy between today's school system and an assembly line, deploring the notion that all children are taught the same thing at the same time, ending in humiliation, disgrace, and failure for some, and nonchallenging academic activities for others. (KC)

  4. Allergic sensitization: screening methods.

    PubMed

    Ladics, Gregory S; Fry, Jeremy; Goodman, Richard; Herouet-Guicheney, Corinne; Hoffmann-Sommergruber, Karin; Madsen, Charlotte B; Penninks, André; Pomés, Anna; Roggen, Erwin L; Smit, Joost; Wal, Jean-Michel

    2014-01-01

    Experimental in silico, in vitro, and rodent models for screening and predicting protein sensitizing potential are discussed, including whether there is evidence of new sensitizations and allergies since the introduction of genetically modified crops in 1996, the importance of linear versus conformational epitopes, and protein families that become allergens. Some common challenges for predicting protein sensitization are addressed: (a) exposure routes; (b) frequency and dose of exposure; (c) dose-response relationships; (d) role of digestion, food processing, and the food matrix; (e) role of infection; (f) role of the gut microbiota; (g) influence of the structure and physicochemical properties of the protein; and (h) the genetic background and physiology of consumers. The consensus view is that sensitization screening models are not yet validated to definitively predict the de novo sensitizing potential of a novel protein. However, they would be extremely useful in the discovery and research phases of understanding the mechanisms of food allergy development, and may prove fruitful to provide information regarding potential allergenicity risk assessment of future products on a case by case basis. These data and findings were presented at a 2012 international symposium in Prague organized by the Protein Allergenicity Technical Committee of the International Life Sciences Institute's Health and Environmental Sciences Institute. PMID:24739743

  5. Sensitivity Analysis Without Assumptions

    PubMed Central

    VanderWeele, Tyler J.

    2016-01-01

    Unmeasured confounding may undermine the validity of causal inference with observational studies. Sensitivity analysis provides an attractive way to partially circumvent this issue by assessing the potential influence of unmeasured confounding on causal conclusions. However, previous sensitivity analysis approaches often make strong and untestable assumptions such as having an unmeasured confounder that is binary, or having no interaction between the effects of the exposure and the confounder on the outcome, or having only one unmeasured confounder. Without imposing any assumptions on the unmeasured confounder or confounders, we derive a bounding factor and a sharp inequality such that the sensitivity analysis parameters must satisfy the inequality if an unmeasured confounder is to explain away the observed effect estimate or reduce it to a particular level. Our approach is easy to implement and involves only two sensitivity parameters. Surprisingly, our bounding factor, which makes no simplifying assumptions, is no more conservative than a number of previous sensitivity analysis techniques that do make assumptions. Our new bounding factor implies not only the traditional Cornfield conditions that both the relative risk of the exposure on the confounder and that of the confounder on the outcome must satisfy but also a high threshold that the maximum of these relative risks must satisfy. Furthermore, this new bounding factor can be viewed as a measure of the strength of confounding between the exposure and the outcome induced by a confounder. PMID:26841057

  6. Allergic sensitization: screening methods

    PubMed Central

    2014-01-01

    Experimental in silico, in vitro, and rodent models for screening and predicting protein sensitizing potential are discussed, including whether there is evidence of new sensitizations and allergies since the introduction of genetically modified crops in 1996, the importance of linear versus conformational epitopes, and protein families that become allergens. Some common challenges for predicting protein sensitization are addressed: (a) exposure routes; (b) frequency and dose of exposure; (c) dose-response relationships; (d) role of digestion, food processing, and the food matrix; (e) role of infection; (f) role of the gut microbiota; (g) influence of the structure and physicochemical properties of the protein; and (h) the genetic background and physiology of consumers. The consensus view is that sensitization screening models are not yet validated to definitively predict the de novo sensitizing potential of a novel protein. However, they would be extremely useful in the discovery and research phases of understanding the mechanisms of food allergy development, and may prove fruitful to provide information regarding potential allergenicity risk assessment of future products on a case by case basis. These data and findings were presented at a 2012 international symposium in Prague organized by the Protein Allergenicity Technical Committee of the International Life Sciences Institute’s Health and Environmental Sciences Institute. PMID:24739743

  7. Climate sensitivity estimated from the past 450,000 years

    NASA Astrophysics Data System (ADS)

    Snyder, C.

    2010-12-01

    The risks of future climate change depend upon the sensitivity of the Earth system to greenhouse gases emissions. However, the upper limit of climate sensitivity has proven particularly difficult to constrain. Here we reconstruct climate sensitivity using a probabilistic framework and paleoclimate records from the past 450kyr, including new reconstructions of radiative forcing from changes in ice sheets, sea level, vegetation, and dust. From this analysis, we estimate climate sensitivity is 4.1K (2.1K-6.6K, 95% interval), a result that is surprisingly stable over the past 450kyr. Although our paleoclimate based results significantly constrain the upper tail of climate sensitivity, we estimate a 36% chance that climate sensitivity is higher than all of the IPCC 2007 climate models. These results have important implications for climate impact assessments and climate policy. A comparison of reconstructions of global average surface temperature (GAST) and global average radiative forcing (GARF) over the past 450kyr. GAST median is a red line, and GAST 95% interval is grey shading. GARF median is a cyan line, and GARF 95% interval is blue shading. Empirically estimated frequency distribution for partial climate sensitivity from the past 450kyr. The rectangles show the frequency of estimates drawn from the full ensembles, and the black line shows the empirically-estimated frequency distribution. The green diamonds show the 19 global climate models summarized in the 2007 IPCC report. The purple bar shows IPCC’s “likely” (66-90% probability) range for partial CS.

  8. A Quantitative Transmission Line Experiment

    ERIC Educational Resources Information Center

    Johnston, D. C.; Silbernagel, B. G.

    1969-01-01

    Describes modifications of a commercially available strip-type transmission line, which makes possible reproducible measurements of standing waves on the line. Experimental data yield values for the characteristic impedance, phase velocity and line wavelength of radiation in the transmission line, and the dielectric constant of material in the…

  9. The Bicycle Assembly Line Game

    ERIC Educational Resources Information Center

    Klotz, Dorothy

    2011-01-01

    "The Bicycle Assembly Line Game" is a team-based, in-class activity that helps students develop a basic understanding of continuously operating processes. Each team of 7-10 students selects one of seven prefigured bicycle assembly lines to operate. The lines are run in real-time, and the team that operates the line that yields the…

  10. CONTINUOUSLY SENSITIVE BUBBLE CHAMBER

    DOEpatents

    Good, R.H.

    1959-08-18

    A radiation detector of the bubble chamber class is described which is continuously sensitive and which does not require the complex pressure cycling equipment characteristic of prior forms of the chamber. The radiation sensitive element is a gas-saturated liquid and means are provided for establishing a thermal gradient across a region of the liquid. The gradient has a temperature range including both the saturation temperature of the liquid and more elevated temperatures. Thus a supersaturated zone is created in which ionizing radiations may give rise to visible gas bubbles indicative of the passage of the radiation through the liquid. Additional means are provided for replenishing the supply of gas-saturated liquid to maintaincontinuous sensitivity.

  11. Printed circuit dispersive transmission line

    DOEpatents

    Ikezi, H.; Lin-Liu, Y.R.; DeGrassie, J.S.

    1991-08-27

    A printed circuit dispersive transmission line structure is disclosed comprising an insulator, a ground plane formed on one surface of the insulator, a first transmission line formed on a second surface of the insulator, and a second transmission line also formed on the second surface of the insulator and of longer length than the first transmission line and periodically intersecting the first transmission line. In a preferred embodiment, the transmission line structure exhibits highly dispersive characteristics by designing the length of one of the transmission line between two adjacent periodic intersections to be longer than the other. 5 figures.

  12. Printed circuit dispersive transmission line

    DOEpatents

    Ikezi, Hiroyuki; Lin-Liu, Yuh-Ren; DeGrassie, John S.

    1991-01-01

    A printed circuit dispersive transmission line structure is disclosed comprising an insulator, a ground plane formed on one surface of the insulator, a first transmission line formed on a second surface of the insulator, and a second transmission line also formed on the second surface of the insulator and of longer length than the first transmission line and periodically intersecting the first transmission line. In a preferred embodiment, the transmission line structure exhibits highly dispersive characteristics by designing the length of one of the transmission line between two adjacent periodic intersections to be longer than the other.

  13. Sensitivity analysis of SPURR

    SciTech Connect

    Witholder, R.E.

    1980-04-01

    The Solar Energy Research Institute has conducted a limited sensitivity analysis on a System for Projecting the Utilization of Renewable Resources (SPURR). The study utilized the Domestic Policy Review scenario for SPURR agricultural and industrial process heat and utility market sectors. This sensitivity analysis determines whether variations in solar system capital cost, operation and maintenance cost, and fuel cost (biomass only) correlate with intuitive expectations. The results of this effort contribute to a much larger issue: validation of SPURR. Such a study has practical applications for engineering improvements in solar technologies and is useful as a planning tool in the R and D allocation process.

  14. RESRAD parameter sensitivity analysis

    SciTech Connect

    Cheng, J.J.; Yu, C.; Zielen, A.J.

    1991-08-01

    Three methods were used to perform a sensitivity analysis of RESRAD code input parameters -- enhancement of RESRAD by the Gradient Enhanced Software System (GRESS) package, direct parameter perturbation, and graphic comparison. Evaluation of these methods indicated that (1) the enhancement of RESRAD by GRESS has limitations and should be used cautiously, (2) direct parameter perturbation is tedious to implement, and (3) the graphics capability of RESRAD 4.0 is the most direct and convenient method for performing sensitivity analyses. This report describes procedures for implementing these methods and presents a comparison of results. 3 refs., 9 figs., 8 tabs.

  15. Temperature-insensitive laser frequency locking near absorption lines

    NASA Astrophysics Data System (ADS)

    Kostinski, Natalie; Olsen, Ben A.; Marsland, Robert; McGuyer, Bart H.; Happer, William

    2011-03-01

    Combined magnetically induced circular dichroism and Faraday rotation of an atomic vapor are used to develop a variant of the dichroic atomic vapor laser lock that eliminates lock sensitivity to temperature fluctuations of the cell. Operating conditions that eliminate first-order sensitivity to temperature fluctuations can be determined by low-frequency temperature modulation. This temperature-insensitive gyrotropic laser lock can be accurately understood with a simple model, that is in excellent agreement with observations in potassium vapor at laser frequencies in a 2 GHz range about the 770.1 nm absorption line. The methods can be readily adapted for other absorption lines.

  16. Temperature-insensitive laser frequency locking near absorption lines

    SciTech Connect

    Kostinski, Natalie; Olsen, Ben A.; Marsland, Robert III; McGuyer, Bart H.; Happer, William

    2011-03-15

    Combined magnetically induced circular dichroism and Faraday rotation of an atomic vapor are used to develop a variant of the dichroic atomic vapor laser lock that eliminates lock sensitivity to temperature fluctuations of the cell. Operating conditions that eliminate first-order sensitivity to temperature fluctuations can be determined by low-frequency temperature modulation. This temperature-insensitive gyrotropic laser lock can be accurately understood with a simple model, that is in excellent agreement with observations in potassium vapor at laser frequencies in a 2 GHz range about the 770.1 nm absorption line. The methods can be readily adapted for other absorption lines.

  17. Coolant line hydrometer

    SciTech Connect

    Barber, M.D.; Kipp, W.G.

    1987-03-17

    This patent describes a hydrometer unit for connection in an automobile coolant flow line comprising: a tubular fitting adapted to be connected to the coolant flow line; a coolant receiving chamber means connected to the tubular fitting for receiving coolant from the tubular fitting; and indicating float elements contained within the coolant receiving chamber means and adapted to rise therein individually as a function of the specific gravity of the coolant. The coolant receiving chamber means includes a closure cap which when connected to the tubular fitting forms a coolant receiving chamber, retaining means for retaining the indicating float elements within the coolant receiving chamber, a viewing window member of a substantially clear material through which the float elements can be visually observed within the coolant receiving chamber means, and air venturi means located within the coolant receiving chamber means for automatically removing air which may collect within the coolant chamber means.

  18. Central line complications

    PubMed Central

    Kornbau, Craig; Lee, Kathryn C; Hughes, Gwendolyn D; Firstenberg, Michael S

    2015-01-01

    Central venous access is a common procedure performed in many clinical settings for a variety of indications. Central lines are not without risk, and there are a multitude of complications that are associated with their placement. Complications can present in an immediate or delayed fashion and vary based on type of central venous access. Significant morbidity and mortality can result from complications related to central venous access. These complications can cause a significant healthcare burden in cost, hospital days, and patient quality of life. Advances in imaging, access technique, and medical devices have reduced and altered the types of complications encountered in clinical practice; but most complications still center around vascular injury, infection, and misplacement. Recognition and management of central line complications is important when caring for patients with vascular access, but prevention is the ultimate goal. This article discusses common and rare complications associated with central venous access, as well as techniques to recognize, manage, and prevent complications. PMID:26557487

  19. CRUCIBLE LINING METHOD

    DOEpatents

    Bone, W.H.; Schmidt, W.W.

    1958-11-01

    A method is presented for forming refractory liners in cylindrical reaction vessels used for the reductlon of uranium tetrafluoride to metallic uranium. A preliminary form, having positioning lugs attached thereto, is inserted into the reaction vessel and the refractory powder, usually CaO, is put in the annular space between the form and the inner wall of the reaction vessel. A jolting table is used to compact this charge of liner material ln place, and after thls has been done, the preliminary form is removed and the flnal form or plug is lnserted without disturbing the partially completed lining. The remainder of the lining charge is then introduced and compacted by jolting, after which the form is removed.

  20. Cryoresistive gas insulated line

    NASA Astrophysics Data System (ADS)

    Hidaka, K.; Matsumoto, S.; Kouno, T.

    An insulation strength of more than 16 kV mm -1 has been realized using nitrogen gas at 133 K and 0.4 MPa with the application of a.c. and impulse voltages. A cryoresistive gas insulated line (CRGIL) using nitrogen gas is proposed on the basis of the measured insulation strength. An efficient method for use of the cooling heat of liquefied natural gas is also proposed so that no refrigerator is required and the cost of cooling is reduced. The CRGIL has the advantages of having a large current carrying capacity, small power loss and small capacitance. Moreover, a given transmission capacity is achieved by a CRGIL whose rated voltage is about half that in a conventional gas insulated line.