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1

Development of Bubble Chambers with Sensitivity to WIMPs  

SciTech Connect

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.

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

2

Development of Bubble Chambers with Sensitivity to WIMPs  

SciTech Connect

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.

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

3

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

NASA Technical Reports Server (NTRS)

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.

Turner, Michael S.; Wilczek, Frank

1989-01-01

4

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

SciTech Connect

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

Kamat, Sharmila; /Case Western Reserve U.

2005-01-01

5

3.5-keV X-ray line from nearly-degenerate WIMP dark matter decays  

E-print Network

The unidentified emission line at the energy of $\\sim$3.5~keV observed in X-rays from galaxy clusters may originate from a process involving a dark matter particle. On the other hand, a weakly interacting massive particle (WIMP) has been an attractive dark matter candidate, due to its well-understood thermal production mechanism and its connection to physics at the TeV scale. In this paper, we pursue the possibility that the 3.5-keV X-ray arises from a late time decay of a WIMP dark matter into another WIMP dark matter, both of which have the mass of $O(100)$~GeV and whose mass splitting is about 3.5~keV. We focus on the simplest case where there are two Majorana dark matter particles and two charged scalars that couple with a standard model matter particle. By assuming a hierarchical structure in the couplings of the two dark matter particles and two charged scalars, it is possible to explain the 3.5-keV line and realize the WIMP dark matter scenario at the same time. Since the effective coupling of the two different Majorana dark matter particles and one photon violates CP symmetry, the model always contains a new source of CP violation, so the model's connection to the physics of electric dipole moments is discussed. The model's peculiar signatures at the LHC are also studied. We show the prospect of detecting the charged scalars through a detailed collider simulation.

Cheng-Wei Chiang; Toshifumi Yamada

2014-07-28

6

Effective WIMPs  

NASA Astrophysics Data System (ADS)

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.

Hutchinson, Jeffrey Paul

7

Expected Sensitivity to Galactic/Solar Axions and Bosonic Super-WIMPs based on the Axio-electric Effect in Liquid Xenon Dark Matter Detectors  

E-print Network

We present systematic case studies to investigate the sensitivity of axion searches by liquid xenon detectors, using the axio-electric effect (analogue of the photoelectric effect) on xenon atoms. Liquid xenon is widely considered to be one of the best target media for detection of WIMPs (Weakly Interacting Massive Particles which may form the galactic dark matter) using nuclear recoils. Since these detectors also provide an extremely low radioactivity environment for electron recoils, very weakly-interacting low-mass particles ( 10^-33 (for mass 1 keV/c^2) or > 10^-27 (for mass 100 keV/c^2).

Arisaka, K; Ghag, C; Kaidi, J; Lung, K; Lyashenko, A; Peccei, R D; Smith, P; Ye, K

2012-01-01

8

Expected Sensitivity to Galactic/Solar Axions and Bosonic Super-WIMPs based on the Axio-electric Effect in Liquid Xenon Dark Matter Detectors  

E-print Network

We present systematic case studies to investigate the sensitivity of axion searches by liquid xenon detectors, using the axio-electric effect (analogue of the photoelectric effect) on xenon atoms. Liquid xenon is widely considered to be one of the best target media for detection of WIMPs (Weakly Interacting Massive Particles which may form the galactic dark matter) using nuclear recoils. Since these detectors also provide an extremely low radioactivity environment for electron recoils, very weakly-interacting low-mass particles ( 10^-33 (for mass 1 keV/c^2) or > 10^-27 (for mass 100 keV/c^2).

K. Arisaka; P. Beltrame; C. Ghag; J. Kaidi; K. Lung; A. Lyashenko; R. D. Peccei; P. Smith; K. Ye

2013-01-23

9

Expected sensitivity to galactic/solar axions and bosonic super-WIMPs based on the axio-electric effect in liquid xenon dark matter detectors  

NASA Astrophysics Data System (ADS)

We present systematic case studies to investigate the sensitivity of axion searches by liquid xenon detectors, using the axio-electric effect (analogue of the photoelectric effect) on xenon atoms. Liquid xenon is widely considered to be one of the best target media for detection of WIMPs (Weakly Interacting Massive Particles which may form the galactic dark matter) using nuclear recoils. Since these detectors also provide an extremely low radioactivity environment for electron recoils, very weakly-interacting low-mass particles (< 100 keV/c2), such as the hypothetical axion, could be detected as well - in this case using the axio-electric effect. Future ton-scale liquid Xe detectors will be limited in sensitivity only by irreducible neutrino background (pp-chain solar neutrino and the double beta decay of 136Xe) in the mass range between 1 and 100 keV/c2. Assuming one ton-year of exposure, galactic axions (as non-relativistic dark matter) could be detected if the axio-electric coupling gAe is greater than 10-14 at 1 keV/c2 axion mass (or 10-13 at 100 keV/c2). Below a few keV/c2, and independent of the mass, a solar axion search would be sensitive to a coupling gAe˜10-12. This limit will set a stringent upper bound on axion mass for the DFSZ and KSVZ models for the mass ranges mA<0.1 eV/c2 and <10 eV/c2, respectively. Vector-boson dark matter could also be detected for a coupling constant ?'/?>10-33 (for mass 1 keV/c2) or >10-27 (for mass 100 keV/c2).

Arisaka, K.; Beltrame, P.; Ghag, C.; Kaidi, J.; Lung, K.; Lyashenko, A.; Peccei, R. D.; Smith, P.; Ye, K.

2013-04-01

10

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.

11

WIMP direct detection overview  

E-print Network

This review on weakly interacting massive particle (WIMP) dark matter direct detection focuses on experimental approaches and the corresponding physics basics. The presentation is intended to provide a quick and concise introduction for non-specialists to this fast evolving topic of astroparticle physics.

Y. Ramachers

2002-11-22

12

Median recoil direction as a WIMP directional detection signal  

SciTech Connect

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

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

2010-03-15

13

WIMP physics with ensembles of direct-detection experiments  

NASA Astrophysics Data System (ADS)

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.

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

2014-12-01

14

Survey of Interferon Production and Sensitivity in Human Cell Lines  

PubMed Central

Seven presumed diploid and 11 established cell lines were studied for their ability to produce free interferon in response to a standardized Newcastle disease virus challenge. Interferon production was evaluated in both serum-containing and serum-free medium. The ability of these cell lines to respond to the application of a standard interferon preparation by becoming resistant to virus was also examined. The diploid lines were distinctly more efficient producers of interferon than were the established lines. They also evidenced a greater requirement for serum to produce their maximum titers, but some were able to produce good titers in serum-free medium. The diploid lines were uniformly more sensitive to the application of exogenous interferon than were the established cell lines and attained greater degrees of virus resistance, but all lines tested displayed measurable sensitivity to interferon. PMID:4329429

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

1971-01-01

15

Abundance sensitive points of line profiles in the stellar spectra  

NASA Astrophysics Data System (ADS)

Many abundance studies are based on spectrum synthesis and ?-squared differences between the synthesized and an observed spectrum. Much of the spectra so compared depend only weakly on the elemental abundances. Logarithmic plots of line depths rather than relative flux make this more apparent. We present simulations that illustrate a simple method for finding regions of the spectrum most sensitive to abundance, and also some caveats for using such information. As expected, we find that weak features are the most sensitive. Equivalent widths of weak lines are ideal features, because of their sensitivity to abundances, and insensitivity to factors that broaden the line profiles. The wings of strong lines can also be useful, but it is essential that the broadening mechanisms be accurately known. The very weakest features, though sensitive to abundance, should be avoided or used with great caution because of uncertainty of continuum placement as well as numerical uncertainties associated with the subtraction of similar numbers.

Sheminova, V. A.; Cowley, C. R.

2014-09-01

16

Radiation sensitivity of human lung cancer cell lines.  

PubMed

X-Ray survival curves were determined using a panel of 17 human lung cancer cell lines, with emphasis on non-small cell lung cancer (NSCLC). In contrast to classic small cell lung cancer (SCLC) cell lines, NSCLC cell lines were generally less sensitive to radiation as evidenced by higher radiation survival curve extrapolation numbers, surviving fraction values following a 2 Gy dose (SF2) and the mean inactivation dose values (D) values. The spectrum of in vitro radiation responses observed was similar to that expected in clinical practice, although mesothelioma was unexpectedly sensitive in vitro. Differences in radiosensitivity were best distinguished by comparison of SF2 values. Some NSCLC lines were relatively sensitive, and in view of this demonstrable variability in radiation sensitivity, the SF2 value may be useful for in vitro predictive assay testing of clinical specimens. PMID:2539297

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

1989-03-01

17

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...

18

The WIMP Forest: Indirect Detection of a Chiral Square  

SciTech Connect

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

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

2009-04-01

19

Post-WIMP user interfaces  

Microsoft Academic Search

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

Andries Van Dam

1997-01-01

20

Bs {yields} {mu}+{mu}- and Detection of Neutralino WIMP  

SciTech Connect

We consider direct detection of neutralino WIMP and the upward-going muon flux due to the WIMP annihilations in the cores of the sun and the earth, including the upper bound on the branching ratio for Bs {yields} {mu}+{mu}- decay. We find that the constraint from Bs {yields} {mu}+{mu}- is very strong in most parameter space, and excludes substantial part of the supergravity parameter space regions where the direct detection rates are within current experimental sensitivities and the expected upward-going muon fluxes are within the expected reach of IceCube.

Kim, Yeong Gyun [Department of Physics, Korea University, Seoul 136-701 (Korea, Republic of)

2005-12-02

21

Light WIMPs in the Sun: Constraints from helioseismology  

SciTech Connect

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

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

2010-11-15

22

Differential Sensitivity in the Survival of Oligodendrocyte Cell Lines to  

E-print Network

Differential Sensitivity in the Survival of Oligodendrocyte Cell Lines to Overexpression of Myelin in oligodendrocyte survival by overexpression studies in vitro and in vivo. The classic and sr proteolipids are targeted to different cellular com- partments in the oligodendrocyte, suggesting different cellular

Bongarzone, Ernesto R.

23

Event rates for WIMP detection  

SciTech Connect

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.

Vergados, J. D. [University of Ioannina, Ioannina, Gr 45110 (Greece); Moustakidis, Ch. C.; Oikonomou, V. [Department of Theoretical Physics, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece)

2006-11-28

24

WIMPs and Un-Naturalness  

E-print Network

The WIMP "miracle" suggests a new physics threshold ranging from the weak scale up to several tens of TeVs. Obtaining the correct dark matter density in many theories aiming to solve the hierarchy problem may thus require some amount of tuning of the weak scale, hinting at a possible connection between WIMP dark matter and unnaturalness. We point out that dark matter direct detection is a very efficient probe of these unnatural models, and that existing data already provide important clues to the nature of the associated WIMPs. We present a model-independent, relativistic analysis of the signatures of a gauge-singlet dark matter candidate of arbitrary spin, and discuss the current experimental bounds from LUX and XENON100. For complex WIMPs, dark matter direct detection is complementary to electroweak precision tests, and can even compete with flavor constraints if the dark matter has spin. Particularly relevant for future searches are couplings to the Higgs mass operator, which are expected to be large if the electroweak scale is finely tuned. Care is devoted to the RG evolution of the effective Lagrangian. We find that the CP-even scalar coupling to charm quarks is enhanced by about 20% compared to the one-loop estimate. When pushed in the unnatural regime, warped extra dimensions -- with or without custodial symmetry -- become attractive theories for flavor, the Higgs mass, and dark matter. The WIMP argument basically sets an upper bound on unnaturalness, whereas direct detection experiments select scalar or real particles as the most compelling dark matter candidates.

Luca Vecchi

2014-09-29

25

Dependence of direct detection signals on the WIMP velocity distribution  

SciTech Connect

The signals expected in WIMP direct detection experiments depend on the ultra-local dark matter distribution. Observations probe the local density, circular speed and escape speed, while simulations find velocity distributions that deviate significantly from the standard Maxwellian distribution. We calculate the energy, time and direction dependence of the event rate for a range of velocity distributions motivated by recent observations and simulations, and also investigate the uncertainty in the determination of WIMP parameters. The dominant uncertainties are the systematic error in the local circular speed and whether or not the MW has a high density dark disc. In both cases there are substantial changes in the mean differential event rate and the annual modulation signal, and hence exclusion limits and determinations of the WIMP mass. The uncertainty in the shape of the halo velocity distribution is less important, however it leads to a ? 5% systematic error in the WIMP mass. The detailed direction dependence of the event rate is sensitive to the velocity distribution. However the numbers of events required to detect anisotropy and confirm the median recoil direction do not change substantially.

Green, Anne M., E-mail: anne.green@nottingham.ac.uk [School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, NG7 2RD (United Kingdom)

2010-10-01

26

Cosmological WIMPs, Higgs Dark Matter and GLAST  

E-print Network

Measurement of the extragalactic background (EGBR) of diffuse gamma-rays is perhaps one of the most challenging tasks for future gamma-ray observatories, such as GLAST. This is because any determination will depend on accurate subtraction of the galactic diffuse and celestial foregrounds, as well as point sources. However, the EGBR is likely to contain very rich information about the high energy-gamma ray sources of the Universe at cosmological distances. We focus on the ability of GLAST to detect a signal from dark matter in the EGBR. We present sensitivities for generic thermal WIMPs and the Inert Higgs Doublet Model. Also we discuss the various aspects of astrophysics and particle physics that determines the shape and strength of the signal, such as dark matter halo properties and different dark matter candidates. Other possible sources to the EGBR are also discussed, such as unresolved AGNs, and viewed as backgrounds.

A. Sellerholm; J. Conrad; L. Bergstrom; J. Edsjo

2007-07-27

27

Dark matter in the solar system II: WIMP annihilation rates in the Sun  

E-print Network

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

Annika H. G. Peter

2009-02-09

28

WIMP Annihilation and Cooling of Neutron Stars  

E-print Network

We study the effect of WIMP annihilation on the temperature of a neutron star. We shall argue that the released energy due to WIMP annihilation inside the neutron stars, might affect the temperature of stars older than 10 million years, flattening out the temperature at $\\sim 10^4$ K for a typical neutron star.

Chris Kouvaris

2007-08-17

29

Towards Direct Detection of WIMPs with the Cryogenic Dark Matter Search  

NASA Astrophysics Data System (ADS)

The Cryogenic Dark Matter Search (CDMS) is carrying out a direct detection search for Weakly Interacting Massive Particles (WIMPs), one of the favored candidates for dark matter. Our latest data has placed some of the most stringent limits on the WIMP-nucleon spin-independent cross section of 6.6×10-44 cm2 for 60 GeV WIMPs at the 90% confidence level. This paper describes our experiment and our latest results; the status of SuperCDMS Soudan, a new expriment at the Soudan mine in Minnesota that will achieve a sensitivity of 5×10-45 cm2 our plans for SuperCDMS SNOLAB, a 100 kg experiment with a projected sensitivity of 3×10-46 cm2 and GEODM, a ton-scale experiment at DUSEL with a projected sensitivity of 2×10-47 cm2.

Figueroa-Feliciano, E.

2010-02-01

30

Soft collinear effective theory for heavy WIMP annihilation  

NASA Astrophysics Data System (ADS)

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

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

2015-01-01

31

WIMP searches with AMANDA-B10  

E-print Network

We report on the search for nearly vertical up-going muon neutrinos from WIMP annihilations in the center of the Earth with the AMANDA-B10 detector. The whole data sample collected in 1997, 10^9 events, has been analyzed and a final sample of 15 up-going events is found in a restricted zenith angular region where a signal from WIMP annihilations is expected. A preliminary upper limit at 90% confidence level on the annihilation rate of WIMPs in the center of the Earth is presented.

The AMANDA Collaboration; X. Bai

2000-12-13

32

Output-sensitive 3D line integral convolution.  

PubMed

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

Falk, Martin; Weiskopf, Daniel

2008-01-01

33

WIMP abundance and lepton (flavour) asymmetry  

SciTech Connect

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)

Stuke, Maik; Schwarz, Dominik J. [Fakultät für Physik, Universität Bielefeld, Postfach 100131, 33501 Bielefeld (Germany); Starkman, Glenn, E-mail: mstuke@physik.uni-bielefeld.de, E-mail: dschwarz@physik.uni-bielefeld.de, E-mail: glenn.starkman@case.edu [CERCA/ISO, Department of Physics, Case Western Reserve University, Cleveland, OH 44106-7079 (United States)

2012-03-01

34

Solar WIMPs unravelled: Experiments, astrophysical uncertainties, and interactive tools  

NASA Astrophysics Data System (ADS)

The absence of a neutrino flux from self-annihilating dark matter captured in the Sun has tightly constrained some leading particle dark matter scenarios. The impact of astrophysical uncertainties on the capture process of dark matter in the Sun and hence also the derived constraints by neutrino telescopes need to be taken into account. In this review we have explored relevant uncertainties in solar WIMP searches, summarized results from leading experiments, and provided an outlook into upcoming searches and future experiments. We have created an interactive plotting tool that allows the user to view current limits and projected sensitivities of major experiments under changing astrophysical conditions.

Danninger, Matthias; Rott, Carsten

2014-12-01

35

SENSITIZATION OF HUMAN OSTEOSARCOMA CELL LINE 143B WITH CALCITRIOL FOR CISPLATIN THERAPY  

E-print Network

. Literature suggests the sensitization of OS cell lines with bone anabolic agents such as statins for example; atrovastatin and bisphosphonates for e.g. zoledronic acid are effective in enhancing the chemotherapeutic response (49, 51). Olivia et al found... of sensitization should be made clear. Differentiation and anti-proliferation effects of calcitriol are well established. Recent research shows sensitization of OS cell lines with bone anabolic agents such as statins, bisphosphonates enhances the anti...

Bhamidi Lakshmi, Surya Kameshwari Priyanka

2012-08-31

36

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

Microsoft Academic Search

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

Steve Sorensen; Michael Palmer; Thomas Dunwiddie; Barry Hoffer

1980-01-01

37

Improved WIMP-search reach of the CDMS II germanium data  

E-print Network

CDMS II data from the 5-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 WIMP-search exposure. An extended analysis was also completed by decreasing the 10 keV analysis threshold to $\\sim$5 keV, to increase sensitivity near a WIMP mass of 8 GeV/$c^2$. After unblinding, there were zero candidate events above a deposited energy of 10 keV and 6 events in the lower-threshold analysis. This yielded minimum WIMP-nucleon spin-independent scattering cross-section limits of $1.8 \\times 10^{-44}$ and $1.18 \\times 10 ^{-41}$ cm$^2$ at 90\\% confidence for 60 and 8.6 GeV/$c^2$ WIMPs, respectively. This improves the previous CDMS II result by a factor of 2.4 (2.7) for 60 (8.6) GeV/$c^2$ WIMPs.

Agnese, R; Asai, M; Balakishiyeva, D; Barker, D; Thakur, R Basu; Bauer, D A; Billard, J; Borgland, A; Bowles, M A; Brandt, D; Brink, P L; Bunker, R; Cabrera, B; Caldwell, D O; Calkins, R; Cerdeño, D G; Chagani, H; Chen, Y; Cooley, J; Cornell, B; Crewdson, C H; Cushman, P; Daal, M; Di Stefano, P C F; Doughty, T; Esteban, L; Fallows, S; Figueroa-Feliciano, E; Godfrey, G L; Golwala, S R; Hall, J; Harris, H R; Hertel, S A; Hofer, T; Holmgren, D; Hsu, L; Huber, M E; Jardin, D; Jastram, A; Kamaev, O; Kara, B; Kelsey, M H; Kennedy, A; Kiveni, M; Koch, K; Leder, A; Loer, B; Asamar, E Lopez; 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

2015-01-01

38

Improved WIMP-search reach of the CDMS II germanium data  

E-print Network

CDMS II data from the 5-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 WIMP-search exposure. An extended analysis was also completed by decreasing the 10 keV analysis threshold to $\\sim$5 keV, to increase sensitivity near a WIMP mass of 8 GeV/$c^2$. After unblinding, there were zero candidate events above a deposited energy of 10 keV and 6 events in the lower-threshold analysis. This yielded minimum WIMP-nucleon spin-independent scattering cross-section limits of $1.8 \\times 10^{-44}$ and $1.18 \\times 10 ^{-41}$ cm$^2$ at 90\\% confidence for 60 and 8.6 GeV/$c^2$ WIMPs, respectively. This improves the previous CDMS II result by a factor of 2.4 (2.7) for 60 (8.6) GeV/$c^2$ WIMPs.

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

2015-04-22

39

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

SciTech Connect

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

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

1992-06-01

40

Improved Constraints on Wimps From the International Germanium Experiment IGEX  

SciTech Connect

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

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

2002-04-18

41

Detecting WIMPs in the Microwave Sky  

E-print Network

The hierarchical clustering observed in cold dark matter simulations results in highly clumped galactic halos. If the dark matter in our halo is made of weakly interacting massive particles (WIMPs), their annihilation products should be detectable in the higher density and nearby clumps. We consider WIMPs to be neutralinos and calculate the synchrotron flux from their annihilation products in the presence of the Galactic magnetic field. We derive a self-consistent emission spectrum including pair annihilation, synchrotron self-absorption, and synchrotron self-Compton reactions. The resulting radiation spans microwave frequencies that can be observed over the anisotropies in the cosmic microwave background. These synchrotron sources should be identifiable as WIMP clumps, either by their spatial structure or by their distinctive radio spectrum.

P. Blasi; A. V. Olinto; C. Tyler

2002-02-05

42

Changes in gene expression profile in two multidrug resistant cell lines derived from a same drug sensitive cell line.  

PubMed

Resistance to chemotherapy is one of the most relevant aspects of treatment failure in cancer. Cell lines are used as models to study resistance. We analyzed the transcriptional profile of two multidrug resistant (MDR) cell lines (Lucena 1 and FEPS) derived from the same drug-sensitive cell K562. Microarray data identified 130 differentially expressed genes (DEG) between K562 vs. Lucena 1, 1932 between K562 vs. FEPS, and 1211 between Lucena 1 versus FEPS. The NOTCH pathway was affected in FEPS with overexpression of NOTCH2 and HEY1. The highly overexpressed gene in MDR cell lines was ABCB1, and both presented the ABCB1 promoter unmethylated. PMID:24996974

Moreira, Miguel Angelo Martins; Bagni, Carolina; de Pinho, Marcos Barcelos; Mac-Cormick, Thaís Messias; dos Santos Mota, Mateus; Pinto-Silva, Flávio Eduardo; Daflon-Yunes, Nathalia; Rumjanek, Vivian Mary

2014-08-01

43

Soft Collinear Effective Theory for Heavy WIMP Annihilation  

E-print Network

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 $\\sim \\alpha \\log^2 (2\\,M/m_W)$ 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 wave-function distortion from electroweak boson exchange leads to observable modifications of the cross section. Careful accounting of momentum regions in the EFT allows the rigorously disentanglement of this so-called Sommerfeld enhancement from the short distance hard annihilation process. The WIMP is modeled as a heavy-particle field, while the light, energetic, final-state electroweak gauge bosons are treated as soft and collinear fields. Hard matching coefficients are computed at renormalization scale $\\mu \\sim 2\\,M$, then evolved down to $\\mu \\sim m_W$, 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 $M \\simeq 3$ TeV, the resummed Sommerfeld enhanced cross section is reduced by a factor of $\\sim 3$ with respect to the tree-level fixed order result.

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

2014-11-03

44

A pulse width modulated power line conditioner for sensitive load centers  

Microsoft Academic Search

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

G. Venkataramanan; B. Johnson

1997-01-01

45

Sensitivity analysis of TRV in TCSC compensated transmission lines during fault clearing by line CB  

Microsoft Academic Search

Thyristor controlled series capacitors (TCSC) are effective devices for transmission lines power delivery enhancement in power systems. Before installation of TCSCs, it is necessary to study side effects of their integration in power system. One of these studies is the effect of series compensation on transient recovery voltage (TRV) of line circuit breaker when clearing a fault. The amplitude and

A. Parvizi; M. Rostami; A. Majzoob Ghadiri

2008-01-01

46

On the Annihilation Rate of WIMPs  

E-print Network

We develop a formalism that allows one to systematically calculate the WIMP annihilation rate into gamma rays whose energy far exceeds the weak scale. A factorization theorem is presented which separates the radiative corrections stemming from initial state potential interactions from loops involving the final state. This separation allows us to go beyond the fixed order calculation, which is polluted by large infrared logarithms. For the case of Majorana WIMPs transforming in the adjoint representation of SU(2), we present the result for the resummed rate at leading double log accuracy in terms of two initial state partial wave matrix elements and one hard matching coefficient. For a given model, one may calculate the cross section by calculating the tree level matching coefficient and determining the value of a local four fermion operator. We find that the effects of resummation can be as large as 100% for a 20 TeV WIMP. The generalization of the formalism to other types of WIMPs is discussed.

Matthew Baumgart; Ira Z. Rothstein; Varun Vaidya

2014-10-29

47

Searches for WIMP Annihilation with GLAST  

SciTech Connect

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

Wai, L.; /SLAC; ,

2005-06-21

48

WIMP Searches at Canfranc with Germanium Detectors  

Microsoft Academic Search

An overview of the searches for Weak Interacting Massive Particles (WIMPs) through their scattering off Germanium nuclei carried out in the Canfranc Tunnel Astroparticle Laboratory (at 2450 metres of water equivalent (m.w.e.)) in a collaboration between the Universities of South Carolina and Zaragoza is given. The main experimental results are sketched both for natural abundance (COSME) and 76Ge enriched (IGEX)

Angel Morales

2001-01-01

49

WIMPS Are Stronger When They Stick Together  

E-print Network

Weakly interacting massive particles (WIMPs) remain the strongest candidates for the dark matter in the Universe. If WIMPs are the dark matter, they will form galactic halos according to the hierarchical clustering observed in N-body simulations. Cold dark matter (CDM) simulations show that large dark matter structures such as galactic and cluster halos are formed by the merging of many smaller clumps of dark matter. Each clump or halo is characterized by a centrally cusped density profile that can enhance the rate of WIMP annihilation and make the annihilation products more easily detectable. Electrons and positrons generated as decay products of WIMP annihilation emit synchrotron radiation in the Galactic magnetic field. We study the synchrotron signature from the clumps of dark matter in our Galactic halo. We find that the emission in the radio and microwave region of the electromagnetic spectrum can be above the CMB anisotropy level and should be detectable by CMB anisotropy experiments. Depending on the density profile of dark matter clumps, hundreds of clumps can have detectable fluxes and angular sizes.

Angela V. Olinto; Pasquale Blasi; Craig Tyler

2001-08-03

50

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

NASA Astrophysics Data System (ADS)

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

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

2013-12-01

51

Human cancer cell line microRNAs associated with in vitro sensitivity to paclitaxel  

PubMed Central

Paclitaxel is a mainstay of treatment for many solid tumors, and frequently, clinical outcome is influenced by paclitaxel sensitivity. Despite this, our understanding of the molecular basis of paclitaxel response is incomplete. Recently, it has been shown that microRNAs (miRNAs) influence messenger RNA (mRNA) transcriptional control and can contribute to human carcinogenesis. In the present study, our objective was to identify miRNAs associated with cancer cell line response to paclitaxel and to evaluate these miRNAs as therapeutic targets to increase paclitaxel sensitivity. We measured the expression of 335 unique miRNAs in 40 human cancer cell lines selected from the NCI panel. We then integrated miRNA expression data with publicly available paclitaxel-sensitivity (GI50) data for each of the 40 cell lines to identify miRNAs associated with paclitaxel sensitivity. Ovarian cancer cell lines with differential miRNA expression and paclitaxel sensitivity were transiently transfected with miRNA precursors and inhibitors, and the effects on in vitro cell paclitaxel sensitivity were evaluated. Pearson’s correlation identified 2 miRNAs (miR-367 and miR-30a-5p) associated with the NCI40 cell line in vitro paclitaxel response (P<0.0003). Ovarian cancer cells were selected based on the association between paclitaxel sensitivity and miR-367/miR-30a-5p expression. Overexpression of miR-367 in the paclitaxel-sensitive cells [PA1; IC50, 1.69 nM, high miR-367 (2.997), low miR-30a-5p (?0.323)] further increased paclitaxel sensitivity, whereas miR-367 depletion decreased paclitaxel sensitivity. In contrast, overexpression and depletion of miR-30a-5p in the paclitaxel-resistant cells [OVCAR4; IC50, 17.8 nM, low miR-367 (?0.640), high miR-30a-5p (3.270)] decreased and increased paclitaxel sensitivity, respectively. We identified and successfully targeted miRNAs associated with human cancer cell line response to paclitaxel. Our strategy of integrating in vitro miRNA expression and drug sensitivity data may not only aid in the characterization of determinants of drug response but also in the identification of novel therapeutic targets to increase activity of existing therapeutics. PMID:24220856

CHEN, NING; CHON, HYE SOOK; XIONG, YIN; MARCHION, DOUGLAS C.; JUDSON, PATRICIA L.; HAKAM, ARDESHIR; GONZALEZ-BOSQUET, JESUS; PERMUTH-WEY, JENNIFER; WENHAM, ROBERT M.; APTE, SACHIN M.; CHENG, JIN Q.; SELLERS, THOMAS A.; LANCASTER, JOHNATHAN M.

2014-01-01

52

RNA-seq identifies determinants of oxaliplatin sensitivity in colorectal cancer cell lines  

PubMed Central

Oxaliplatin-based chemotherapy, such as FOLFOX, is the first-line therapy for advanced colorectal cancer (CRC) or metastatic CRC patients. However, the partial response of patients to these regimes and the severe peripheral neuropathy toxicity induced by oxaliplatin makes it urgent to figure out biomarkers for oxaliplatin sensitivity to select suitable patients who benefit from these treatments. In present work, 21 CRC cell lines with different sensitivities to oxaliplatin were applied to RNA-seq. The basal expression profiles of these cell lines were correlated to their response to oxaliplatin. Bioinformatics analysis suggested that expression of 58 genes was correlated, negatively or positively, to oxaliplatin response across the 21 CRC cell lines. These 58 genes were mainly enriched in small molecules biochemistry, Wnt/?-catenin signaling and EMT pathways. The latter two pathways were predicted to be activated in oxaliplatin-resistant CRC cell lines. Moreover, 15 genes were validated by qPCR that their expression levels were actually closely correlated to their response to oxaliplatin, in line with the biocomputation prediction. Taken together, our work might provide potential biomarkers for oxaliplatin sensitivity in CRC cell lines and therapeutic targets for combinational therapy with oxaliplatin. PMID:25120752

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

2014-01-01

53

Differentiating hidden sector dark matter from light WIMPs with Germanium detectors  

E-print Network

Light WIMP dark matter and hidden sector dark matter have been proposed to explain the DAMA, CoGeNT and CRESST-II data. Both of these approaches feature spin independent elastic scattering of dark matter particles on nuclei. Light WIMP dark matter invokes a single particle species which interacts with ordinary matter via contact interactions. By contrast hidden sector dark matter is typically multi-component and is assumed to interact via the exchange of a massless mediator. Such hidden sector dark matter thereby predicts a sharply rising nuclear recoil spectrum, $dR/dE_R \\sim 1/E_R^2$ due to this dynamics, while WIMP dark matter predicts a spectrum which depends sensitively on the WIMP mass, $m_\\chi$. We compare and contrast these two very different possible origins of the CoGeNT low energy excess. In the relevant energy range, the recoil spectra predicted by these two theories approximately agree provided $m_\\chi \\simeq 8.5$ GeV - close to the value favoured from fits to the CoGeNT and CDMS low energy data. Forthcoming experiments including C-4, CDEX, and the MAJORANA demonstrator, are expected to provide reasonably precise measurements of the low energy Germanium recoil spectrum, including the annual modulation amplitude, which should differentiate between these two theoretical possibilities.

R. Foot

2012-11-14

54

Membrane transport changes in an adriamycin-resistant murine leukemia cell line and in its sensitive parental cell line  

Microsoft Academic Search

Multidrug resistance in cancer chemotherapy occurs when cells develop resistance towards structurally and functionally unrelated drugs. It is speculated that alteration of some fundamental process(es) in the cells leads to the development of multidrug resistance. The sodium pump activity of murine leukemia cell lines P388\\/S (sensitive) and P388\\/ADR (resistant) was measured and found to be different in the two cell

Ratna Bose; Hing-Yat Peter Lain

1988-01-01

55

Selective breeding of two rat lines differing in sensitivity to GHB and baclofen  

Microsoft Academic Search

Two Wistar-derived rat lines, one sensitive (GHB-S) and the other resistant (GHB-R) to the anesthetic effect of ?-hydroxybutyric acid (GHB), have been selectively bred. GHB-S and GHB-R rats were also sensitive and resistant, respectively, to the anesthetic effect of baclofen, the prototype GABAB receptor agonist, suggesting that they may be useful to elucidate not only the role of endogenous GHB

Giancarlo Colombo; Carla Lobina; Roberta Agabio; Giuliana Brunetti; Giacomo Diaz; Martino Littera; Samuele Melis; Marialaura Pani; Roberta Reali; Salvatore Serra; Giovanni Vacca; Mauro A. M Carai; Gian Luigi Gessa

2001-01-01

56

Ethacrynic Acid and Piriprost as Enhancers of Cytotoxicity in Drug Resistant and Sensitive Cell Lines1  

Microsoft Academic Search

Ethacrynic acid and piriprost (6,9-deepoxy-6,9-(phenylimino)-A''8- prostaglandin I,) have been shown to potentiate the cytotoxic activity of chlorambucil in rat and human tumor cell lines. Walker 256 rat breast carcinoma cells (WS), with acquired resistance to nitrogen mustards (WR), and two human colon carcinoma cell lines, HT 29 and BE, were sensitized to chlorambucil when either ethacrynic acid or piriprost was

Kenneth D. Tew; Annette M. Bomber; Sandra J. Hoffman

57

Improved constraints on wimps from the international germanium experiment IGEX  

Microsoft Academic Search

One IGEX 76Ge double-beta decay detector is currently operating in the Canfranc Underground Laboratory in a search for dark matter WIMPs, through the Ge nuclear recoil produced by the WIMP elastic scattering. A new exclusion plot, ?(m), has been derived for WIMP-nucleon spin-independent interactions. To obtain this result, 40 days of data from the IGEX detector (energy threshold Ethr?4 keV), recently collected,

A. Morales; C. E. Aalseth; F. T. Avignone III; R. L. Brodzinski; S. Cebrián; E. Garc??a; I. G. Irastorza; I. V. Kirpichnikov; A. A. Klimenko; H. S. Miley; J. Morales; A. Ortiz de Solórzano; S. B. Osetrov; V. S. Pogosov; J. Puimedón; J. H. Reeves; M. L. Sarsa; A. A. Smolnikov; A. G. Tamanyan; A. A. Vasenko; S. I. Vasiliev; J. A. Villar

2002-01-01

58

Low mass stellar evolution with WIMP capture and annihilation  

E-print Network

Recent work has indicated that WIMP annihilation in stellar cores has the potential to contribute significantly to a star's total energy production. We report on progress in simulating the effects of WIMP capture and annihilation upon stellar structure and evolution near supermassive black holes, using the new DarkStars code. Preliminary results indicate that low-mass stars are the most influenced by WIMP annihilation, which could have consequences for upcoming observational programs.

Pat Scott; Joakim Edsjö; Malcolm Fairbairn

2007-11-07

59

BBN And The CMB Constrain Light, Electromagnetically Coupled WIMPs  

E-print Network

(Abridged) In the presence of a light WIMP (scalar WIMPs that couple to electrons, positrons, and photons. In a separate paper this analysis is repeated for WIMPs that couple only to the standard model neutrinos, and constraints for the two cases are contrasted. Without a light WIMP but allowing for equivalent neutrinos, the combined BBN and CMB constraints favor N_eff = 3.46 +/- 0.17, Omega_B h^2 = 0.0224 +/- 0.0003, and Delta N_nu = 0.40 +/- 0.17. In this case, standard BBN (Delta N_nu = 0) is disfavored at ~98% confidence, and the presence of one sterile neutrino (Delta N_nu = 1) is disfavored at > 99% confidence. Allowing a light WIMP and Delta N_nu equivalent neutrinos together, the combined BBN and CMB data provide lower limits to the WIMP masses (> 0.5 - 5 MeV) that depend on the nature of the WIMP, favor m_chi ~8 MeV slightly over no WIMP, and loosen constraints on equivalent neutrinos, Delta N_nu = 0.65+0.46-0.35. While Delta N_nu = 0 is still disfavored at ~95% confidence with a light WIMP, Delta N_nu = 1 is now allowed.

Kenneth M. Nollett; Gary Steigman

2014-04-04

60

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

Microsoft Academic Search

We demonstrate a compact in-line interferometer for direction-sensitive displacement measurement by optical feedback detection with a semiconductor laser (SL) light source. Two reflected beams from a semitransparent reference mirror and a reflecting test object interfere in the SL medium, causing a variation in its output power. The reference mirror is located between the SL output facet and the test object.

Alvarado Tarun; Julius Jecong; Caesar Saloma

2005-01-01

61

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

SciTech Connect

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.

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

2010-05-28

62

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

PubMed

Clinicians successfully utilize high uptake of radiolabeled glucose via PET scanning to localize metastases in melanoma patients. To take advantage of this altered metabolome, 3-bromopyruvate (BrPA) was used to overcome the notorious resistance of melanoma to cell death. Using four melanoma cell lines, BrPA triggered caspase independent necrosis in two lines, whilst the other two lines were resistant to killing. Mechanistically, sensitive cells differed from resistant cells by; constitutively lower levels of glutathione, reduction of glutathione by BrPA only in sensitive cells; increased superoxide anion reactive oxygen species, loss of outer mitochondrial membrane permeability, and rapid ATP depletion. Sensitive cell killing was blocked by N-acetylcysteine or glutathione. When glutathione levels were reduced in resistant cell lines, they became sensitive to killing by BrPA. Taken together, these results identify a metabolic-based Achilles' heel in melanoma cells to be exploited by use of BrPA. Future pre-clinical and clinical trials are warranted to translate these results into improved patient care for individuals suffering from metastatic melanoma. PMID:20430010

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

2010-05-28

63

SENSITIVE AND RESISTANT LINES OF SNAPBEAN (PHASEOLUS VULGARIS L.) II. DAILY WATER USE.  

Technology Transfer Automated Retrieval System (TEKTRAN)

Experiments were conducted to determine the relative growth, yield and selected physiological responses of ozone resistant (R331) and sensitive (S156) lines of snapbean Phaseolus vulgaris to a range of chronic Ozone exposures. Plants were grown in mini-greenhouses in the field which allow 90% of ful...

64

Sensitivity studies of tapped delay line filters applied to a passive sonar system†  

Microsoft Academic Search

Performance sensitivity of a tapped delay line filter is studied by varying system parameters such as tap coefficients, tap spacings, and the spectra and bandwidth of signal, noise, and directional noises. The optimum filter is designed both with and without the directional noise by using mean-square-error criterion for the case of single and multiple hydrophones. After prescribing the spectra of

M. YILDIZ

1970-01-01

65

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

PubMed

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

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

2014-01-01

66

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

PubMed Central

Blocking oncogenic signaling induced by the BRAFV600E mutation is a promising approach for melanoma treatment. We tested the anti-tumor effects of a specific inhibitor of Raf protein kinases, PLX4032/RG7204, in melanoma cell lines. PLX4032 decreased signaling through the MAPK pathway only in cell lines with the BRAFV600E mutation. Seven out of 10 BRAFV600E mutant cell lines displayed sensitivity based on cell viability assays and three were resistant at concentrations up to 10 ?M. Among the sensitive cell lines, four were highly sensitive with IC50 values below 1 ?M, and three were moderately sensitive with IC50 values between 1 and 10 ?M. There was evidence of MAPK pathway inhibition and cell cycle arrest in both sensitive and resistant cell lines. Genomic analysis by sequencing, genotyping of close to 400 oncogeninc mutations by mass spectrometry, and SNP arrays demonstrated no major differences in BRAF locus amplification or in other oncogenic events between sensitive and resistant cell lines. However, metabolic tracer uptake studies demonstrated that sensitive cell lines had a more profound inhibition of FDG uptake upon exposure to PLX4032 than resistant cell lines. In conclusion, BRAFV600E mutant melanoma cell lines displayed a range of sensitivities to PLX4032 and metabolic imaging using PET probes can be used to assess sensitivity. PMID:20406486

2010-01-01

67

Is radiosensitive cell line cross-sensitive to heat?: Effect of heat on two rat yolk sac tumor cell lines with different radiosensitivity  

Microsoft Academic Search

The differences between two rat yolk sac tumor cell lines, which are of the same origin but differ in their response to irradiation, in thermal sensitivity and development of thermotolerance were investigated. A radiosensitive cell line NMT-1 is consistently less heat sensitive than the radioresistant cell line NMT-1R. The thermotolerances in NMT-1 and in NMT-1R preheated at 43°C for 30

Norio Mitsuhashi; Mohammad Shahidul Islam; Hideyuki Sakurai; Takeo Takahashi; Osamu Murata; Katsuya Maebayashi; Miwako Nozaki; Tetsuo Akimoto; Hiroyuki Muramatsu; Hideo Niibe

1999-01-01

68

BBN and the CMB constrain light, electromagnetically coupled WIMPs  

NASA Astrophysics Data System (ADS)

In the presence of a light weakly interacting massive particle (WIMP; m??30 MeV), there are degeneracies among the nature of the WIMP (fermion or boson), its couplings to the standard-model particles (electromagnetic or to neutrinos only), the WIMP mass m?, and the number of equivalent neutrinos beyond the standard model ?N? (including possible sterile neutrinos). These degeneracies cannot be broken by the cosmic microwave background (CMB) constraint on the effective number of neutrinos, Neff. However, big bang nucleosynthesis (BBN) is affected by the presence of a light WIMP and equivalent neutrinos, so the combination of BBN and CMB constraints can help to break some of these degeneracies. Here, the BBN predictions for the primordial abundances of deuterium and He4 (along with He3 and Li7) in the presence of a light WIMP and equivalent neutrinos are explored, and the most recent estimates of their observationally determined relic abundances are used to limit the light-WIMP mass, the number of equivalent neutrinos, and the present Universe baryon density (?Bh2). These constraints are explored here for Majorana and Dirac fermion WIMPs, as well as for real and complex scalar WIMPs that couple to electrons, positrons, and photons. In a separate paper, this analysis is repeated for WIMPs that couple only to the standard-model neutrinos, and the constraints for the two cases are contrasted. In the absence of a light WIMP, but allowing for ?N? equivalent neutrinos, the combined BBN and CMB constraints favor Neff=3.46±0.17, ?Bh2=0.0224±0.0003, and ?N?=0.40±0.17 (all at a 68% C.L.). In this case, standard BBN (?N?=0) is disfavored at ˜98% confidence, and the presence of one sterile neutrino (?N?=1) is disfavored at ?99% confidence. Allowing for a light WIMP and ?N? equivalent neutrinos together, the combined BBN and CMB data provide lower limits to the WIMP masses (m??0.5-5 MeV) that depend on the nature of the WIMP, favor m?˜8 MeV (with small variations depending on the WIMP type) slightly over standard BBN, and loosen the constraints on the allowed number of equivalent neutrinos, ?N?=0.65-0.35+0.46. As a result, while ?N?=0 is still disfavored at ˜95% confidence when there is a light WIMP, ?N?=1 is now allowed.

Nollett, Kenneth M.; Steigman, Gary

2014-04-01

69

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

PubMed Central

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

2013-01-01

70

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

PubMed Central

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

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

2014-01-01

71

Metformin inhibits growth and sensitizes osteosarcoma cell lines to cisplatin through cell cycle modulation.  

PubMed

Osteosarcoma (OS) is the most common cancer that affects the bone and appears to be resistant to several chemotherapeutic drugs. The aim of the present study was to verify whether the combination of metformin and cisplatin has an effect on OS cell lines. OS cell lines U2OS, 143B and MG63 were treated with metformin, cisplatin or a combination of both drugs. Viability, apoptosis and cell cycle were evaluated to characterize the effects of the treatments. Western blot analyses were used to evaluate protein expression. All OS cell lines were found to be sensitive to metformin with different values of IC50, showing a slowdown of cell cycle associated or not with apoptosis. In particular, metformin was able to sensitize cells to cisplatin, to which all OS cell lines were resistant, demonstrating a synergistic effect in the combined treatment of the two drugs. The data obtained may have clinical relevance for novel therapeutic strategies for the treatment of OS; metformin inhibits tumor cell growth and amplifies the effect of cisplatin. PMID:24253938

Quattrini, Irene; Conti, Amalia; Pazzaglia, Laura; Novello, Chiara; Ferrari, Stefano; Picci, Piero; Benassi, Maria Serena

2014-01-01

72

Alterations in root proteome of salt-sensitive and tolerant barley lines under salt stress conditions.  

PubMed

Salinity is one of the most important abiotic stresses causing a significant reduction of crop plants yield. To gain a better understanding of salinity tolerance mechanisms in barley (Hordeum vulgare), we investigated the changes in root proteome of salt-sensitive (DH14) and tolerant (DH187) lines in response to salt-stress. The seeds of both barley lines were germinating in water or in 100mM NaCl for 6 days. The root proteins were separated by two-dimensional gel electrophoresis. To identify proteins regulated in response to salt stress, MALDI-TOF/TOF mass spectrometry was applied. It was demonstrated that the sensitive and tolerant barley lines respond differently to salt stress. Some of the identified proteins are well-documented as markers of salinity resistance, but several proteins have not been detected in response to salt stress earlier, although they are known to be associated with other abiotic stresses. The most significant differences concerned the proteins that are involved in signal transduction (annexin, translationally-controlled tumor protein homolog, lipoxygenases), detoxification (osmotin, vacuolar ATP-ase), protein folding processes (protein disulfide isomerase) and cell wall metabolism (UDP-glucuronic acid decarboxylase, ?-d-glucan exohydrolase, UDP-glucose pyrophosphorylase). The results suggest that the enhanced salinity tolerance of DH187 line results mainly from an increased activity of signal transduction mechanisms eventually leading to the accumulation of stress protective proteins and cell wall structure changes. PMID:25462980

Mostek, Agnieszka; Börner, Andreas; Badowiec, Anna; Weidner, Stanis?aw

2015-02-01

73

New class of biological detectors for WIMPs  

NASA Astrophysics Data System (ADS)

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.

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

74

Detecting Dark Matter annihilation lines with Fermi  

SciTech Connect

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

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

2009-05-15

75

Annihilation Lines from Dark Matter with the Fermi-LAT  

SciTech Connect

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

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

2010-06-23

76

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

NASA Astrophysics Data System (ADS)

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

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

2014-03-01

77

CMB Constraints On The Thermal WIMP Annihilation Cross Section  

E-print Network

A thermal relic, often referred to as a weakly interacting massive particle (WIMP),is a particle produced during the early evolution of the Universe whose relic abundance (e.g., at present) depends only on its mass and its thermally averaged annihilation cross section (annihilation rate factor) sigma*v_ann. Late time WIMP annihilation has the potential to affect the cosmic microwave background (CMB) power spectrum. Current observational constraints on the absence of such effects provide bounds on the mass and the annihilation cross section of relic particles that may, but need not be dark matter candidates. For a WIMP that is a dark matter candidate, the CMB constraint sets an upper bound to the annihilation cross section, leading to a lower bound to their mass that depends on whether or not the WIMP is its own antiparticle. For a self-conjugate WIMP, m_min = 50f GeV, where f is an electromagnetic energy efficiency factor. For a non self-conjugate WIMP, the minimum mass is a factor of two larger. For a WIMP t...

Steigman, Gary

2015-01-01

78

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

E-print Network

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, PRD 89 064023], a Bayesian model selection approach was used to derive line-robust detection statistics for CW signals, generalising both the F-statistic and the F-statistic consistency veto technique and yielding improved performance in line-affected data. Here we investigate a generalisation 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.

David Keitel; Reinhard Prix

2015-01-16

79

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

NASA Astrophysics Data System (ADS)

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.

Keitel, David; Prix, Reinhard

2015-02-01

80

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

E-print Network

Dark Matter experiments are recently focusing their detection techniques in low-mass WIMPs, which requires the use of light elements and low energy threshold. In this context, we present the TREX-DM experiment, a low background Micromegas-based TPC for low-mass WIMP detection. Its main goal is the operation of an active detection mass $\\sim$0.300 kg, with an energy threshold below 0.4 keVee and fully built with previously selected radiopure materials. This article describes the actual setup, the first results of the comissioning in Ar+2\\%iC$_4$H$_{10}$ at 1.2 bar and the future updates for a possible physics run at the Canfranc Underground Laboratory in 2016. A first background model is also presented, based on Geant4 simulations and a muon/electron discrimination method. In a conservative scenario, TREX-DM could be sensitive to DAMA/LIBRA and other hints of positive WIMPs signals, with some space for improvement with a neutron/electron discrimination method or the use of other light gases.

F. J. Iguaz; J. G. Garza; F. Aznar; J. F. Castel; S. Cebrian; T. Dafni; J. A. Garcia; H. Gomez; D. Gonzalez-Diaz; I. G. Irastorza; A. Lagraba; G. Luzon; A. Peiro; A. Rodriguez

2015-03-24

81

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

E-print Network

Dark Matter experiments are recently focusing their detection techniques in low-mass WIMPs, which requires the use of light elements and low energy threshold. In this context, we present the TREX-DM experiment, a low background Micromegas-based TPC for low-mass WIMP detection. Its main goal is the operation of an active detection mass $\\sim$0.300 kg, with an energy threshold below 0.4 keVee and fully built with previously selected radiopure materials. This article describes the actual setup, the first results of the comissioning in Ar+2\\%iC$_4$H$_{10}$ at 1.2 bar and the future updates for a possible physics run at the Canfranc Underground Laboratory in 2016. A first background model is also presented, based on Geant4 simulations and a muon/electron discrimination method. In a conservative scenario, TREX-DM could be sensitive to DAMA/LIBRA and other hints of positive WIMPs signals, with some space for improvement with a neutron/electron discrimination method or the use of other light gases.

Iguaz, F J; Aznar, F; Castel, J F; Cebrian, S; Dafni, T; Garcia, J A; Gomez, H; Gonzalez-Diaz, D; Irastorza, I G; Lagraba, A; Luzon, G; Peiro, A; Rodriguez, A

2015-01-01

82

Nuclear structure aspects of spin-independent WIMP scattering off xenon  

E-print Network

We study the structure factors for spin-independent WIMP scattering off xenon based on state-of-the-art large-scale shell-model calculations, which are shown to yield a good spectroscopic description of all experimentally relevant isotopes. Our results are based on the leading scalar one-body currents only. At this level and for the momentum transfers relevant to direct dark matter detection, the structure factors are in very good agreement with the phenomenological Helm form factors used to give experimental limits for WIMP-nucleon cross sections. In contrast to spin-dependent WIMP scattering, the spin-independent channel, at the one-body level, is less sensitive to nuclear structure details. In addition, we explicitly show that the structure factors for inelastic scattering are suppressed by ~ 10^{-4} compared to the coherent elastic scattering response. This implies that the detection of inelastic scattering will be able to discriminate clearly between spin-independent and spin-dependent scattering. Finall...

Vietze, L; Menéndez, J; Haxton, W C; Schwenk, A

2014-01-01

83

Nuclear structure aspects of spin-independent WIMP scattering off xenon  

E-print Network

We study the structure factors for spin-independent WIMP scattering off xenon based on state-of-the-art large-scale shell-model calculations, which are shown to yield a good spectroscopic description of all experimentally relevant isotopes. Our results are based on the leading scalar one-body currents only. At this level and for the momentum transfers relevant to direct dark matter detection, the structure factors are in very good agreement with the phenomenological Helm form factors used to give experimental limits for WIMP-nucleon cross sections. In contrast to spin-dependent WIMP scattering, the spin-independent channel, at the one-body level, is less sensitive to nuclear structure details. In addition, we explicitly show that the structure factors for inelastic scattering are suppressed by ~ 10^{-4} compared to the coherent elastic scattering response. This implies that the detection of inelastic scattering will be able to discriminate clearly between spin-independent and spin-dependent scattering. Finally, we provide fits for all calculated structure factors.

L. Vietze; P. Klos; J. Menéndez; W. C. Haxton; A. Schwenk

2015-02-19

84

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

PubMed Central

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

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

1999-01-01

85

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

NASA Astrophysics Data System (ADS)

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 ?=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.

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

2009-06-01

86

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

PubMed

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

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

2014-11-01

87

Drug sensitivity patterns of HHV8 carrying body cavity lymphoma cell lines  

PubMed Central

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

2011-01-01

88

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

NASA Astrophysics Data System (ADS)

We have developed an image intensifier tube with delay-line anode for time- and position-sensitive detection of single photons. By combining two well-approved techniques, the helical-wire delay-line readout for single particle detection and the production capability for large-format sealed photo-multiplier tubes with microchannel-plates, it is possible to build single photon sensors with 40 and 75 mm diameter. Applications are found wherever precise time tagging (< 1 ns) in combination with high position resolution (1000×1000 pixel) for single photon detection is of equal importance. Due to the low background this technique is especially suited for imaging at very low light intensity or for "3d" imaging and timing applications such as fluorescence microscopy or coincident photon detection experiments. We present the performance of prototype detectors with 75 mm low-noise S-20 and 40 mm S-20 red-enhanced photo-cathodes.

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

2007-10-01

89

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

SciTech Connect

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

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

2008-01-17

90

The magnetic sensitivity of the Stokes I Profile of the 15260 A line of Mn I  

SciTech Connect

The near-IR line of Mn I at 15262.7 A 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.

Asensio Ramos, A. [Instituto de AstrofIsica de Canarias, 38205, La Laguna, Tenerife (Spain)], E-mail: aasensio@iac.es

2009-01-01

91

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

SciTech Connect

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.

Emter, Roger [Givaudan Schweiz AG, Ueberlandstrasse 138, CH-8600 Duebendorf (Switzerland); Ellis, Graham [Givaudan Schweiz AG, 5 Rue de la Parfumerie, CH-1214 Vernier (Switzerland); Natsch, Andreas, E-mail: andreas.natsch@givaudan.co [Givaudan Schweiz AG, Ueberlandstrasse 138, CH-8600 Duebendorf (Switzerland)

2010-06-15

92

Limits on the spin-dependent WIMP-nucleon cross sections from the first science run of the ZEPLIN-III experiment.  

PubMed

We present new experimental constraints on the WIMP-nucleon spin-dependent elastic cross sections using data from the first science run of ZEPLIN-III, a two-phase xenon experiment searching for galactic dark matter weakly interacting massive particles based at the Boulby mine. Analysis of approximately 450 kg x days fiducial exposure allow us to place a 90%-confidence upper limit on the pure WIMP-neutron cross section of sigma(n)=1.9x10(-2) pb at 55 GeV/c(2) WIMP mass. Recent calculations of the nuclear spin structure based on the Bonn charge-dependent nucleon-nucleon potential were used for the odd-neutron isotopes 129Xe and 131Xe. These indicate that the sensitivity of xenon targets to the spin-dependent WIMP-proton interaction could be much lower than implied by previous calculations, whereas the WIMP-neutron sensitivity is impaired only by a factor of approximately 2. PMID:19905617

Lebedenko, V N; Araújo, H M; Barnes, E J; Bewick, A; Cashmore, R; Chepel, V; Currie, A; Davidge, D; Dawson, J; Durkin, T; Edwards, B; Ghag, C; Horn, M; Howard, A S; Hughes, A J; Jones, W G; Joshi, M; Kalmus, G E; Kovalenko, A G; Lindote, A; Liubarsky, I; Lopes, M I; Lüscher, R; Lyons, K; Majewski, P; Murphy, A St J; Neves, F; da Cunha, J Pinto; Preece, R; Quenby, J J; Scovell, P R; Silva, C; Solovov, V N; Smith, N J T; Smith, P F; Stekhanov, V N; Sumner, T J; Thorne, C; Walker, R J

2009-10-01

93

Development of Gaseous Tracking Devices for the Search of WIMPs  

E-print Network

The Time Projection Chamber (TPC) has been recognized as a potentially powerful detector for the search of WIMPs by measuring the directions of nuclear recoils, in which the most convincing signature of WIMPs, caused by the Earth's motion around the Galaxy, appears. We report on the first results of a performance study of the neutron exposure of our prototype micro-TPC with Ar-C$_2$H$_6$ (90:10) and CF$_4$ gas of 150 Torr.

H. Sekiya; K. Hattori; S. Kabuki; H. Kubo; K. Miuchi; T. Nagayoshi; H. Nishimura; Y. Okada; R. Orito; A. Takada; A. Takeda; T. Tanimori; K. Ueno

2006-02-14

94

Development of Gaseous Tracking Devices for the Search of WIMPs  

E-print Network

The Time Projection Chamber (TPC) has been recognized as a potentially powerful detector for the search of WIMPs by measuring the directions of nuclear recoils, in which the most convincing signature of WIMPs, caused by the Earth's motion around the Galaxy, appears. We report on the first results of a performance study of the neutron exposure of our prototype micro-TPC with Ar-C$_2$H$_6$ (90:10) and CF$_4$ gas of 150 Torr.

Sekiya, H; Kabuki, S; Kubo, H; Miuchi, K; Nagayoshi, T; Nishimura, H; Okada, Y; Orito, R; Takada, A; Takeda, A; Tanimori, T; Ueno, K

2006-01-01

95

JF-305, a pancreatic cancer cell line is highly sensitive to the PARP inhibitor olaparib  

PubMed Central

Poly(ADP-ribose) polymerase-1 (PARP-1) is a DNA nick sensor involved in the base excision repair (BER) pathway. Olaparib, a PARP inhibitor, has demonstrated antitumor activity in homologous recombination (HR)-deficient cancers. To extend this specific therapy to other types of carcinomas, a panel of 11 different cancer cells were screened in the present study. JF-305, a pancreatic cancer cell line of Chinese origin, demonstrated sensitivity to the PARP inhibitor 6(5H)-phenanthridinone. In the present study, 3 ?M olaparib conferred a cell survival rate of 25% following four days of treatment. The colony formation efficiency was 83% at 10 nM, and dropped to 12% at 1 ?M following seven days of treatment. Furthermore, olaparib induced cell cycle arrest in the S and G2/M phases prior to the initiation of apoptosis. Although the incidence of double-strand breaks (DSBs) was increased in the olaparib-treated JF-305 cells, the RAD51 foci were well formed at the sites of ?-H2AX recruitment, indicating an activated HR mechanism. Furthermore, tumor growth was reduced by 49.8% following 22 days of consecutive administration of 10 mg/kg olaparib in the JF-305 xenograft mouse model. In summary, the JF-305 cell line was sensitive to olaparib and provided a prospective model for the preclinical assessment of PARP inhibitors in the therapy of pancreatic cancer. PMID:25621047

YANG, XUELI; NDAWULA, CHARLES; ZHOU, HAIYAN; GONG, XIAOHAI; JIN, JIAN

2015-01-01

96

Heavy WIMP through Higgs portal at the LHC  

NASA Astrophysics Data System (ADS)

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

Endo, Motoi; Takaesu, Yoshitaro

2015-04-01

97

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

PubMed

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

Overstreet, David H; Wegener, Gregers

2013-01-01

98

A Novel Delay-Line Anode Design for Position and Time Sensitive Read-Out of MCP-Based Detectors  

NASA Astrophysics Data System (ADS)

We have developed a novel delay-line anode design based on L/2 shifted maeander-lines for the readout of open-faced and sealed MCP-based detectors. In combination with the sealed detector (image intensifier) we are able to provide position and time sensitive single photon detection from near UV to near IR.

Spillmann, U.; Jagutzki, O.; Spielberger, L.; Dörner, R.; Mergel, V.; Ullmann-Pfleger, K.; Schmidt-Böcking, H.

99

BBN and the CMB constrain neutrino coupled light WIMPs  

NASA Astrophysics Data System (ADS)

In the presence of a light weakly interacting massive particle (WIMP) with mass m??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 m?, and the number of equivalent (additional) neutrinos, ? N?. 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 m?, ? N?, 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 (?Bh2 ). Allowing for a neutrino coupled light WIMP and ? N? 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 m??35 MeV , equivalent to no light WIMP at all. The analysis here excludes all neutrino coupled WIMPs with masses below a few MeV, with specific limits varying from 4 to 9 MeV depending on the nature of the WIMP. In the absence of a light WIMP (either EM or neutrino coupled), BBN alone prefers ? N? =0.50 ±0.23 , favoring neither the absence of equivalent neutrinos (? N?=0 ), nor the presence of a fully thermalized sterile neutrino (? N?=1 ). This result is consistent with the CMB constraint, Neff=3.30 ±0.27 [1], constraining "new physics" between BBN and recombination. Combining the BBN and CMB constraints gives ? N? =0.35 ±0.16 and Neff=3.40 ±0.16 . As a result, while BBN and the CMB combined require ? N? ?0 at ˜98 % confidence, they disfavor ? N? ?1 at >99 % confidence. Adding the possibility of a neutrino-coupled light WIMP extends the allowed range slightly downward for ? N? and slightly upward for Neff simultaneously, while leaving the best-fit values unchanged.

Nollett, Kenneth M.; Steigman, Gary

2015-04-01

100

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

SciTech Connect

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

Tarun, Alvarado; Jecong, Julius; Saloma, Caesar

2005-12-01

101

Nonlinear Quantitative Radiation Sensitivity Prediction Model Based on NCI-60 Cancer Cell Lines  

PubMed Central

We proposed a nonlinear model to perform a novel quantitative radiation sensitivity prediction. We used the NCI-60 panel, which consists of nine different cancer types, as the platform to train our model. Important radiation therapy (RT) related genes were selected by significance analysis of microarrays (SAM). Orthogonal latent variables (LVs) were then extracted by the partial least squares (PLS) method as the new compressive input variables. Finally, support vector machine (SVM) regression model was trained with these LVs to predict the SF2 (the surviving fraction of cells after a radiation dose of 2?Gy ?-ray) values of the cell lines. Comparison with the published results showed significant improvement of the new method in various ways: (a) reducing the root mean square error (RMSE) of the radiation sensitivity prediction model from 0.20 to 0.011; and (b) improving prediction accuracy from 62% to 91%. To test the predictive performance of the gene signature, three different types of cancer patient datasets were used. Survival analysis across these different types of cancer patients strongly confirmed the clinical potential utility of the signature genes as a general prognosis platform. The gene regulatory network analysis identified six hub genes that are involved in canonical cancer pathways. PMID:25032244

Zhang, Chunying; Girard, Luc; Das, Amit; Chen, Sun; Zheng, Guangqiang

2014-01-01

102

Decreased in vivo ?2 adrenoceptor binding in the Flinders Sensitive Line rat model of depression.  

PubMed

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 ?2 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 ?2 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

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

2015-04-01

103

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

SciTech Connect

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.

Ageberg, Malin, E-mail: Malin.Ageberg@med.lu.se [Division of Hematology and Transfusion Medicine, Lund University, BMC C14, 221 84 Lund (Sweden)] [Division of Hematology and Transfusion Medicine, Lund University, BMC C14, 221 84 Lund (Sweden); Rydstroem, Karin, E-mail: Karin.Rydstom@skane.se [Department of Oncology, Skanes University Hospital, Allmaenmott, Onkologiska kliniken i Lund, 221 85 Lund (Sweden)] [Department of Oncology, Skanes University Hospital, Allmaenmott, Onkologiska kliniken i Lund, 221 85 Lund (Sweden); Linden, Ola, E-mail: Ola.Linden@skane.se [Department of Oncology, Skanes University Hospital, Allmaenmott, Onkologiska kliniken i Lund, 221 85 Lund (Sweden)] [Department of Oncology, Skanes University Hospital, Allmaenmott, Onkologiska kliniken i Lund, 221 85 Lund (Sweden); Linderoth, Johan, E-mail: Johan.Linderoth@skane.se [Department of Oncology, Skanes University Hospital, Allmaenmott, Onkologiska kliniken i Lund, 221 85 Lund (Sweden)] [Department of Oncology, Skanes University Hospital, Allmaenmott, Onkologiska kliniken i Lund, 221 85 Lund (Sweden); Jerkeman, Mats, E-mail: Mats.Jerkeman@skane.se [Department of Oncology, Skanes University Hospital, Allmaenmott, Onkologiska kliniken i Lund, 221 85 Lund (Sweden)] [Department of Oncology, Skanes University Hospital, Allmaenmott, Onkologiska kliniken i Lund, 221 85 Lund (Sweden); Drott, Kristina, E-mail: Kristina.Drott@med.lu.se [Division of Hematology and Transfusion Medicine, Lund University, BMC C14, 221 84 Lund (Sweden)] [Division of Hematology and Transfusion Medicine, Lund University, BMC C14, 221 84 Lund (Sweden)

2011-05-01

104

Proteomics study of changes in soybean lines resistant and sensitive to Phytophthora sojae  

PubMed Central

Background Phytophthora sojae causes soybean root and stem rot, resulting in an annual loss of 1-2 billion US dollars in soybean production worldwide. A proteomic technique was used to determine the effects on soybean hypocotyls of infection with P. sojae. Results In the present study, 46 differentially expressed proteins were identified in soybean hypocotyls infected with P. sojae, using two-dimensional electrophoresis and matrix-assisted laser desorption/ionization tandem time of flight (MALDI-TOF/TOF). The expression levels of 26 proteins were significantly affected at various time points in the tolerant soybean line, Yudou25, (12 up-regulated and 14 down-regulated). In contrast, in the sensitive soybean line, NG6255, only 20 proteins were significantly affected (11 up-regulated and 9 down-regulated). Among these proteins, 26% were related to energy regulation, 15% to protein destination and storage, 11% to defense against disease, 11% to metabolism, 9% to protein synthesis, 4% to secondary metabolism, and 24% were of unknown function. Conclusion Our study provides important information on the use of proteomic methods for studying protein regulation during plant-oomycete interactions. PMID:21899734

2011-01-01

105

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

NASA Technical Reports Server (NTRS)

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.

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

2001-01-01

106

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

PubMed Central

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

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

2009-01-01

107

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

NASA Astrophysics Data System (ADS)

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

Beltran, Berta; Picasso Collaboration

2010-01-01

108

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

PubMed Central

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

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

2014-01-01

109

Sensitivities of human glioma cell lines to interferons and double-stranded RNAs individually and in synergistic combinations  

Microsoft Academic Search

The antiproliferative effects of human interferons (IFNs) and double-stranded RNAs (dsRNAs) were studied in five human glioma cell lines. Dose response curves were generated over a 72 hour treatment period. The concentration of interferon or double-stranded RNA necessary to produce a 50% antiproliferative response (GI50) was calculated by linear regression analysis. Two cell lines were more sensitive to IFN-ß than

Robbin S. Dick; Howard R. Hubbell

1987-01-01

110

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

PubMed

We present here the first high resolution melt (HRM) assay to quantitatively analyze differences in murine DNA methylation levels utilizing CpG methylation of Long Interspersed Elements-1 (LINE1 or L1). By calculating the integral difference in melt temperature between samples and a methylated control, and biasing PCR primers for unmethylated CpGs, the assay demonstrates enhanced sensitivity to detect changes in methylation in a cell line treated with low doses of 5-aza-2'-deoxycytidine (5-aza). The L1 assay was confirmed to be a good marker of changes in DNA methylation of L1 elements at multiple regions across the genome when compared with total 5-methyl-cytosine content, measured by Liquid Chromatography-Mass Spectrometry (LC-MS). The assay design was also used to detect changes in methylation at other murine repeat elements (B1 and Intracisternal-A-particle Long-terminal Repeat elements). Pyrosequencing analysis revealed that L1 methylation changes were non-uniform across the CpGs within the L1-HRM target region, demonstrating that the L1 assay can detect small changes in CpG methylation among a large pool of heterogeneously methylated DNA templates. Application of the assay to various tissues from Balb/c and CBA mice, including previously unreported peripheral blood (PB), revealed a tissue hierarchy (from hypermethylated to hypomethylated) of PB > kidney > liver > prostate > spleen. CBA mice demonstrated overall greater methylation than Balb/c mice, and male mice demonstrated higher tissue methylation compared with female mice in both strains. Changes in DNA methylation have been reported to be an early and fundamental event in the pathogenesis of many human diseases, including cancer. Mouse studies designed to identify modulators of DNA methylation, the critical doses, relevant time points and the tissues affected are limited by the low throughput nature and exorbitant cost of many DNA methylation assays. The L1 assay provides a high throughput, inexpensive and sensitive screening tool for identifying and characterizing DNA methylation changes to L1 elements at multiple regions across the genome. PMID:22274612

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

2012-01-01

111

Methoxyamine sensitizes the resistant glioblastoma T98G cell line to the alkylating agent temozolomide.  

PubMed

Chemoresistance represents a major obstacle to successful treatment for malignant glioma with temozolomide. N (7)-methyl-G and N (3)-methyl-A adducts comprise more than 80 % of DNA lesions induced by temozolomide and are processed by the base excision repair, suggesting that the cellular resistance could be caused, in part, by this efficient repair pathway, although few studies have focused on this subject. The aim of this study was to evaluate the cellular responses to temozolomide treatment associated with methoxyamine (blocker of base excision repair) in glioblastoma cell lines, in order to test the hypothesis that the blockage of base excision repair pathway might sensitize glioblastoma cells to temozolomide. For all the tested cell lines, only T98G showed significant differences between temozolomide and temozolomide plus methoxyamine treatment, observed by reduced survival rates, enhanced the levels of DNA damage, and induced an arrest at G2-phase. In addition, ~10 % of apoptotic cells (sub-G1 fraction) were observed at 48 h. Western blot analysis demonstrated that APE1 and FEN1 presented a slightly reduced expression levels under the combined treatment, probably due to AP sites blockade by methoxyamine, thus causing a minor requirement of base excision repair pathway downstream to the AP removal by APE1. On the other hand, PCNA expression in temozolomide plus methoxyamine-treated cells does not rule out the possibility that such alteration might be related to the blockage of cell cycle (G2-phase), as observed at 24 h of recovery time. The results obtained in the present study demonstrated the efficiency of methoxyamine to overcome glioblastoma resistance to temozolomide treatment. PMID:22828727

Montaldi, Ana P; Sakamoto-Hojo, Elza T

2013-11-01

112

Heavy WIMP through Higgs portal at the LHC  

E-print Network

LHC constraints on Higgs-portal WIMPs are studied. Scalar, vector and anti-symmetric tensor fields are considered. They are assumed to be heavier than a half of the Higgs boson mass. We investigate 8 TeV LHC results on signatures of the vector boson fusion, mono-jet and associated production of the $Z$ boson, which proceed via virtual exchange of the Higgs boson. We show that Higgs-portal interactions of the vector and tensor WIMPs are constrained to be less than 0.43 and 0.16, respectively, while those for the scalar are very weak. Prospects of the 14 TeV LHC are also discussed.

Motoi Endo; Yoshitaro Takaesu

2014-07-25

113

Bolometric WIMP search at Canfranc with different absorbers  

NASA Astrophysics Data System (ADS)

The rare objects search with bolometers underground (ROSEBUD) is an experiment to search for weakly interacting massive particles (WIMPs) at the Canfranc Underground Laboratory with bolometric detectors. We present the progress achieved in the second phase of the experiment with three different absorbers (Al2O3, Ge and scintillating CaWO4). For the first time, different target nuclei have been used simultaneously in a common set-up, sharing identical external background conditions. Moreover, a discrimination of nuclear against electron recoils based on the simultaneous measurement of light and heat has been developed and applied to derive limits for WIMP candidates.

Cebrián, S.; Coron, N.; Dambier, G.; García, E.; Irastorza, I. G.; Leblanc, J.; de Marcillac, P.; Morales, A.; Morales, J.; Ortiz de Solórzano, A.; Puimedón, J.; Sarsa, M. L.; Villar, J. A.

2004-04-01

114

BBN And The CMB Constrain Neutrino Coupled Light WIMPs  

E-print Network

(abridged) In the presence of a light WIMP (mass m_chi nature, its couplings to standard model particles, its mass, and the number of equivalent (additional) neutrinos, Delta N_nu. These degeneracies cannot be broken by the CMB constraint on the effective number of neutrinos, N_eff. However, since big bang nucleosynthesis (BBN) is also affected by a light WIMP and equivalent neutrinos, complementary BBN and CMB constraints can break some of the degeneracy. In a previous paper BBN and CMB were combined to explore allowed ranges for m_chi, Delta N_nu, and N_eff for light WIMPs that annihilate electromagnetically (EM) to photons and/or electrons/positrons. In this paper BBN predictions with a light WIMP that only couples to neutrinos are calculated. Recent observed abundances of ^2H and ^4He are used to limit m_chi, Delta N_nu, N_eff, and the present-day baryon density. Allowing for a neutrino coupled light WIMP and nonzero Delta N_nu, combined BBN and CMB data give lower limits to m_chi, with a best fit m_chi > 35 MeV, equivalent to no light WIMP at all. All masses below 4--9 MeV (depending on spin) are excluded. Without any light WIMP, BBN alone prefers Delta N_nu = 0.50 +- 0.23, favoring neither Delta N_nu = 0, nor a fully thermalized sterile neutrino (Delta N_nu = 1). This result is consistent with the CMB constraint, N_eff = 3.30 +- 0.27, limiting "new physics" between BBN and recombination. Combining BBN and CMB data gives Delta N_nu = 0.35 +- 0.16 and N_eff = 3.40 +- 0.16; while BBN and the CMB combined require Delta N_nu > 0 at ~98% confidence, they disfavor Delta N_nu > 1 at > 99% confidence. Allowing a neutrino-coupled light WIMP extends the allowed range slightly downward for Delta N_nu and slightly upward for N_eff simultaneously, leaving best-fit values unchanged.

Kenneth M. Nollett; Gary Steigman

2015-02-12

115

High-count-rate operation of a TFTR position-sensitive x-ray detector with delay-line readouts  

NASA Astrophysics Data System (ADS)

X-ray spectra obtained with position-sensitive detectors which use delay-line readout systems are subject to distortions at count rates comparable to the inverse of the temporal length of the delay line. These distortions are due to the simultaneous existence of pulses from different photons on the delay line. High incident rates up to several MHz can be obtained on the detectors of the TFTR crystal spectrometer under certain conditions. This paper describes improvements which can be obtained by an interarrival time discriminator circuit.

Hsuan, H.; Bitter, M.; von Goeler, S.; Harder, J. A.; Hill, K. W.; Lemunyan, G.

1990-10-01

116

Sensitivity to voltage-independent inhibition determined by pore-lining region of the acetylcholine receptor.  

PubMed Central

Some noncompetitive inhibitors (e.g., ganglionic blockers) exhibit selectivity for the inhibition of neuronal nicotinic acetylcholine receptors (nAChRs). This study characterizes the mechanism of selective long-term inhibition of neuronal and muscle-neuronal chimeric nAChRs by bis(2,2,6,6-tetramethyl-4-piperidinyl) sebacate (bis-TMP-10 or BTMPS), a bifunctional form of the potent ganglionic blocker tetramethylpiperidine. Long-term inhibition of neuronal nAChRs by bis-TMP-10 has been previously demonstrated to arise, at least in part, from the binding of the bis compound to neuronal beta-subunits. In this study, long-term inhibition is demonstrated to be dependent upon the presence of sequence element(s) within the pore-lining second transmembrane domain (tm2) of neuronal beta-subunits; however, the inhibitor binding site itself does not appear to be contained within the segment of the channel pore influenced by the membrane electric field. Specifically, our results imply that bis-TMP-10 interacts with an activation-sensitive element, the availability of which may be regulated by a sequence in the tm2 domain. Furthermore, we demonstrate a compound length requirement for long-term inhibition that would be consistent with binding to multiple sites located on the extracellular portion of the receptor. PMID:9591658

Francis, M M; Choi, K I; Horenstein, B A; Papke, R L

1998-01-01

117

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

SciTech Connect

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

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

2006-04-01

118

Drug Sensitivity Prediction by CpG Island Methylation Profile in the NCI60 Cancer Cell Line Panel  

Microsoft Academic Search

Aberrant promoter hypermethylation and associated gene silencing are epigenetic hallmarks of tumorigenesis. It has been suggested that aberrant DNA methylation can affect the sensitivity of cancers to antineoplastic agents by altering expression of genes critical to drug response. To study this issue, we used bisulfite PCR to assess DNA methylation of 32 promoter-associated CpG islands in human cancer cell lines

Lanlan Shen; Yutaka Kondo; Saira Ahmed; Yanis Boumber; Kazuo Konishi; Xinli Chen; Jill N. Vilaythong; Jean-Pierre J. Issa

119

Dynamics of WIMPs in the solar system and implications for direct and indirect detection  

E-print Network

Semi-analytic treatments of the evolution of orbits of weakly interacting massive particles (WIMPs) in the solar system suggest that the WIMPs bound to the solar system may enhance the direct detection rate relative to that of the unbound population by up to a factor of order unity, and boost the flux of neutrinos from WIMP annihilation in the Earth by up to two orders of magnitude. To test these important but uncertain results, we perform a suite of numerical orbit integrations to explore the properties of the bound WIMP population as a function of the WIMP mass and the scattering cross section with baryonic matter. For regions of WIMP parameter space presently allowed by experiments, we find that (i) the bound WIMP population enhances the direct detection rate by at most ~1% relative to the rate from unbound halo WIMPs; (ii) it is unlikely that planned km^3-scale neutrino telescopes will detect neutrinos from WIMP annihilation in the Earth; (iii) the event rate from neutrinos produced by WIMP annihilation in the Sun may be much smaller than implied by the usual calculations, which assume that WIMPs scattered onto bound orbits are rapidly thermalized in the Sun.

Annika H. G. Peter; Scott Tremaine

2008-10-14

120

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

Microsoft Academic Search

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

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

2006-01-01

121

Improved constraints on WIMPs from the International Germanium Experiment IGEX  

E-print Network

One IGEX 76Ge double-beta decay detector is currently operating in the Canfranc Underground Laboratory in a search for dark matter WIMPs, through the Ge nuclear recoil produced by the WIMP elastic scattering. A new exclusion plot, has been derived for WIMP-nucleon spin-independent interactions. To obtain this result, 40 days of data from the IGEX detector (energy threshold E \\~ 4 keV), recently collected, have been analyzed. These data improve the exclusion limits derived from all the other ionization germanium detectors in the mass region from 20 GeV to 200 GeV, where a WIMP supposedly responsible for the annual modulation effect reported by the DAMA experiment would be located. The new IGEX exclusion contour enters, by the first time, the DAMA region by using only raw data, with no background discrimination, and excludes its upper left part. It is also shown that with a moderate improvement of the detector performances, the DAMA region could be fully explored.

Morales, A; Brodzinski, R L; Cebrián, S; García, E; Irastorza, I G; Kirpichnikov, I V; Klimenko, A A; Miley, H S; Morales, J; De Solorzano, A O; Osetrov, S B; Pogosov, V S; Puimedón, J; Reeves, J H; Sarsa, M L; Smolnikov, A A; Tamanyan, A G; Vasenko, A A; Vasilev, S I; Villar, J A

2002-01-01

122

Improved constraints on WIMPs from the International Germanium Experiment IGEX  

E-print Network

One IGEX 76Ge double-beta decay detector is currently operating in the Canfranc Underground Laboratory in a search for dark matter WIMPs, through the Ge nuclear recoil produced by the WIMP elastic scattering. A new exclusion plot, has been derived for WIMP-nucleon spin-independent interactions. To obtain this result, 40 days of data from the IGEX detector (energy threshold E \\~ 4 keV), recently collected, have been analyzed. These data improve the exclusion limits derived from all the other ionization germanium detectors in the mass region from 20 GeV to 200 GeV, where a WIMP supposedly responsible for the annual modulation effect reported by the DAMA experiment would be located. The new IGEX exclusion contour enters, by the first time, the DAMA region by using only raw data, with no background discrimination, and excludes its upper left part. It is also shown that with a moderate improvement of the detector performances, the DAMA region could be fully explored.

A. Morales; C. E. Aalseth; F. T. Avignone III; R. L. Brodzinski; S. Cebrian; E. Garcia; I. G. Irastorza; I. V. Kirpichnikov; A. A. Klimenko; H. S. Miley; J. Morales; A. Ortiz de Solorzano; S. B. Osetrov; V. S. Pogosov; J. Puimedon; J. H. Reeves; M. L. Sarsa; A. A. Smolnikov; A. G. Tamanyan; A. A. Vasenko; S. I. Vasiliev; J. A. Villar

2002-01-16

123

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

SciTech Connect

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.

Katsumi, Yoshiki; Iehara, Tomoko; Miyachi, Mitsuru; Yagyu, Shigeki; Tsubai-Shimizu, Satoko; Kikuchi, Ken; Tamura, Shinichi; Kuwahara, Yasumichi; Tsuchiya, Kunihiko; Kuroda, Hiroshi; Sugimoto, Tohru [Department of Pediatrics, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kawaramachi-hirokoji, Kamigyo-ku, Kyoto 602-8566 (Japan)] [Department of Pediatrics, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kawaramachi-hirokoji, Kamigyo-ku, Kyoto 602-8566 (Japan); Houghton, Peter J. [Molecular Pharmacology, St. Jude Children's Research Hospital, 332 N. Lauderdale St. Memphis, TN 38105-2794 (United States)] [Molecular Pharmacology, St. Jude Children's Research Hospital, 332 N. Lauderdale St. Memphis, TN 38105-2794 (United States); Hosoi, Hajime, E-mail: hhosoi@koto.kpu-m.ac.jp [Department of Pediatrics, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kawaramachi-hirokoji, Kamigyo-ku, Kyoto 602-8566 (Japan)] [Department of Pediatrics, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kawaramachi-hirokoji, Kamigyo-ku, Kyoto 602-8566 (Japan)

2011-09-16

124

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

NASA Astrophysics Data System (ADS)

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

Cabrera, Blas

2013-04-01

125

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

NASA Astrophysics Data System (ADS)

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

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

2012-05-01

126

Effect of aberrant p53 function on temozolomide sensitivity of glioma cell lines and brain tumor initiating cells from glioblastoma.  

PubMed

The most effective chemotherapeutic for glioblastoma (GBM) is the DNA alkylating agent temozolomide (TMZ). In a recent study by Hegi et al. benefit from TMZ was significantly associated with methylation of the promoter of the O6-methylguanine-DNA methyltransferase (MGMT) gene; however, the correlation was imperfect. Some patients with methylated tumors were short survivors and others with unmethylated tumors were long survivors. These exceptions have raised the possibility that TMZ response might be influenced by non-MGMT mechanisms. The effect of p53 status on response to TMZ was explored in traditional glioma cell lines (U87MG, U251MG, U343MG, U373MG, SF767, LN443 and LNZ308) and brain tumor initiating cells (BTICs--BT012, BT025, BT042, BT048, BT060 and BT069) in two ways: (1) inhibition of p53 by RNAi and (2) sensitivity in relation to intrinsic p53 status, either wild-type or mutant. Traditional glioma cell lines that did not express a functional p53 were significantly more sensitive to TMZ than cell lines with functionally intact wild-type p53 expression. Altered p53 expression or function had only minor effects on TMZ sensitivity in BTICs and tended to decrease sensitivity to TMZ. RNAi specific for p53 had little effect on sensitivity in p53 null glioma cells. Absence of a functional p53 increases TMZ sensitivity in traditional glioma cell lines, an effect that is independent of MGMT status, and not seen in BTICs. P53 status may influence response to TMZ in differentiated cells in a GBM with a negligible affect on its initiating cells. PMID:20593219

Blough, Michael D; Beauchamp, Desiree C; Westgate, Morgan R; Kelly, John J; Cairncross, J Gregory

2011-03-01

127

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

PubMed Central

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

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

2014-01-01

128

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

PubMed Central

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

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

2014-01-01

129

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

PubMed

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

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

2014-03-15

130

Luteolin sensitizes two oxaliplatin-resistant colorectal cancer cell lines to chemotherapeutic drugs via inhibition of the Nrf2 pathway.  

PubMed

Oxaliplatin is a first-line therapy for colorectal cancer, but cancer cell resistance to the drug compromises its efficacy. To explore mechanisms of drug resistance, we treated colorectal cancer cells (HCT116 and SW620) long-term with oxaliplatin and established stable oxaliplatin-resistant lines (HCT116-OX and SW620-OX). Compared with parental cell lines, IC50s for various chemotherapeutic agents (oxaliplatin, cisplatin and doxorubicin) were increased in oxaliplatin-resistant cell lines and this was accompanied by activation of nuclear factor erythroid-2 p45-related factor 2 (Nrf2) and NADPH quinone oxidoreductase 1 (NQO1). Furthermore, luteolin inhibited the Nrf2 pathway in oxaliplatin-resistant cell lines in a dose-dependent manner. Luteolin also inhibited Nrf2 target gene [NQO1, heme oxygenase-1 (HO-1) and GST?1/2] expression and decreased reduced glutathione in wild type mouse small intestinal cells. There was no apparent effect in Nrf2-/- mice. Luteolin combined with other chemotherapeutics had greater anti-cancer activity in resistant cell lines (combined index values below 1), indicating a synergistic effect. Therefore, adaptive activation of Nrf2 may contribute to the development of acquired drug-resistance and luteolin could restore sensitivity of oxaliplatin-resistant cell lines to chemotherapeutic drugs. Inhibition of the Nrf2 pathway may be the mechanism for this restored therapeutic response. PMID:24761924

Chian, Song; Li, Yin-Yan; Wang, Xiu-Jun; Tang, Xiu-Wen

2014-01-01

131

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

Microsoft Academic Search

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

M. Uusi-Oukari; E. R. Korpi

1989-01-01

132

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

NASA Astrophysics Data System (ADS)

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

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

2014-11-01

133

Report on a position sensitive parallel plate avalanche counter with a distributed constants delay-line-cathode  

SciTech Connect

A position sensitive parallel plate (PSPP) stop detector for heavy ions with an active area of 70 x 76 mm/sup 2/ has been developed. The cathode is a printed circuit board with parallel strips which form a distributed constant delay-line. The position resolution is better than 1 mm in the x direction (orthogonal to the strips) and 2 cm in the y direction (along the strips). The anode time resolution is about 300 psec fwhm.

Lombardi, M.; Jilian, T.; Potenza, R.; D'Amico, V.

1986-02-01

134

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

PubMed Central

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

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

135

Highly-sensitive gas pressure sensor using twin-core fiber based in-line Mach-Zehnder interferometer.  

PubMed

A Mach-Zehnder interferometer based on a twin-core fiber was proposed and experimentally demonstrated for gas pressure measurements. The in-line Mach-Zehnder interferometer was fabricated by splicing a short section of twin-core fiber between two single mode fibers. A micro-channel was created to form an interferometer arm by use of a femtosecond laser to drill through one core of the twin-core fiber. The other core of the fiber was remained as the reference arm. Such a Mach-Zehnder interferometer exhibited a high gas pressure sensitivity of -9.6 nm/MPa and a low temperature cross-sensitivity of 4.4 KPa/°C. Moreover, ultra-compact device size and all-fiber configuration make it very suitable for highly-sensitive gas pressure sensing in harsh environments. PMID:25836884

Li, Zhengyong; Liao, Changrui; Wang, Yiping; Xu, Lei; Wang, Dongning; Dong, Xiaopeng; Liu, Shen; Wang, Qiao; Yang, Kaiming; Zhou, Jiangtao

2015-03-01

136

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

PubMed

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

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

2014-01-01

137

A light scalar WIMP through the Higgs portal?  

E-print Network

In these proceedings, I report on the status of a simple singlet scalar dark matter model in the light of recent results from both direct detection experiments, in particular DAMA, CoGeNT, CDMS-II and Xenon10/100, and indirect searches, in particular Fermi-LAT. Specifically, I confront the light scalar WIMP candidates, M_DM ~ few GeV, that are consistent with CoGeNT and/or DAMA, to constraints that may be set using the recent Fermi-LAT data on Milky Way dwarf spheroidal galaxies (dSphs) and the isotropic diffuse gamma-ray emission. I show that the latter observations set relevant exclusion limits on the lightest WIMP candidates.

Michel H. G. Tytgat

2010-12-02

138

WIMP Dark Matter Direct-Detection Searches in Noble Gases  

E-print Network

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

Laura Baudis

2014-08-19

139

Cosmological radio emission induced by WIMP Dark Matter  

SciTech Connect

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

Fornengo, N.; Regis, M. [Dipartimento di Fisica Teorica, Università di Torino, via P. Giuria 1, I-10125 Torino (Italy); Lineros, R.; Taoso, M., E-mail: fornengo@to.infn.it, E-mail: rlineros@ific.uv.es, E-mail: regis@to.infn.it, E-mail: mtaoso@phas.ubc.ca [IFIC, CSIC-Universidad de Valencia, Ed. Institutos, Apdo. Correos 22085, E-46071 Valencia (Spain)

2012-03-01

140

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

SciTech Connect

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

Yaguna, Carlos E., E-mail: carlos.yaguna@uni-muenster.de [Institut für Theoretische Physik, Universität Münster, Wilhelm-Klemm-Straße 9, D-48149 Münster (Germany)

2012-02-01

141

Cosmological Radio Emission induced by WIMP Dark Matter  

E-print Network

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

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

2012-03-05

142

WIMP dark matter direct-detection searches in noble gases  

NASA Astrophysics Data System (ADS)

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

Baudis, Laura

2014-09-01

143

The zero age main sequence of WIMP burners  

SciTech Connect

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

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

2008-02-15

144

Final state sensitivity of particle dynamics in a magnetic neutral line field  

NASA Astrophysics Data System (ADS)

We examine chaotic scattering of charged particles in magnetic neutral line fields in the Earth's magnetotail. ThisHamiltonian system exhibits chaotic scattering over a wide range of parameter values. In the simpler current sheet field there is a well defined energy resonance that governs the dynamics, and we show that the neutral line model has no such resonance. Current sheet scattering has been shown to have a fractal exit basin boundary structure that closely follows the energy resonance. We show that the neutral line model has a more complex final state structure, which nonetheless indicates self-similarity, and a more complicated fractal behavior.

Martin, R. F.; Holland, D. L.; Svetich, J.; Brennan, C.

2013-12-01

145

Results of a search for annual modulation of WIMP signals  

Microsoft Academic Search

A search for particle cold dark matter (CDM) has been carried out at the Canfranc Underground Laboratory (Spain) with a set of three sodium iodide scintillators of 10.7 kg each, during about 2 yr of data taking. The results, corresponding to an exposure of 4613.6 kg day are presented in the form of exclusion plots of the WIMP-target nuclei cross

M. L. Sarsa; A. Morales; J. Morales; E. García; A. Ortiz de Solórzano; J. Puimedón; C. Sáenz; A. Salinas; J. A. Villar

1997-01-01

146

Bolometric WIMP search at Canfranc with different absorbers  

Microsoft Academic Search

The rare objects search with bolometers underground (ROSEBUD) is an experiment to search for weakly interacting massive particles (WIMPs) at the Canfranc Underground Laboratory with bolometric detectors. We present the progress achieved in the second phase of the experiment with three different absorbers (Al2O3, Ge and scintillating CaWO4). For the first time, different target nuclei have been used simultaneously in

S. Cebrián; N. Coron; G. Dambier; E Garc??a; I. G Irastorza; J. Leblanc; P de Marcillac; A. Morales; J. Morales; A Ortiz de Solórzano; J. Puimedón; M. L Sarsa; J. A Villar

2004-01-01

147

No WIMP mini-spikes in dwarf spheroidal galaxies  

NASA Astrophysics Data System (ADS)

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

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

2015-04-01

148

Dark Matter; Modification of f(R) or Wimps Miracle  

E-print Network

The identity of dark matter is one of the key outstanding problems in both particle and astrophysics. In this thesis, I review some candidates of dark matter, especially WIMPs (weakly interacting massive particles) which is one of the best candidate so it is called that WIMPs miracle. In addition of this, there are also some theories of modification of gravity, by changing the law of gravity, it could be possible that the dark matter observations are explained. Until the dark matter particle is detected, there is some room for uncertainty. So we should consider every part of the problem and solve it. Dark matter problem is covering a large area so every possibility is important. So f(R) gravity is also reviewed in this thesis and some theories are considered as a possible solution of dark matter problem. Finally we highlight that, even in the case of WIMPs or another particles solution, f(R) gravity is also can be used for this problem. However, last words will be said by experiments.

A. Övgün

2013-01-23

149

Can WIMP dark matter overcome the nightmare scenario?  

SciTech Connect

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

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

2010-09-01

150

Light WIMPs, equivalent neutrinos, BBN, and the CMB  

NASA Astrophysics Data System (ADS)

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

Steigman, Gary; Nollett, Kenneth M.

151

Collateral sensitivity to cold stress and differential BCL-2 family expression in new daunomycin-resistant lymphoblastoid cell lines.  

PubMed

The acquisition of a multidrug-resistant (MDR) phenotype by tumor cells is one of the main causes of chemotherapy failure in cancer, and, usually, is due to the increased expression of P-glycoprotein (MDR-1, P-gp, ABCB1), a pump that expels chemotherapeutics from the cell and/or regulates apoptosis. Thus, it is fundamental to find drugs or stress stimuli with a capacity to induce apoptosis in such cells and to identify the mechanisms involved. We address this matter in human cells and establish new daunomycin (DNM)-resistant cell lines (IM-9R) by exposing the parental lymphoblastic cells (IM-9) to increasing doses of the anti-neoplastic drug, daunomycin. The resistance level of IM-9R cell lines, MDR-1 expression and functionality, collateral sensitivity and Bcl-2 and caspases protein expression are analyzed. As a result, we show for the first time that, unlike the parental cells, human lymphoblastic resistant cells exhibit collateral sensitivity to cold stress, confirming that this phenomenon is not exclusive to murine leukemic cells, but a broader one associated with the acquisition of drug resistance. Furthermore, the new resistant cell lines undergo a significant increase in active caspase-3 and -9 levels and drastic changes in Bcl-2 family protein expression during the process of MDR phenotype acquisition. PMID:25498972

Cerezo, David; Cánovas, Manuel; García-Peñarrubia, Pilar; Martín-Orozco, Elena

2015-02-01

152

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

PubMed Central

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

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

2013-01-01

153

OZONE SENSITIVE AND RESISTANT LINES OF SNAP BEAN. I. PHOTOSYNTHESIS AND CHLOROPHYLL FLUORESCENCE  

Technology Transfer Automated Retrieval System (TEKTRAN)

Widespread areas of crop production are at risk for damage at ambient ozone (O3) concentrations. Past research has not determined the plant mechanisms that cause differences in O3 sensitivity. Therefore, a study was undertaken to examine the effects of O3 on three snap bean (Phaseolus vulgaris) ge...

154

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...

155

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

NASA Astrophysics Data System (ADS)

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

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

2005-09-01

156

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

NASA Astrophysics Data System (ADS)

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.

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

2014-11-01

157

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

PubMed Central

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

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

2014-01-01

158

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

PubMed Central

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

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

2014-01-01

159

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

PubMed

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

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

2013-04-01

160

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

PubMed Central

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

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

2014-01-01

161

The presence of two Fc receptors on mouse macrophages: evidence from a variant cell line and differential trypsin sensitivity  

PubMed Central

A stable variant of a clone of the P388D1 macrophage line was isolated using four cycles of treatment with mouse IgG2a-rabbit anti-kappa complexes and rabbit complement. The variant had the same Ka and about the same number of sites per cell for IgG2a as the parent line. However, the variant had 10% as many binding sites for rabbit IgG in soluble antigen-antibody complexes, and the affinity of binding was threefold higher. This change in binding of complexes to cells of a cloned line without alternation of IgG2a binding provides evidence for the presence of two distinct Fc receptors. The two receptors could also be distiguished on the P388D1 line and on thioglycollate-induced mouse peritoneal macrophages by differential sensitivity to trypsinization. The receptors that bind monomeric IgG2a, sheep erythrocytes (SRBC) covalently bound with IgG2a or rabbit IgG using glutaraldehyde, and Sephadex beads coupled with IgG2a or rabbit IgG using cyanogen bromide activitation, is sensitive to trypsinization. The receptor that binds soluble rabbit antibody-antigen complexes, trinitrophenyl-SRBC and dinitrophenyl(DNP)-bovine serum albumin Sephadex beads coated with rabbit anti-DNP IgG is trypsin resitant, the observation that uncomplexed rabbit IgG oes not bind to the trypsin-resistant receptor, whereas the same IgG bound to its antigen does, suggests that conformational changes induced by the binding of ligand may be of consequence in macrophage function. PMID:323399

1977-01-01

162

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

SciTech Connect

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

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

2007-11-15

163

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

NASA Astrophysics Data System (ADS)

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.

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

1998-12-01

164

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

SciTech Connect

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

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

1983-07-01

165

Goodbye to WIMPs: A Scalable Interface for ALMA Operations  

NASA Astrophysics Data System (ADS)

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

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

2011-07-01

166

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

PubMed Central

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.

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

2015-01-01

167

A Neutron Sensitive Microchannel Plate Detector with Cross Delay Line Readout  

SciTech Connect

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

Berry, Kevin D [ORNL; Bilheux, Hassina Z [ORNL; Crow, Lowell [ORNL; Diawara, Yacouba [ORNL; Feller, W Bruce [Nova Scientific, Inc., Sturbridge, MA; Iverson, Erik B [ORNL; Martin, Adrian [Sensor Sciences, LLC; Robertson, Lee [ORNL

2012-01-01

168

Isolation of a heterogeneous population of temperature-sensitive mutants of measles virus from persistently infected human lymphoblastoid cell lines.  

PubMed

Two human lymphoblastoid B-cell lines, WI-L2 and 8866, were infected with the Edmonston strain of measles virus at a multiplicity of infection of 10(-6), and stable persistent infections were established. By immunofluorescence and electron microscopy, the vast majority of cells from both cell lines were expressing viral antigens and releasing virion-like particles. However, very little infectious virus could be detected at 37 degrees C, either by an infectious centers assay or by titration of supernates from persistently infected cultures. When cultures were shifted to 31 degrees C, the cells released a population of virus that was temperature-sensitive. Clonal analysis of supernatant virus at 31 degrees C revealed a highly heterogeneous population of temperature-sensitive mutants, differing in plating efficiency ratios, thermolability, and antigen production at the nonpermissive temperature. Factors such as interferon, defective interfering particles, and extracellular virus do not appear to be important in maintaining the persistent carrier state. These studies have important implications for persistent infections of lymphoid cells in vivo, and the slow neurological diseases associated with measles, subacute sclerosing panencephalitis, and multiple sclerosis. PMID:210247

Ju, G; Udem, S; Rager-Zisman, B; Bloom, B R

1978-06-01

169

Dark matter search by exclusive studies of X-rays following WIMPs nuclear interactions  

E-print Network

It is shown that weakly interacting massive particles (WIMPs), which are possible cold dark matter candidates, can be studied by exclusive measurements of X-rays following WIMPs nuclear interactions. Inner-shell atomic electrons are ionized through WIMP-nuclear interaction, and then mono-energetic X-rays are emitted when they are filled by outer-shell electrons. The number of inner-shell holes amounts to as large as one per five nuclear recoils for K-shell and several per recoil for L-shell in the case of medium heavy target nuclei interacting with 100-300 GeV WIMPs. Then the K and L X-ray peaks show up in the 5-50 keV region. Consequently exclusive studies of the X-rays in coincidence with the nuclear recoils and the ionization electrons are found to provide excellent opportunities to detect WIMPs such as the Lightest Super Symmetric Particles (LSP)

H. Ejiri; Ch. C. Moustakidis; J. D. Vergados

2006-03-14

170

NQR Line Broadening Due to Crystal Lattice Imperfections and Its Relationship to Shock Sensitivity  

NASA Astrophysics Data System (ADS)

The hydrodynamic hot spot model is used to explain the difference between shock sensitive and shock insensitive explosives. Among the major factors that influence the shock sensitivity of energetic compounds are the quality and particle size of the energetic crystals used to formulate the cast plastic bonded explosive. As do all energetic compounds, RDX and HMX exhibit internal crystal defects the magnitude and type of which depend on the manufacturing process used to synthesize and re-crystallize the energetic compound. Nuclear Quadrupole Resonance (NQR) spectroscopy was used to determine the crystal quality of RDX, HMX and CL-20 obtained from various manufacturers. The NQR experimental results are discussed. Cast plastic bonded explosives were made using the RDX and HMX obtained from the various manufacturers and subsequently subjected to the NOL large-scale gap test (LSGT). The results of the LSGT are discussed and correlated with the NQR results. A relationship between the crystal defect density and shock initiation pressure of the plastic bonded explosive is developed and discussed.

Caulder, S. M.; Buess, M. L.; Garroway, A. N.; Miller, P. J.

2004-07-01

171

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

PubMed Central

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

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

2014-01-01

172

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

Microsoft Academic Search

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

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

1995-01-01

173

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

PubMed

We investigate the sensitivity of the composite cellular automaton of  H. Fuk? [Phys. Rev. E 55, R2081 (1997)] to noise and assess the density classification performance of the resulting probabilistic cellular automaton (PCA) numerically. We conclude that the composite PCA performs the density classification task reliably only up to very small levels of noise. In particular, it cannot outperform the noisy Gacs-Kurdyumov-Levin automaton, an imperfect classifier, for any level of noise. While the original composite CA is nonergodic, analyses of relaxation times indicate that its noisy version is an ergodic automaton, with the relaxation times decaying algebraically over an extended range of parameters with an exponent very close (possibly equal) to the mean-field value. PMID:21517459

Mendonça, J Ricardo G

2011-03-01

174

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

NASA Astrophysics Data System (ADS)

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

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

2007-09-01

175

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

SciTech Connect

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

Boeer, Rainer; Knoll, Alfred [Framatome ANP GmbH (France)

2003-05-15

176

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)

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

Manungu Kiveni, Joseph

177

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

PubMed

Clinical oncology is still challenged by the development of drug resistance of tumors that result in poor prognosis for patients. There is an urgent necessity to understand the molecular mechanisms of resistance and to develop novel therapy strategies. Artesunate (ART) is an anti-malarial drug, which also exerts profound cytotoxic activity towards cancer cells. We first applied a gene-hunting approach using cluster and COMPARE analyses of microarray-based transcriptome-wide mRNA expression profiles. Among the genes identified by this approach were genes from diverse functional groups such as structural constituents of ribosomes (RPL6, RPL7, RPS12, RPS15A), kinases (CABC1, CCT2, RPL41), transcriptional and translational regulators (SFRS2, TUFM, ZBTB4), signal transducers (FLNA), control of cell growth and proliferation (RPS6), angiogenesis promoting factors (ITGB1), and others (SLC25A19, NCKAP1, BST1, DBH, FZD7, NACA, MTHFD2). Furthermore, we applied a candidate gene approach and tested the role of resistance mechanisms towards established anti-cancer drugs for ART resistance. By using transfected or knockout cell models we found that the tumor suppressor p16(INK4A) and the anti-oxidant protein, catalase, conferred resistance towards ART, while the oncogene HPV-E6 conferred sensitivity towards ART. The tumor suppressor p53 and its downstream protein, p21, as well as the anti-oxidant manganese-dependent superoxide dismutase did not affect cellular response to ART. In conclusion, our pharmacogenomic approach revealed that response of tumor cells towards ART is multi-factorial and is determined by gene expression associated with either ART sensitivity or resistance. At least some of the functional groups of genes (e.g. angiogenesis promoting factors, cell growth and proliferation-associated genes signal transducers and kinases) are also implicated in clinical responsiveness of tumors towards chemotherapy. It merits further investigation, whether ART is responsive in clinically refractory tumors and whether the genes identified in the present study also determine clinical responsiveness towards ART. PMID:20144594

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

2010-04-15

178

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

PubMed

Epigenetic changes have been suggested to drive prostate cancer (PCa) development and progression. Therefore, in this study, we aimed to identify novel epigenetics-related genes in PCa tissues, and to examine their expression in metastatic PCa cell lines. We analyzed the expression of epigenetics-related genes via a clustering analysis based on gene function in moderately and poorly differentiated PCa glands compared to normal glands of the peripheral zone (prostate proper) from PCa patients using Whole Human Genome Oligo Microarrays. Our analysis identified 12 epigenetics-related genes with a more than 2-fold increase or decrease in expression and a p-value <0.01. In modera-tely differentiated tumors compared to normal glands of the peripheral zone, we found the genes, TDRD1, IGF2, DICER1, ADARB1, HILS1, GLMN and TRIM27, to be upregulated, whereas TNRC6A and DGCR8 were found to be downregulated. In poorly differentiated tumors, we found TDRD1, ADARB and RBM3 to be upregulated, whereas DGCR8, PIWIL2 and BC069781 were downregulated. Our analysis of the expression level for each gene in the metastatic androgen-sensitive VCaP and LNCaP, and -insensitive PC3 and DU-145 PCa cell lines revealed differences in expression among the cell lines which may reflect the different biological properties of each cell line, and the potential role of each gene at different metastatic sites. The novel epigenetics-related genes that we identified in primary PCa tissues may provide further insight into the role that epigenetic changes play in PCa. Moreover, some of the genes that we identified may play important roles in primary PCa and metastasis, in primary PCa only, or in metastasis only. Follow-up studies are required to investigate the functional role and the role that the expression of these genes play in the outcome and progression of PCa using tissue microarrays. PMID:23135352

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

2013-01-01

179

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

SciTech Connect

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

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

2006-01-04

180

Dark matter in the solar system III: The distribution function of WIMPs at the Earth from gravitational capture  

E-print Network

In this last paper in a series of three on weakly interacting massive particle (WIMP) dark matter in the solar system, we focus on WIMPs bound to the system by gravitationally scattering off of planets. We present simulations of WIMP orbits in a toy solar system consisting of only the Sun and Jupiter. As previous work suggested, we find that the density of gravitationally captured WIMPs at the Earth is small and largely insensitive to the details of elastic scattering in the Sun. However, we find that the density of gravitationally captured WIMPs may be affected by external Galactic gravitational fields. If such fields are unimportant, the density of gravitationally captured WIMPs at the Earth should be similar to the maximum density of WIMPs captured in the solar system by elastic scattering in the Sun. Using standard assumptions about the halo WIMP distribution function, we find that the gravitationally captured WIMPs contribute negligibly to direct detection event rates. While these WIMPs do dominate the annihilation rate of WIMPs in the Earth, the resulting event rate in neutrino telescopes is too low to be observed in next-generation neutrino telescopes.

Annika H. G. Peter

2009-02-09

181

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

PubMed

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

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

2014-01-01

182

Determining ratios of WIMP-nucleon cross sections from direct dark matter detection data  

SciTech Connect

Weakly Interacting Massive Particles (WIMPs) are one of the leading candidates for Dark Matter. So far the usual procedure for constraining the WIMP-nucleon cross sections in direct Dark Matter detection experiments have been to fit the predicted event rate based on some model(s) of the Galactic halo and of WIMPs to experimental data. One has to assume whether the spin-independent (SI) or the spin-dependent (SD) WIMP-nucleus interaction dominates, and results of such data analyses are also expressed as functions of the as yet unknown WIMP mass. In this article, I introduce methods for extracting information on the WIMP-nucleon cross sections by considering a general combination of the SI and SD interactions. Neither prior knowledge about the local density and the velocity distribution of halo WIMPs nor about their mass is needed. Assuming that an exponential-like shape of the recoil spectrum is confirmed from experimental data, the required information are only the measured recoil energies (in low energy ranges) and the number of events in the first energy bin from two or more experiments.

Shan, Chung-Lin, E-mail: clshan@mail.ncku.edu.tw [Department of Physics, National Cheng Kung University, No. 1, University Road, Tainan City 70101, Taiwan, R.O.C. (China)

2011-07-01

183

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

PubMed Central

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

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

2014-01-01

184

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

PubMed

Tumor growth is estrogen independent in approximately one-third of all breast cancers, which makes these patients unresponsive to hormonal treatment. This unresponsiveness to hormonal treatment may be explained through the absence of the estrogen receptor alpha (ESR1). The ESR1 gene re-expression through epigenetic modulators such as DNA methyltransferase inhibitors and/or histone deacetylase inhibitors restores tamoxifen sensitivity in ESR1 negative breast cancer cell lines and opens new treatment horizons in patients who were previously associated with a poor prognosis.In the study presented herein, we tested the ability of ribavirin, which shares some structural similarities with the DNA-methyltransferase inhibitor 5-azacytidine and which is widely known as an anti-viral agent in the treatment of hepatitis C, to restore ESR1 gene re-expression in ESR1 negative breast cancer cell lines.In our study we identified ribavirin to restore ESR1 gene re-expression alone and even more in combination with suberoylanilide hydroxamic acid (SAHA - up to 276 fold induction).Ribavirin and analogs could pave the way to novel translational research projects that aim to restore ESR1 gene re-expression and thus the susceptibility to tamoxifen-based endocrine treatment strategies. PMID:22414275

Sappok, Anne; Mahlknecht, Ulrich

2011-01-01

185

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

PubMed Central

Tumor growth is estrogen independent in approximately one-third of all breast cancers, which makes these patients unresponsive to hormonal treatment. This unresponsiveness to hormonal treatment may be explained through the absence of the estrogen receptor alpha (ESR1). The ESR1 gene re-expression through epigenetic modulators such as DNA methyltransferase inhibitors and/or histone deacetylase inhibitors restores tamoxifen sensitivity in ESR1 negative breast cancer cell lines and opens new treatment horizons in patients who were previously associated with a poor prognosis. In the study presented herein, we tested the ability of ribavirin, which shares some structural similarities with the DNA-methyltransferase inhibitor 5-azacytidine and which is widely known as an anti-viral agent in the treatment of hepatitis C, to restore ESR1 gene re-expression in ESR1 negative breast cancer cell lines. In our study we identified ribavirin to restore ESR1 gene re-expression alone and even more in combination with suberoylanilide hydroxamic acid (SAHA - up to 276 fold induction). Ribavirin and analogs could pave the way to novel translational research projects that aim to restore ESR1 gene re-expression and thus the susceptibility to tamoxifen-based endocrine treatment strategies. PMID:22414275

2011-01-01

186

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

NASA Astrophysics Data System (ADS)

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

Desai, S.; Ashie, Y.; Fukuda, S.; Fukuda, Y.; Ishihara, K.; Itow, Y.; Koshio, Y.; Minamino, A.; Miura, M.; Moriyama, S.; Nakahata, M.; Namba, T.; Nambu, R.; Obayashi, Y.; Sakurai, N.; Shiozawa, M.; Suzuki, Y.; Takeuchi, H.; Takeuchi, Y.; Yamada, S.; Ishitsuka, M.; Kajita, T.; Kaneyuki, K.; Nakayama, S.; Okada, A.; Ooyabu, T.; Saji, C.; Earl, M.; Kearns, E.; Stone, J. L.; Sulak, L. R.; Walter, C. W.; Wang, W.; Goldhaber, M.; Barszczak, T.; Casper, D.; Cravens, J. P.; Gajewski, W.; Kropp, W. R.; Mine, S.; Liu, D. W.; Smy, M. B.; Sobel, H. W.; Sterner, C. W.; Vagins, M. R.; Ganezer, K. S.; Hill, J.; Keig, W. E.; Kim, J. Y.; Lim, I. T.; Ellsworth, R. W.; Tasaka, S.; Guillian, G.; Kibayashi, A.; Learned, J. G.; Matsuno, S.; Takemori, D.; Messier, M. D.; Hayato, Y.; Ichikawa, A. K.; Ishida, T.; Ishii, T.; Iwashita, T.; Kameda, J.; Kobayashi, T.; Maruyama, T.; Nakamura, K.; Nitta, K.; Oyama, Y.; Sakuda, M.; Totsuka, Y.; Suzuki, A. T.; Hasegawa, M.; Hayashi, K.; Inagaki, T.; Kato, I.; Maesaka, H.; Morita, T.; Nakaya, T.; Nishikawa, K.; Sasaki, T.; Ueda, S.; Yamamoto, S.; Haines, T. J.; Dazeley, S.; Hatakeyama, S.; Svoboda, R.; Blaufuss, E.; Goodman, J. A.; Sullivan, G. W.; Turcan, D.; Scholberg, K.; Habig, A.; Jung, C. K.; Kato, T.; Kobayashi, K.; Malek, M.; Mauger, C.; McGrew, C.; Sarrat, A.; Sharkey, E.; Yanagisawa, C.; Toshito, T.; Mitsuda, C.; Miyano, K.; Shibata, T.; Kajiyama, Y.; Nagashima, Y.; Takita, M.; Yoshida, M.; Kim, H. I.; Kim, S. B.; Yoo, J.; Okazawa, H.; Ishizuka, T.; Choi, Y.; Seo, H. K.; Gando, Y.; Hasegawa, T.; Inoue, K.; Shirai, J.; Suzuki, A.; Koshiba, M.; Hashimoto, T.; Nakajima, Y.; Nishijima, K.; Harada, T.; Ishino, H.; Morii, M.; Nishimura, R.; Watanabe, Y.; Kielczewska, D.; Zalipska, J.; Gran, R.; Shiraishi, K. K.; Washburn, K.; Wilkes, R. J.

2004-10-01

187

Quantifying galactic propagation uncertainty in WIMP dark matter search with AMS01 Z=-1 spectrum  

E-print Network

A search for a WIMP dark matter annihilation signal is carried out in the AMS01 negatively charged (Z=-I) particle spectrum, following a set of supersymmetric benchmark scenarios in the mSUGRA framework. The result is ...

Xiao, Sa, Ph. D. Massachusetts Institute of Technology

2009-01-01

188

Nuclear ? terms and scalar-isoscalar WIMP-nucleus interactions from lattice QCD  

E-print Network

It has been argued that the leading scalar-isoscalar weakly interacting massive particle (WIMP) -nucleus interactions receive parametrically enhanced contributions in the context of nuclear effective field theories [1]. ...

Beane, S.?R.

189

New Gastric Epithelial Cell Lines from Mice Transgenic for Temperature-Sensitive Simian Virus 40 Large T Antigen Show Distinct Types of Cell Differentiation  

Microsoft Academic Search

Aim: To develop conditionally immortalized gastric mucosal cell lines that show distinct types of cell differentiation from transgenic mice harboring temperature-sensitive simian virus 40 (tsSV40) large T antigen. Methods: Gastric mucosal cells from the transgenic mice were cultured at a permissive temperature (33°C), and proliferative cells were then cloned by colony formation. Results: Eight gastric cell lines showed epithelial-like morphology

Yoshiaki Tabuchi; Yuko Arai; Hiroki Shioya; Ryosuke Kuribayashi; Kotaro Ishibashi; Norifumi Sugiyama; Masuo Obinata; Noriaki Takeguchi; Shinji Asano

2003-01-01

190

CMB Constraints On The Thermal WIMP Mass And Annihilation Cross Section  

E-print Network

A thermal relic, often referred to as a weakly interacting massive particle (WIMP), is a particle produced during the early evolution of the Universe whose present (relic) abundance depends only on its mass and its thermally averaged annihilation cross section (annihilation rate factor) sigma*v_ann. Late time WIMP annihilation has the potential to affect the cosmic microwave background (CMB) power spectrum. Current observational constraints on the absence of such effects provide bounds on the mass and the annihilation cross section of relic particles that may, but need not be dark matter candidates. For a WIMP that is a dark matter candidate, the CMB constraint sets an upper bound to the annihilation cross section, leading to a lower bound to its mass that depends on whether or not the WIMP is its own antiparticle. For a self-conjugate WIMP, m_min = 50f GeV, where f is an electromagnetic energy efficiency factor. For a non self-conjugate WIMP, the minimum mass is a factor of two larger. For a WIMP that is a subdominant component of the dark matter density there is no bound on its mass and the upper bound to its annihilation cross section imposed by the CMB transforms into a lower bound to its annihilation cross section. These results are outlined and quantified here using the latest CMB constraints for a stable, symmetric (equal number of particles and antiparticles), WIMP whose annihilation is s-wave dominated, and for particles that are, or are not, their own antiparticle.

Gary Steigman

2015-03-05

191

New constraints on WIMPS from the Canfranc IGEX dark matter search  

Microsoft Academic Search

The IGEX Collaboration enriched 76Ge double-beta decay detectors are currently operating in the Canfranc Underground Laboratory with an overburden of 2450 m.w.e. A recent upgrade has made it possible to use them in a search for WIMPs. A new exclusion plot, ?(m), has been derived for WIMP-nucleon spin-independent interaction. To obtain this result, 30 days of data from one IGEX

A. Morales; C. E Aalseth; F. T Avignone III; R. L Brodzinski; S. Cebrián; E Garc??a; D. González; W. K Hensley; I. G Irastorza; I. V. Kirpichnikov; A. A. Klimenko; H. S Miley; J. Morales; A Ortiz de Solórzano; S. B Osetrov; V. S Pogosov; J. Puimedón; J. H Reeves; M. L. Sarsa; S. Scopel; A. A. Smolnikov; A. G. Tamanyan; A. A. Vasenko; S. I. Vasiliev; J. A. Villar

2000-01-01

192

Searching for annual modulations of WIMPs with NaI scintillators  

Microsoft Academic Search

A search for cold dark matter has been carried out at the Canfranc Underground Laboratory (Spain) with 32.1 kg of sodium iodide scintillators during about two years of data taking. Bounds on WIMP masses and cross-sections for an exposure of 4613.6 kg day are presented, both for spin-independent and spin-dependent WIMP-matter interactions. The predicted annual modulation of the signal has

M. L. Sarsa; A. Morales; J. Morales; E. García; A. Ortiz de Solórzano; J. Puimedón; C. Sáenz; A. Salinas; J. A. Villar

1996-01-01

193

Supersymmetry with radiatively-driven naturalness: implications for WIMP and axion searches  

E-print Network

By insisting on naturalness in both the electroweak and QCD sectors of the MSSM, the portrait for dark matter production is seriously modified from the usual WIMP miracle picture. In SUSY models with radiatively-driven naturalness (radiative natural SUSY or RNS) which include a DFSZ-like solution to the strong CP and SUSY mu problems, dark matter is expected to be an admixture of both axions and higgsino-like WIMPs. The WIMP/axion abundance calculation requires simultaneous solution of a set of coupled Boltzmann equations which describe quasi-stable axinos and saxions. In most of parameter space, axions make up the dominant contribution of dark matter although regions of WIMP dominance also occur. We show the allowed range of PQ scale f_a and compare to the values expected to be probed by the ADMX axion detector in the near future. We also show WIMP detection rates which are suppressed from usual expectations because now WIMPs comprise only a fraction of the total dark matter. Nonetheless, ton-scale noble liq...

Bae, Kyu Jung; Barger, Vernon; Savoy, Michael R; Serce, Hasan

2015-01-01

194

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

NASA Astrophysics Data System (ADS)

Ultrahigh loadings of photoacid generators (PAGs) in phenolic extreme ultraviolet (EUV) resists have generated the highest known film quantum yields (FQYs). We evaluate the performance of these resists in terms of resolution, line-edge roughness (LER), and sensitivity and collectively evaluate these three parameters (known as RLS) in terms of KLUP and Z-Parameter figures of merit. An analytical model describing the kinetics of photodecomposition was developed to explain the relationship between film quantum yield and PAG concentration. Resists were prepared using a broad range of concentrations of iodonium (DTBPI-PFBS), sulfonium (TPS-PFBS), and non-ionic (NDI-PFBS) PAGs. The model fits the experimental data (correlation coefficient R2 = 0.998, 0.994, and 0.995) and compares the rate at which electrons react with PAGs or recombine with holes. Resists prepared with 15-20 wt % of iodonium nonaflate PAG exhibit both high quantum yields and the best RLS performance as determined using both KLUP and Z-Parameter methodologies. The improvement in RLS performance correlates with the increase in FQY at higher PAG concentrations.

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

2011-03-01

195

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

Microsoft Academic Search

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

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

2006-01-01

196

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

Microsoft Academic Search

In experiments to assess the in vitro impact of the candidate microbicides nonoxynol 9 (N-9), C31G, and sodium dodecyl sulfate (SDS) on human immune and epithelial cell viability, cell lines and primary cell populations of lymphocytic and monocytic origin were generally shown to be equally sensitive to exposures ranging from 10 min to 48 h. However, U-937 cells were more

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

2002-01-01

197

Increased activity and sensitivity of mitochondrial respiratory enzymes to tumor necrosis factor alpha-mediated inhibition is associated with increased cytotoxicity in drug-resistant leukemic cell lines.  

PubMed

The drug-resistant leukemic cell lines, CEM/VLB100 and K/DAU600, are more sensitive to tumor necrosis factor alpha (TNFalpha)-mediated cytotoxicity compared with their parental cell lines, CCRF-CEM and K562 cl.6. Drug-resistant leukemic cell lines have more active mitochondrial function, which is associated with a greater susceptibility to TNFalpha-induced respiratory inhibition. TNFalpha blocked electron transfer at three sites, NADH dehydrogenase (complex I), succinate dehydrogenase (complex II), and cytochrome c oxidase (complex IV). Respiratory rate and electron transport chain enzyme activities were significantly inhibited in the drug-resistant, TNF-sensitive cell lines. Respiratory inhibition preceded cell death by at least 5 to 8 hours. The respiratory failure was not compensated for by appropriate up-regulation of the glycolytic pathway. Increasing mitochondrial respiratory rate and enzyme activities by long-term culture with 2 mmol/L adenosine 5'-diphosphate (ADP) and Pi sensitized both drug-sensitive and drug-resistant cells to TNFalpha-induced cytolysis. Intramitochondrial free radicals generated by paraquat only had a limited and delayed effect on respiratory inhibition and cytolysis in comparison with the effect of TNFalpha. We conclude that TNFalpha-induced cytotoxicity in leukemic cells is, at least in part, mediated by inhibition of mitochondrial respiration. Free radical generation by TNFalpha may not directly lead to the observed inhibition of the mitochondrial electron transport and other mechanisms must be involved. PMID:8630404

Jia, L; Kelsey, S M; Grahn, M F; Jiang, X R; Newland, A C

1996-03-15

198

Procedure of bidirectional selective outbreeding for production of two rat lines differing in sensitivity to the sedative\\/hypnotic effect of ?-hydroxybutyric acid  

Microsoft Academic Search

The exogenous administration of ?-hydroxybutyric acid (GHB), a constituent of the mammalian brain where it likely functions as a neurotransmitter or a neuromodulator, exerts a number of pharmacological effects, including sedation and hypnosis. The present paper describes a procedure for selective breeding of two rat lines which markedly differ in sensitivity to the sedative\\/hypnotic effect of GHB. Selective breeding originated

Carla Lobina; Giancarlo Colombo; Giuliana Brunetti; Giacomo Diaz; Samuele Melis; Marialaura Pani; Salvatore Serra; Giovanni Vacca; Gian Luigi Gessa; Mauro A. M. Carai

2001-01-01

199

Temperature-sensitive Line Ratios Diagnostics of the non-flaring Corona based on Satellite-to-Resonance Line Ratios for 1s^2-1s(np) Transitions  

NASA Astrophysics Data System (ADS)

One of the most convenient electron temperature diagnostics of hot astrophysical plasmas is the intensity ratio of dielectronic satellite lines to resonance lines in the X-ray region. Until now, this diagnostic has been applied to satellites near the 1s-2p lines of H-like ions or the 1s^2 - 1s2p lines of He-like ions, these lines being extensively observed with crystal spectrometers during flares. However, satellites near the 1s^2 - 1snp (n>2) lines of He-like ions, unlike those near the 1s^2 - 1s2p lines, have the important advantage of being well separated from their parent lines and unblended with other lines. Spectra from the RESIK spectrometer on Coronas-F, covering the wavelength range 3.4 Å,- 6.1 Å, are highly suited for observation of these satellites, due to transitions from the n = 3, 4 and 5 levels to the n = 1 level, near corresponding resonance lines of H-like and He-like Si (Si XIII, Si XIV) and S (S XV, S XVI) ions. New calculations of satellite intensity factors presented in this paper enable temperatures to be calculated from observed ratios of Li-like Si (Si XII) 1s^2 2p ^2P1/2,3/2 - 1s 2p (^3P) 3p ^2D3/2,5/2 satellite complex (5.816 Å) near He-like Si (Si XIII) 1s^2 ^1S_0 - 1s 3p ^1P_1} resonance (5.681 Å) line. These lines are well observed in recent quiet and non-flaring active region RESIK X-ray spectra, and therefore provide the most sensitive temperature diagnostic tool for physical conditions in weakly active corona.

Phillips, K. J. H.; Dubau, J.; Sylwester, J.; Sylwester, B.; Kordylewski, Z.; Culhane, J. L.; Doschek, G. A.; Lang, J.

200

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

PubMed Central

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-related protein and stathmin suggested mechanisms for rapid cytoskeletal reorganization on return to euthermy during torpor-arousal cycles. PMID:23951209

Hindle, Allyson G.; Martin, Sandra L.

2013-01-01

201

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

PubMed

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-related protein and stathmin suggested mechanisms for rapid cytoskeletal reorganization on return to euthermy during torpor-arousal cycles. PMID:23951209

Hindle, Allyson G; Martin, Sandra L

2013-01-01

202

Equivalent Neutrinos, Light WIMPs, and the Chimera of Dark Radiation  

E-print Network

According to conventional wisdom, in the standard model (SM) of particle physics and cosmology the effective number of neutrinos is Neff=3 (more precisely, 3.046). In extensions of the standard model allowing for the presence of DeltaNnu equivalent neutrinos (or dark radiation), Neff is generally >3. The canonical results are reconsidered here, revealing that a measurement of Neff>3 can be consistent with DeltaNnu=0 (dark radiation without dark radiation). Conversely, a measurement consistent with Neff=3 is not inconsistent with the presence of dark radiation (DeltaNnu>0). In particular, if there is a light WIMP that annihilates to photons after the SM neutrinos have decoupled, the photons are heated beyond their usual heating from e+- annihilation, reducing the late time ratio of neutrino and photon temperatures (and number densities), leading to Neff3 even in the absence of equivalent neutrinos or dark radiation. A measurement of Neff>3 is thus no guarantee of the presence of equivalent neutrinos or dark ra...

Steigman, Gary

2013-01-01

203

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

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.

Li Bo; Torossian, Artour [Department of Radiation Oncology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee (United States)] [Department of Radiation Oncology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Sun, Yunguang [Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States)] [Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Du, Ruihong [Department of Radiation Oncology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee (United States)] [Department of Radiation Oncology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Dicker, Adam P. [Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States)] [Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Lu Bo, E-mail: bo.lu@jefferson.edu [Department of Radiation Oncology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States)

2012-11-15

204

The Effects of QCD Equation of State on the Relic Density of WIMP Dark Matter  

E-print Network

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 $\\Omega_{c}h^2=0.1193\\pm0.0014$, 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.

Manuel Drees; Fazlollah Hajkarim; Ernany Rossi Schmitz

2015-03-11

205

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

PubMed Central

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

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

2014-01-01

206

Relationship between Resolution, Line Edge Roughness, and Sensitivity in Chemically Amplified Resist of Post-Optical Lithography Revealed by Monte Carlo and Dissolution Simulations  

NASA Astrophysics Data System (ADS)

The simultaneous achievement of high resolution and low line width (edge) roughness (LWR, LER) at acceptable sensitivity (RLS) in chemically-amplified resist (CAR) is in strong demand to realize the mass production of ultra-small electric circuit using extreme ultraviolet. We performed Monte Carlo and dissolution simulations of positive-tone CAR of electron beam lithography to clarify this RLS formation. The trade-off RLS relationship was successfully reproduced and discussed in terms of non-scaling law of exposed line width. It was demonstrated that LER follows the inverse of square root of exposure dose at moderate acid diffusion length.

Saeki, Akinori; Kozawa, Takahiro; Tagawa, Seiichi

2009-07-01

207

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

NASA Astrophysics Data System (ADS)

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

Nygren, David

2013-04-01

208

Standard Model anatomy of WIMP dark matter direct detection. II. QCD analysis and hadronic matrix elements  

NASA Astrophysics Data System (ADS)

Models of weakly interacting massive particles (WIMPs) specified at the electroweak scale are systematically matched to effective theories at hadronic scales where WIMP-nucleus scattering observables are evaluated. Anomalous dimensions and heavy-quark threshold matching conditions are computed for the complete basis of lowest-dimension effective operators involving quarks and gluons. The resulting QCD renormalization group evolution equations are solved. The status of relevant hadronic matrix elements is reviewed and phenomenological illustrations are given, including details for the computation of the universal limit of nucleon scattering with heavy S U (2 )W×U (1 )Y charged WIMPs. Several cases of previously underestimated hadronic uncertainties are isolated. The results connect arbitrary models specified at the electroweak scale to a basis of nf=3 -flavor QCD operators. The complete basis of operators and Lorentz invariance constraints through order v2/c2 in the nonrelativistic nucleon effective theory are derived.

Hill, Richard J.; Solon, Mikhail P.

2015-02-01

209

Standard Model anatomy of WIMP dark matter direct detection II: QCD analysis and hadronic matrix elements  

E-print Network

Models of Weakly Interacting Massive Particles (WIMPs) specified at the electroweak scale are systematically matched to effective theories at hadronic scales where WIMP-nucleus scattering observables are evaluated. Anomalous dimensions and heavy quark threshold matching conditions are computed for the complete basis of lowest-dimension effective operators involving quarks and gluons. The resulting QCD renormalization group evolution equations are solved. The status of relevant hadronic matrix elements is reviewed and phenomenological illustrations are given, including details for the computation of the universal limit of nucleon scattering with heavy $SU(2)_W\\times U(1)_Y$ charged WIMPs. Several cases of previously underestimated hadronic uncertainties are isolated. The results connect arbitrary models specified at the electroweak scale to a basis of $n_f=3$ flavor QCD operators. The complete basis of operators and Lorentz invariance constraints through order $v^2/c^2$ in the nonrelativistic nucleon effective theory are derived.

Richard J. Hill; Mikhail P. Solon

2014-09-29

210

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

SciTech Connect

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 ? 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{sup +}e{sup ?} collider with ?(s)?500–600 GeV should provide a thorough search for the predicted light higgsinos.

Baer, Howard [Dep't of Physics and Astronomy, University of Oklahoma, Norman, OK 73019 (United States)

2014-06-24

211

Probing low WIMP masses with the next generation of CRESST detector  

E-print Network

The purpose of this document is to describe the upgrade of the CRESST dark matter search at LNGS. The proposed strategy will allow to explore a region of the parameter space for spin-independent WIMP-nucleon elastic scattering corresponding to WIMP masses below 10GeV/c$^\\text{2}$, that has not been covered by other experiments. These results can be achieved only with outstanding detector performances in terms of threshold and background. This proposal shows how CRESST can match these performance requirements, adding a unique piece of information to the dark matter puzzle. The results of this program will fix a new state-of-the-art in the low mass WIMP exploration, opening new perspectives of understanding the dark matter scenario.

Angloher, G; Bucci, C; Canonica, L; Erb, A; Feilitzsch, F v; Iachellini, N Ferreiro; Gorla, P; Gütlein, A; Hauff, D; Jochum, J; Kiefer, M; Kluck, H; Kraus, H; Lanfranchi, J -C; Loebell, J; Münster, A; Petricca, F; Potzel, W; Pröbst, F; Reindl, F; Schäffner, K; Schieck, J; Scholl, S; Schönert, S; Seidel, W; Stodolsky, L; Strandhagen, C; Strauss, R; Tanzke, A; Uffinger, M; Ulrich, A; Usherov, I; Wawoczny, S; Willers, M; Wüstrich, M; Zöller, A

2015-01-01

212

Limits on spin-dependent WIMP-nucleon cross-sections from the XENON10 experiment  

E-print Network

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

J. Angle; E. Aprile; F. Arneodo; L. Baudis; A. Bernstein; A. Bolozdynya; P. Brusov; L. C. C. Coelho; C. E. Dahl; L. DeViveiros; A. D. Ferella; L. M. P. Fernandes; S. Fiorucci; R. J. Gaitskell; K. L. Giboni; R. Gomez; R. Hasty; L. Kastens; J. Kwong; J. A. M. Lopes; N. Madden; A. Manalaysay; A. Manzur; D. N. McKinsey; M. E. Monzani; K. Ni; U. Oberlack; J. Orboeck; G. Plante; R. Santorelli; J. M. F. dos Santos; P. Shagin; T. Shutt; P. Sorensen; S. Schulte; C. Winant; M. Yamashita; for the XENON10 Collaboration

2008-09-10

213

The XENON10 WIMP Search Experiment at the Gran Sasso Underground Laboratory  

E-print Network

XENON10 is a new direct dark matter detection experiment using liquid xenon as target for weakly interacting, massive particles (WIMPs). A two-phase (liquid/gas) time projection chamber with 15 kg fiducial mass has been installed in a low-background shield at the Gran Sasso Underground Laboratory in July 2006. After initial performance tests with various calibration sources, the science data run started on August 24, 2006. The detector has been running stably since then, and a full analysis of more than 75 live days of WIMP search data is now in progress. We present first results on gamma and neutron calibration runs, as well as a preliminary analysis of a subset of the WIMP search data.

Laura Baudis

2007-03-08

214

ATP-sensitive potassium channels and efaroxan-induced insulin release in the electrofusion-derived BRIN-BD11 beta-cell line  

Microsoft Academic Search

The properties of ATP-sensitive K + ( K AT P ) channels were explored in the electrofusion-derived, glucose- responsive, insulin-secreting cell line BRIN-BD11 using patch-clamp techniques. In intact cells, K AT P c h a n n e l s were inhibited by glucose, the sulfonylurea tolbuta- mide, and the imidazoline compounds efaroxan and phentolamine. Each of these agents initiated

Joanna C. Chapman; Neville H. McClenaghan; Karen E. Cosgrove; Molly N. Hashmi; Ruth M. Shepherd; Aukje N. Giesberts; Stanley J. White; C. Ammala; Peter R. Flatt; Mark J. Dunne

1999-01-01

215

Immunological Quantitation of Thymidylate Synthase Using the Monoclonal Antibody TS 106 in 5-Fluorouracil-sensitive and -resistant Human Cancer Cell Lines  

Microsoft Academic Search

Thymidylate synthase (TS) (EC 2.1.1.45) is an important cellular target for the fluoropyrimidinecytotoxic drugs that are widely used in the treatmentof solid tumors. Using the TS 106 monoclonalantibodyto humanTS, we have comparedthe ¡mmunological quantitationof TS by Western immunoblotand immunofluorescenttechniques to the conven tional biochemical 5-fluorodeoxyuridinemonophosphate binding assay in a panel of 5-fluorouracil(S-FU)-sensitive and -resistant human can cer cell lines. Densitometric

Patrick G. Johnston; James C. Drake; Jane Trepel; Carmen J. Allegra

216

Anxiety-like behaviors in pre-pubertal rats of the Flinders Sensitive Line (FSL) and Wistar-Kyoto (WKY) animal models of depression  

Microsoft Academic Search

Animal models have been used in understanding the neuro-biological basis of depression and predicting successful treatment strategies. The current study focused on two genetic models of depression, the Flinder's Sensitive Line (FSL) and Wister-Kyoto (WKY). Our laboratory showed depressive symptomatology in pre-pubertal WKY and FSL rats, and the current study focused on the strains’ anxiety-like traits. Since human depression–anxiety comorbidity

Y. Braw; O. Malkesman; M. Dagan; A. Bercovich; Y. Lavi-Avnon; M. Schroeder; D. H. Overstreet; A. Weller

2006-01-01

217

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

E-print Network

We present new experimental constraints on the elastic, spin-dependent WIMP-nucleon cross section using recent data from the XENON100 experiment, operated in the Laboratori Nazionali del Gran Sasso in Italy. An analysis of 224.6 live days x 34 kg of exposure acquired during 2011 and 2012 revealed no excess signal due to axial-vector WIMP interactions with 129-Xe and 131-Xe nuclei. This leads to the most stringent upper limits on WIMP-neutron cross sections for WIMP masses above 6 GeV, with a minimum cross section of 3.5 x 10^{-40} cm^2 at a WIMP mass of 45 GeV, at 90% confidence level.

XENON100 collaboration; E. Aprile; M. Alfonsi; K. Arisaka; F. Arneodo; C. Balan; L. Baudis; B. Bauermeister; A. Behrens; P. Beltrame; K. Bokeloh; A. Brown; E. Brown; G. Bruno; R. Budnik; J. M. R. Cardoso; W. -T. Chen; B. Choi; A. P. Colijn; H. Contreras; J. P. Cussonneau; M. P. Decowski; E. Duchovni; S. Fattori; A. D. Ferella; W. Fulgione; F. Gao; M. Garbini; C. Ghag; K. -L. Giboni; L. W. Goetzke; C. Grignon; E. Gross; W. Hampel; F. Kaether; A. Kish; J. Lamblin; H. Landsman; R. F. Lang; M. Le Calloch; D. Lellouch; C. Levy; K. E. Lim; Q. Lin; S. Lindemann; M. Lindner; J. A. M. Lopes; K. Lung; T. Marrodan Undagoitia; F. V. Massoli; A. J. Melgarejo Fernandez; Y. Meng; M. Messina; A. Molinario; K. Ni; U. Oberlack; S. E. A. Orrigo; E. Pantic; R. Persiani; G. Plante; N. Priel; A. Rizzo; S. Rosendahl; J. M. F. dos Santos; G. Sartorelli; J. Schreiner; M. Schumann; L. Scotto Lavina; P. R. Scovell; M. Selvi; P. Shagin; H. Simgen; A. Teymourian; D. Thers; O. Vitells; H. Wang; M. Weber; C. Weinheimer

2013-01-29

218

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

E-print Network

We present new experimental constraints on the elastic, spin-dependent WIMP-nucleon cross section using recent data from the XENON100 experiment, operated in the Laboratori Nazionali del Gran Sasso in Italy. An analysis of 224.6 live days x 34 kg of exposure acquired during 2011 and 2012 revealed no excess signal due to axial-vector WIMP interactions with 129-Xe and 131-Xe nuclei. This leads to the most stringent upper limits on WIMP-neutron cross sections for WIMP masses above 6 GeV, with a minimum cross section of 3.5 x 10^{-40} cm^2 at a WIMP mass of 45 GeV, at 90% confidence level.

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

2013-01-01

219

Comparison of chloroplast DNA between photoperiod-sensitive genic male sterile (PGMS) rice Nongken58S and its derivative sterile lines.  

PubMed

The ORF100, ORF29-TrnC(GCA) spacer, rps16 gene intron and TrnT(UGU)-TrnL(UAA) spacer of chloroplast DNA (cpDNA) of 6 photoperiod-sensitive genic male sterile (PGMS) rice, Nongken58S and its 5 derivatives, were amplified and sequenced. According to the result of ORF100 and ORF29-TrnC(GCA) spacer analysis, the cpDNA of japonica PGMS line Nongken58S was Japonica, and among those PGMS lines derived from Nongken58S, cpDNA of japonica 7001S and 3 indica lines 1103S, Peiai64S and Guangzhan63S were that of japonica, which was in accordance with the cytoplasm pedigree provided by their breeders. But the cpDNA of indica PGMS line W6154S was that of indica, which disaccorded with the cytoplasm pedigree, so we conjectured that the breeders had used the PGMS line as the male parent. Basing on the result of sequence analysis, we found single nucleotide polymorphism in rps16 gene intron and TrnT(UGU)-TrnL(UAA) spacer of these 5 japonica PGMS lines. PMID:16775395

Huang, Guang-Wen; Chen, Jue-Liang; Ou, Li-Jun; Lu, Xiang-Yang; Chen, Liang-Bi

2006-06-01

220

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

PubMed Central

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

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

2006-01-01

221

Multifactorial Resistance to Adriamycin: Relationship of DNA Repair, Glutathione Transferase Activity, Drug Efflux, and P-Glycoprotein in Cloned Cell Lines of Adriamycin-sensitive and -resistant P388 Leukemia1  

Microsoft Academic Search

Cloned lines of Adriamycin (ADR)-sensitive and -resistant P388 leu kemia have been established, including P388\\/ADR\\/3 and P388\\/ADR\\/7 that are 5- and 10-fold more resistant than the cloned sensitive cell line P388\\/4 (Cancer Res., 46: 2978, 1986). A time course of ADR-induced DNA double-strand breaks revealed that in sensitive P388\\/4 cells, evi dence of DNA repair was noted 4 h after

Abdul M. Deffie; Tawfiq Alam; Charita Seneviratne; Samuel W. Beenken; Janendra K. Batra; Thomas C. Shea; William D. Henner; Gerald J. Goldenberg

222

The response of primary rat and human osteoblasts and an immortalized rat osteoblast cell line to orthopaedic materials: comparative sensitivity of several toxicity indices.  

PubMed

When studying the biocompatibility of orthopaedic biomaterials it is often necessary to discriminate between responses which show mild cytotoxicity. It is therefore essential to use a very sensitive index of toxicity. We have compared the sensitivity of four well-established indices of toxicity: total cell protein content, leakage of lactate dehydrogenase (LDH), reduced glutathione content and the MTT assay, with that of a novel index, alkaline phosphatase (ALP) activity. Comparisons were made by detecting nickel chloride toxicity in osteoblasts. ALP activity, the novel method, proved the most sensitive index of toxicity and it provides a convenient automated assay for assessing the interactions of materials with osteoblasts. The responses to nickel chloride and to aqueous extracts prepared from carbon fibre reinforced epoxy and polyetheretherketone (peek), two candidate materials for orthopaedic implants, were compared in primary and immortalized rat osteoblasts, and in primary human osteoblasts. Although the immortalized rat osteoblast cell line, FFC, was consistently the most sensitive cell type, the responses of the human cells and the FFC cell line were similar in terms of ALP activity throughout the range of nickel concentrations studied. Neither peek nor epoxy material extracts showed a significant decrease in the MTT or ALP responses in any of the three cell types. Our data suggest that immortalized rat osteoblasts may provide an in vitro model system for screening the biocompatibility of orthopaedic polymers. PMID:15348778

Macnair, R; Rodgers, E H; Macdonald, C; Wykman, A; Goldie, I; Grant, M H

1997-02-01

223

An X-Ray Line from eXciting Dark Matter  

NASA Astrophysics Data System (ADS)

The recently reported 3.5 keV line from galaxy clusters and M31 has rekindled interest in dark matter production of lines at X-ray energies. We propose a model in which WIMPs are collisionally excited and de-excite via photon production, thereby converting WIMP kinetic energy into photons. Such a mechanism has different dependencies on density and velocity than sterile neutrino decay, and has more flexibility for explaining the data. I will summarize the current observational status of the 3.5 keV line and the merits of various scenarios to explain it.

Finkbeiner, Douglas P.; Weiner, Neal

2014-06-01

224

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

SciTech Connect

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

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

2007-01-01

225

The development of a sensitive method to study volatile organic compounds in gaseous emissions of lung cancer cell lines  

E-print Network

is different and unique when compared to previous methods because cell lines have not been studied extensively for cancer markers. We have studied cancer cell lines which are adherent, immortalized cultures originating from primary tumors obtained from... cancer (SCLC) and non?small-cell lung cancer (NSCLC), which includes several types of tumors. NSCLC consists of squamous cell carcinoma, adenocarcinoma and large cell carcinoma (Fig 1). Fig. 1. Types of lung cancer LUNG...

Maroly, Anupam

2005-08-29

226

hMena+11a Isoform Serves as a Marker of Epithelial Phenotype and Sensitivity to EGFR Inhibition in Human Pancreatic Cancer Cell Lines  

PubMed Central

Purpose hMena, member of the Ena/VASP protein family, is a cytoskeletal protein that is involved in the regulation of cell motility and adhesion. The aim of this study was to determine whether or not the expression of hMena isoforms correlated with sensitivity to EGFR tyrosine kinase inhibitors and could serve as markers with potential clinical use. Experimental design Human pancreatic ductal adenocarcinoma (PDAC) cell lines were characterized for in vitro sensitivity to erlotinib, expression of HER family receptors, markers of epithelial to mesenchymal transition (EMT), and expression of hMena and its isoform hMena+11a. The effects of EGF and erlotinib on hMena expression as well as the effect of hMena knock-down on cell proliferation were also evaluated. Results hMena was detected in all of the pancreatic tumor cell lines tested as well as in the majority of the human tumor samples [primary (92%) and metastatic (86%)]. Intriguingly, in vitro hMena+11a isoform was specifically associated with an epithelial phenotype, EGFR dependency and sensitivity to erlotinib. In epithelial BxPC3 cells EGF upregulated hMena/hMena+11a and erlotinib downregulated expression. hMena knock-down reduced cell proliferation and MAPK and AKT activation in BxPC3 cells and promoted the growth inhibitory effects of erlotinib. Conclusions Collectively, our data indicate that the hMena+11a isoform is associated with an epithelial phenotype and identifies EGFR dependent cell lines that are sensitive to the EGFR inhibitor erlotinib. The availability of anti-hMena+11a specific probes may offer a new tool in pancreatic cancer management if these results can be verified prospectively in cancer patients. PMID:18676769

Pino, Maria S.; Balsamo, Michele; Di Modugno, Francesca; Mottolese, Marcella; Alessio, Massimo; Melucci, Elisa; Milella, Michele; McConkey, David J.; Philippar, Ulrike; Gertler, Frank B.; Natali, Pier Giorgio; Nistico, Paola

2008-01-01

227

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

PubMed

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

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

2009-01-01

228

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

NASA Astrophysics Data System (ADS)

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 ?m-long-MFC and a microfiber 44 ?m in diameter in different droplets. Ultrahigh sensitivities of 34.65 nm/°C (˜88 380 nm/RIU) and -493.7 nm/N (˜-590 pm/??) are experimentally achieved using a droplet with a refractive index of ˜1.44.

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

2015-02-01

229

Atmospheric Neutrinos, WIMPs and Monopoles: Physics with the AMANDA Neutrino Telescope  

E-print Network

Atmospheric Neutrinos, WIMPs and Monopoles: Physics with the AMANDA Neutrino Telescope W. Rhode , S. Richter 13 , J. Rodr#19;#16;guez Martino 16 , P. Romenesko 13 , D. Ross 9 , H.-G. Sander 10 , T, Dienst ELEM, B-1050 Brussel, Belgium #12; 2 Wolfgang Rhode et al. Abstract. AMANDA is a neutrino

Woschnagg, Kurt

230

Impacts of WIMP dark matter upon stellar evolution: main-sequence stars  

E-print Network

The presence of large amounts of WIMP dark matter in stellar cores has been shown to have significant effects upon models of stellar evolution. We present a series of detailed grids of WIMP-influenced stellar models for main sequence stars, computed using the DarkStars code. We describe the changes in stellar structure and main sequence evolution which occur for masses ranging from 0.3 to 2.0 solar masses and metallicities from Z = 0.0003-0.02, as a function of the rate of energy injection by WIMPs. We then go on to show what rates of energy injection can be obtained using realistic orbital parameters for stars near supermassive black holes, including detailed considerations of dark matter halo velocity and density profiles. Capture and annihilation rates are strongly boosted when stars follow elliptical rather than circular orbits, causing WIMP annihilation to provide up to 100 times the energy of hydrogen fusion in stars at the Galactic centre.

Pat Scott; Malcolm Fairbairn; Joakim Edsjö

2008-10-30

231

Model-independent WIMP Scattering Responses and Event Rates: A Mathematica Package for Experimental Analysis  

E-print Network

The community's reliance on simplified descriptions of WIMP-nucleus interactions reflects the absence of analysis tools that integrate general theories of dark matter with standard treatments of nuclear response functions. To bridge this gap, we have constructed a public-domain Mathematica package for WIMP analyses based on our effective theory formulation. Script inputs are 1) the coefficients of the effective theory, through which one can characterize the low-energy consequences of arbitrary ultraviolet theories of WIMP interactions; and 2) one-body density matrices for commonly used targets, the most compact description of the relevant nuclear physics. The generality of the effective theory expansion guarantees that the script will remain relevant as new ultraviolet theories are explored; the use of density matrices to factor the nuclear physics from the particle physics will allow nuclear structure theorists to update the script as new calculations become available, independent of specific particle-physics contexts. The Mathematica package outputs the resulting response functions (and associated form factors) and also the differential event rate, once a galactic WIMP velocity profile is specified, and thus in its present form provides a complete framework for experimental analysis. The Mathematica script requires no a priori knowledge of the details of the non-relativistic effective field theory or nuclear physics, though the core concepts are reviewed here and in arXiv:1203.3542.

Nikhil Anand; A. Liam Fitzpatrick; W. C. Haxton

2013-08-28

232

The Pressure of Misalignment Axions: a Difference from WIMPs in Galaxy Formation?  

E-print Network

Two populations of axions can contribute to cold dark matter: the classical field produced via the misalignment mechanism, and the modes produced in the decay of strings. The classical field has extra pressure, as compared to WIMPs, which could have observable consequences in non-linear galaxy formation.

Sacha Davidson

2014-10-18

233

ON METEORS, EARTHWORMS AND WIMPS SARA BILLEY, KRZYSZTOF BURDZY, SOUMIK PAL, AND BRUCE E. SAGAN  

E-print Network

ON METEORS, EARTHWORMS AND WIMPS SARA BILLEY, KRZYSZTOF BURDZY, SOUMIK PAL, AND BRUCE E. SAGAN of the graph holds mass Mx t 0 at time t. When a "meteor hits" x at time t, the mass Mx t of the soil present) left at x just after a meteor hit. Meteor hits are modeled as independent Poisson processes, one

Sagan, Bruce

234

Fast and sensitive time-multiplexed gas sensing of multiple lines using a miniature telecom diode laser between 1529 nm and 1565 nm  

NASA Astrophysics Data System (ADS)

High-sensitive multi-species detection around 1550 nm using a modulated grating Y-branch, MG-Y, diode laser tunable between 1529 nm and 1565 nm is presented. The MG-Y diode laser is based on the Vernier effect of two modulated gratings, and exhibits quasi-continuous tuning over 36 nm. Multi-species detection is achieved by fast sequential scanning of single absorption lines of CH4, CO, C2H2, and CO2 distributed over the tuning range of the diode laser. The laser wavelength is scanned about 10 GHz around each absorption line for 5 ms and this is followed by a discrete large jump in operating wavelength to the next line. The MG-Y diode laser has a good repeatability in output frequency between sequential scan segments (<10 MHz) enabling averaging of the scans. The setup employs digital wavelength modulation spectroscopy, dWMS, with Fourier-based WMS retrieval, applicable through the use of data acquisition cards and coherent sampling. Absorbance sensitivity using 2 f-WMS signals of 7×10-7 in 30 s (all precisions in this paper are at the 1 ? level) is demonstrated for sensing of four gases and 2×10-7 when only one gas is detected. Corresponding numbers for 0.5 s of averaging are 4×10-6 and 1×10-6.

Lewander, M.; Fried, A.; Weibring, P.; Richter, D.; Spuler, S.; Rippe, L.

2011-09-01

235

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

NASA Technical Reports Server (NTRS)

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.

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

1999-01-01

236

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

Microsoft Academic Search

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

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

2006-01-01

237

First measurement of the Head-Tail directional nuclear recoil signature at energies relevant to WIMP dark matter searches  

E-print Network

We present first evidence for the so-called Head-Tail asymmetry signature of neutron-induced nuclear recoil tracks at energies down to 1.5 keV/amu using the 1m^3 DRIFT-IIc dark matter detector. This regime is appropriate for recoils induced by Weakly Interacting Massive Particle (WIMPs) but one where the differential ionization is poorly understood. We show that the distribution of recoil energies and directions induced here by Cf-252 neutrons matches well that expected from massive WIMPs. The results open a powerful new means of searching for a galactic signature from WIMPs.

S. Burgos; E. Daw; J. Forbes; C. Ghag; M. Gold; C. Hagemann; V. A. Kudryavtsev; T. B. Lawson; D. Loomba; P. Majewski; D. Muna; A. StJ. Murphy; G. G. Nicklin; S. M. Paling; A. Petkov; S. J. S. Plank; M. Robinson; N. Sanghi; D. P. Snowden-Ifft; N. J. C. Spooner; J. Turk; E. Tziaferi

2008-09-10

238

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

NASA Astrophysics Data System (ADS)

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

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

2013-03-01

239

Comparative proteomic analysis of paclitaxel sensitive A549 lung adenocarcinoma cell line and its resistant counterpart A549Taxol  

Microsoft Academic Search

Purpose  Paclitaxel is used as the first-line chemotherapy for Non-Small Cell Lung Cancer (NSCLC), but acquired resistance becomes\\u000a a critical problem. Several mechanisms have been proposed in paclitaxel resistance, but they are not sufficient to exhaustively\\u000a explain this resistance emergence. To better investigate molecular resistance mechanisms, a comparative proteomic approach\\u000a was carried out to identify differentially expressed proteins between human lung

Qiang-ling Sun; Hui-fang Sha; Xiao-hua Yang; Guo-liang Bao; Jing Lu; Yin-yin Xie

2011-01-01

240

Sensitivity and resistance towards isoliquiritigenin, doxorubicin and methotrexate in T cell acute lymphoblastic leukaemia cell lines by pharmacogenomics.  

PubMed

The development of drug resistance in cancer cells necessitates the identification of novel agents with improved activity towards cancer cells. In the present investigation, we compared the cytotoxicity of the chalcone flavonoide, isoliquiritigenin (ISL), with that of doxorubicin (DOX) and methotrexate (MTX) in five T cell acute lymphoblastic leukaemia (T-ALL) cell lines (Jurkat, J-Jhan, J16, HUT78 and Karpas 45). To gain insight into the molecular mechanisms which determine the response of T-ALL cells towards ISL, DOX and MTX, we applied array-based matrix comparative genomic hybridisation and microarray-based mRNA expression profiling and compared the genomic and transcriptomic profiles of the cell lines with their 50% inhibition (IC(50)) values for these three drugs. The IC(50) values for ISL did not correlate with those for DOX or MTX, indicating that ISL was still active in DOX- or MTX-unresponsive cell lines. Likewise, the genomic imbalances of chromosomal clones and mRNA expression profile significantly correlating with IC(50) values for ISL were different from thoses correlating with IC(50) values for DOX and MTX. In conclusion, ISL represents a cytotoxic natural product with activity towards T-ALL cell lines. There was no cross-resistance between ISL and DOX or MTX, and the genomic and transcriptomic profiles pointed to different molecular modes of action of ISL as compared to DOX and MTX, indicating that ISL may be a valuable adjunct for cancer therapy to treat otherwise drug-resistant tumours. PMID:20668838

Youns, Mahmoud; Fu, Yu-Jie; Zu, Yuan-Gang; Kramer, Anne; Konkimalla, V Badireenath; Radlwimmer, Bernhard; Sültmann, Holger; Efferth, Thomas

2010-09-01

241

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

SciTech Connect

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

Jackson, C.B. [University of Texas at Arlington, Arlington, TX 76019 (United States); Servant, Géraldine [CERN Physics Department, Theory Division, CH-1211, Geneva 23 (Switzerland); Shaughnessy, Gabe [Department of Physics, University of Wisconsin, Madison, WI 53706 (United States); Tait, Tim M.P. [Department of Physics and Astronomy, University of California, Irvine, CA 92697 (United States); Taoso, Marco, E-mail: geraldine.servant@cern.ch, E-mail: chris@uta.edu, E-mail: gshau@hep.wisc.edu, E-mail: ttait@uci.edu, E-mail: marco.taoso@cea.fr [Institut de Physique Théorique, CEA/Saclay, F-91191 Gif-sur-Yvette Cédex (France)

2013-07-01

242

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

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-1?, 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.

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

2012-08-01

243

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

PubMed Central

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

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

2013-01-01

244

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

PubMed

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

Olschläger, Veronika; Schrader, Andreas; Hockertz, Stefan

2009-01-01

245

Dark matter in the solar system I: The distribution function of WIMPs at the Earth from solar capture  

E-print Network

The next generation of dark matter (DM) direct detection experiments and neutrino telescopes will probe large swaths of dark matter parameter space. In order to interpret the signals in these experiments, it is necessary to have good models of both the halo DM streaming through the solar system and the population of DM bound to the solar system. In this paper, the first in a series of three on DM in the solar system, we present simulations of orbits of DM bound to the solar system by solar capture in a toy solar system consisting of only the Sun and Jupiter, assuming that DM consists of a single species of weakly interacting massive particle (WIMP). We describe how the size of the bound WIMP population depends on the WIMP mass, spin-independent cross section, and spin-dependent cross section. Using a standard description of the Galactic DM halo, we find that the maximum enhancement to the direct detection event rate, consistent with current experimental constraints on the WIMP-nucleon cross section, is < 1% relative to the event rate from halo WIMPs, while the event rate from neutrinos from WIMP annihilation in the center of the Earth is unlikely to meet the threshold of next-generation, km^3-sized (IceCube, KM3NeT) neutrino telescopes.

Annika H. G. Peter

2009-02-09

246

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

PubMed Central

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

2012-01-01

247

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

PubMed

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

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

1999-01-01

248

Transfection of rat dermal papilla cells with a gene encoding a temperature-sensitive polyomavirus large T antigen generates cell lines retaining a differentiated phenotype.  

PubMed

The dermal papilla is a discrete group of cells at the base of the hair follicle and is implicated in controlling the hair growth cycle. Early passage dermal papilla cells can induce hair growth in vivo, but, upon further culturing, this property is lost. In order to study the events occurring in hair induction, a representative dermal papilla cell line was required. We have transfected passage 1 rat vibrissa dermal papilla cells with a polyomavirus large T gene encoding a temperature-sensitive T antigen, and generated permanent cell lines in which the immortalizing function can be switched off by temperature shift. The cells established without crisis, resembled cells in the starting population, and retained the aggregative properties of early passage dermal papilla cells. Growth studies were performed on the immortalized cell lines, which showed that transferring the cells to the restrictive temperature for the large T gene product resulted in cell senescence or quiescence, and changes in morphology. Implantation of cell pellets into the ears of immunologically compatible rats showed that the immortal cells retained hair-inductive ability. Cytokines are believed to have an important role in the control of hair growth. The pattern of cytokine gene expression in the immortal cell lines was compared with early passage dermal papilla cells and a non-hair-inducing dermal papilla cell line, using reverse transcriptase-polymerase chain reaction. Epidermal growth factor, tumour necrosis factor, and interleukin-1a were detected in the immortalized and non-hair-inducing dermal papilla cell lines, but were absent in passage 2 dermal papilla cells. All other cytokines examined were detected in all the cell types under study. These results demonstrate that the polyomavirus large Ttsa-immortalized dermal papilla cell lines are very similar to passage 2 dermal papilla cells and thus provide a good model for hair growth studies. Cytokine expression profiles indicate that the expression of several cytokines may be implicated in hair induction. Further studies are under way to investigate the relationship between cytokine expression and the hair growth cycle. PMID:7983146

Filsell, W; Little, J C; Stones, A J; Granger, S P; Bayley, S A

1994-07-01

249

Luteolin potentiates the sensitivity of colorectal cancer cell lines to oxaliplatin through the PPAR?/OCTN2 pathway.  

PubMed

Oxaliplatin is a chemotherapeutic agent used in the treatment of colorectal cancers. However, the mechanism controlling the cellular uptake and efflux of oxaliplatin is not completely understood. Organic cation/carnitine transporter 2 (OCTN2) is a member of the solute carrier superfamily and is a determinant of oxaliplatin uptake. OCTN2 is regulated by peroxisome proliferator-activated receptor ? (PPAR?) binding to the PPAR-response element within the first intron. Luteolin is a naturally occurring flavonoid and an agonist of PPAR?. Thus, we hypothesize that luteolin-mediated OCTN2 expression and activity potentiate the sensitivity of cancer cells to oxaliplatin. In this study, luteolin increased mRNA and protein expression of OCTN2 in a time-dependent and dose-dependent manner in colorectal cancer SW480 cells. This induction was attenuated by PPAR? antagonist GW9662 as well as by PPAR? knockdown, suggesting that the induction by luteolin is dependent on PPAR?. In uptake studies, luteolin increased the binding affinity of OCTN2 toward oxaliplatin and enhanced intracellular concentration of oxaliplatin. This finding is likely because of the increase of PDZ domain containing 1 (PDZK1) and PDZ domain containing 3 (PDZK2), which are known to facilitate the expression of OCTN2 on the cell surface and/or enhance transporter activity. Moreover, cell viability and cell apoptosis assays showed that luteolin increased oxaliplatin uptake and intracellular accumulation through OCTN2. Thus, our study showed that luteolin increased the sensitivity of colorectal cancer SW480 cells to oxaliplatin, likely through the PPAR?/OCTN2 pathway. PMID:25075794

Qu, Qiang; Qu, Jian; Guo, Yong; Zhou, Bo-Ting; Zhou, Hong-Hao

2014-10-01

250

Downregulation of c-Met expression does not enhance the sensitivity of gastric cancer cell line MKN-45 to gefitinib.  

PubMed

The aim of the present study was to investigate the effect of downregulation of the c?Met gene on signal transduction and apoptosis in gastric cancer MKN?45 cells; furthermore, the study aimed to determine whether altered c?Met gene expression affected MKN?45 sensitivity to gefitinib. Three c?Met?specific small interfering RNAs (siRNAs) were synthesized and transfected into MKN?45 cells. Messenger RNA (mRNA) and protein levels of c?Met and its downstream signaling molecules [phosphoinositide 3?kinase (PI3K) and AKT] were examined using reverse transcription polymerase chain reaction and western blot analysis 48 h following transfection. Cell apoptosis was evaluated using Annexin?V/propidium iodide double staining and fluorescence?activated cell sorting analysis. An MTT assay was performed in order to measure the 50% inhibitory concentration (IC50) of gefitinib on MKN?45 cells. The results of the present study demonstrated that 48 h post?transfection with c?Met siRNA, MKN?45 cells showed significantly downregulated expression of c?Met mRNA and protein as well as an increased rate of apoptosis (P<0.05). In addition, following c?Met siRNA transfection mRNA and protein levels of PI3K and AKT were not significantly altered in MKN?45 cells (P>0.05); however, a marked decrease in the expression levels of phosphorylated (p)?PI3K and p?AKT was observed (P<0.05). Furthermore, the IC50 of gefitinib in MKN?45 cells was not significantly decreased. In conclusion, knockdown of the c?Met gene promoted gastric cancer cell apoptosis and inhibited downstream p?PI3K and p?AKT; however, the sensitivity of MKN?45 cells to gefitinib was not increased. PMID:25395073

Ma, Jin-An; Hu, Chunhong; Li, Wenjuan; Ren, Jing; Zou, Fangwen; Zhou, Dongai; Zou, Wen; Wei, Yajun; Zhou, Ying

2015-03-01

251

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

PubMed Central

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

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

2014-01-01

252

Single-channel properties of a stretch-sensitive chloride channel in the human mast cell line HMC-1.  

PubMed

A stretch-activated (SA) Cl(-) channel in the plasma membrane of the human mast cell line HMC-1 was identified in outside-out patch-clamp experiments. SA currents, induced by pressure applied to the pipette, exhibited voltage dependence with strong outward rectification (55.1 pS at +100 mV and an about tenfold lower conductance at -100 mV). The probability of the SA channel being open (P (o)) also showed steep outward rectification and pressure dependence. The open-time distribution was fitted with three components with time constants of tau(1o) = 755.1 ms, tau(2o) = 166.4 ms, and tau(3o) = 16.5 ms at +60 mV. The closed-time distribution also required three components with time constants of tau(1c) = 661.6 ms, tau(2c) = 253.2 ms, and tau(3c) = 5.6 ms at +60 mV. Lowering extracellular Cl(-) concentration reduced the conductance, shifted the reversal potential toward chloride reversal potential, and decreased the P (o) at positive potentials. The SA Cl(-) currents were reversibly blocked by the chloride channel blocker 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) but not by (Z)-1-(p-dimethylaminoethoxyphenyl)-1,2-diphenyl-1-butene (tamoxifen). Furthermore, in HMC-1 cells swelling due to osmotic stress, DIDS could inhibit the increase in intracellular [Ca(2+)] and degranulation. We conclude that in the HMC-1 cell line, the SA outward currents are mediated by Cl(-) influx. The SA Cl(-) channel might contribute to mast cell degranulation caused by mechanical stimuli or accelerate membrane fusion during the degranulation process. PMID:19823818

Wang, Lina; Ding, Guanghong; Gu, Quanbao; Schwarz, Wolfgang

2010-04-01

253

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

SciTech Connect

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

Bernal, Nicolás [Bethe Center for Theoretical Physics and Physikalisches Institut, Universität Bonn, Nußallee 12, D-53115 Bonn (Germany); Martín-Albo, Justo; Palomares-Ruiz, Sergio, E-mail: nicolas@th.physik.uni-bonn.de, E-mail: justo.martin-albo@ific.uv.es, E-mail: sergio.palomares.ruiz@ific.uv.es [Instituto de Física Corpuscular (IFIC), CSIC-Universitat de València, Apartado de Correos 22085, E-46071 València (Spain)

2013-08-01

254

New constraints on WIMPs from the Canfranc IGEX dark matter search  

E-print Network

The IGEX Collaboration enriched 76Ge double-beta decay detectors are currently operating in the Canfranc Underground Laboratory with an overburden of 2450 m.w.e. A recent upgrade has made it possible to use them in a search for WIMPs. A new exclusion plot has been derived for WIMP-nucleon spin-independent interaction. To obtain this result, 30 days of data from one IGEX detector, which has an energy threshold of ~4 keV, have been considered. These data improve the exclusion limits derived from other germanium diode experiments in the ~50 GeV DAMA region, and show that with a moderate improvement of the background below 10 keV, the DAMA region may be tested with an additional 1 kg-year of exposure.

A. Morales; C. E. Aalseth; F. T. Avignone III; R. L. Brodzinski; S. Cebrian; E. Garcia; D. Gonzalez; W. K. Hensley; I. G. Irastorza; I. V. Kirpichnikov; A. A. Klimenko; H. S. Miley; J. Morales; A. Ortiz de Solorzano; S. B. Osetrov; V. S. Pogosov; J. Puimedon; J. H. Reeves; M. L. Sarsa; S. Scopel; A. A. Smolnikov; A. G. Tamanyan; A. A. Vasenko; S. I. Vasiliev; J. A. Villar

2000-02-21

255

New constraints on WIMPs from the Canfranc IGEX dark matter search  

E-print Network

The IGEX Collaboration enriched 76Ge double-beta decay detectors arecurrently operating in the Canfranc Underground Laboratory with an overburdenof 2450 m.w.e. A recent upgrade has made it possible to use them in a searchfor WIMPs. A new exclusion plot has been derived for WIMP-nucleonspin-independent interaction. To obtain this result, 30 days of data from oneIGEX detector, which has an energy threshold of ~4 keV, have been considered.These data improve the exclusion limits derived from other germanium diodeexperiments in the ~50 GeV DAMA region, and show that with a moderateimprovement of the background below 10 keV, the DAMA region may be tested withan additional 1 kg-year of exposure.

Morales, A; Avignone, F T; Brodzinski, R L; Cebrián, S; García, E; González, D; Hensley, W K; Irastorza, I G; Kirpichnikov, I V; Klimenko, A A; Miley, H S; Morales, J; De Solorzano, A O; Osetrov, S B; Pogosov, V S; Puimedón, J; Reeves, J H; Sarsa, M L; Scopel, S; Smolnikov, A A; Tamanyan, A G; Vasenko, A A; Vasilev, S I; Villar, J A

2000-01-01

256

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

NASA Astrophysics Data System (ADS)

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

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

2015-03-01

257

The Diurnal Variation of the Wimp Detection Event Rates in Directional Experiments  

E-print Network

The recent WMAP data have confirmed that exotic dark matter together with the vacuum energy (cosmological constant) dominate in the flat Universe. Modern particle theories naturally provide viable cold dark matter candidates with masses in the GeV-TeV region. Supersymmetry provides the lightest supersymmetric particle (LSP), theories in extra dimensions supply the lightest Kaluza-Klein particle (LKP) etc. The nature of dark matter can only be unraveled only by its direct detection in the laboratory. All such candidates will be called WIMPs (Weakly Interacting Massive Particles). In any case the direct dark matter search, which amounts to detecting the recoiling nucleus, following its collision with WIMP, is central to particle physics and cosmology. In this work we briefly review the theoretical elements relevant to the direct dark matter detection experiments, paying particular attention to directional experiments. i.e experiments in which, not only the energy but the direction of the recoiling nucleus is ob...

Vergados, J D

2009-01-01

258

Out-of-equilibrium Baryogenesis and SuperWIMP Dark Matter  

E-print Network

The experimental fact that the energy density in Dark Matter and in Baryons is of the same order is one of the most puzzling in cosmology. In this letter we suggest a new mechanism able to explain this coincidence in the context of out-of-equilibrium baryogenesis with DM production "\\`a la" SuperWIMP starting from the same initial particle. We then discuss two simple implementations of this scenario within supersymmetric models with gravitino DM.

Arcadi, Giorgio; Nardecchia, Marco

2013-01-01

259

The Effects of QCD Equation of State on the Relic Density of WIMP Dark Matter  

E-print Network

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 $\\Omega_{c}h^2=0.1193\\pm0.0014$, 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 comp...

Drees, Manuel; Schmitz, Ernany Rossi

2015-01-01

260

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

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 use of this plant. These data indicate the potential for the use of ethyl acetate fraction of Sauromatum giganteum (Engl.) Cusimano & Hett Tuber in tumor therapy, anti-tumor activity on cancer cell line in descending order is SGC-7901 > SMMC-7721 > MCF-7 > HT-29 > A549 > HeLa > MDA-MB-231. PMID:25756649

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

261

Enhanced TRAIL sensitivity by E1A expression in human cancer and normal cell lines: inhibition by adenovirus E1B19K and E3 proteins.  

PubMed

TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily of cytokines that induces apoptosis in a variety of cancer cells, but not in normal cells. However, more and more tumor cells remain resistant to TRAIL, which limited its application for cancer therapy. Expression of the adenovirus serotype 5 (Ad5) E1A sensitizes tumor cells to apoptosis by TNF-alpha, Fas-ligand, and TRAIL. Here we asked whether E1A overcomes this resistance and enhances TRAIL-induced apoptosis in the tumor cells. Our results revealed that the tumor cell lines, HeLa and HepG2, with infection by Ad-E1A, were highly sensitive to TRAIL-induced apoptosis. Importantly, we found that in normal primary human lung fibroblast cells (HLF) TRAIL is capable of inducing apoptosis in combination with E1A as efficiently as in some tumor cell lines. The adenovirus type 5 encoding proteins, E1B19K and E3 gene products, have been shown to inhibit E1A and TRAIL-induced apoptosis of HLF cells by using the recombinant adenovirus AdDeltaE1B55K, with mutation of E1B55K, containing E1B19K and complete E3 region. Further results demonstrated that the expression of DR5 and TRAIL was down-regulated in the AdDeltaE1B55K co-infected HLF cells. These findings suggest that TRAIL may play an important role in limiting virus infections and the ability of adenovirus to inhibit killing may prolong acute and persistent infections. The results from this study have also suggested the possibility that the combination of E1A with TRAIL could be used in the treatment of human malignancy, or in the selection of the optimal adenovirus mutant as effective delivering vector for cancer therapy. PMID:15555548

Hu, Baoli; Zhu, Huabin; Qiu, Songbo; Su, Yue; Ling, Weifang; Xiao, Wei; Qi, Yipeng

2004-12-24

262

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

PubMed

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

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

2014-08-21

263

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

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

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

2013-12-01

264

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

PubMed Central

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

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

2012-01-01

265

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

PubMed

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

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

2013-11-15

266

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

PubMed Central

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 ??I and ??III tubulin isoforms are the most important isoforms in establishing predictive response of cancer cell sensitivity to colchicine derivatives. However, since ??I tubulin is widely distributed in the human body, targeting it would lead to severe adverse side effects. Consequently, we have identified tubulin isotype ??III as the most important molecular target for inhibition of microtubule polymerization and hence cancer cell cytotoxicity. Tubulin isotypes ??I and ??II 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 ??III as a target for optimized chemotherapy drug design. PMID:20509970

2010-01-01

267

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

SciTech Connect

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

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

1987-12-01

268

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

PubMed

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

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

2015-05-01

269

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

PubMed Central

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

NERADIL, JAKUB; PAVLASOVA, GABRIELA; SRAMEK, MARTIN; KYR, MICHAL; VESELSKA, RENATA; STERBA, JAROSLAV

2015-01-01

270

An Interface for Sensitive Analysis of Monoamine Neurotransmitters by Ion-Pair Chromatography–ESI-MS with Continuous On-Line Elimination of Ion-Pair Reagents  

PubMed Central

A challenge in coupling ion-pair chromatography (IPC) on-line with electrospray ionization-mass spectrometry (ESI-MS) is that the nonvolatile ion-pair reagent (e.g., alkyl sulfate for amines or tetrabutylammonium for carboxylic acids) in the mobile phase suppresses the ESI-MS signals in the gas phase and their accumulation can clog the MS sampling interface. Consequently, IPC–ESI-MS is conducted either with a volatile ion-pair reagent, which could compromise the analyte separation efficiency, or with a downstream ion-exchange column to rid the ion-pair reagents of the mobile phase. In the latter approach, the limited capacity of ion-exchange columns requires frequent off-line column regeneration, which affects the separation throughput and prohibits long separations from being performed. A dual-valve, dual-ion exchange column interface of IPC–ESI-MS is designed for undisrupted separations and simultaneous column regeneration. Owing to the efficacy in removing the ion-pair reagent, the detection of eluents of monoamine neurotransmitters by an ion trap MS results in the limits of detection of 0.03 ?M for dopamine or DA and 0.01 ?M for 5-hydroxytryptamine or 5-HT. These values are lower than those obtained with ion trap MS of similar sensitivity when combined with the use of specialized chromatographic columns or sample preconcentration. Excellent reproducibility was attained with repeatedly regenerated ion-exchange columns (RSD = 4–6%) for an extended period of time (RSD < 6% for six days). DA and 5-HT in rat straital extracts were analyzed and our data demonstrate that interferences inherent in the tissues and the ion-pair reagent have been successfully eliminated. This simple interface should be readily amenable to the separation and MS analysis of other types of polar compounds in complex sample media. PMID:23767971

Shi, Shuyun; Zhao, Binqing; Yagnik, Gargey; Zhou, Feimeng

2013-01-01

271

Effects of maternal separation on neuropeptide Y and calcitonin gene-related peptide in "depressed" Flinders Sensitive Line rats: a study of gene-environment interactions.  

PubMed

Interactions between genetic vulnerability to stress/depression and early life experience may play a crucial role in the pathogenesis of mood disorders. Here we explore this hypothesis by superimposing early life trauma in the form of maternal deprivation for 180 min per day from postnatal day 2 to 14 onto a genetic model of depression/susceptibility to depression, Flinders Sensitive Line (FSL) and their controls, Flinders Resistant Line (FRL) rats. We investigate effects on neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) like immunoreactivity (LI) in 10 brain regions as these neuropeptides are affected by antidepressants and are altered in cerebrospinal fluid of depressed patients. NPY-LI was reduced while CGRP-LI was elevated in hippocampus and frontal cortex of "genetically depressed" FSL rats. The two peptides displayed a significant negative correlation in these regions that was strongest in the FSL strain. Maternal deprivation exacerbated the strain difference in hippocampal CGRP-LI, while it was without effect on NPY-LI. FSL rats had higher tissue concentration of both neuropeptides in periaqueductal grey and higher NPY-LI in caudate/putamen. Maternal deprivation selectively raised CGRP-LI in amygdala of the FRL control stain. Thus, in two brain regions implicated in the neurobiology of depression, hippocampus and frontal cortex, changes in CGRP-LI and NPY-LI were in opposite direction, and CGRP-LI appears to be more responsive to adverse experience. Our findings thus support the hypothesis that genetic disposition and developmental stress may contribute to the susceptibility to depression by exerting selective neuropeptide- and brain region-specific effects on adult neurobiology. PMID:16600456

Wörtwein, Gitta; Husum, Henriette; Andersson, Weronica; Bolwig, Tom G; Mathé, Aleksander A

2006-06-01

272

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

E-print Network

Results are presented from the first underground data run of ZEPLIN-II, a 31 kg two phase xenon detector developed to observe nuclear recoils from hypothetical weakly interacting massive dark matter particles. Discrimination between nuclear recoils and background electron recoils is afforded by recording both the scintillation and ionisation signals generated within the liquid xenon, with the ratio of these signals being different for the two classes of event. This ratio is calibrated for different incident species using an AmBe neutron source and Co-60 gamma-ray sources. From our first 31 live days of running ZEPLIN-II, the total exposure following the application of fiducial and stability cuts was 225 kgxdays. A background population of radon progeny events was observed in this run, arising from radon emission in the gas purification getters, due to radon daughter ion decays on the surfaces of the walls of the chamber. An acceptance window, defined by the neutron calibration data, of 50% nuclear recoil acceptance between 5 keVee and 20 keVee, had an observed count of 29 events, with a summed expectation of 28.6+/-4.3 gamma-ray and radon progeny induced background events. These figures provide a 90% c.l. upper limit to the number of nuclear recoils of 10.4 events in this acceptance window, which converts to a WIMP-nucleon spin-independent cross-section with a minimum of 6.6x10^-7 pb following the inclusion of an energy dependent, calibrated, efficiency. A second run is currently underway in which the radon progeny will be eliminated, thereby removing the background population, with a projected sensitivity of 2x10^-7 pb for similar exposures as the first run.

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

2007-01-31

273

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

SciTech Connect

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

Wai, Larry; /SLAC

2007-02-05

274

Standard model anatomy of WIMP dark matter direct detection. I. Weak-scale matching  

NASA Astrophysics Data System (ADS)

We present formalism necessary to determine weak-scale matching coefficients in the computation of scattering cross sections for putative dark matter candidates interacting with the Standard Model. We pay particular attention to the heavy-particle limit. A consistent renormalization scheme in the presence of nontrivial residual masses is implemented. Two-loop diagrams appearing in the matching to gluon operators are evaluated. Details are given for the computation of matching coefficients in the universal limit of WIMP-nucleon scattering for pure states of arbitrary quantum numbers, and for singlet-doublet and doublet-triplet mixed states.

Hill, Richard J.; Solon, Mikhail P.

2015-02-01

275

A closer look at CMB constraints on WIMP dark matter  

E-print Network

We use Cosmic Microwave Background data from the WMAP, SPT, BICEP, and QUaD experiments to obtain constraints on the dark matter particle mass $m_\\chi$, and show that the combined data requires $m_\\chi > 7.6$ GeV at the 95% confidence level for the $\\chi \\chi \\rightarrow b \\bar b$ channel assuming $s-$wave annihilation and a thermal cross section $ = 3 \\times 10^{-26}$ cm$^3/$s. We examine whether the bound on $m_\\chi$ is sensitive to $\\sigma_8$ measurements made by galaxy cluster observations. The large uncertainty in $\\sigma_8$ and the degeneracy with $\\Omega_{\\rm m}$ allow only small improvements in the dark matter mass bound. Increasing the number of effective neutrino-like degrees of freedom to $N_{\\rm eff} = 3.85$ improves the mass bound to $m_\\chi > 8.6$ GeV at 95% confidence, for the $\\chi \\chi \\rightarrow b \\bar b$ channel. We also study models in which dark matter halos at $zthe Universe. We compute the Ostriker-Vishniac power resulting from partial reionization at intermediate redshifts $10the effect to be small. We discuss the importance of the large angle polarization as a complementary probe of dark matter annihilation. By performing Monte Carlo simulations, we show that future experiments that measure the $EE$ power spectrum from $20 the 2 (3) $\\sigma$ level provided the error bars are smaller than 4 (3) $\\times$ cosmic variance. We show that the Planck experiment will significantly improve our knowledge of dark matter properties.

Aravind Natarajan

2012-05-09

276

Reconstructing the WIMP Velocity Distribution from Direct Dark Matter Detection Data with a Non-negligible Threshold Energy  

E-print Network

In this paper, we investigate the modification of our expressions developed for the model-independent data analysis procedure of the reconstruction of the (time-averaged) one-dimensional velocity distribution of Galactic Weakly Interacting Massive Particles (WIMPs) with a non-negligible experimental threshold energy. Our numerical simulations show that, for a minimal reconstructable velocity of as high as O(200) km/s, our model-independent modification of the estimator for the normalization constant could provide precise reconstructed velocity distribution points to match the true WIMP velocity distribution with a <~ 10% bias.

Shan, Chung-Lin

2015-01-01

277

GENIUS and the Genius TF: A New Observatory for WIMP Dark Matter and Neutrinoless Double Beta Decay  

E-print Network

The GENIUS proposal is described and some of it's physics potential is outlined. Also in the light of the contradictive results from the DAMA and CDMS experiments the Genius TF, a new experimental setup is proposed. The Genius TF could probe the DAMA evidence region using the WIMP nucleus recoil signal and WIMP annual modulation signature simultaneously. Besides that it can prove the long term feasibility of the detector technique to be implemented into the GENIUS setup and will in this sense be a first step towards the realization of the GENIUS experiment.

H. V. Klapdor-Kleingrothaus; B. Majorovits

2001-03-07

278

GENIUS and the Genius TF A New Observatory for WIMP Dark Matter and Neutrinoless Double Beta Decay  

E-print Network

The GENIUS proposal is described and some of it's physics potential is outlined. Also in the light of the contradictive results from the DAMA and CDMS experiments the Genius TF, a new experimental setup is proposed. The Genius TF could probe the DAMA evidence region using the WIMP nucleus recoil signal and WIMP annual modulation signature simultaneously. Besides that it can prove the long term feasibility of the detector technique to be implemented into the GENIUS setup and will in this sense be a first step towards the realization of the GENIUS experiment.

Klapdor-Kleingrothaus, Hans Volker

2001-01-01

279

RNAi-mediated knockdown of the c-jun gene sensitizes radioresistant human nasopharyngeal carcinoma cell line CNE-2R to radiation.  

PubMed

This study aimed to investigate the effect of RNA interference (RNAi)-mediated downregulation of the expression of the c-jun gene (a proto-oncogene) on the radiosensitivity of a radioresistant human nasopharyngeal carcinoma cell line (CNE-2R) and to validate its potential as an anticancer target. A lentiviral vector with c-jun small hairpin RNA (shRNA) was constructed and transfected into CNE-2R cells. The gene silencing efficiency of these recombinants was confirmed by RT-PCR and western blotting. Radiosensitivity, cell proliferation, cell cycle profile and apoptosis were assessed using colony formation assay, CCK-8 assay and flow cytometry, respectively. The lentiviral shRNA efficiently knocked down the expression of c-jun at both the mRNA and protein levels (P<0.05). c-jun-downregulated CNE-2R cells exhibited significantly decreased cell proliferation and enhanced radiosensitivity compared to the control group (P<0.05), and the effects were likely due to G2/M phase arrest and enhanced cell apoptosis. These data provide evidence that c-jun may be involved in the radioresistance of nasopharyngeal carcinoma (NPC) and knockdown of the c-jun gene may be a potential strategy to enhance the radiation sensitivity of NPC. PMID:25571870

Guo, Si-Yan; Zhu, Xiao-Dong; Ge, Lian-Ying; Qu, Song; Li, Ling; Su, Fang; Guo, Ya

2015-03-01

280

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

PubMed Central

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

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

2015-01-01

281

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

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 compounds were detected by both laboratories, o,p'-DDT and DBP had no androgenic activity. Across the two laboratories EC(50)-values for MDHT, 17alpha-MT, and levonorgestrel varied by not more than a factor of 3.4, for norethynodrel by a factor of 9.7. Progesterone effects could not fully be evaluated, as frequently concentration response curves were incomplete. In the absence of cytotoxicity anti-androgenic properties of reference and test compounds were also detected in both laboratories. DBP, the putative negative reference compound, was inactive, norethynodrel rather showed agonistic properties. Progesterone was an antagonist at low concentrations, but agonistic properties were observed in one laboratory at high concentrations. Since the highest test concentration was limited to 10 microM, for some compounds no complete concentration response curves were obtained and estimation of EC(50)-values was less robust. Our data demonstrated that the SOP was transferable, and that the assay was able to rank compounds with strong, weak, and without affinity for the AR and to discriminate agonists and antagonists. The sensitivity of the assay could be improved further, if the limit of solubility or beginning cytotoxicity was chosen as the highest test concentration. The assay avoids the use of tissues from laboratory animals, and thus contributes to the 3R concept. Furthermore, it could be adjusted to an intermediate/high throughput format. On the whole, this PALM assay is a promising candidate for further validation. PMID:19836445

Freyberger, A; Witters, H; Weimer, M; Lofink, W; Berckmans, P; Ahr, H-J

2010-08-01

282

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)

A rapidly expanding understanding of molecular derangements in cancer cell function has led to the development of selective, targeted chemotherapeutic agents. Growth factor signal transduction networks are frequently activated in an aberrant fashion, particularly through the activity of receptor tyrosine kinases (RTK). This has spurred an intensive effort to develop receptor tyrosine kinase inhibitors (RTKI) that are targeted to specific receptors, or receptor subfamilies. Chapter 1 reviews the pharmacology, preclinical, and clinical aspects of RTKIs that target the epidermal growth factor receptor (EGFR). EGFR inhibitors demonstrate significant success at inhibiting phosphorylation-based signaling pathways that promote cancer cell proliferation. Additionally RTKIs have physicochemical and structural characteristics that enable them to function as inhibitors of multi-drug resistance transport proteins. Thus EGFR inhibitors and other RTKIs have both on-target and off-target activities that could be beneficial in cancer therapy. However, these agents exert a number of side effects, some of which arise from their hydrophobic nature and large in vivo volume of distribution. Side effects of the EGFR inhibitor gefitinib include skin rash, severe myelotoxicity when combined with certain chemotherapeutic agents, and impairment of the blood brain barrier to xenobiotics. Weighing the preclinical and clinical observations with the EGFR inhibitors, we developed the primary overall hypothesis of this research: that drug-carrier formulations of RTKIs such as the EGFR inhibitors could be developed based on nanoparticulate liposomal carriers. Theoretically, this carrier strategy would ameliorate toxicity and improve the biodistribution and tumor selectivity of these agents. We hypothesized specifically that liposomal formulations could shift the biodistribution of EGFR inhibitors such as gefitinib away from skin, bone marrow, and the blood brain barrier, and toward solid tumors, due to leaky tumor vasculature and the resulting Enhanced Permeability and Retention (EPR) phenomenon. In Chapter 2 we report that both gefitinib and the structurally similar EGFR inhibitor erlotinib display environment-dependent fluorescence properties. Peak excitation was 345 nm, and the emission peak ranged from 365 to 476 nm, depending upon the polarity of the environment and physical state of the drug. The fluorescence was negligible in aqueous solution, but intense in organic solvents or membrane bilayers. The environment-sensitive fluorescence properties of these drugs enabled rapid evaluation of numerous parameters affecting liposomal drug incorporation and performance. Up to 4-6 mol% of gefitinib could be incorporated in the liposome bilayer, based upon hydrophobic interactions with membrane bilayers. In contrast, 40-60 mol% could be loaded into the aqueous core of pre-formed liposomes at high efficiency, using a remote loading procedure. A stable formulation consisting of distearoylphosphatidylcholine: polyethylene glycol-distereoylphosphatidylethanolamine: cholesterol (DSPC:PEGDSPE:Chol, 9:1:5 mol:mol:mol) and containing drug at 50-60 mol% gefitinib (L-GEF) showed minimal leakage in serum-containing medium over 24 h at 37°C, which should be sufficient to improve biodistribution in vivo. Chapter 3 investigated the pharmacological activity of liposome-encapsulated gefitinib, alone and in combination with several prevalent anticancer agents. Experiments with MCF7 breast cancer cell lines demonstrated that liposome encapsulated gefitinib formulation (L-GEF) had a 2-fold higher IC50 (concentration of drug resulting in half-maximal growth inhibition) than free gefitinib. Lower in vitro potency would be consistent with delayed drug release from the carrier. Therapeutic effects were investigated in combination with the cytotoxic agents paclitaxel and doxorubicin. The drug-resistant MCF7R cell line was 23-fold more resistant to paclitaxel than the parental, drug-sensitive MCF7S cell line, and MCF7R was 12-fold more resistant than MCF7S to doxorubicin. A conce

Trummer, Brian J.

283

Dark Matter Spin-Dependent Limits for WIMP Interactions on 19-F by PICASSO  

E-print Network

The PICASSO experiment at SNOLAB reports new results for spin-dependent WIMP interactions on $^{19}$F 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 $^{19}$F of 65 g and 69 g respectively and a total exposure of 13.75 $\\pm$ 0.48 kgd. No dark matter signal was found and for WIMP masses around 24 GeV/c$^2$ new limits have been obtained on the spin-dependent cross section on $^{19}$F of $\\sigma_F$ = 13.9 pb (90% C.L.) which can be converted into cross section limits on protons and neutrons of $\\sigma_p$ = 0.16 pb and $\\sigma_n$ = 2.60 pb respectively (90% C.L). The obtained limits on protons restrict recent interpretations of the DAMA/LIBRA annual modulations in terms of spin-dependent interactions.

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

2009-11-10

284

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

NASA Astrophysics Data System (ADS)

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

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

285

The WIMP Capture Process for Dark Stars in the Early Universe  

NASA Astrophysics Data System (ADS)

The first stars to form in the universe may have been dark stars, powered by dark matter annihilation instead of nuclear fusion. The initial amount of dark matter gathered by the star gravitationally can sustain it only for a limited period of time. It has been suggested that capture of additional dark matter from the environment can prolong the dark star phase even to the present day. Here we show that this capture process is ineffective to prolong the life of the first generation of dark stars. We construct a Monte Carlo simulation that follows each weakly interacting massive particle (WIMP) in the dark matter halo as its orbit responds to the formation and evolution of the dark star, as it scatters off the star's nuclei, and as it annihilates inside the star. A rapid depletion of the WIMPs on orbits that cross the star causes the demise of the first generation of dark stars. We suggest that a second generation of dark stars may in principle survive much longer through capture. We comment on the effect of relaxing our assumptions.

Sivertsson, Sofia; Gondolo, Paolo

2011-03-01

286

Search for very high energy gamma rays from WIMP annihilations near the Sun with the Milagro detector  

E-print Network

Search for very high energy gamma rays from WIMP annihilations near the Sun with the Milagro ``dark matter''. A profusion of such neutralinos can accumulate near the Sun when they lose energy upon of the Sun with an angular resolution of 0:75. Analysis of Milagro data with an exposure to the Sun of 1165

California at Santa Cruz, University of

287

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

E-print Network

We perform state-of-the-art large-scale shell-model calculations of the structure factors for elastic spin-dependent WIMP scattering off 129,131Xe, 127I, 73Ge, 19F, 23Na, 27Al, and 29Si. This comprehensive survey covers the non-zero-spin nuclei relevant to direct dark matter detection. We include a pedagogical presentation of the formalism necessary to describe elastic and inelastic WIMP-nucleus scattering. The valence spaces and nuclear interactions employed have been previously used in nuclear structure calculations for these mass regions and yield a good spectroscopic description of these isotopes. We use spin-dependent WIMP-nucleus currents based on chiral effective field theory (EFT) at the one-body level and including the leading long-range two-body currents due to pion exchange, which are predicted in chiral EFT. Results for all structure factors are provided with theoretical error bands due to the nuclear uncertainties of WIMP currents in nuclei.

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

2015-01-23

288

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

SciTech Connect

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

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

2011-03-15

289

A coaxially heated membrane introduction mass spectrometry interface for the rapid and sensitive on-line measurement of volatile and semi-volatile organic contaminants in air and water at parts-per-trillion levels.  

PubMed

A coaxially heated membrane introduction mass spectrometry (MIMS) sampling interface is presented that demonstrates improved on-line performance for the direct measurement of semi-volatile organic compounds (SVOCs) in air and water samples at parts-per-trillion levels. The device is based on a polydimethylsiloxane (PDMS) capillary hollow fibre membrane (HFM) in a pneumatically assisted "flow-over" configuration that is resistively heated on the membrane interior via a coaxial nichrome wire, establishing a thermal gradient counter to the analyte concentration gradient. This arrangement allows for continuous and/or pulsed heating modes, affording excellent sensitivity for the on-line measurement of SVOCs while retaining sensitivity for volatile organic compounds (VOCs). In addition, the signal response time for SVOCs is reduced substantially over conventional "flow-over" MIMS interfaces. Separation and quantitation of analytes are achieved using quadrupole ion trap tandem mass spectrometry. PMID:16770756

Thompson, Alexander J; Creba, A Skye; Ferguson, Robyn M; Krogh, Erik T; Gill, Christopher G

2006-01-01

290

Characterization of three B-cell lymphoma cell lines from chemotherapy resistant patients with respect to in vitro sensitivity to 21 antitumor agents, ABC-transporter expression and cellular redox status  

Microsoft Academic Search

Purpose  The aim of this study was to characterize three new, recently established non-Hodgkin lymphoma cell lines (GUMBUS, DOGUM,\\u000a and DOGKIT), isolated from patients developing high-clinical resistance to cytotoxic therapy, with respect to sensitivity\\u000a toward 21 antitumor drugs from different classes of action, expression of three ABC transporters: P glycoprotein (Pgp) (MDR1\\u000a and ABCB1), multidrug resistance related proteins (MRP1) (ABCC1), and

Karin Bracht; Thomas Kiefer; Gottfried Dölken; Patrick J. Bednarski

2007-01-01

291

Effect of interferon ? on the sensitivity of bovine-papilloma-virus(BPV1)-transformed cell lines to cell-mediated cytotoxicity  

Microsoft Academic Search

Summary The effect of interferon ? (IFN?) on the immunogenicity and immunosensitivity of mouse cell lines transformed by bovine papillomavirus type 1 (BPV1) DNA was examined in a syngeneic mouse model. The overnight incubation of BPV1-transformed cell lines with 100 IU\\/ml IFN? did not affect their ability to induce the generation of cytotoxic effector cells but it clearly increased their

Aino Laatikainen; Leslie Schultz-Suhonen; Rauno Mäntyjärvi

1992-01-01

292

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

PubMed

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

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

293

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

E-print Network

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

C. Galbiati; R. Purtschert

2007-12-03

294

Direction-sensitive dark matter search results in a surface laboratory  

E-print Network

We developed a three-dimensional gaseous tracking device and performed a direction-sensitive dark matter search in a surface laboratory. By using 150 Torr carbon-tetrafluoride (CF_4 gas), we obtained a sky map drawn with the recoil directions of the carbon and fluorine nuclei, and set the first limit on the spin-dependent WIMP (Weakly Interacting Massive Particles)-proton cross section by a direction-sensitive method. Thus, we showed that a WIMP-search experiment with a gaseous tracking device can actually set limits. Furthermore, we demonstrated that this method will potentially play a certain role in revealing the nature of dark matter when a low-background large-volume detector is developed.

Miuchi, Kentaro; Kabuki, Shigeto; Kubo, Hidetoshi; Kurosawa, Shunsuke; Nishimura, Hironobu; Okada, Yoko; Takada, Atsushi; Tanimori, Toru; Tsuchiya, Ken'ichi; Ueno, Kazuki; Sekiya, Hiroyuki; Takeda, Atsushi

2007-01-01

295

First underground results with NEWAGE-0.3a direction-sensitive dark matter detector  

E-print Network

A direction-sensitive dark matter search experiment at Kamioka underground laboratory with the NEWAGE-0.3a detector was performed. The NEWAGE- 0.3a detector is a gaseous micro-time-projection chamber filled with CF4 gas at 152 Torr. The fiducial volume and target mass are 20*25*31 cm3 and 0.0115 kg, respectively. With an exposure of 0.524 kgdays, improved spin-dependent weakly interacting massive particle (WIMP)-proton cross section limits by a direction-sensitive method were achieved including a new record of 5400 pb for 150 GeV/c2 WIMPs. We studied the remaining background and found that ambient gamma-rays contributed about one-fifth of the remaining background and radioactive contaminants inside the gas chamber contributed the rest.

Miuchi, Kentaro; Hattori, Kaori; Higashi, Naoki; Ida, Chihiro; Iwaki, Satoshi; Kabuki, Shigeto; Kubo, Hidetoshi; Kurosawa, Shunsuke; Nakamura, Kiseki; Parker, Joseph; Sawano, Tatsuya; Takahashi, Michiaki; Tanimori, Toru; Taniue, Kojiro; Ueno, Kazuki; Sekiya, Hiroyuki; Takeda, Atsushi; Tsuchiya, Ken'ichi; Takada, Atsushi

2010-01-01

296

Direction-sensitive dark matter search results in a surface laboratory  

E-print Network

We developed a three-dimensional gaseous tracking device and performed a direction-sensitive dark matter search in a surface laboratory. By using 150 Torr carbon-tetrafluoride (CF_4 gas), we obtained a sky map drawn with the recoil directions of the carbon and fluorine nuclei, and set the first limit on the spin-dependent WIMP (Weakly Interacting Massive Particles)-proton cross section by a direction-sensitive method. Thus, we showed that a WIMP-search experiment with a gaseous tracking device can actually set limits. Furthermore, we demonstrated that this method will potentially play a certain role in revealing the nature of dark matter when a low-background large-volume detector is developed.

Kentaro Miuchi; Kaori Hattori; Shigeto Kabuki; Hidetoshi Kubo; Shunsuke Kurosawa; Hironobu Nishimura; Yoko Okada; Atsushi Takada; Toru Tanimori; Ken'ichi Tsuchiya; Kazuki Ueno; Hiroyuki Sekiya; Atsushi Takeda

2007-08-20

297

The isolation of abscisic acid (ABA) deficient mutants by selection of induced revertants in non-germinating gibberellin sensitive lines of Arabidopsis thaliana (L.) heynh  

Microsoft Academic Search

By selecting for germinating seeds in the progeny of mutagen-treated non-germinating gibberellin responsive dwarf mutants of the ga-1 locus in Arabidopsis thaliana, germinating lines (revertants) could be isolated. About half of the revertants were homozygous recessive for a gene (aba), which probably regulates the presence of abscisic acid (ABA). Arguments for the function of this gene were obtained from lines

M. Koornneef; M. L. Jorna; D. L. C. Brinkhorst-van der Swan; C. M. Karssen

1982-01-01

298

Selection and characterization of BCR-ABLpositive cell lines with differential sensitivity to the tyrosine kinase inhibitor STI571: diverse mechanisms of resistance  

Microsoft Academic Search

Targeting the tyrosine kinase activity of Bcr-Abl with STI571 is an attractive thera- peutic strategy in chronic myelogenous leukemia (CML). A few CML cell lines and primary progenitors are, however, resis- tant to this compound. We investigated the mechanism of this resistance in clones of the murine BaF\\/3 cells trans- fected with BCR-ABL and in 4 human cell lines from

Francois Xavier Mahon; Michael W. N. Deininger; Beate Schultheis; Jerome Chabrol; Josy Reiffers; John M. Goldman; Junia V. Melo

2000-01-01

299

Comparing predictions of mean performance and environmental sensitivity of recombinant inbred lines based upon F3 and triple test cross families  

Microsoft Academic Search

We have previously shown that statistics estimated from the F1, F2, B1 and B2 families of a cross between two inbred lines or from a triple test cross on the F2 of such a cross can be successfully used to predict the properties of the pure breeding lines extractable from the cross by single seed descent. In this paper we

J L Jinks; H S Pooni

1980-01-01

300

Limits on WIMP dark matter using scintillating CaWO 4 cryogenic detectors with active background suppression  

Microsoft Academic Search

We present first significant limits on WIMP dark matter by the phonon-light technique, where combined phonon and light signals from a scintillating cryogenic detector are used. Data from early 2004 with two 300g CRESST-II prototype detector modules are presented, with a net exposure of 20.5kg days. The modules consist of a CaWO4 scintillating “target” crystal and a smaller cryogenic light

G. Angloher; C. Bucci; P. Christ; C. Cozzini; F. von Feilitzsch; D. Hauff; S. Henry; Th. Jagemann; J. Jochum; H. Kraus; B. Majorovits; J. Ninkovic; F. Petricca; W. Potzel; F. Probst; Y. Ramachers; M. Razeti; W. Rau; W. Seidel; M. Stark; L. Stodolsky; A. J. B. Tolhurst; W. Westphal; H. Wulandari

2005-01-01

301

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)

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.

Chakravarty, Swapnajit; Lai, Wei-Cheng; Zou, Yi; Gemmill, Robert M.; Chen, Ray T.

2013-03-01

302

Neutrino Telescopes' Sensitivity to Dark Matter  

E-print Network

The nature of the dark matter of the Universe is yet unknown and most likely is connected with new physics. The search for its composition is under way through direct and indirect detection. Fundamental physical aspects such as energy threshold, geometry and location are taken into account to investigate proposed neutrino telescopes of km^3 volume sensitivities to dark matter. These sensitivities are just sufficient to test a few WIMP scenarios. Telescopes of km^3 volume, such as IceCube, can definitely discover or exclude superheavy (M > 10^10 GeV) Strong Interacting Massive Particles (Simpzillas). Smaller neutrino telescopes such as ANTARES, AMANDA-II and NESTOR can probe a large region of the Simpzilla parameter space.

Ivone F. M. Albuquerque; Jodi Lamoureux; George F. Smoot

2002-05-13

303

Absence of IFNA and IFNB genes from human malignant glioma cell lines and lack of correlation with cellular sensitivity to interferons.  

PubMed

We report that 5 of 19 human malignant glioma cell lines have neither interferon alpha (IFNA) nor interferon beta (IFNB) genes that are detectable by Southern blotting. Of 5 other of these malignant glioma lines that have a single IFNB gene copy, 3 lack the IFNA genes entirely and two have one copy. One of the lines that lacks the IFNA genes entirely but has one copy of the IFNB gene has a rearrangement near the IFNB gene that is most easily interpreted as an insertion of a large segment of DNA (at least 50 kilobases) the 3' end of which is less than 1.3 kilobases 5' to the known regulatory sequences of the IFNB gene. In spite of the rearrangement, IFNB-specific RNA is highly inducible in this line by poly(I)-poly(C). The ability of interferon alpha or interferon beta to inhibit cell growth does not depend upon the presence or absence of the respective gene. This finding adds solid tumors to those tumor cell lines (acute lymphocytic leukemia, chronic myelogeneous leukemia) previously determined to lack the IFNA and IFNB genes (Diaz et al., Proc. Natl. Acad. Sci. USA, 85:5259-5263, 1988). PMID:2295067

Miyakoshi, J; Dobler, K D; Allalunis-Turner, J; McKean, J D; Petruk, K; Allen, P B; Aronyk, K N; Weir, B; Huyser-Wierenga, D; Fulton, D

1990-01-15

304

Establishment and characterization of six human lung cancer cell lines: EGFR, p53 gene mutations and expressions of drug sensitivity genes  

Microsoft Academic Search

Background  Six human lung cancer cell lines (SNU-371, SNU-963, SNU-1327, SNU-1330, SNU-2292 and SNU-2315) were newly established through\\u000a primary cell cultures. These cell lines were derived from a pulmonary blastoma, a small cell lung cancer, three adenocarcinomas\\u000a and a squamous cell carcinoma of the lung of six Korean lung cancer patients.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  The histopathology of the primary tumors and their in vitro

Ja-Lok Ku; Kyung-Hee Kim; Jin-Sung Choi; You-Kyung Jeon; Sung-Hee Kim; Young-Kyoung Shin; Tae-You Kim; Yung-Jue Bang; Woo Ho Kim; Jae-Gahb Park

2011-01-01

305

High Sensitivity CW-Cavity Ring Down Spectroscopy of five 13 isotopologues of carbon dioxide in the 1.26-1.44 m region (I): Line positions  

E-print Network

1 High Sensitivity CW-Cavity Ring Down Spectroscopy of five 13 CO2 isotopologues of carbon dioxide, Tomsk, Russia 12/11/2009 Key words: Carbon dioxide, CO2, Cavity Ring Down Spectroscopy, effective;2 Abstract The absorption spectrum of highly enriched 13 C carbon dioxide has been investigated by CW

Boyer, Edmond

306

Theoretical direct WIMP detection rates for transitions to nuclear excited states  

E-print Network

The recent WMAP and Planck data have confirmed that exotic dark matter together with the vacuum energy (cosmological constant) dominate in the flat Universe. Many extensions of the standard model provide dark matter candidates, in particular Weakly Interacting Massive Particles (WIMPs). Thus the direct dark matter detection is central to particle physics and cosmology. Most of the research on this issue has hitherto focused on the detection of the recoiling nucleus. In this paper we study transitions to the excited states, possible in some nuclei, which have sufficiently low lying excited states. Examples considered previously were the first excited states of $^{127}$I and $^{129}$Xe. We examine here $^{83}$Kr, which offers some kinematical advantages and is currently considered as a possible target. We find appreciable branching ratios for the inelastic scattering mediated by the spin cross sections, with an inelastic event rate of $4.4\\times 10^{-4}$kg$^{-1}$d$^{-1}$. So, the extra signature of the gamma ra...

Vergados, J D; Pirinen, P; Srivastava, P C; Kortelainen, M; Suhonen, J

2015-01-01

307

Theoretical direct WIMP detection rates for transitions to nuclear excited states  

E-print Network

The recent WMAP and Planck data have confirmed that exotic dark matter together with the vacuum energy (cosmological constant) dominate in the flat Universe. Many extensions of the standard model provide dark matter candidates, in particular Weakly Interacting Massive Particles (WIMPs). Thus the direct dark matter detection is central to particle physics and cosmology. Most of the research on this issue has hitherto focused on the detection of the recoiling nucleus. In this paper we study transitions to the excited states, possible in some nuclei, which have sufficiently low lying excited states. Examples considered previously were the first excited states of $^{127}$I and $^{129}$Xe. We examine here $^{83}$Kr, which offers some kinematical advantages and is currently considered as a possible target. We find appreciable branching ratios for the inelastic scattering mediated by the spin cross sections, with an inelastic event rate of $4.4\\times 10^{-4}$kg$^{-1}$d$^{-1}$. So, the extra signature of the gamma ray following the de-excitation of these states can, in principle, be exploited experimentally. A brief discussion of the experimental feasibility is given

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

2015-04-10

308

Dark matter formation at Schwarz scales: primordial fog particles and WIMP superhalos  

E-print Network

Dark matter appears in two forms as a consequence of the fluid mechanics of self-gravitational condensation. Condensation occurs primarily on non-acoustic nuclei rather than on the acoustic nuclei of the Jeans (1902) criterion, leading to a very different scenario for structure formation. Viscous forces at 10^12 s (30,000 y) after the big bang permit decelerations of 10^47 kg protosupercluster plasma masses, and 10^42 kg protogalaxy masses at 10^13 s (300,000 y). Then gas formed, and all the baryonic universe became a "primordial fog" of 10^23 kg particles at the viscous Schwarz scale: 100% dark matter. Some of these H-He objects have collected to form stars, but most persist as dark dwarfs in galaxy halos. They manifest themselves in quasar microlensing observations as "rogue planets", Schild (1996), "dark galaxies", Hawkins (1996), and as comets "brought out of cold storage", O'Dell and Handron (1996). Non-baryonic WIMP fluids are superviscous, with large viscous Schwarz scales, and condense slowly to form most of the dark matter of galaxy superclusterhalos and clusterhalos.

Carl H. Gibson

1999-04-21

309

SUSY Implications from WIMP Annihilation into Scalars at the Galactic Centre  

E-print Network

An excess in gamma-rays emanating from the galactic centre has recently been observed in the Fermi-LAT data. This signal can be interpreted as resulting from WIMP annihilation, with the spectrum well-fit by dark matter annihilating dominantly into either bottom-quark or Higgs pairs. Supersymmetric models provide a well-motivated framework to study the implications of this signal in these channels. With a neutralino dark matter candidate, the gamma-ray excess cannot be easily accommodated in the minimal supersymmetric model, which in any case requires tuning below the percent level to explain the observed Higgs mass. Instead we are naturally led to consider the next-to-minimal model with a singlet superfield. This not only allows for the annihilation channel into bottom-quark pairs to be implemented, but also provides new possibilities for annihilation into Higgs-pseudoscalar pairs. We show that the fit to the gamma-ray excess for the Higgs-pseudoscalar channel can be just as good as for annihilation into bott...

Gherghetta, Tony; Medina, Anibal D; Schmidt, Michael A; Trott, Timothy

2015-01-01

310

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

PubMed

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

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

2014-10-01

311

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

PubMed

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

Wang, Zhaoyan; Liu, Chao; Kang, Jingwu

2011-04-01

312

A novel method using Autographa californica multiple nucleopolyhedrovirus for increasing the sensitivity of insecticide through calcium influx in insect cell line.  

PubMed

Due to an intensive use of chemical insecticides, resistance mechanisms to insecticides together with adverse effects on non-target organisms have been largely reported. Improvement in pest control strategy represents an urgent need to optimize efficiency in the control of pest insects. In this context, a novel method based on the use of insect specific virus applied in combination with chemical insecticide, which could lead to sensitization of the insect target to insecticides is described. Insect virus, the baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV), applied onto Sf9 cells induces an increase of intracellular calcium concentration via extracellular calcium influx. Co-application of AcMNPV with chlorpyrifos-ethyl onto Sf9 cells expressing the key enzyme acetylcholinesterase (AChE), known to be targeted by organophosphate insecticides, increases 1.5-fold the sensitivity of AChE to the insecticide. This effect is correlated with intracellular calcium concentration rise since AcMNPV-induced potentiating insecticide effect is counteracted by pretreatment with the calcium channel blocker, cadmium chloride. Increasing insecticide target sensitivity through intracellular calcium modulation by using insect virus co-applied with a chemical insecticide is a very promising strategy allowing optimization of insecticide treatment while reducing the concentration of insecticides used. PMID:24140515

Licznar, Patricia; List, Olivier; Goven, Delphine; Nna, Rolande Ndong; Lapied, Bruno; Apaire-Marchais, Véronique

2014-01-01

313

A chemical screen in diverse breast cancer cell lines reveals genetic enhancers and suppressors of sensitivity to PI3K isotype-selective inhibition  

PubMed Central

Synopsis The Phosphoinositide-3-kinase (PI3K) pathway regulates cell proliferation, survival and migration and is consequently of great interest for targeted cancer therapy. Using a panel of small molecule PI3K isoform-selective inhibitors in a diverse set of breast cancer cell lines, we demonstrate that the biochemical and biological responses were highly variable and dependent on the genetic alterations present. p110? inhibitors were generally effective in inhibiting the phosphorylation of Akt and S6, two downstream components of PI3K signaling, in most cell lines examined. In contrast, 110? selective inhibitors only reduced Akt phosphorylation in PTEN mutant cell lines, and was associated with a lesser decrease in S6 phosphorylation. PI3K inhibitors reduced cell viability by causing a cell cycle arrest in the G1 phase of the cell cycle, with multi-targeted inhibitors causing the most potent effects. Cells expressing mutant Ras were resistant to the cell cycle effects of PI3K inhibition, which could be reversed using inhibitors of Ras signaling pathways. Taken together our data indicates that these compounds, alone or in suitable combinations, may be useful as breast cancer therapeutics, when used in appropriate genetic contexts. PMID:18498248

Torbett, Neil E; Luna, Antonio; Knight, Zachary A.; Houk, Andrew; Moasser, Mark; Weiss, William; Shokat, Kevan M.; Stokoe, David

2011-01-01

314

Tumor necrosis factor alpha induces stronger cytotoxicity in ABCG2-overexpressing resistant breast cancer cells compared with their drug-sensitive parental line.  

PubMed

Tumor necrosis factor alpha (TNF-?) has been reported to modulate the multidrug resistance (MDR) phenotype in vitro and in vivo. Multidrug-resistant cells overexpressing the ABCB1 transporter are more susceptible to inhibition of proliferation and induction of apoptosis by TNF-? than their drug-sensitive counterparts. This study was aimed to investigate TNF-? modulatory and antiproliferative effects on drug-resistant cells overexpressing ABCG2. The effects of TNF-? on viability and proliferation rate of MCF-7 breast cancer cells and their ABCG2-overexpressing sublines MCF-7/mitoxantrone (MX) cells were studied using dye exclusion assay, dimethylthiazolyl-2,5-diphenyl tetrazolium bromide technique, and flow cytometric analysis of cell cycle. TNF-? influence on MX accumulation was investigated by flow cytometry. ABCG2-overexpressing cells were more susceptible to antiproliferative and cytotoxic effects of TNF-? than their parental cells. TNF-? increased accumulation of MX in both parental and resistant cells. Higher sensitivity of MDR cells to TNF-? cytotoxicity would help in characterization of its complex modulatory effects on cancer cells and benefit us in designing new approaches to overcome MDR. PMID:21323575

Mosaffa, Fatemeh; Kalalinia, Fatemeh; Parhiz, Bibi Hamideh; Behravan, Javad

2011-06-01

315

Limits on light WIMPs from the CDEX-1 experiment with a p-type point-contact germanium detector at the China Jingping Underground Laboratory  

E-print Network

We report results of a search for light Dark Matter WIMPs with CDEX-1 experiment at the China Jinping Underground Laboratory, based on 53.9 kg-days of data from a p-type point-contact germanium detector enclosed by a NaI(Tl) crystal scintillator as anti-Compton detector. The event rate and spectrum above the analysis threshold of 475 eVee are consistent with the understood background model. Part of the allowed regions for WIMP-nucleus coherent elastic scattering at WIMP mass of 6-20 GeV are probed and excluded. Independent of interaction channels, this result contradicts the interpretation that the anomalous excesses of the CoGeNT experiment are induced by Dark Matter, since identical detector techniques are used in both experiments.

Q. Yue; W. Zhao; K. J. Kang; J. P. Cheng; Y. J. Li; S. T. Lin; J. P. Chang; N. Chen; Q. H. Chen; Y. H. Chen; Y. C. Chuang; Z. Deng; Q. Du; H. Gong; X. Q. Hao; H. J. He; Q. J. He; H. X. Huang; T. R. Huang; H. Jiang; H. B. Li; J. M. Li; J. Li; J. Li; X. Li; X. Y. Li; Y. L. Li; H. Y. Liao; F. K. Lin; S. K. Liu; L. C. Lv; H. Ma; S. J. Mao; J. Q. Qin; J. Ren; J. Ren; X. C. Ruan; M. B. Shen; L. Singh; M. K. Singh; A. K. Soma; J. Su; C. J. Tang; C. H. Tseng; J. M. Wang; L. Wang; Q. Wang; H. T. Wong; S. Y. Wu; Y. C. Wu; Y. C. Wu; Z. Z. Xianyu; R. Q. Xiao; H. Y. Xing; F. Z. Xu; Y. Xu; X. J. Xu; T. Xue; L. T. Yang; S. W. Yang; N. Yi; C. X. Yu; H. Yu; X. Z. Yu; X. H. Zeng; Z. Zeng; L. Zhang; Y. H. Zhang; M. G. Zhao; Z. Y. Zhou; J. J. Zhu; W. B. Zhu; X. Z. Zhu; Z. H. Zhu

2014-11-11

316

In-line separation by capillary electrophoresis prior to analysis by top-down mass spectrometry enables sensitive characterization of protein complexes.  

PubMed

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

Han, Xuemei; Wang, Yueju; Aslanian, Aaron; Fonslow, Bryan; Graczyk, Beth; Davis, Trisha N; Yates, John R

2014-12-01

317

RNA silencing of integrin-linked kinase increases the sensitivity of the A549 lung cancer cell line to cisplatin and promotes its apoptosis.  

PubMed

The expression of integrin?linked kinase (ILK) has been reported to be involved in the regulation of integrin?mediated processes, including cancer cell proliferation, migration and invasion. Previous studies have demonstrated that inhibition of ILK may be an underlying approach for treating cancer. However, whether the knock down of ILK affects growth and apoptosis of lung cancer cells remains to be elucidated. Importantly, whether downregulation of ILK increases the sensitivity of lung cancer cells to cisplatin and amplifies cell apoptosis also remains to be elucidated. In the present study, ILK downregulation was mediated by lentivirus?mediated RNA interference. The expression levels of associated genes were determined by reverse?transcription quantitative polymerase chain reaction and western blotting. Cell proliferation was evaluated using a modified 3?(4,5?dimethylthiazol?2?yl)?2,5?diphenyltetrazolium bromide assay and clone formation assay. The cell cycle and apoptosis were analyzed using flow cytometry. The current data revealed that lentivirus?mediated ILK gene silencing alone inhibited A549 cell proliferation and promotes cell cycle arrest, however, had no detectable effect on cell apoptosis. However, combined treatment with lentivirus?mediated ILK interference and cisplatin chemotherapy induced significantly more cell apoptosis than mono?chemotherapy or knockdown. The increased cell apoptosis and proliferation inhibition were attributed to abnormal downstream protein expression of ILK, including phospho?glycogen synthase kinase 3?, p?AKT, activator protein?1, ??catenin, cyclin D1 and matrix metalloproteinase?9. ILK inhibition may suppress the proliferation of A549 and increase A549 sensitivity to cisplatin. The combined treatment of ILK gene knockdown and chemotherapy has the potential to improve anticancer efficacy. PMID:25760437

Zhao, Xiaozhen; Xu, Zhenye; Wang, Zhongqi; Wu, Zhonghua; Gong, Yabin; Zhou, Lijuan; Xiang, Yi

2015-07-01

318

Multifactorial resistance to adriamycin: relationship of DNA repair, glutathione transferase activity, drug efflux, and P-glycoprotein in cloned cell lines of adriamycin-sensitive and -resistant P388 leukemia.  

PubMed

Cloned lines of Adriamycin (ADR)-sensitive and -resistant P388 leukemia have been established, including P388/ADR/3 and P388/ADR/7 that are 5- and 10-fold more resistant than the cloned sensitive cell line P388/4 (Cancer Res., 46: 2978, 1986). A time course of ADR-induced DNA double-strand breaks revealed that in sensitive P388/4 cells, evidence of DNA repair was noted 4 h after removal of drug, whereas in resistant clone 3 and 7 cells repair was observed 1 h after drug removal. The earlier onset of DNA repair was statistically significant (p = 0.0154 for clone 3 cells, and p = 0.0009 for clone 7 cells). By contrast, once the repair process was initiated, the rate of repair was similar for all three cell lines. The level of glutathione transferase activity was determined in whole cell extracts. Enzyme activity (mean +/- SE) in sensitive cells was 9.49 +/- 1.00 nmol/min/mg protein, that in resistant clone 3 cells was 13.36 +/- 1.03 nmol/min/mg, and that in clone 7 cells was 13.96 +/- 1.44 nmol/min/mg; the 1.44-fold increase in enzyme activity in resistant cells was statistically significant (p = 0.01). Further evidence of induction of glutathione transferase was provided by Northern blot analysis using a 32P-labeled cDNA for an anionic glutathione transferase, which demonstrated approximately a twofold increase in mRNA in resistant clone 7 cells. Western blot analysis with a polyvalent antibody against anionic glutathione transferase also revealed a proportionate increase in gene product in resistant cells. Dose-survival studies showed that ADR-resistant cells were cross-resistant to actinomycin D, daunorubicin, mitoxantrone, colchicine, and etoposide, but not to the alkylating agent melphalan; this finding provided evidence that these cells are multidrug resistant. Using a cDNA probe for P-glycoprotein, a phenotypic marker for multidrug resistance, Northern blot analysis showed an increase in the steady state level of mRNA of approximately twofold in resistant clone 3 and 7 cells. Southern analysis with the same cDNA probe showed no evidence of gene amplification or rearrangement. Western blot analysis with monoclonal C219 antibody demonstrated a distinct increase in P-glycoprotein in resistant cells. Efflux of Adriamycin as measured by the efflux rate constant was identical in all three cell lines. Furthermore, the metabolic inhibitors azide and dinitrophenol did not augment drug uptake in either sensitive or resistant cells. These findings suggest that despite the increase in P-glycoprotein, an active extrusion pump was not operational in these cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2897875

Deffie, A M; Alam, T; Seneviratne, C; Beenken, S W; Batra, J K; Shea, T C; Henner, W D; Goldenberg, G J

1988-07-01

319

Sensitive determination of four ?2-agonists in pig feed by capillary electrophoresis using on-line sample preconcentration with contactless conductivity detection.  

PubMed

In this work, an on-line preconcentration method of field-enhanced sample injection (FESI) was implemented in the determination of four ?2-agoinsts terbutaline (TER), procaterol (PRO), formoterol (FOR) and bambuterol (BAM) by capillary electrophoresis coupled with capacitively coupled contactless conductivity detection (CE-C(4)D). Under optimized conditions the background electrolyte (BGE) was 5mM Tris(hydroxymethyl)aminomethane (Tris) and 10mM citric acid (Cit) at a pH of 3.2 while the sample dilution solution was obtained by methanol. The detection limits (defined as S/N=3) of this method were 0.02mg/L for TER, PRO, FOR, BAM, which were much lower than that of the conventional CE-C(4)D method without preconcentration procedure, the enhancement factors were greatly improved to be 30-40-fold. The linearity ranges of four ?2-agoinsts were 0.1-15mg/L, with good linear correlation coefficients (r(2)>0.9900). In order to evaluate the application potential of the developed method, real sample from pig feed was analyzed with recoveries of 91.4-106.2%. PMID:25464091

Gao, Fan; Wu, Minglei; Zhang, Yi; Wang, Guan; Wang, Qingjiang; He, Pingang; Fang, Yuzhi

2014-10-12

320

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

SciTech Connect

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

Gómez-Vargas, Germán A.; Huh, Ji-Haeng; Peiró, Miguel; Cerdeño, David G.; Muñoz, Carlos [Departamento de Física Teórica, Universidad Autónoma de Madrid, Campus de Cantoblanco, 28049 Madrid (Spain); Sánchez-Conde, Miguel A. [SLAC National Accelerator Laboratory and Kavli Intitute for Particle Astrophysics and Cosmology, 2575 Sand Hill Road, Menlo Park, CA 94025 (United States); Prada, Francisco [Instituto de Física Teórica UAM-CSIC, Campus de Cantoblanco UAM, 28049 Madrid (Spain); Morselli, Aldo [Istituto Nazionale di Fisica Nucleare, Sez. Roma Tor Vergata, Via della Ricerca Scientifica, 00133 Roma (Italy); Klypin, Anatoly [Astronomy Department, New Mexico State University, Astronomy building, Las Cruces NM (United States); Mambrini, Yann, E-mail: germanarturo.gomez@uam.es, E-mail: masc@stanford.edu, E-mail: jhhuh@physics.ucla.edu, E-mail: miguel.peiro@uam.es, E-mail: fprada@iaa.es, E-mail: aldo.morselli@roma2.infn.it, E-mail: klypin@nmsu.edu, E-mail: davidg.cerdeno@uam.es, E-mail: yann.mambrini@th.u-psud.fr, E-mail: carlos.munnoz@uam.es [Laboratoire de Physique Théorique Université Paris-Sud, F-91405 Orsay (France)

2013-10-01

321

Effect of magnetic field exposure on anchorage-independent growth of a promoter-sensitive mouse epidermal cell line (JB6).  

PubMed Central

The anchorage-independent growth of mouse epidermal cells (JB6) exposed to 60-Hz magnetic fields (MF) was investigated. Promotion-responsive JB6 cells were suspended in agar (10(4)cells/plate) and exposed continuously to 0.10 or 0.96 mT, 60-Hz magnetic fields for 10-14 days, with or without concurrent treatment with the tumor promoter tetradecanoylphorbol acetate (TPA). Exposures to MF were conducted in a manner such that the experimenter was blind to the treatment group of the cells. At the end of the exposure period, the anchorage-independent growth of JB6 cells on soft agar was examined by counting the number of colonies larger than 60 microm (minimum of 60 cells). The use of a combined treatment of the cells with both MF and TPA was to provide an internal positive control to estimate the success of the assay and to allow evaluation of co-promotion. Statistical analysis was performed by a randomized block design analysis of variance to examine both the effect of TPA treatment (alone and in combination with MF exposure) and the effect of intra-assay variability. Transformation frequency of JB6 cells displayed a dose-dependent response to increasing concentrations of TPA. Coexposure of cells to both TPA and 0.10 or 0.96 mT, 60-Hz MF did not result in any differences in transformation frequency for any TPA concentrations tested (0-1 ng/ml). These data indicate that exposure to a 0.10 or 0.96 mT, 60-Hz MF does not act as a promoter or co-promoter in promotion-sensitive JB6 cell anchorage-independent growth. Images Figure 1 PMID:10064548

Snawder, J E

1999-01-01

322

A sensitive emulsification liquid phase microextraction coupled with on-line phase separation followed by HPLC for trace determination of sulfonamides in water samples.  

PubMed

For the first time, ion-pair based emulsification liquid phase microextraction coupled with a novel approach for phase separation followed by high performace liquid chromatgraphy (HPLC) was utilized for trace determination of sulfonamides in water samples. After the formation of ion-pair complex with a cationic surfactant, sulfonamides were extracted into the drops of dispersed organic extracting solvent. Then, the cloudy solution was passed through an in-line filter located in a suitable holder and was separated based on emulsion filtration. By changing the HPLC valve position, the filter was laid in the mobile phase path, and the extraction phase was eluted by the mobile phase and introduced into the separation column for analysis. The effects of important parameters, such as type of extraction solvent, type of ion-pair agent and its concentration, pH of sample solution, ionic strength, and volume of extraction phase, on the extraction efficiency, were investigated and optimized. Under optimal conditions, the linear range, limits of detection, and precision (relative standard deviations) were 0.3-100, 0.1-0.3 ?g L(-1), and 4.7-5.8%, respectively. Preconcentration factors (PFs) for the compounds studied were obtained in the range of 268-664. These PFs correspond to extraction recoveries in the range of 41-97%. The sample throughput of the method was 3 samples per hour, regarding 20 min analysis time for a single procedure. Finally, the method was successfully applied to determine the selected sulfonamides in some water samples. PMID:25427828

Ebrahimpour, Behnam; Yamini, Yadollah; Rezazadeh, Maryam

2015-01-01

323

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E-print Network

(NodeNew=K=Yes) decision threshold " ?" NodeNew=K . , BN . , NodeNew=K NodeAnswer . 4. 4.1 m4650 . Windows 6.0 , GPS GPS , . SASOM . Acknowledgments [blank line] 2010 ( ) (2010-0018948). [blank line] [1] Butler, M. (2011., Mantyjarvi, J., Kela, J., Keranen, H. and Malm, E.-J. (2003). "Managing Context Information in Mobile Devices

Cho, Sung-Bae

324

WIMPs search by scintillators possible strategy for annual modulation search with large-mass highly-radiopure NaI(Tl)  

E-print Network

The DAMA experiments are running deep underground in the Gran Sasso National Laboratory. Several interesting results have been achieved so far. Here a maximum likelihood method to search for the WIMP annual modulation signature is discussed and applied to a set of preliminary test data collected with large mass highly radiopure NaI(Tl) detectors. Various related technical arguments are briefly addressed.

Bernabei, R; Belli, P; Dai Chang Jiang; Ding, L K; Incicchitti, A; Kuang Hao Huai; Ma, J M; Montecchia, F; Nicolantonio, W D; Prosperi, D

1999-01-01

325

Durham, July 14 2009 Aldo Morselli, INFN Roma Tor Vergata 15th Patras Workshop on Axions, WIMPs and WISPs, Durham 13-17 July 2009 Aldo Morselli  

E-print Network

Durham, July 14 2009 Aldo Morselli, INFN Roma Tor Vergata 15th Patras Workshop on Axions, WIMPs and WISPs, Durham 13-17 July 2009 Aldo Morselli INFN Roma Tor Vergata Search for Dark matter in the sky in the Fermi, Atic and Pamela era #12;Durham, July 14 2009 Aldo Morselli, INFN Roma Tor Vergata 2 #12;Durham

Morselli, Aldo

326

Sensitivity to gefitinib (Iressa, ZD1839) in non-small cell lung cancer cell lines correlates with dependence on the epidermal growth factor (EGF) receptor/extracellular signal-regulated kinase 1/2 and EGF receptor/Akt pathway for proliferation.  

PubMed

Gefitinib (Iressa, ZD1839), a quinazoline tyrosine kinase inhibitor that targets the epidermal growth factor receptor (EGFR), is approved for patients with advanced non-small cell lung cancer (NSCLC) in several countries including Japan. However, the mechanism of drug sensitivity to gefitinib is not fully understood. In this study, we examined the molecular basis of sensitivity to gefitinib using nine human lung cancer cell lines derived from NSCLC. PC9 was the most sensitive to gefitinib of the nine NSCLC cell lines when assayed either by colony formation or MTS assays. The various cell lines expressed different levels of EGFR, HER2, HER3, and HER4, but there was no correlation between levels of EGFR and/or HER2 expression and drug sensitivity. Phosphorylation of EGFR, protein kinase B/AKT (Akt), and extracellular signal-regulated kinase (ERK) 1/2 was inhibited by much lower concentration of gefitinib in PC9 cells than in the other eight cell lines under exponential growing conditions. About 80% of cell surface EGFR in PC-9 was internalized within 10 min, whereas only about 30-50% of the cell surface EGFR was internalized in more drug-resistant cell lines in 15-60 min. The present study is the first to demonstrate that sensitivity to growth inhibition by gefitinib in NSCLC cell lines under basal growth condition is associated with dependence on Akt and ERK1/2 activation in response to EGFR signaling for survival and proliferation and also that drug sensitivity may be related to the extent of EGF-induced down-regulation of cell surface EGFR. PMID:15078990

Ono, Mayumi; Hirata, Akira; Kometani, Takuro; Miyagawa, Miho; Ueda, Shu-ichi; Kinoshita, Hisafumi; Fujii, Teruhiko; Kuwano, Michihiko

2004-04-01

327

Signaling and drug sensitivity  

Microsoft Academic Search

Even though alterations in receptor and nonreceptor kinases are involved in the development of human cancer, many cancer cell lines still retain their responsiveness to growth factors. We have investigated the hypothesis that cellular signaling events regulate the sensitivity of cancer cells to chemotherapeutic agents. In 2008 human ovarian carcinoma cells, activation of a number of different transduction pathways resulted

Randolph D. Christen; Seiji Isonishi; Jeffrey A. Jones; Antti P. Jekunen; Doreen K. Hom; Relef Kröning; Dennis P. Gately; Franz B. Thiebaut; Gerrit Los; Stephen B. Howell

1994-01-01

328

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

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 10?L 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

Galán-Cano, Francisco; Bernabé-Zafón, Virginia; Lucena, Rafael; Cárdenas, Soledad; Herrero-Martínez, José Manuel; Ramis-Ramos, Guillermo; Valcárcel, Miguel

2011-04-01

329

$B_s \\to ?^+ ?^-$ and the upward-going muon flux from the WIMP annihilation in the sun or the earth  

E-print Network

We consider the upward-going muon flux due to the WIMP annihilations in the cores of the sun and the earth, including the upper bound on the branching ratio for $B_s \\to \\mu^+ \\mu^-$ decay. We find that the constraint from $B_s \\to \\mu^+ \\mu^-$ is very strong in most parameter space, and exclude the supergravity parameter space regions where the expected upward-going muon fluxes are within the expected reach of AMANDA II.

Seungwon Baek; Yeong Gyun Kim; P. Ko

2005-06-13

330

Evidence for efficient phosphorylation of EGFR and rapid endocytosis of phosphorylated EGFR via the early/late endocytic pathway in a gefitinib-sensitive non-small cell lung cancer cell line.  

PubMed

Gefitinib (Iressa)-a specific inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase-has been shown to suppress the activation of EGFR signaling required for cell survival and proliferation in non-small cell lung cancer (NSCLC) cell lines. We recently provided novel evidence that gefitinib-sensitive PC9 cells show normal endocytosis of EGFR: internalized EGF-EGFR complexes were transported to late endosomes/lysosomes 15 min after EGF stimulation, and then degraded within the lysosomes. However, gefitinib-resistant QG56 cells showed internalized EGFR accumulation in early endosomes after 60 min of internalization, instead of its trafficking to lysosomes, indicating an aberration in some steps of EGF-EGFR trafficking from the early endosomes to late endosomes/lysosomes. Therefore, we postulate that impairment in some steps of EGF-EGFR trafficking from early endosomes to late endosomes/lysosomes might confer gefitinib-resistance in NSCLC cell lines. To further substantiate the detailed internalization mechanism of gefitinib-sensitive and gefitinib-resistant cells, using confocal immunofluorescence microscopy, we examined the endocytic trafficking of phosphorylated EGFR (pEGFR) in the absence or presence of gefitinib. In PC9 and QG56 cells without EGF stimulation, a large number of pEGFR-positive small vesicular structures not colocalized with late endosomes/lysosomes were spread throughout the cytoplasm, and some pEGFR staining was distributed in the nucleus. This implies a novel intracellular trafficking pathway for pEGFR from cytoplasmic vesicles to the nucleus. Furthermore, an aggregated vesicular structure of early endosomes was observed in the perinuclear region of QG56 cells; it was revealed to be associated with SNX1, originally identified as a protein that interacts with EGFR. Therefore, we confirmed our previous data that an aberration in some steps of EGF-EGFR trafficking from the early endosomes to late endosomes/lysosomes occurs in QG56 cells. Furthermore, in PC9 cells, efficient phosphorylation of EGFR and rapid internalization of pEGFR was observed at 3 min after EGF stimulation; these internalized pEGFR-positive vesicles were trafficked to late endosomes at 15 min, indicating rapid trafficking of EGF-pEGFR complexes from early to late endosomes in PC9 cells. Gefitinib treatment strongly reduced the phosphorylation level of EGFR, and subsequent endocytosis of EGFR was significantly suppressed in PC9 cells. In contrast, in QG56 cells, EGFR trafficking via the early endocytic pathway was basically impaired; therefore, gefitinib appeared to slightly suppress the internalization of pEGFR. Collectively, our data provide novel evidence that extensive impairment in pEGFR endocytosis via the early endocytic pathway might confer gefitinib-resistance in QG56 cells. PMID:18492291

Nishimura, Yukio; Yoshioka, Kiyoko; Bereczky, Biborka; Itoh, Kazuyuki

2008-01-01

331

Cell lines.  

PubMed

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

Cherbas, Lucy; Gong, Lei

2014-06-15

332

A genetic rat model of depression, Flinders Sensitive Line, has a lower density of 5-HT1A receptors, but a higher density of 5-HT1B receptors, compared to control rats  

PubMed Central

Deficiencies in brain serotonergic neurotransmission, which is in part associated with the alteration of brain serotonin (5-HT) receptors, have been proposed as part of a neurochemical imbalance in affective disorders, including depression. The drugs used for the treatment of these disorders generally act through and/or on the serotonergic system. Different animal models of depression have provided researchers with tools to obtain a better understanding of drug actions and possibilities to obtain insight into the neurochemical bases of these disorders. The measurements of the 5-HT1A and 5-HT1B receptor densities in a rat model of depression, Flinders Sensitive Line (FSL) rats, and comparisons with Sprague-Dawley (SPD) and Flinders Resistant Line (FRL) rats, are reported here. The receptor sites were quantified by autoradiography in more than twenty-five distinct brain regions known to have relatively large densities of respective sites. Some brain regions (e.g., dental gyrus, septal nucleus) were divided into several parts, according to previously known subdivisions, because of a substantial heterogeneity of these receptors. The densities in the FSL rats (“depressed” rats) were compared statistically to those in the SPD rats. In addition, comparisons were made to the densities in the FRL rats (rats not showing depressive symptoms). Comparisons were performed with the SPD and FRL rats because both of these strains have been used as control animals in studies of FSL rats. The results show that the densities of 5-HT1A receptors are not significantly different between the FSL and SPD rats, but they are significantly different from the FRL rats. 5-HT1A receptor density is significantly higher in the FRL rats than the SPD rats. The 5-HT1B receptors were significantly greater in the FSL rats than in either the SPD or FRL rats. In addition, the FRL rats have 5-HT1B receptor densities significantly lower in many brain regions than the SPD rats. The data presented here, in addition to previously reported differences in regional synthesis between these strains and the effect of acute citalopram on synthesis, suggest that SPD rats are likely a more appropriate control than FRL rats, when studies of FSL rats are performed with drugs acting directly or indirectly on, or through, the brain serotonergic system. However, comparisons, particularly of neurochemical and/or biological parameters in FRL rats, may reveal new insight into the alterations of 5-HT neurotransmission in this animal model of depression and possibly human depression, as well as the elevation of symptoms with treatments. The data also suggest that there could be a different fraction of 5-HT1A receptors in high and low affinity states in these strains, as well as the possibility of different intracellular signalling. PMID:19121358

Nishi, Kyoko; Kanemaru, Kazuya; Diksic, Mirko

2008-01-01

333

Sensitive Periods  

PubMed Central

This chapter reviews sensitive periods in human brain development based on the literature on children raised in institutions. Sensitive experiences occur when experiences are uniquely influential for the development of neural circuitry. Because in humans, we make inferences about sensitive periods from evaluations of complex behaviors, we underestimate the occurrence of sensitive periods at the level of neural circuitry. Although we are most interested in complex behaviors, such as IQ or attachment or externalizing problems, many different sensitive periods at the level of circuits probably underlie these complex behaviors. Results from a number of studies suggest that across most, but not all, domains of development, institutional rearing limited to the first 4–6 months of life is associated with no significant increase risk for long-term adverse effects relative to non-institutionalized children. Beyond that, evidence for sensitive periods is less compelling, meaning that “the earlier the better” rule for enhanced caregiving is a reasonable conclusion at the current state of the science. PMID:25125708

Zeanah, Charles H.; Gunnar, Megan R.; McCall, Robert B.; Kreppner, Jana M.; Fox, Nathan A.

2010-01-01

334

The sensitivity of lung cancer cell lines to the EGFR-selective tyrosine kinase inhibitor ZD1839 (‘Iressa’ 1 1 Iressa’ is a trademark of the AstraZeneca group of companies. ) is not related to the expression of EGFR or HER2 or to K-ras gene status  

Microsoft Academic Search

ZD1839 (‘Iressa’) is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that inhibits EGFR signaling. Emerging evidence indicates that ZD1839 has clinical potential in lung cancer, but very little is known about the molecular characteristics of lung cancers that may determine sensitivity to ZD1839. We examined a panel of 19 lung cancer cell lines to investigate possible association between

Takeshi Suzuki; Taku Nakagawa; Hideki Endo; Tetsuya Mitsudomi; Akira Masuda; Yasushi Yatabe; Takahiko Sugiura; Takashi Takahashi; Toyoaki Hida

2003-01-01

335

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

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.

Ji, Xiangpan; Xu, Ye, E-mail: xuye76@nankai.edu.cn; Lin, Junsong; Feng, Yulong; Li, Haolin [Nankai University, School of Physics (China)

2013-11-15

336

The local dark matter phase-space density and impact on WIMP direct detection  

SciTech Connect

We present a new determination of the local dark matter phase-space density. This result is obtained implementing, in the limit of isotropic velocity distribution and spherical symmetry, Eddington's inversion formula, which links univocally the dark matter distribution function to the density profile, and applying, within a Bayesian framework, a Markov Chain Monte Carlo algorithm to sample mass models for the Milky Way against a broad and variegated sample of dynamical constraints. We consider three possible choices for the dark matter density profile, namely the Einasto, NFW and Burkert profiles, finding that the velocity dispersion, which characterizes the width in the distribution, tends to be larger for the Burkert case, while the escape velocity depends very weakly on the profile, with the mean value we obtain being in very good agreement with estimates from stellar kinematics. The derived dark matter phase-space densities differ significantly — most dramatically in the high velocity tails — from the model usually taken as a reference in dark matter detection studies, a Maxwell-Boltzmann distribution with velocity dispersion fixed in terms of the local circular velocity and with a sharp truncation at a given value of the escape velocity. We discuss the impact of astrophysical uncertainties on dark matter scattering rates and direct detection exclusion limits, considering a few sample cases and showing that the most sensitive ones are those for light dark matter particles and for particles scattering inelastically. As a general trend, regardless of the assumed profile, when adopting a self-consistent phase-space density, we find that rates are larger, and hence exclusion limits stronger, than with the standard Maxwell-Boltzmann approximation. Tools for applying our result on the local dark matter phase-space density to other dark matter candidates or experimental setups are provided.

Catena, Riccardo [Institut für Theoretische Physik, Friedrich-Hund-Platz 1, 37077 Göttingen (Germany); Ullio, Piero, E-mail: riccardo.catena@theorie.physik.uni-goettingen.de, E-mail: ullio@sissa.it [SISSA and INFN, Sezione di Trieste, Via Bonomea, 265, 34136 Trieste (Italy)

2012-05-01

337

Case for a 700+GeV WIMP: Cosmic ray spectra from PAMELA, Fermi, and ATIC  

SciTech Connect

Multiple lines of evidence indicate an anomalous injection of high-energy e{sup +}e{sup -} in the galactic halo. The recent e{sup +} fraction spectrum from the payload for antimatter matter exploration and light-nuclei astrophysics (PAMELA) shows a sharp rise up to 100 GeV. The Fermi gamma-ray space telescope has found a significant hardening of the e{sup +}e{sup -} cosmic-ray spectrum above 100 GeV, with a break, confirmed by HESS at around 1 TeV. The advanced thin ionization calorimeter (ATIC) has also detected a similar excess, falling back to the expected spectrum at 1 TeV and above. Excess microwaves towards the galactic center in the WMAP data are consistent with hard synchrotron radiation from a population of 10-100 GeV e{sup +}e{sup -} (the WMAP 'Haze'). We argue that dark matter annihilations can provide a consistent explanation of all of these data, focusing on dominantly leptonic modes, either directly or through a new light boson. Normalizing the signal to the highest energy evidence (Fermi and HESS), we find that similar cross sections provide good fits to PAMELA and the Haze, and that both the required cross section and annihilation modes are achievable in models with Sommerfeld-enhanced annihilation. These models naturally predict significant production of gamma rays in the galactic center via a variety of mechanisms. Most notably, there is a robust inverse-Compton scattered (ICS) gamma-ray signal arising from the energetic electrons and positrons, detectable at Fermi/GLAST energies, which should provide smoking gun evidence for this production.

Cholis, Ilias; Goodenough, Lisa; Weiner, Neal [Center for Cosmology and Particle Physics, Department of Physics, New York University, New York, New York 10003 (United States); Dobler, Gregory; Finkbeiner, Douglas P. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, Massachusetts 02138 (United States)

2009-12-15

338

Circumstellar radio molecular lines  

NASA Technical Reports Server (NTRS)

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.

NGUYEN-QUANG-RIEU

1987-01-01

339

An assessment of the sensitivity of a low pressure time projection chamber to the direction of WIMP-induced nuclear recoils/  

E-print Network

Direct directional detection of dark matter could provide an unambiguous observation of dark matter due to the predicted directional anisotropy of dark matter particles in the galactic reference frame. The Dark Matter Time ...

Henderson, Shawn Wesley

2013-01-01

340

Zip Line  

NSDL National Science Digital Library

In this design challenge activity, learners build a device to carry a Ping-Pong ball from the top of a zip line to the bottom in four seconds (or less!). Learners follow the design process to build the carrier that slides quickly down a zip line string, figure out how to keep something balanced, and identify ways to reduce friction.

2012-12-13

341

Polarization Sensitivity  

NASA Astrophysics Data System (ADS)

Optical coherence tomography (OCT) (Huang et al. Science 254(5035): 1178-1181, 1991; Fercher et al. Rep Prog Phys 66:239-303, 2003; Drexler and Fujimoto Prog Retin Eye Res 27(1):45-88, 2008) is a well-established tool for high-resolution cross-sectional imaging of human ocular structures. Despite its great success in improving ocular diagnostic imaging, conventional OCT cannot directly differentiate between different tissues. However, polarization-sensitive (PS) OCT is able to generate tissue-specific contrast that can be further used to segment ocular structures and to obtain quantitative information.

Schmidt-Erfurth, U.; Schlanitz, F.; Bolz, M.; Vass, C.; Lammer, J.; Schütze, C.; Pircher, M.; Götzinger, E.; Baumann, B.; Hitzenberger, C. K.

342

Number Line  

NSDL National Science Digital Library

This iOS app helps students to visualize number sentences and create models for addition, subtractions, multiplication, and division. The number line can be adjusted to represent multiples of numbers from one to one hundred.

Clarity Innovations, Inc.

2013-11-22

343

Poverty Lines  

NSDL National Science Digital Library

The World Bank has released the November 1997 issue of Poverty Lines, a newsletter that summarizes current research studies on poverty. The latest issue looks at how public works programs can help people who are poor.

344

Number Line  

NSDL National Science Digital Library

In this brief article the numerous uses of the number line are detailed: counting, measurement, addition, subtraction, decimals, and fractions. The article contains visual representations of the some of the concepts and links to related topics.

2012-08-27

345

Beau's Lines  

MedlinePLUS

... A A A Beau's lines (crosswise nail plate grooves) are due to severe illness or certain medications. ... occur along the fingernails and the toenails. The grooves extending across the nail plate often span its ...

346

Stochastic resonance in visual sensitivity.  

PubMed

It is well known from psychophysical studies that stochastic resonance, in its simplest threshold paradigm, can be used as a tool to measure the detection sensitivity to fine details in noise contaminated stimuli. In the present manuscript, we report simulation studies conducted in the similar threshold paradigm of stochastic resonance. We have estimated the contrast sensitivity in detecting noisy sine-wave stimuli, with varying area and spatial frequency, as a function of noise strength. In all the cases, the measured sensitivity attained a peak at intermediate noise strength, which indicate the occurrence of stochastic resonance. The peak sensitivity exhibited a strong dependence on area and spatial frequency of the stimulus. We show that the peak contrast sensitivity varies with spatial frequency in a nonmonotonic fashion and the qualitative nature of the sensitivity variation is in good agreement with human contrast sensitivity function. We also demonstrate that the peak sensitivity first increases and then saturates with increasing area, and this result is in line with the results of psychophysical experiments. Additionally, we also show that critical area, denoting the saturation of contrast sensitivity, decreases with spatial frequency and the associated maximum contrast sensitivity varies with spatial frequency in a manner that is consistent with the results of psychophysical experiments. In all the studies, the sensitivities were elevated via a nonlinear filtering operation called stochastic resonance. Because of this nonlinear effect, it was not guaranteed that the sensitivities, estimated at each frequency, would be in agreement with the corresponding results of psychophysical experiments; on the contrary, close agreements were observed between our results and the findings of psychophysical investigations. These observations indicate the utility of stochastic resonance in human vision and suggest that this paradigm can be useful in psychophysical studies. PMID:25398687

Kundu, Ajanta; Sarkar, Sandip

2015-04-01

347

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

E-print Network

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 $2^\\circ\\times2^\\circ$ region around the Galactic centre. Our results show that CTA will be able to probe gamma-ray boxes down to annihilation cross sections of $10^{-27}-10^{-26}\\,\\text{cm}^3\\text{/s}$ 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.

Alejandro Ibarra; Anna S. Lamperstorfer; Sergio López Gehler; Miguel Pato; Gianfranco Bertone

2015-03-23

348

WIMP annihilation in caustics  

E-print Network

The continuous infall of dark matter with low velocity dispersion from all directions in a galactic halo leads to the formation of caustics which are very small scale ($\\sim$parsec) high density structures. If the dark matter is made up of SUSY neutralinos, the annihilation of these particles produces a characteristic spectrum of gamma rays which in principle, could be detected. The annihilation signal at different energy bands is computed and compared with the expected gamma ray background.

Aravind Natarajan

2007-05-22

349

Multivariate Ensemble Sensitivity with Localization  

NASA Astrophysics Data System (ADS)

So far in the literature, covariance localization (tapering) has not been applied when performing ensemble sensitivity analysis. Sampling error in computing the sensitivities via lagged covariances leads to an over-estimation of the impact of a perturbation. Most commonly when computing sensitivities, the analysis covariance is approximated with the corresponding diagonal matrix. Two consequences follow: (1) the multi-variate sensitivity is approximated by a univariate sensitivity, and (2) sampling error in off-diagonal elements are obviated. It is unknown, however, how much information is lost by ignoring the off-diagonal elements in the full covariance. When forecasts depend on many details of the previous analysis, it is reasonable to expect that the diagonal approximation is too severe. The purpose of this presentation is to clarify the effects of the diagonal approximation, and investigate the need for localization when off-diagonal elements are considered. Motivated by examples arising from sensitivities estimated within a cycling mesoscale ensemble data assimilation system, for easier interpretation we turn to the two-scale model first presented by Lorenz in 2005. We show that for most problems, an efficient matrix inversion is possible by finding a minimum-norm solution, and employing appropriate matrix factorization. Comparing the full inversion with off-diagonal elements, the fine-scale sensitivity estimates can be substantially different from those arising when the diagonal approximation is used. Localization on the sensitivity can be handled by an off-line empirical or Bayesian estimation technique. Because the sensitivity estimated from the full inversion is subject to sampling error, it is sensitive to the localization. The results show that compared to typical practices, more complete ensemble sensitivity formulations may be needed to draw robust inferences in general.

Hacker, Joshua; Lei, Lili

2014-05-01

350

Diatomic predissociation line widths  

NASA Technical Reports Server (NTRS)

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.

Child, M. S.

1973-01-01

351

High Voltage Lines: Hazard at a Distance.  

ERIC Educational Resources Information Center

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)

Marino, Andrew A.; Becker, Robert O.

1978-01-01

352

Line liquids  

Microsoft Academic Search

We review the long wavelength description of three-dimensional liquids of entangled lines with an average orientation along the z-axis. Originally developed for polymer nematics, a closely related approach is applicable to the vortex liquid state of high temperature superconductors, and to ferro- and electrorheological fluids. The theory predicts unusual behavior of the three-dimensional structure function near the origin of reciprocal

David R. Nelson

1991-01-01

353

Temperature sensitive cells in the study of carcinogenic transformation  

Microsoft Academic Search

Two temperature sensitive variants (ts13 and ts14) of an African green monkey tetraploid kidney cell line (epithelial), carrying temperature sensitive lesions in thymidine metabolism, were transformed by methylnitrosourea (MNU) at the permissive temperature of 33 degrees C, nor was there any transformation in the wild type parental cell line of BSC-1 at these temperatures under similar conditions. A comparative study

P M Naha

1975-01-01

354

Gravitational-wave sensitivity curves  

E-print Network

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 \\url{http://rhcole.com/apps/GWplotter}.

Christopher J. Moore; Robert H. Cole; Christopher P. L. Berry

2014-12-11

355

Gravitational-wave sensitivity curves  

NASA Astrophysics Data System (ADS)

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.

Moore, C. J.; Cole, R. H.; Berry, C. P. L.

2015-01-01

356

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

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.

Lee, Young Sook; Oh, Jung-Hwa; Yoon, Seokjoo; Kwon, Myung-Sang [Toxicogenomics Team, Korea Institute of Toxicology, Daejeon (Korea, Republic of)

2010-07-01

357

Robust Video Streaming over Power Lines  

Microsoft Academic Search

The upcoming HomePlug AV standard enables power line communication (PLC) networks to transmit high quality video streams applicable for various video on demand and video relay services in digital homes. However, video streaming over power lines is sensitive to the interference caused by electrical appliances and to the degradation of quality of service (QoS) caused by the increase of transmission

Chang-Kuan Lin; Hao-Wei Chu; Shiann-Chang Yen; Meng-Ting Lu; Jason Yao; Homer Chen

2006-01-01

358

Factor Lines  

NSDL National Science Digital Library

This flash applet provides students with an activity to become more familiar with factors and multiples. The challenge is to arrange the four number cards (1, 2, 3 and 21) on a square of the grid to make as many different diagonal, vertical or horizontal lines as possible. The number card can be placed on a square of the grid if the square is the same number, a multiple of that number and or a factor of that number. Users have the ability to change the difficulty level. The Teachers' Notes page offers rationale, suggestions for implementation, key discussion questions, ideas for extension and support.

359

Sensitivity analysis of hydrodynamic stability operators  

NASA Technical Reports Server (NTRS)

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.

Schmid, Peter J.; Henningson, Dan S.; Khorrami, Mehdi R.; Malik, Mujeeb R.

1992-01-01

360

A plan for directional dark matter sensitivity in high-pressure xenon detectors through the addition of wavelength shifting gaseous molecules  

NASA Astrophysics Data System (ADS)

Xenon is an especially attractive candidate for both direct WIMP and 0??? decay searches. Although the current trend has exploited the liquid phase, the gas phase xenon offers remarkable performance advantages for: energy resolution, topology visualization, and discrimination between electron and nuclear recoils. The NEXT-100 experiment, now under construction in the Canfranc Underground Laboratory, Spain, will operate at ~ 15 bars with 100 kg of 136Xe for the 0??? decay search. We will describe recent results with small prototypes, indicating that NEXT-100 can provide about 0.5% FWHM energy resolution at the decay's Q value (2457.83 keV), as well as rejection of ?-rays with topological cuts. However, sensitivity goals for WIMP dark matter and 0??? decay searches indicate the probable need for ton-scale active masses. NEXT-100 provides the springboard to reach this scale with xenon gas. We describe a scenario for performing both searches in a single, high-pressure, ton-scale xenon gas detector, without significant compromise to either. In addition, even in a single ton-scale, high-pressure xenon gas TPC, an intrinsic sensitivity to the nuclear recoil direction may exist. This plausibly offers an advance of more than two orders of magnitude relative to current low-pressure TPC concepts. We argue that, in an era of deepening fiscal austerity, such a dual-purpose detector may be possible at acceptable cost, within the time frame of interest, and deserves our collective attention.

Gehman, V. M.; Goldschmidt, A.; Nygren, D.; Oliveira, C. A. B.; Renner, J.

2013-10-01

361

Imatinib sensitizes CLL lymphocytes to chlorambucil  

Microsoft Academic Search

The effect of imatinib on chlorambucil (CLB) cytotoxicity in chronic lymphocytic leukemia (CLL) lymphocytes was examined in vitro. Imatinib sensitizes the WSU and I83 human CLL cell lines, 10- and two-fold, respectively, to CLB. Furthermore, in primary cultures of malignant B-lymphocytes obtained from 12 patients with CLL (seven patients were untreated and five treated with CLB), imatinib synergistically sensitized these

R Aloyz; K Grzywacz; Z-Y Xu; M Loignon; M A Alaoui-Jamali; L Panasci

2004-01-01

362

Nuclear spin-dependent interactions: searches for WIMP, axion and topological defect dark matter, and tests of fundamental symmetries  

NASA Astrophysics Data System (ADS)

We calculate the proton and neutron spin contributions for nuclei using semi-empirical methods, as well as a novel hybrid ab initio/semi-empirical method, for interpretation of experimental data. We demonstrate that core-polarisation corrections to ab initio nuclear shell model calculations generally reduce discrepancies in proton and neutron spin expectation values from different calculations. We derive constraints on the spin-dependent P,T-violating interaction of a bound proton with nucleons, which for certain ranges of exchanged pseudoscalar boson masses improve on the most stringent laboratory limits by several orders of magnitude. We derive a limit on the CPT and Lorentz-invariance-violating parameter GeV, which improves on the most stringent existing limit by a factor of 8, and we demonstrate sensitivities to the parameters and at the level - GeV, which is a one order of magnitude improvement compared to the corresponding existing sensitivities. We extend previous analysis of nuclear anapole moment data for Cs to obtain new limits on several other CPT and Lorentz-invariance-violating parameters: GeV, , GeV and.

Stadnik, Y. V.; Flambaum, V. V.

2015-03-01

363

Dependence of Weak Localization Magnetoconductivity on Flux Line Structure  

Microsoft Academic Search

A numerical simulation in real space was developed to investigate weak localization corrections to the conductivity in inhomogeneous magnetic fields created by flux lines. Both cylinder model and exponential one of flux lines were studied. It was shown that the corrections are sensitive to the flux line structure. Comparing to the experiments of Bending et al., the results show that

Guohong Li; Min Wang; Guoliang Liu; Sangtian Liu; Shiguang Wang; Shousheng Yan

1995-01-01

364

Geometric sensitivity of ClearPET™ Neuro  

NASA Astrophysics Data System (ADS)

ClearPET™ Neuro is a small-animal positron emission tomography (PET) scanner dedicated to brain studies on rats and primates. The design of ClearPET™ Neuro leads to a specific geometric sensitivity, characterized by inhomogeneous and, depending on the measurement setup, even incomplete data. With respect to reconstruction techniques, homogeneous and complete data sets are a 'must' for analytical reconstruction methods, whereas iterative methods take the geometrical sensitivity into account during the reconstruction process. Nevertheless, here a homogeneous geometric sensitivity over the field of view is highly desirable. Therefore, this contribution aims at studying the impact of different scanner geometries and measurement setups on the geometric sensitivity. A data set of coincident events is computed for certain settings that contains each possible crystal combination once. The lines of response are rebinned into normalizing sinograms and backprojected into sensitivity images. Both, normalizing sinograms and sensitivity images mirror the geometric sensitivity and therefore, provide information which setting enables most complete and homogeneous data sets. An optimal measurement setup and scanner geometry in terms of homogeneous geometric sensitivity is found by analyzing the sensitivity images.

Gundlich, Brigitte; Weber, Simone

2007-02-01

365

Delay-line readout for multicell detectors  

NASA Astrophysics Data System (ADS)

A simple delay-line readout method has been tested with a position-sensitive photomultiplier. Position accuracies of the reconstruction by means of a time-to-amplitude convertor are quite comparable to those obtained by a conventional centroid method using a number of analog-to-digital convertors. In this way, a simple and economic solution can be conceived for the readout of not only position-sensitive photomultipliers, but also arrays of different kinds of position detectors.

Ditta, J.; Kuroda, K.; Nemoz, C.; Sillou, D.

1986-09-01

366

Pressure Sensitive Paints  

NASA Technical Reports Server (NTRS)

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.

Liu, Tianshu; Bencic, T.; Sullivan, J. P.

1999-01-01

367

Crack Imaging by Scanning Laser Line Thermography  

NASA Astrophysics Data System (ADS)

3D finite difference modeling results showing the sensitivity of laser line thermography to cracks of varying lengths, depths and openings are presented. A novel crack imaging technique based on assembling second spatial derivative thermal images of a scanned laser line is presented. Experimental results show the technique to image cracks with openings of a few micrometres. The technique is found to have an imaging rate twenty times higher than that of scanning laser spot thermography.

Li, T.; Almond, D. P.; Rees, D. A. S.

2011-06-01

368

78 FR 68076 - Request for Information on Alternative Skin Sensitization Test Methods and Testing Strategies and...  

Federal Register 2010, 2011, 2012, 2013, 2014

...in vitro methods (the direct peptide reactivity assay, human cell line activation test, KeratinoSens\\SM\\, and myeloid U937 skin sensitization test), which cover key events in the AOP for skin sensitization (Adler et al., 2011)....

2013-11-13

369

Poison Help Line  

MedlinePLUS

... Poison Help Line The toll-free Poison Help line, 1-800-222-1222 , which connects you to your ... and Services Administration (HRSA) , funds the Poison Help line ( 1-800-222-1222 ), which connects you to your ...

370

Supervisor Moral Sensitivity.  

ERIC Educational Resources Information Center

Assesses the moral sensitivity of 147 counselor supervisors (75 women, 71 men). Reports that 35% and 67% of supervisors received low moral sensitivity scores for breach of confidentiality and the dual relationship case, respectively. Supervisors scored significantly higher in moral sensitivity for the less ambiguous case, breach of…

Erwin, Wesley J.

2000-01-01

371

Sensitivity in Power Systems  

Microsoft Academic Search

Sensitivity is defined as the ratio ¿x\\/¿y relating small changes ¿x of some dependent variable to small changes ¿y of some independent or controllable variable y. In power systems, two dominant types of sensitivity relations are defined, namely 1) sensitivity of one electrical variable, such as the voltage Vi at node i, with respect to another electrical variable, such as

John Peschon; Dean Piercy; William Tinney; Odd Tveit

1968-01-01

372

First on-line results from the CRIS (Collinear Resonant Ionisation Spectroscopy) beam line at ISOLDE  

NASA Astrophysics Data System (ADS)

The CRIS (Collinear Resonant Ionisation Spectroscopy) experiment at the on-line isotope separator facility, ISOLDE, CERN, has been constructed for high-sensitivity laser spectroscopy measurements on radioactive isotopes. The technique determines the magnetic dipole and electric quadrupole moments, nuclear spin and changes in mean-square charge radii of exotic nuclei via measurement of their hyperfine structures and isotope shifts. In November 2011 the first on-line run was performed using the CRIS beam line, when the hyperfine structure of 207Fr was successfully measured. This paper will describe the technique and experimental setup of CRIS and present the results from the first on-line experiment.

Procter, T. J.; Flanagan, K. T.

2013-04-01

373

Abstract Line Designs  

ERIC Educational Resources Information Center

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…

Nevinskas, Nancy

2011-01-01

374

Implementing Product Line Variabilities  

Microsoft Academic Search

Software product lines have numerous members. Thus, a product line infrastructure must cover various systems. This is the significant difference to usual software systems and the reason for additional requirements on the various assets present during software product line engineering. It is imperative that they support the description of the product line as a whole, as well as its instantiation

Michalis Anastasopoulos; Cristina Gacek

2000-01-01

375

Implementing product line variabilities  

Microsoft Academic Search

Software product lines have numerous members. Thus, a product line infrastructure must cover various systems. This is the significant difference to usual software systems and the reason for additional requirements on the various assets present during software product line engineering. It is imperative that they support the description of the product line as a whole, as well as its instantiation

Critina Gacek; Michalis Anastasopoules

2001-01-01

376

A behavior-genetic approach to multiple chemical sensitivity.  

PubMed

This report emphasizes the application of behavior-genetic designs to the study of sensitivity to toxic chemicals, and features of multiple chemical sensitivity and substance abuse that are polar opposites. The implications of these issues for future research are discussed in relation to twin, adoption, and sibling pair studies, as well as in relation to the degree to which genetically selected lines of rodents that have been developed in the alcoholism field are applicable to multiple chemical sensitivity. PMID:9167987

Newlin, D B

1997-03-01

377

Easy observation of infrared spectral lines  

Microsoft Academic Search

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

Adolf Cortel

2012-01-01

378

In-line Sagnac interferometer current sensor  

Microsoft Academic Search

The authors demonstrate for the first time a near shot noise limited in-line Sagnac interferometer current sensor. It is shown to have a number of advantages over the optical current sensors based on polarimetric Faraday and Faraday\\/Sagnac loop interferometer topologies, including lower sensitivity to environmental disturbances, less demanding optical components, and easy installation.

J. Blake; P. Tantaswadi; R. T. de Carvalho

1996-01-01

379

Easy Observation of Infrared Spectral Lines  

ERIC Educational Resources Information Center

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…

Cortel, Adolf

2012-01-01

380

Power Line Monitoring  

Microsoft Academic Search

Overhead power lines are periodically inspected using both on-ground and helicopter-aided visual inspection. Factors including sun glare, cloud cover, close proximity to power lines, and rapidly changing visual circumstances make airborne inspection of power lines a particularly hazardous task. In this study, the feasibility of continuous, on-line monitoring of power lines using ultrasonic waves is considered. A sending\\/receiving transducer located

Mike S. Wilson; Stefan Hurlebaus

2007-01-01

381

Taste sensitivity in pregnancy.  

PubMed

Taste sensitivity to Phenyl-thio-Carbamide (PTC) and glucose were studied in 150 females during the 3 trimesters of their pregnancy periods. The taste sensitivity to PTC was determined by Harris and Kalmus method. For taste intensity and hedonic evaluation, 7 concentrations of glucose solutions were used. Taste sensitivity to both PTC and glucose increases during the 1st trimester of pregnancy. In comparison to non-pregnant females (from previous study) taste thresholds and hedonics decreases in pregnancy. PMID:1791044

Bhatia, S; Puri, R

1991-04-01

382

Breastfeeding, Sensitivity, and Attachment  

Microsoft Academic Search

OBJECTIVE.Our goal was to test the hypothesis that breastfeeding is associated with enhanced infant-mother attachment and its antecedent maternal sensitivity. METHODS.Breastfeeding intent and practice were assessed by questionnaires admin- istered to 152 mothers between 32 weeks of gestation and 12 months postpartum. Early maternal sensitivity was measured by the Sensitivity to Cues subscale of the Nursing Child Assessment Satellite Training

John R. Britton; Helen L. Britton; Virginia Gronwaldt

2010-01-01

383

Flash Mob Project Creates Awareness of Environmental Sensitivities: Making "Multiple Chemical Sensitivity" a Household Name  

ERIC Educational Resources Information Center

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…

Smith, Melva Gail

2011-01-01

384

Fabrics Protect Sensitive Skin from UV Rays  

NASA Technical Reports Server (NTRS)

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.

2009-01-01

385

Sensitivity of inbred Fayoumi chicks to seasonal variations F. H. ABDOU, M. SOLTAN, M. ABD ELLATIF H. AYOUB  

E-print Network

Sensitivity of inbred Fayoumi chicks to seasonal variations F. H. ABDOU, M. SOLTAN, M. ABD ELLATIF of Fayoumi chicks to seasonal variations. The results indicate that the inbred lines were more sensitive that sensitivity of inbred lines decreased as chicks advanced in age. Therefore, these findings are important

Paris-Sud XI, Université de

386

Sexuality Sensitive Schooling  

Microsoft Academic Search

American schools, especially their physical education and sport programs, provide some of the most hostile social geographies in all of society for gay youth. With the aim of transforming schools toward more democratic and sexuality sensitive institutions, this paper reviews the literature on sexuality and education. In the review, three themes, critical for educators pursuing sexuality sensitive change in schools,

Nate McCaughtry; Suzanna Rocco Dillon; Elizabeth Jones; Sara Smigell

2005-01-01

387

Sense and Sensitivities  

NSDL National Science Digital Library

A Java applet that illustrates the utility of the sensitivity and complementary sensitivity functions for linear control system design. Sketch a reference input and disturbance input with the mouse, and select a sensor noise level. Then drag open-loop system poles and zeros with the mouse to track the reference while rejecting the disturbance and noise. Includes an audio introduction with suggested exercises.

Kahn, Seth

388

Mentoring Emotionally Sensitive Individuals.  

ERIC Educational Resources Information Center

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.…

Shaughnessy, Michael F.; Self, Elizabeth

389

LEVEL 1 BIOASSAY SENSITIVITY  

EPA Science Inventory

The report, based on a survey of published literature, establishes a set of sensitivity estimates for the Level 1 environmental assessment (EA) bioassays recommended by EPA's IERL-RTP. The estimates permit comparison of bioassay sensitivity for detecting toxicity or mutagenicity ...

390

Multiwavelength Observation of WIMP Annihilation  

E-print Network

The annihilation of neutralino dark matter may result in observable signals in different wavelength. In the present paper we will discuss the effect of neutralino annihilation in the halo of our Galaxy and in its center. According to high resolution cold dark matter simulations, large virialized halos are formed through the constant merging of smaller halos appeared at previous times. At each epoch, dark matter halos have then a clumpy component which is made of these merging subhalos. The annihilation of dark matter in these clumps, always present in the halo of our Galaxy, may be responsible for appreciable fluxes of $\\gamma$-rays, potentially detectable. We find that, depending on the fundamental parameters of the clump density profile and on the distribution of clumps in the Galactic halo, the contribution to the diffuse $\\gamma$-ray background from clumps could be used to obtain constraints on the neutralino properties such as mass and annihilation cross section. On the other hand the annihilation of neutralino dark matter in the galactic center may result in radio signals. At the galactic center, infact, the accretion flow onto the central black hole sustains strong magnetic fields that can induce synchrotron emission, in the radio wavelength, by electrons and positrons generated in neutralino annihilations during advection onto the black hole. We find that the observed emission from the galactic center is consistent with neutralinos following a Navarro Frenk and White density profile at the galactic center while it is inconsistent with the presence of a spike density profile, supposed to be generated by the formation history of the central black hole.

Roberto Aloisio

2004-05-06

391

WIMP Dark Matter and Baryogenesis  

E-print Network

In the present universe visible and dark matter contribute comparable energy density although they have different properties. This coincidence can be elegantly explained if the dark matter relic density, originating from a dark matter asymmetry, is fully determined by the baryon asymmetry. Thus the dark matter mass is not arbitrary, rather becomes predictive. We realize this scenario in baryon(lepton) number conserving models where two or more neutral singlet scalars decay into two or three baryonic(leptonic) dark matter scalars, and also decay into quarks(leptons) through other on-shell and/or off-shell exotic scalar bilinears. The produced baryon(lepton) asymmetries in the dark matter scalar and in the standard model quarks(leptons) are thus equal and opposite. The dark matter mass can be predicted in a range from a few GeV to a few TeV depending on the baryon(lepton) numbers of the decaying scalars and the dark matter scalar. The dark matter scalar can interact with the visible matter through the exchange of the standard model Higgs boson, opening a window for the dark matter direct detection experiments. These models also provide testable predictions in the searches for the exotic scalar bilinears at LHC.

Pei-Hong Gu; Manfred Lindner; Utpal Sarkar; Xinmin Zhang

2010-09-14

392

WIMP Dark Matter and Baryogenesis  

Microsoft Academic Search

In the present universe visible and dark matter contribute comparable energy\\u000adensity although they have different properties. This coincidence can be\\u000aelegantly explained if the dark matter relic density, originating from a dark\\u000amatter asymmetry, is fully determined by the baryon asymmetry. Thus the dark\\u000amatter mass is not arbitrary, rather becomes predictive. We realize this\\u000ascenario in baryon(lepton) number

Pei-Hong Gu; Manfred Lindner; Utpal Sarkar; Xinmin Zhang

2010-01-01

393

Visual experience without lines: effect on developing cortical neurons.  

PubMed

Kittens were reared in a planetarium-like visual environment that lacked straight line contours. Cortical neurons were subsequently highly sensitive to spots of light but not to straight lines, in marked contrast to those from a normal cat. If linear contour processing is an innate function it appears to be subject to substantial modification by early visual experience. PMID:4746487

Pettigrew, J D; Freeman, R D

1973-11-01

394

DREAM regulates BDNF-dependent spinal sensitization  

Microsoft Academic Search

BACKGROUND: The transcriptional repressor DREAM (downstream regulatory element antagonist modulator) controls the expression of prodynorphin and has been involved in the modulation of endogenous responses to pain. To investigate the role of DREAM in central mechanisms of pain sensitization, we used a line of transgenic mice (L1) overexpressing a Ca2+- and cAMP-insensitive DREAM mutant in spinal cord and dorsal root

Ivan Rivera-Arconada; Tomaso Benedet; Carolina Roza; Begoña Torres; Jorge Barrio; Agnieszka Krzyzanowska; Carlos Avendaño; Britt Mellström; José A Lopez-Garcia; José R Naranjo

2010-01-01

395

A sensitive direct human telomerase activity assay  

Microsoft Academic Search

Expression of telomerase, the specialized reverse transcriptase that adds 5?-TTAGGG-3? repeats to the ends of human chromosomes, is upregulated in ?85% of human cancers and tumor cell lines. We describe a direct primer-extension activity assay for human telomerase that displays sensitivity to ?106 telomerase-positive cells, making the method suitable for use with standard cell culture–based research (Fig. 1). Telomerase is

Scott B Cohen; Roger R Reddel

2008-01-01

396

The potential effectiveness of nanoparticles as radio sensitizers for radiotherapy  

PubMed Central

Introduction: Application of nanoparticles as radio sensitizer is a promising field to improve efficiency of radiotherapy. Methods: This study was conducted to review nano radio sensitizers. PubMed, Ovid Medline, Science Direct, Scopus, ISI web of knowledge, and Springer databases were searched from 2000 to May 2013 to identify relevant studies. Search was restricted to English language. Results: We included any study that evaluated nanoparticles, volunteer of radio enhancement at radiotherapy on animals or cell lines. Nanoparticles can increase radio sensitivity of tumor cells. This effect was shown in vivo and in vitro, at kilovltage or megavoltage energies, in 24 reviewed studies. Focus of studies was on gold nanoparticles. Radio sensitizing effects of nanoparticles depend on nanoparticles’ size, type, concentration, intracellular localization, used irradiation energy and tested cell line. Conclusion: Literature suggests potency of nanoparticles for increasing cell radio sensitivity. Reviewed results are promising and warrant future clinical trials. PMID:24790894

Babaei, Mohammad; Ganjalikhani, Maryam

2014-01-01

397

Central line infections - hospitals  

MedlinePLUS

... and increase how long you are in the hospital. Your central line needs special care to prevent ... The hospital staff will use aseptic technique when a central line is put in your chest or arm. Aseptic ...

398

Peripheral intravenous line (image)  

MedlinePLUS

A peripheral intraveouos line is a small, short plastic catheter that is placed through the skin into a vein, usually in the hand, elbow, or foot, but occasionally in the head. A peripheral intraveouos line is ...

399

Traceability of line graphs  

Microsoft Academic Search

Brualdi and Shanny [R.A. Brualdi, R.F. Shanny, Hamiltonian line graphs, J. Graph Theory 5 (1981) 307–314], Clark [L. Clark, On hamitonian line graphs, J. Graph Theory 8 (1984) 303–307] and Veldman [H.J. Veldman, On dominating and spanning circuits in graphs, Discrete Math. 124 (1994) 229–239] gave minimum degree conditions of a line graph guaranteeing the line graph to be hamiltonian.

Liming Xiong; Minmin Zong

2009-01-01

400

The LISA Optimal Sensitivity  

E-print Network

The multiple Doppler readouts available on the Laser Interferometer Space Antenna (LISA) permit simultaneous formation of several interferometric observables. All these observables are independent of laser frequency fluctuations and have different couplings to gravitational waves and to the various LISA instrumental noises. Within the functional space of interferometric combinations LISA will be able to synthesize, we have identified a triplet of interferometric combinations that show optimally combined sensitivity. As an application of the method, we computed the sensitivity improvement for sinusoidal sources in the nominal, equal-arm LISA configuration. In the part of the Fourier band where the period of the wave is longer than the typical light travel-time across LISA, the sensitivity gain over a single Michelson interferometer is equal to $\\sqrt{2}$. In the mid-band region, where the LISA Michelson combination has its best sensitivity, the improvement over the Michelson sensitivity is slightly better than $\\sqrt{2}$, and the frequency band of best sensitivity is broadened. For frequencies greater than the reciprocal of the light travel-time, the sensitivity improvement is oscillatory and $\\sim \\sqrt{3}$, but can be greater than $\\sqrt{3}$ near frequencies that are integer multiples of the inverse of the one-way light travel-time in the LISA arm.

Thomas A. Prince; Massimo Tinto; Shane L. Larson; J. W. Armstrong

2003-06-04

401

Method for rapid isolation of sensitive mutants  

DOEpatents

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.

Freyer, James P. (Los Alamos, NM)

1997-01-01

402

Method for rapid isolation of sensitive mutants  

DOEpatents

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.

Freyer, J.P.

1997-07-29

403

A study of eigenvalue sensitivity for hydrodynamic stability operators  

NASA Technical Reports Server (NTRS)

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.

Schmid, Peter J.; Henningson, Dan S.; Khorrami, Mehdi R.; Malik, Mujeeb R.

1993-01-01

404

The EVE Doppler Sensitivity and Flare Observations  

NASA Technical Reports Server (NTRS)

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

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

2011-01-01

405

The EVE Doppler Sensitivity and Flare Observations  

NASA Astrophysics Data System (ADS)

The Extreme-ultraviolet Variability Experiment (EVE; see Woods et al., 2009) obtains continuous EUV spectra of the Sun viewed as a star. Its primary objective is the characterization of solar spectral irradiance, but its sensitivity and stability make it extremely interesting for observations of variability on time scales down to the limit imposed by its basic 10 s sample interval. In this paper we characterize the Doppler sensitivity of the EVE data. We find that the 30.4 nm line of He ii has a random Doppler error below 0.001 nm (1 pm, better than 10 km s-1 as a redshift), with ample stability to detect the orbital motion of its satellite, the Solar Dynamics Observatory (SDO). Solar flares also displace the spectrum, both because of Doppler shifts and because of EVE's optical layout, which (as with a slitless spectrograph) confuses position and wavelength. As a flare develops, the centroid of the line displays variations that reflect Doppler shifts and therefore flare dynamics. For the impulsive phase of the flare SOL2010-06-12, we find the line centroid to have a redshift of 16.8 ± 5.9 km s-1 relative to that of the flare gradual phase (statistical errors only). We find also that high-temperature lines, such as Fe xxiv 19.2 nm, have well-determined Doppler components for major flares, with decreasing apparent blueshifts as expected from chromospheric evaporation flows.

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

2011-10-01

406

Line of Best Fit  

NSDL National Science Digital Library

When data is displayed with a scatter plot, it is often useful to attempt to represent that data with the equation of a straight line for purposes of predicting values that may not be displayed on the plot. Such a straight line is called the "line of best fit." In this activity, students discover the relationship between the fat grams and the total calories in fast food by graphing the given data, estimate the line of best fit using a strand of spaghetti, calculate the slope of that line, and translate it into an equation. Then, they use that equation to predict information not originally included in the scatter plot.

Roberts, Donna

407

Building a Zip Line  

NSDL National Science Digital Library

A zip line is a way to glide from one point to another while hanging from a cable. Design and create a zip line that is safe for a hard-boiled egg. After designing a safety egg harness, connect the harness to fishing line or wire connected between two chairs of different heights using a paper clip. Learn to improve your zip line based on data. Attach a motion sensor at the bottom of your zip line and display a graph to show how smooth a ride your egg had!

2012-07-19

408

August 2006 PROTECTING SENSITIVE  

E-print Network

to disposal in a way that is appropriate to the sensitivity and value of the information. When they discard and value of the information. When they discard media and devices, organizations and individuals should make

409

Contact sensitization in children.  

PubMed

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

Manzini, B M; Ferdani, G; Simonetti, V; Donini, M; Seidenari, S

1998-01-01

410

Sensitivity of photoacoustic microscopy  

PubMed Central

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

Yao, Junjie; Wang, Lihong V.

2014-01-01

411

Collective Phase Sensitivity  

E-print Network

The collective phase response to a macroscopic external perturbation of a population of interacting nonlinear elements exhibiting collective oscillations is formulated for the case of globally-coupled oscillators. The macroscopic phase sensitivity is derived from the microscopic phase sensitivity of the constituent oscillators by a two-step phase reduction. We apply this result to quantify the stability of the macroscopic common-noise induced synchronization of two uncoupled populations of oscillators undergoing coherent collective oscillations.

Yoji Kawamura; Hiroya Nakao; Kensuke Arai; Hiroshi Kori; Yoshiki Kuramoto

2008-07-08

412

Sensitivity to wild vegetation.  

PubMed

74 patients suspected of having allergic contact dermatitis to wild vegetation were patch tested with either extracts of 13 plants of the family Compositae and 7 other weeds or trees. Anthemis cotula (dog fennel) and Xanthium strumarium (cocklebur) gave the most frequent positive results, demonstrating a change of frequency in sensitivity compared to the 1950s, when Ambrosia artemisiifolia (ragweed) was recognized as the most frequently sensitizing weed. The reasons for these changes of incidence and clinical patterns are examined. PMID:3581826

Menz, J; Winkelmann, R K

1987-03-01

413

Gamma ray line astronomy  

NASA Technical Reports Server (NTRS)

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.

Ramaty, R.

1984-01-01

414

Allergic sensitization: screening methods  

PubMed Central

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

2014-01-01

415

Allergic sensitization: screening methods.  

PubMed

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

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

416

High energy beam lines  

NASA Astrophysics Data System (ADS)

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.

Marchetto, M.; Laxdal, R. E.

2014-01-01

417

Infant Allergies and Food Sensitivities  

MedlinePLUS

... Food Sensitivities Ages & Stages Listen Infant Allergies and Food Sensitivities Article Body Human breast milk typically does ... tell your pediatrician about your family’s medical history. Food Sensitivities A few mothers notice minor reactions to ...

418

Linear Polarization Measurements of Chromospheric Emission Lines  

NASA Technical Reports Server (NTRS)

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.

Sheeley, N. R., Jr.; Keller, C. U.

2003-01-01

419

Series Transmission Line Transformer  

DOEpatents

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.

Buckles, Robert A. (Livermore, CA); Booth, Rex (Livermore, CA); Yen, Boris T. (El Cerrito, CA)

2004-06-29

420

Interactive Fraction Number Lines  

NSDL National Science Digital Library

In this lesson students make models of fractions, including a human number line. Using a number line, students develop conceptual understanding of fractions. Students use the number line to represent and compare fractions less than one. The activities are engaging and include full participation/engagement of all students. The fractions are limited to positive fractions less than one with a denominator of 2 or 4 including 0 and 1 whole.

Michael Green

2012-05-25

421

Monopoles and Wilson Lines  

E-print Network

We present a semi-classical description of BPS monopoles interacting with Wilson lines. The Wilson lines are represented as non-Abelian spin impurities. These spins interact with the monopole degrees of freedom through a natural connection on the moduli space. We employ this technology in N = 2 SU(2) gauge theory to count the number of framed BPS states of a single monopole bound to Wilson lines in different representations.

David Tong; Kenny Wong

2014-05-19

422

Plasma stable, pH-sensitive fusogenic polymer-modified liposomes: A promising carrier for mitoxantrone.  

PubMed

pH-sensitive liposomes are designed to undergo acid-triggered destabilization. In the present study, we prepared polymer-modified, plasma stable, pH-sensitive fusogenic mitoxantrone liposomes to increase efficacy and selectivity on cancer cell lines. Conventional liposomes were prepared using cholesterol and dipalmitoyl-sn-glycero-3-phosphatidylethanolamine. Dioleoylphosphatidylethanolamine and a cholesteryl derivative, poly(monomethylitaconate)-co-poly(N,N-dimethylaminoethyl methacrylate) (PMMI-co-PDMAEMA), were used for the preparation of pH-sensitive fusogenic liposomes. Using polyethylene glycol (PEG)-poly(monomethylitaconate)-CholC6 (PEG-PMMI-CholC6) copolymers instead of cholesterol introduced pH-sensitive and plasma stability properties simultaneously in prepared liposomes. All formulations were prepared by thin film hydration method and subsequently, pH-sensitivity and stability in human serum were evaluated. The ability of pH-sensitive fusogenic liposomes to enhance the mitoxantrone cytotoxicity and selectivity in cancerous cell lines was assessed in vitro compared to normal cell line using human breast cancer cell line (MCF-7), human prostate cancer cell line (PC-3), and human umbilical vein endothelial cells line. Results revealed that both PMMI-co-PDMAEMA and PEG-PMMI-CholC6-based formulations showed pH-sensitive property and were found to rapidly release mitoxantrone under mildly acidic conditions. Nevertheless, only the PEG-PMMI-CholC6-based liposomes preserved pH-sensitivity after incubation in plasma. Mitoxantrone loaded-pH-sensitive fusogenic liposomes exhibited a higher cytotoxicity than the control conventional liposomes on MCF-7 and PC-3 cell lines. On the contrary, both pH-sensitive fusogenic liposomes showed lower cytotoxic effect on human umbilical vein endothelial cell line. Plasma stable, pH-sensitive fusogenic liposomes are promising carriers for enhancing the efficiency and selectivity, besides reduction of the side effects of anticancer agents. PMID:24336315

Ghanbarzadeh, Saeed; Arami, Sanam; Pourmoazzen, Zhaleh; Ghasemian-Yadegari, Javad; Khorrami, Arash

2013-12-11

423