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1

Development of bubble chambers with sensitivity to WIMPs  

NASA Astrophysics Data System (ADS)

Bubble nucleation in moderately superheated liquids can be triggered by nuclear recoils from WIMPs. This phenomenon is the basis for superheated droplet detectors. The droplet technique is currently limited by insensitivity to spin-independent interactions, due to lack of heavy elements in the usual target liquids, and sensitivity to contamination of the gel by alpha emitters. As an alternative, we have developed a new type of homogeneous bubble chamber, which can contain heavy liquids, including CF 3Br, CF 3I, and C 3F 8. Detectors of this type may be scalable to large size at modest cost and could have very low backgrounds. We discuss results obtained with a 12 ml prototype and plans for a 1 liter chamber.

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

2005-05-01

2

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

3

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

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

2014-01-01

4

Uniformly-Sensitive Line Hydrophones.  

National Technical Information Service (NTIS)

A uniformly-sensitive line hydrophone under development at the Woods Hole Oceanographic Institution has been used to receive broadband seismic reflection signals. The directivity characteristics of an adequately-long continuous line sensor used in a broad...

S. T. Knott F. R. Hess R. T. Nowak

1969-01-01

5

E-WIMPs  

SciTech Connect

Extremely weakly interacting massive particles (E-WIMPs) are intriguing candidates for cold dark matter in the Universe. We review two well motivated E-WIMPs, an axino and a gravitino, and point out their cosmological and phenomenological similarities and differences, the latter of which may allow one to distinguishing them in LHC searches for supersymmetry.

Choi, Ki-Young; Roszkowski, Leszek [Department of Physics and Astronomy, University of Sheffield, Sheffield, S3 7RH (United Kingdom)

2005-12-02

6

NITPC technical work in progress and sketch for a WIMP observatory  

Microsoft Academic Search

Direction-sensitive WIMP detection is important for conclusively identifying a halo-WIMP signal. It would also make possible the study of galactic halo dynamics through WIMP astronomy. A large low-pressure Negative Ion TPC (NITPC) is the only technique presently known which is capable of direction sensitive WIMP detection. Several advances in NITPC technology reported here. A new capture agent (CH3NO3) with several

C. J. Martoff

2007-01-01

7

Direct detection of WIMPs  

NASA Astrophysics Data System (ADS)

A generic weakly interacting massive particle (WIMP) is one of the most attractive candidates to account for the cold dark matter in our Universe, since it would be thermally produced with the correct abundance to account for the observed dark matter density. WIMPs can be searched for directly through their elastic scattering with a target material, and a variety of experiments are currently operating or planned with this aim. In these notes we overview the theoretical calculation of the direct detection rate of WIMPs as well as the different detection signals. We discuss the various ingredients (from particle physics and astrophysics) that enter the calculation and review the theoretical predictions for the direct detection of WIMPs in particle physics models.

Cerdeño, D. G.; Green, A. M.

8

Neutrinos from WIMP Annihilations  

NASA Astrophysics Data System (ADS)

In this talk, we make an improved analysis on the production of neutrinos coming from WIMP annihilations inside the Sun as well as the Earth. We treat both neutrino interaction and oscillation effects in a consistent three-flavor framework. Our numerical simulations are performed in an event-based setting, which is useful for both theoretical studies and creating neutrino telescope Monte Carlo simulations. We find that the yield of muon-type neutrinos is enhanced or suppressed depending on the dominant WIMP annihilation channel. In addition, we find that oscillations can significantly affect the neutrino yields from WIMP annihilations in the Sun. Effectively, the neutrino flavors are mixed. Finally, for the Earth, the oscillations have no large impact at energies for the new neutrino telescopes such as IceCube, ANTARES, and NESTOR.

Ohlsson, Tommy

2008-04-01

9

Direct detection of multicomponent secluded WIMPs  

SciTech Connect

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

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

2009-06-01

10

The WIMP Paradigm: Current Status  

SciTech Connect

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

Feng, Jonathan (University of California, Irvine) [University of California, Irvine

2011-03-23

11

Combined Limits on WIMPs from the CDMS and EDELWEISS Experiments  

SciTech Connect

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

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

2011-05-01

12

First Dark Matter Results from the CDMS 5-Tower Run and the path towards ? = 10-46 cm2 Wimp sensitivity  

NASA Astrophysics Data System (ADS)

This paper will report on the recently released results from the Cryogenic Dark Matter Search (CDMS II) experiment. Data from 30 cryogenic particle detectors operated at the Soudan Underground Laboratory between October 2006 and July 2007 was collected. The results from from a blind analysis of 15 Ge detectors corresponding to total exposure of 121.3 kg-d (averaged over the recoil energy range 10-100 keV, and weighted for a weakly interacting massive particle (WIMP) mass of 60 GeV/c2) are presented here. With zero observed events an upper limit on WIMP-nucleon spin-independent cross section of 6.6×10-44 cm2 is obtained from this data set alone. The limit improves to 4.6×10-44 cm2 when combined with previous CDMS data. The paper will also describe current efforts at designing and building larger mass detectors (~few kg/detector) which will form the basis of a future 1-Ton cryogenic Ge detector experiment.

Saab, T.

2008-11-01

13

First Dark Matter Results from the CDMS 5-Tower Run and the path towards {sigma} = 10{sup -46} cm{sup 2} Wimp sensitivity  

SciTech Connect

This paper will report on the recently released results from the Cryogenic Dark Matter Search (CDMS II) experiment. Data from 30 cryogenic particle detectors operated at the Soudan Underground Laboratory between October 2006 and July 2007 was collected. The results from from a blind analysis of 15 Ge detectors corresponding to total exposure of 121.3 kg-d (averaged over the recoil energy range 10-100 keV, and weighted for a weakly interacting massive particle (WIMP) mass of 60 GeV/c{sup 2}) are presented here. With zero observed events an upper limit on WIMP-nucleon spin-independent cross section of 6.6x10{sup -44} cm{sup 2} is obtained from this data set alone. The limit improves to 4.6x10{sup -44} cm{sup 2} when combined with previous CDMS data. The paper will also describe current efforts at designing and building larger mass detectors ({approx}few kg/detector) which will form the basis of a future 1-Ton cryogenic Ge detector experiment.

Saab, T. [Department of Physics, University of Florida, Gainesville, FL 32611 (United States)

2008-11-23

14

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

15

Spin-Dependent WIMP Limits from a Bubble Chamber  

NASA Astrophysics Data System (ADS)

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

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

2008-02-01

16

COUPP, A Heavy-Liquid Bubble Chamber for WIMP Detection  

NASA Astrophysics Data System (ADS)

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

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

2005-04-01

17

NITPC technical work in progress and sketch for a WIMP observatory  

NASA Astrophysics Data System (ADS)

Direction-sensitive WIMP detection is important for conclusively identifying a halo-WIMP signal. It would also make possible the study of galactic halo dynamics through WIMP astronomy. A large low-pressure Negative Ion TPC (NITPC) is the only technique presently known which is capable of direction sensitive WIMP detection. Several advances in NITPC technology reported here. A new capture agent (CH3NO3) with several advantages over the standard CS2 is identified. Simulations with GARFIELD show that tracks completely contained within a single drift cell can be measured using the ''radial drift chamber'' structure proposed by Nygren. DRIFT I neutron source calibration data is shown in which the ''head-tail'' orientation of tracks is able to be determined. (Supported by the U.S. NSF under NSF-PHY-0300766.)

Martoff, C. J.; Drift I Collaboration

2007-04-01

18

New limits on low-mass WIMP dark matter with sub-keV germanium detector  

Microsoft Academic Search

The current goals of the TEXONO research program are on the development of germanium detectors with sub-keV sensitivities to realize experiments on neutrino magnetic moments, neutrino-nucleus coherent scattering, as well as WIMP dark matter searches. A threshold of 220 eV was achieved with prototype detectors at the Kuo-Sheng Neutrino Laboratory. New limits were placed for the couplings of low-mass WIMPs

Henry T. Wong

2010-01-01

19

Search for WIMPs in liquid argon  

Microsoft Academic Search

Our group from the University of Zurich is performing R&D work towards the design of a large liquid argon detector to detect Weakly Interacting Massive Particles (WIMPs). This project is developed within the DARWIN Collaboration funded by ASPERA to prepare a proposal for the next generation of WIMP searches using noble liquids. We are performing R&D to detect the VUV

C. Amsler

2011-01-01

20

Photon spectra from quark generation by WIMPs  

SciTech Connect

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

Cembranos, J. A. R.; Cruz-Dombriz, A.; Maroto, A. L. [Departamento de Fisica Teorica I, Universidad Complutense de Madrid, E-28040 Madrid (Spain) and Department of Mathematics and Applied Mathematics, University of Cape Town, 7700 (South Africa); Dobado, A.; Lineros, R. [IFIC, CSIC-Universitat de Valencia, Ed. Instituts, Apt. 22085, 46071 Valencia (Spain)

2011-05-23

21

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

ScienceCinema

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

22

Oh to Be Rid of Administrative Wimps!  

ERIC Educational Resources Information Center

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

Weissberg, Robert

2007-01-01

23

Nuclear Recoil Background Evaluation for WIMP Searches  

Microsoft Academic Search

Nuclear recoils produced by neutrons, alphas and neutrinos as they scatter from target nuclei are important sources of background which must be considered in WIMP searches. PMTs and other detector components may contribute neutrons which generate a source of background. Alphas on the surface of the vessel can also be a serious issue for some of the experiments. And, neutrino-induced

Dongming Mei; Andrew Hime; Christina Keller; Zhongbao Yin

2007-01-01

24

WIMP Dark Matter and the First Stars  

NASA Astrophysics Data System (ADS)

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

Iocco, Fabio

2010-11-01

25

Radiation sensitivity of Merkel cell carcinoma cell lines  

SciTech Connect

Merkel cell carcinoma (MCC), being a small cell carcinoma, would be expected to be sensitive to radiation. Clinical analysis of patients at our center, especially those with macroscopic disease, would suggest the response is quite variable. We have recently established a number of MCC cell lines from patients prior to radiotherapy, and for the first time are in a position to determine their sensitivity under controlled conditions. Some of the MCC lines grew as suspension cultures and could not be single cell cloned; therefore, it was not possible to use clonogenic survival for all cell lines. A tetrazolium based (MTT) assay was used for these lines, to estimate cell growth after {gamma} irradiation. Control experiments were conducted on lymphoblastoid cell lines (LCL) and the adherent MCC line, MCC13, to demonstrate that the two assays were comparable under the conditions used. We have examined cell lines from MCC, small cell lung cancer (SCLC), malignant melanomas, Epstein Barr virus (EBV) transformed lymphocytes (LCL), and skin fibroblasts for their sensitivity to {gamma} irradiation using both clonogenic cell survival and MTT assays. The results show that the tumor cell lines have a range of sensitivities, with melanoma being more resistant (surviving fraction at 2 Gy (SF2) 0.57 and 0.56) than the small cell carcinoma lines, MCC (SF2 range 0.21-0.45, mean SF2 0.30, n = 8) and SCLC (SF2 0.31). Fibroblasts were the most sensitive (SF2 0.13-0.20, mean 0.16, n = 5). The MTT assay, when compared to clonogenic assay for the MCC13 adherent line and the LCL, gave comparable results under the conditions used. Both assays gave a range of SF2 values for the MCC cell lines, suggesting that these cancers would give a heterogeneous response in vivo. The results with the two derivative clones of MCC14 (SF2 for MCC14/1 0.38, MCC14/2 0.45) would further suggest that some of them may develop resistance during clonogenic evolution. 25 refs., 3 figs., 1 tab.

Leonard, J.H.; Ramsay, J.R.; Birrell, G.W. [Queensland Institute of Medical Research (Australia)] [and others] [Queensland Institute of Medical Research (Australia); and others

1995-07-30

26

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

27

In-line phase sensitive amplifier based on PPLN waveguides.  

PubMed

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

Umeki, Takeshi; Asobe, Masaki; Takenouchi, Hirokazu

2013-05-20

28

The DRIFT project: searching for WIMPs with a directional detector  

Microsoft Academic Search

A low pressure time projection chamber for the detection of WIMPs is discussed. Discrimination against Compton electron background in such a device should be very good, and directional information about the recoil atoms would be obtainable. If a full 3-D reconstruction of the recoil tracks can be achieved, Monte Carlo studies indicate that a WIMP signal could be identified with

M. J. Lehner; K. Griest; C. J. Martoff; G. E. Masek; T. Ohnuki; D. Snowden-Ifft; N. J. C. Spooner

1999-01-01

29

Celecoxib increases retinoid sensitivity in human colon cancer cell lines  

Microsoft Academic Search

Retinoid resistance has limited the clinical application of retinoids as differentiation-inducing and apoptosis-inducing drugs.\\u000a This study was designed to investigate whether celecoxib, a selective COX-2 inhibitor, has effects on retinoid sensitivity\\u000a in human colon cancer cell lines, and to determine the possible mechanism of said effects. Cell viability was measured using\\u000a the MTT assay. Apoptosis was detected via Annexin-V\\/PI staining

Jian-Pei Liu; Hong-Bo Wei; Zong-Heng Zheng; Wei-Ping Guo; Jia-Feng Fang

2010-01-01

30

iLine sensitive photoacid generators for UV curing  

Microsoft Academic Search

UV curing systems based on cationic processes are very significant because the systems have several advantages compared to the radical process. Photoacid generator (PAG) is essential for the cationic UV curing system including epoxides and vinyl ethers. Although many types of PAG have been developed, most of them are not sensitive to i-line (365nm) from a high-pressure mercury lamp. In

Masamitsu Shirai; Haruyuki Okamura

2009-01-01

31

Boron-lined proportional counters with improved neutron sensitivity  

NASA Astrophysics Data System (ADS)

Boron-lined proportional counters with higher neutron sensitivity have been developed by introducing baffle structures within the sensitive volume. the results are compared to devices developed with multiple cathode assemblies in a single enclosure. in either case, the increase in the boron-coated surface area results in higher neutron sensitivity. one of these counters has 51 annular baffles coated with natural boron with 10 mm hole for the anode wire to pass through. filled with p-10 gas at 20 cm hg, it has an overall diameter of 30 and 300 mm length. multiple dip coating method was employed for better uniformity in boron thickness. the neutron sensitivity of this counter is 1.6 cps/nv, which is 2.5 times that of a counter with standard electrode geometry. another counter was developed with three cathode assemblies (30 mm ID×300 mm) coated with 92% 10B while the third has seven assemblies coated with natural boron (16 mm ID×750 mm length). the neutron sensitivity is 10 and 5.5 cps/nv, respectively. the change in neutron sensitivity in 8 R/h gamma background was 12%, 18% and 22% in the case of the counter with baffles, 3 and 7 cathode assemblies.

Dighe, P. M.; Prasad, D. N.; Prasad, K. R.; Kataria, S. K.; Athavale, S. N.; Pappachan, A. L.; Grover, A. K.

2003-01-01

32

Tracking differential interference contrast diffraction line images with nanometre sensitivity.  

PubMed

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

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

2000-04-01

33

DARWIN dark matter WIMP search with noble liquids  

NASA Astrophysics Data System (ADS)

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

Baudis, Laura; DARWIN Consortium

2012-07-01

34

WIMP-nucleus scattering in chiral effective theory  

NASA Astrophysics Data System (ADS)

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

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

2012-10-01

35

A sensitive search for methanol line emission toward evolved stars  

NASA Astrophysics Data System (ADS)

We present a sensitive search for methanol line emission in evolved stars at 1 cm, aiming to detect, for the first time, methanol masers in this type of objects. Our sample comprised post-AGB stars and young planetary nebulae (PNe), whose mass-loss processes and circumstellar structures resemble those of young stellar objects (YSOs), where methanol masers are detected. Class I masers were searched for in 73 objects, whereas Class II ones were searched in 16. No detection was obtained. The non-detection of Class I methanol masers indicated that methanol production in dust grains and/or the enhancement of its gas-phase abundance in the shocked regions of evolved objects are not as efficient as in YSOs. We suggest that relatively more evolved PNe might have a better probability of harboring Class II masers.

Gómez, J. F.; Uscanga, L.; Suárez, O.; Rizzo, J. R.; de Gregorio-Monsalvo, I.

2014-04-01

36

Cellular determinants of oxaliplatin sensitivity in colon cancer cell lines.  

PubMed

Oxaliplatin (L-OHP) is a new platinum analogue that has shown antitumour activity against colon cancer both in vitro and in vivo and is now used in the chemotherapeutic treatment of metastatic colon and rectal cancer. L-OHP like cisplatin (CDDP), is detoxified by glutathione (GSH)-related enzymes and forms platinum (Pt)-DNA adducts lesions that are repaired by the nucleotide excision repair system (NER). We investigated the cytotoxicity and the pharmacology of L-OHP and CDDP on a panel of six colon cell lines in vitro. We showed that GSH and glutathione S-transferase (GST) activity were not correlated to oxaliplatin cytotoxicity. Pt-DNA adducts formation and repair were correlated with CDDP, but not with L-OHP cytotoxicity. The determination of ERCC1 and XPA expression, two enzymes of the NER pathway, by reverse transcriptase-polymerase chain reaction (RT-PCR), demonstrated that ERCC1 expression was predictive of L-OHP sensitivity (r(2)=0.67, P=0.02) and XPA level after oxaliplatin exposure was also correlated to L-OHP IC(50) (r(2)=0.5; P=0.04). The knowledge of such correlations could help predict the sensitivity of patients with colon cancer to L-OHP. PMID:12504667

Arnould, S; Hennebelle, I; Canal, P; Bugat, R; Guichard, S

2003-01-01

37

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

SciTech Connect

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

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

2009-10-09

38

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

39

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

NASA Astrophysics Data System (ADS)

A direct Weakly Interacting Massive Particle (WIMP) detector with a neutron veto system is designed to better reject neutrons. An experimental configuration is studied in the present paper: a WIMP detectors with CsI(Na) target is placed inside a reactor neutrino detector. The neutrino detector is used as a neutron veto device. The neutron background for the experimental design has been estimated using the Geant4 simulation. The results show that the neutron background can decrease to O(0.01) events per year per tonne of CsI(Na). We calculate the sensitivity to spin-independent WIMP-nucleon elastic scattering. An exposure of 1 tonne year could reach a cross-section of about 3 pb.

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

2014-04-01

40

WIMP-induced gamma ray spectrum of active Galactic nuclei  

NASA Astrophysics Data System (ADS)

As direct and indirect dark matter detection experiments continue to place stringent constraints on WIMP masses and couplings, it becomes imperative to expand the scope of the search for particle dark matter by looking in new and exotic places. One such place may be the core of active Galactic nuclei (AGN) where the density of dark matter is expected to be extremely high. Recently, several groups have explored the possibility of observing signals of dark matter from its interactions with the high-energy jets emanating from these galaxies. In this work, we build upon these analyses by including the other components of the WIMP-induced gamma ray spectrum of active Galactic nuclei; namely, (i) the continuum from WIMP annihilation into light standard model states which subsequently radiate and/or decay into photons and (ii) the direct (loop-induced) decay into photons. We work in the context of models of universal extra dimensions (in particular, a model with two extra dimensions) and compute all three components of the gamma ray spectrum and compare with current data. We find that the model with two extra dimensions exhibits several interesting features which may be observable with the Fermi gamma ray telescope. We also show that, in conjunction with other measurements, the gamma ray spectrum from AGN can be an invaluable tool for restricting WIMP parameter space.

Gómez, M. A.; Jackson, C. B.; Shaughnessy, G.

2013-07-01

41

ZEPLIN-II limits on WIMP-nucelon interactions  

SciTech Connect

ZEPLIN II is a two-phase xenon detector designed to detect dark matter in the form of Weakly Interacting Massive Particles (WIMPs). Following the first 31-day underground run in Boulby Mine, UK, the collaboration published dark matter limits in January 2007; the first such limits using two-phase xenon technology. We outline the key detector design, performance and results here.

Alner, G. J.; Bungau, C.; Camanzi, B.; Durkin, T.; Edwards, B.; Lewin, J. D.; Luescher, R.; Preece, R. M.; Smith, N. J. T.; Smith, P. F.; Sumner, T. J.; Thorne, C. [Particle Physics Dept., CCLRC Rutherford Appleton Laboratory (United Kingdom); Araujo, H. M. [Blackett Laboratory, Imperial College London (United Kingdom); Particle Physics Dept., CCLRC Rutherford Appleton Laboratory (United Kingdom); Bewick, A.; Davidge, D.; Dawson, J.; Howard, A. S.; Jones, W. G.; Joshi, M.; Lebedenko, V. N. [Blackett Laboratory, Imperial College London (United Kingdom)] (and others)

2009-09-08

42

Explaining Differences in Sensitivity to Killing by Ionizing Radiation between Human Lymphoid Cell Lines  

Microsoft Academic Search

We surveyed five human hematopoietic cell lines (IISlt-2, MOI, I -4. Reh, CEM, and III,-60) to determine whether any simple correlates with sensitivity to killing by y-irradiation might be revealed. The clonogenic survival y-ray dose-response curves for these cell lines cover a wide range of sensitivities. Consistent with previous results for murine hematopoietic cell lines, there was a clear correlation

David R. Aldridge; Ian R. Radford

1998-01-01

43

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

SciTech Connect

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

Colafrancesco, Sergio [INAF-Osservatorio Astronomico di Roma, via Frascati 33, I-00040 Monteporzio (Italy) and Istituto Nazionale di Fisica Nucleare, Sezione di Roma 2, I-00133 Rome (Italy); Profumo, Stefano [Division of Physics, Mathematics and Astronomy, California Institute of Technology, Mail Code 106-38, Pasadena, California 91125 (United States); Ullio, Piero [Scuola Internazionale Superiore di Studi Avanzati, Via Beirut 2-4, I-34014 Trieste (Italy) and Istituto Nazionale di Fisica Nucleare, Sezione di Trieste, I-34014 Trieste (Italy)

2007-01-15

44

DARWIN: dark matter WIMP search with noble liquids  

Microsoft Academic Search

DARWIN (DARk matter WImp search with Noble liquids) is an R&D and design study towards the realization of a multi-ton scale dark matter search facility in Europe, based on the liquid argon and liquid xenon time projection chamber techniques. Approved by ASPERA in late 2009, DARWIN brings together several European and US groups working on the existing ArDM, XENON and

Laura Baudis

2010-01-01

45

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

NASA Astrophysics Data System (ADS)

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

Steigman, Gary

2013-05-01

46

The molecular mechanism of different sensitivity of breast cancer cell lines to TRAIL  

Microsoft Academic Search

Although Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis of various cancer cells,\\u000a some caner cell lines are resistant to TRAIL-induced cell death. To investigate the molecular mechanisms underlying TRAIL-resistance,\\u000a two human breast cancer cell lines, MCF-7 (resistant to TRAIL) and MDA-MB-231 (sensitive to TRAIL), were used as a model system\\u000a to analyze the different sensitivities to TRAIL cytotoxicity.

Jindan Zhang; Yanxin Liu; Shilian Liu; Dexian Zheng

2004-01-01

47

PICO-LON project for WIMPs search  

Microsoft Academic Search

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

Ken-Ichi Fushimi; Kensuke Yasudai; Yuuki Kamedai; Hiroyasu Ejiri; Ryuta Hazama; Kayoko Ichihara; Kyoshiro Imagawa; Hiroshi Ito; Norihiko Koori; Hidehito Nakamura; Shintaro Nakayama; Masaharu Nomachi; Tatsushi Shima; Saori Umehara; Sei Yoshida

2008-01-01

48

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

Microsoft Academic Search

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

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

1988-01-01

49

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

50

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.

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

51

Enhancing a WIMP based interface with speech, gaze tracking and agents  

Microsoft Academic Search

This paper describes an attempt to enhance a windows based (WIMP - Windows Icon Menu Pointer) environment. The goal is to establish whether user interaction on the common desktop PC can be augmented by adding new modalities to the WIMP inter- face, thus bridging the gap between todays interaction p atterns and future interfaces comprising e.g. advanced conversational capabilities, VR

Lau Bakman; Mads Blidegn; Martin Wittrup; Lars Bo Larsen; Thomas B. Moeslund

1998-01-01

52

Isolation and characterization of Chinese hamster ovary cell lines sensitive to mitomycin C and bleomycin  

SciTech Connect

Seven Chinese hamster ovary K1 cell lines exhibiting sensitivity to anticancer drugs have been isolated by a replica-plating technique. Five of the mutants are hypersensitive to the DNA cross-linking agent mitomycin C. Of these, one is also appreciably sensitive to UV light. Significant variations in their cross-sensitivity to cis-platinum(II) diammine dichloride, chlorambucil, and Adriamycin have also been observed. Two additional mutants have been isolated on the basis of sensitivity to the radiomimetic agent bleomycin. One of these shows greater than 6-fold sensitivity to bleomycin, while the other is approximately 14 times more sensitive than the parental strain to bleomycin and is also hypersensitive to a number of other DNA-damaging agents, including cis-platinum(II) diammine dichloride, chlorambucil, X-rays, and UV light. Both bleomycin-sensitive mutants also exhibit some degree of sensitivity to Adriamycin. In all cases, the cell lines have been grown in continuous culture for 3 months without evidence of reversion and should act as suitable recipients in DNA transfection experiments aimed at identifying human DNA repair genes.

Robson, C.N.; Harris, A.L.; Hickson, I.D.

1985-11-01

53

Reactivation of death receptor 4 (DR4) expression sensitizes medulloblastoma cell lines to TRAIL  

Microsoft Academic Search

Object Apoptosis, a key cellular response to therapeutic agents is often inactivated in tumor cells. In this study, we evaluated\\u000a the expression of the tumor necrosis family of death receptors, DR4 and DR5, in medulloblastoma tumor samples and cell lines to determine if epigenetic modulation of gene expression could sensitize\\u000a tumor cell lines to TRAIL-mediated apoptosis. Methods Human medulloblastoma samples

Dolly G. Aguilera; Chandra M. Das; Neeta D. Sinnappah-Kang; Celine Joyce; Pete H. Taylor; Sijin Wen; Martin Hasselblatt; Werner Paulus; Greg Fuller; Johannes E. Wolff; Vidya Gopalakrishnan

2009-01-01

54

O6-alkylguanine-DNA-alkyltransferase activity and nitrosourea sensitivity in human cancer cell lines.  

PubMed Central

The DNA repair enzyme, O6-alkylguanine-DNA-alkyltransferase (ATase), is thought to be the principal mechanism controlling resistance to nitrosoureas and related alkylating agents. We compared the sensitivities of five human testis and five bladder tumour cell lines to two nitrosoureas (N-nitroso-N-methylurea (MNU) and mitozolomide) with cellular levels of ATase. Enzyme levels ranged from 3 to 206 fmol mg-1 protein (0.1 x 10(4) to 5.1 x 10(4) molecules/cell) in the testis lines and from 11 to 603 fmol mg-1 (0.4 x 10(4) to 9.1 x 10(4) molecules/cell) in the bladder lines. Based on IC50s in an MTT assay, the testis tumour cell lines were, on average, four times more sensitive to MNU and six times more sensitive to mitozolomide than the bladder cell lines. The cytotoxicities of MNU and mitozolomide were closely related (R = 0.9). In the testis cell lines ATase activity (molecules/cell) was related to IC50s for mitozolomide (R = 0.97) but not MNU (R = 0.78). In the bladder cell lines and overall, ATase activity correlated with cellular sensitivity to neither agent. Relatively high levels of resistance occurred in cells expressing low levels of ATase, and amongst cell lines expressing high levels of ATase, large differences in IC50s were observed. These results support the suggestion that resistance to nitrosoureas can be mediated by mechanisms other than ATase and that at relatively high levels of expression, ATase does not confer resistance in proportion to its activity.

Walker, M. C.; Masters, J. R.; Margison, G. P.

1992-01-01

55

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

Microsoft Academic Search

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 75mm diameter. Applications are found wherever precise

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

2007-01-01

56

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

NASA Technical Reports Server (NTRS)

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

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

1985-01-01

57

Optimum design of cooling lines of injection mold based on boundary element design sensitivity analysis  

NASA Astrophysics Data System (ADS)

In this paper, a boundary integral design sensitivity formulation for steady-state heat conduction problems is presented and applied to the optimum design of the arrangement of the cooling lines in an injection mold. The cost function for the present optimization problem is approximated with the first-order Taylor series expansion; its first-order design sensitivities with respect to the design variables are calculated from the boundary element design sensitivity analysis. The sensitivity boundary integral equation which relates the boundary temperatures and heat fluxes with their sensitivity coefficients are derived by differentiating directly a regularized boundary integral equation for the steady-state heat conduction problems with respect to design variables. Some two-dimensional numerical examples illustrate the effectiveness of the present approach.

Matsumoto, T.; Tanaka, M.; Hirata, H.

58

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

59

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

PubMed Central

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

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

1985-01-01

60

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

NASA Astrophysics Data System (ADS)

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

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

2013-10-01

61

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

62

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.

2013-01-01

63

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

64

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

NASA Astrophysics Data System (ADS)

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

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

1992-06-01

65

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.

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

2014-01-01

66

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

SciTech Connect

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

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

1983-01-01

67

A sensitivity of squall-line intensity to environmental static stability under various shear and moisture conditions  

Microsoft Academic Search

Squall lines develop in various climate regions having diverse environmental profiles of wind shear, moisture, and temperature. In order to explore the sensitivity of squall lines to these environmental profiles, we have performed an extensive set of numerical simulations under various shear and moisture conditions in midlatitude-continental and tropical–oceanic temperature environments. From the results of the sensitivity simulations and the

Tetsuya Takemi

2007-01-01

68

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

PubMed Central

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

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

1995-01-01

69

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

SciTech Connect

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.; Earl, M.; Kearns, E.; Stone, J.L.; Sulak, L.R.; Walter, C.W.; Wang, W. [Department of Physics, Boston University, Boston, Massachusetts 02215 (United States); 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. [Kamioka Observatory, Institute for Cosmic Ray Research, University of Tokyo, Kamioka, Gifu, 506-1205 (Japan)] [and others

2004-10-15

70

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

PubMed

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

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

2014-02-01

71

A software model and specification language for non-WIMP user interfaces  

Microsoft Academic Search

We present a software model and language for describing and programming the fine-grained aspects of interaction in a non-WIMP user interface, such as a virtual environment. Our approach is based on our view that the essence of a non-WIMP dialogue is a set of continuous relationships—most of which are temporary. The model combines a data-flow or constraint-like component for the

Robert J. K. Jacob; Leonidas Deligiannidis; Stephen Morrison

1999-01-01

72

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

Microsoft Academic Search

Many cell lines derived from tumors as well as transformed cell lines are far more sensitive to V-ATPase inhibitors than normal counterparts. The molecular mechanisms underlying these differences in sensitivity are not known. Using global gene expression data, we show that the most sensitive responses to HeLa cells to low doses of V-ATPase inhibitors involve genes responsive to decreasing intracellular

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

2010-01-01

73

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

74

Ultra high-sensitivity fission counter with transmission line electrode configuration  

SciTech Connect

An ultrahigh-sensitivity fission counter (UHSFC) prototype was designed, fabricated, and tested. The objective of this research was development of a fission counter system for ex-vessel, source-range flux monitoring having a neutron sensitivity of greater than or equal to 40 counts s/sup -1/ (neutrons/(cm/sup 2/xs))/sup -1/ (greater than or equal to 40 cps/nv) and a size comparable to that of a BF/sub 3/ proportional counter system. Also, the UHSFC system was required to be operable under conditions beyond the capabilities of BF/sup 3/ counters: up to a temperature of 450 K and in a gamma radiation field of 7.2 x 10/sup -4/ C(kg.s)/sup -1/ (i.e., 10/sup 4/ R/h). The sensitivity requirement (40 cps/nv) was met by assembling two transmission line fission counters (TLFCs) within a common envelope. The size requirement (less than or equal to 14 cm diameter, less than or equal to 80 cm length) was met by using electrodes arranged to maximize the ratio of electrode area to sensitive volume. The measured neutron sensitivity for each TLFC is 23.5 cps/nv at 4.5 x 10/sup 4/ R/h and 450 K. The UHSFC is filled with a recently developed gas (80% Ar, 20% CF/sub 4/ at 263 kPa pressure) of high electron drift velocity. The electrode area (5 m/sup 2/) is coated with 88 g of enriched uranium (93.15% /sup 235/U, 0.99% /sup 234/U, balance /sup 238/U). The impedance of the lumped element LC transmission lines is 25 ..cap omega.., the bandwidth 100 MHz, and the delay 4 ns per node (each TLFC has 58 nodes). Pulse-height and time discrimination is used to mitigate the effects of noise from the alpha pileup current of the uranium coating.

Valentine, K.H.; Allin, G.W.; Clay, W.T.; Fowler, C.E.; Guerrant, G.C.; Harter, J.A.; Kopp, M.K.

1983-02-01

75

Drug sensitivity patterns of HHV8 carrying body cavity lymphoma cell lines  

PubMed Central

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

2011-01-01

76

WIMP: web server tool for missing data imputation.  

PubMed

The imputation of unknown or missing data is a crucial task on the analysis of biomedical datasets. There are several situations where it is necessary to classify or identify instances given incomplete vectors, and the existence of missing values can much degrade the performance of the algorithms used for the classification/recognition. The task of learning accurately from incomplete data raises a number of issues some of which have not been completely solved in machine learning applications. In this sense, effective missing value estimation methods are required. Different methods for missing data imputations exist but most of the times the selection of the appropriate technique involves testing several methods, comparing them and choosing the right one. Furthermore, applying these methods, in most cases, is not straightforward, as they involve several technical details, and in particular in cases such as when dealing with microarray datasets, the application of the methods requires huge computational resources. As far as we know, there is not a public software application that can provide the computing capabilities required for carrying the task of data imputation. This paper presents a new public tool for missing data imputation that is attached to a computer cluster in order to execute high computational tasks. The software WIMP (Web IMPutation) is a public available web site where registered users can create, execute, analyze and store their simulations related to missing data imputation. PMID:23017251

Urda, D; Subirats, J L; García-Laencina, P J; Franco, L; Sancho-Gómez, J L; Jerez, J M

2012-12-01

77

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

78

Selection and characterization of a novel photoperiod-sensitive male sterile line in upland cotton.  

PubMed

Upland cotton (Gossypium hirsutum L.) shows strong heterosis. However, heterosis is not widely utilized owing to the high cost of hybrid seed production. Creation of a photoperiod-sensitive genetic male sterile line could substantially reduce the cost of hybrid seed production in upland cotton. Such a mutant with virescent marker was found by space mutation in near-earth orbit and its traits had been stable after 4 years of selection in Anyang and Sanya, China. This mutant was fertile with an 11-12.5?h photoperiod when the temperature was higher than 21.5?°C and was sterile with a 13-14.5?h photoperiod. Genetic analysis indicated that both traits were controlled by a single recessive gene or two closely linked genes. Also, the cytological observations and transcriptome profiling analysis showed that the degradation of pollen grain cytoplasm should be the primary reason why the mutant line were male sterile under long-day conditions. PMID:23691935

Ma, Jianhui; Wei, Hengling; Liu, Ji; Song, Meizhen; Pang, Chaoyou; Wang, Long; Zhang, Wenxiang; Fan, Shuli; Yu, Shuxun

2013-07-01

79

Somaclonal-variation-induced aluminum-sensitive mutant from an aluminum-inbred maize tolerant line  

Microsoft Academic Search

Somaclonal-variation-induced multiple mutations were observed in a progeny of the S1587 plant, regenerated from type I calli\\u000a of the aluminum-tolerant inbred maize line Cat-100-6. After five generations of self-pollination, 14 progeny families of the\\u000a S1587 somaclone were found to show aluminum toxicity symptoms with altered root tip morphology and reduced primary root growth.\\u000a The most sensitive progeny, S1587-17, was crossed

D. H. Moon; L. M. M. Ottoboni; A. P. Souza; S. T. Sibov; M. Gaspar; P. Arruda

1997-01-01

80

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

81

Systematic assessment of analytical methods for drug sensitivity prediction from cancer cell line data.  

PubMed

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

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

2014-01-01

82

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

SciTech Connect

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

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

2009-02-20

83

Cellular basis for differential sensitivity to cisplatin in human germ cell tumour and colon carcinoma cell lines.  

PubMed Central

Cisplatin (CDDP) resistance mechanisms were studied in a model of three germ cell tumour and three colon carcinoma cell lines representing intrinsically CDDP-sensitive and -resistant tumours respectively. The CDDP sensitivity of the cell lines mimicked the clinical situation. The glutathione levels of the cell lines correlated with CDDP concentrations inhibiting cell survival by 50% (IC50); total cellular sulphydryl content (TSH) was unexpectedly inversely correlated with IC50. IC50 correlated neither with glutathione S-transferase (GST) nor with GST pi expression, topoisomerase I or II activity. Immediately after 4 h incubation with CDDP, platinum (Pt) accumulation and Pt bound to DNA were not correlated, but after another 24 h drug-free culture, Pt binding to DNA in germ cell tumour but not in colon carcinoma cell lines correlated with IC50. With the exception of in vitro sensitivity and TSH, none of the parameters studied discriminated between the two groups of cell lines. Correction of CDDP sensitivity parameters for phenotypical differences did not influence statistical correlations. Analysis of variance revealed a correlation between IC50 and the combination of glutathione, GST activity and Pt bound to DNA. But at other CDDP cytotoxicity levels sensitivity was also correlated with Pt accumulation, topoisomerase II activity and TSH in various combinations. This model of intrinsic CDDP resistance showed that multiple parameters ought to be studied to explain CDDP resistance, but did not elucidate the cause of the unique sensitivity of germ cell carcinoma, although the unexpected values of TSH deserve further attention.

Sark, M. W.; Timmer-Bosscha, H.; Meijer, C.; Uges, D. R.; Sluiter, W. J.; Peters, W. H.; Mulder, N. H.; de Vries, E. G.

1995-01-01

84

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

PubMed

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

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

2003-12-01

85

Exclusion Limits on the WIMP: Nucleon Cross-section from the Cryogenic Dark Matter Search  

NSDL National Science Digital Library

From University of California-Berkeley's Center for Particle Astrophysics, this paper entitled "Exclusion Limits on the WIMP-Nucleon Cross-section from the Cryogenic Dark Matter Search" is a collaboration of the Cryogenic Dark Matter Search (CDMS). The CDMS consists of "looking for dark matter in the form of Weakly Interacting Massive Particles, or WIMPs. One attempt to solve the dark matter problem hypothesizes the existence of an undiscovered particle that was in thermal equilibrium with the very early universe." This paper delves into aspects of solving the dark matter problem.

Abusaidi, R.; Akerib, Daniel S.; Barnes, P. D.; Bauer, D. A.; Bolozdyna, A.; Brink, P. L.

2000-01-01

86

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

PubMed Central

Background Recent landmark studies have profiled cancer cell lines for molecular features, along with measuring the corresponding growth inhibitory effects for specific drug compounds. These data present a tool for determining which subsets of human cancer might be more responsive to particular drugs. To this end, the NCI-DREAM-sponsored DREAM7: Drug Sensitivity Prediction Challenge (sub-challenge 1) set out to predict the sensitivities of 18 breast cancer cell lines to 31 previously untested compounds, on the basis of molecular profiling data and a training subset of cell lines. Methods and Results With 47 teams submitting blinded predictions, team Creighton scored third in terms of overall accuracy. Team Creighton's method was simple and straightforward, incorporated multiple expression data types (RNA-seq, gene array, RPPA), and incorporated all profiled features (not only the “best” predictive ones). As an extension of the approach, cell line data, from public datasets of expression profiling coupled with drug sensitivities (Barretina, Garnett, Heiser) were used to “predict” the drug sensitivities in human breast tumors (using data from The Cancer Genome Atlas). Drug sensitivity correlations within human breast tumors showed differences by expression-based subtype, with many associations in line with the expected (e.g. Lapatinib sensitivity in HER2-enriched cancers) and others inviting further study (e.g. relative resistance to PI3K inhibitors in basal-like cancers). Conclusions Molecular patterns associated with drug sensitivity are widespread, with potentially hundreds of genes that could be incorporated into making predictions, as well as offering biological clues as to the mechanisms involved. Applying the cell line patterns to human tumor data may help generate hypotheses on what tumor subsets might be more responsive to therapies, where multiple cell line datasets representing various drugs may be used, in order to assess consistency of patterns.

Creighton, Chad J.

2013-01-01

87

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.

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

2014-01-01

88

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

89

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.

2011-01-01

90

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

SciTech Connect

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

Ho, T.-F. [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Department of Medical Technology, Central Taiwan University of Science and Technology, Taichung, Taiwan (China); Peng, Y.-T.; Chuang, S.-M.; Lin, S.-C.; Feng, B.-L. [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Lu, C.-H. [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Yu, W.-J. [Department of Chemical Engineering, National Cheng Kung University, Tainan, Taiwan (China); Chang, J.-S. [Department of Chemical Engineering, National Cheng Kung University, Tainan, Taiwan (China); Sustainable Environment Research Center, National Cheng Kung University, Tainan, Taiwan (China)], E-mail: changjs@mail.ncku.edu.tw; Chang, C.-C. [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China)], E-mail: chia_che@dragon.nchu.edu.tw

2009-03-01

91

Chemotypes sensitivity and predictivity of in vivo outcomes for cytotoxic assays in THLE and HepG2 cell lines.  

PubMed

In the present study, we demonstrate the utility of in vitro ATP depletion assays in both THLE and HepG2 cells for predicting the toxicological outcome in Exploratory Toxicology Studies across 446 Pfizer proprietary compounds. Our results suggest a higher likelihood of selecting suitable compounds for in vivo safety studies by using cytotoxicity assays in multiple cell-lines over a single cell line. In addition, we demonstrate that different cell-lines have different sensitivities to compounds depending on their ionization state, that is, acid, base or neutral. HepG2 cells are more sensitive for basic compounds, whereas THLE cells have a relatively higher sensitivity for the acidic and neutral compounds. These in vitro cytotoxicity assays when combined with physicochemical properties (cLogP >3 and topological polar surface area (TPSA) <75Å(2)), are the most effective means to prioritize compounds having a lower probability of causing adverse events in vivo. PMID:24794102

Shah, Falgun; Louise-May, Shirley; Greene, Nigel

2014-06-15

92

TCF4 silencing sensitizes the colon cancer cell line to oxaliplatin as a common chemotherapeutic drug.  

PubMed

Colon cancer is among the most prevalent cancers worldwide. Although the main modality of treatment is surgery, resistance to chemoradiotherapy raises concerns. Hence, we aimed to determine the effect of RNA-mediated silencing of tcf4, the downstream effector of the wnt signaling pathway, on the response of the SW480 cell line to oxaliplatin, a common chemotherapeutic drug. For this, two different silencing sequences against TCF4 mRNA were selected and cloned into pSilencer neo2.1. The SW480 cell line was stably transfected with the silencing constructs (namely p1396, p1874, and p silencer containing a scrambled sequence) and labeled SW1396, SW1874, and SW-Sc, respectively. Subsequently, the effect of oxaliplatin (from 0 to 11.25 ?mol/l) on these cells was studied using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide proliferation assay. Suppression of tcf4 expression in stable transfected cells with p1396 and p1874 was confirmed by quantitative reverse transcription-PCR and western blot analysis. Although oxaliplatin was not toxic to SW480 and SW-sc in the range tested, in SW1396 and SW1874 cells, a toxic effect was evident at 3.75 and 4.375 ?mol/l. Also, SW1396 and SW1874 cells appeared to have a round shape in comparison with SW480 and SW-Sc cells. Only for SW1396, the number of apoptotic cells was significantly different before and after the addition of oxaliplatin (LC50 of oxaliplatin). The proliferating cells in SW480, SW1874, and SW-Sc increased after treatment with oxaliplatin; however, this was not observed in SW1396. Although silencing the tcf4 gene would confer sensitivity to oxaliplatin in SW1874 and especially SW1396, in SW480 and SW-Sc, the lethal effect of oxaliplatin was compensated by its effect in increasing the proliferation of cells. This sensitization effect may be because of different mechanisms including TCF4 motifs in the ABCB1 promoter or defects in nucleotide excision repair or double-strand break repair systems after tcf4 silencing. PMID:24869759

Gheidari, Fatemeh; Bakhshandeh, Behnaz; Teimoori-Toolabi, Ladan; Mehrtash, Amirhosein; Ghadir, Mahdis; Zeinali, Sirous

2014-09-01

93

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

PubMed Central

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

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

2012-01-01

94

TOWARDS DETECTION OF LOW MASS WIMPs (MWIMP<10 GeV/c2): MINI-REVIEW  

NASA Astrophysics Data System (ADS)

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

Drukier, A. K.; Nussinov, S.

2013-10-01

95

Uma Interface Híbrida para Desktop Integrando Realidade Virtual, Realidade Aumentada e 2D WIMP  

Microsoft Academic Search

Hybrid user interfaces, which create a heterogeneous environment providing different interaction forms and devices, may be enhanced by exploring more extensively the mixed reality continuum. This work presents an alternative to include immersive virtual reality in hybrid user interfaces in a common desktop setup. In addition, it is proposed the integration of a 2D WIMP (Windows, Icons, Menus and Pointing

Alberto Raposo; Marcelo Gattass

2007-01-01

96

Antiviral effects of interferon on a somatic cell hybrid between two Burkitt's lymphoma cell lines of different interferon sensitivities.  

PubMed Central

A somatic cell hybrid between two human Burkitt's lymphoma cell lines, Raji and Daudi, was infected with either Epstein-Barr virus or vesicular stomatitis virus after interferon treatment. Raji cells are resistant to the antiviral effects of exogenously added interferon, whereas Daudi cells are interferon sensitive. The Raji-Daudi hybrid showed an interferon sensitivity that was intermediary to that of the parental cells against both viruses.

Lidin, B; Lamon, E W

1982-01-01

97

INTENSITY RATIO OF DENSITY-SENSITIVE LINES IN Fe IONS OBSERVED WITH A WELL-DEFINED LABORATORY PLASMA  

SciTech Connect

We present spectra of highly charged Fe ions in the extreme ultraviolet range observed using an electron beam ion trap equipped with a flat-field grazing incidence spectrometer. The density dependence of line intensity ratios is investigated for several density-sensitive lines of Fe XIII, XIV, and XV. Unlike previous studies where the electron density was estimated from theoretical considerations, here it is derived from electron beam profile measurements. The experimental data are compared with model calculations.

Nakamura, Nobuyuki; Watanabe, Etsushi [Institute for Laser Science, The University of Electro-Communications, Chofu, Tokyo 182-8585 (Japan); Sakaue, Hiroyuki A.; Kato, Daiji; Murakami, Izumi [National Institute for Fusion Science, Toki, Gifu 509-5292 (Japan); Yamamoto, Norimasa [Institute of Laser Engineering, Osaka University, Suita, Osaka 565-0871 (Japan); Hara, Hirohisa; Watanabe, Tetsuya, E-mail: n_nakamu@ils.uec.ac.jp [National Astronomical Observatory of Japan, Mitaka, Tokyo 181-8588 (Japan)

2011-09-20

98

Exclusion limits on the WIMP-nucleon cross section from the Cryogenic Dark Matter Search  

NASA Astrophysics Data System (ADS)

The Cryogenic Dark Matter Search (CDMS) employs low-temperature Ge and Si detectors to search for weakly interacting massive particles (WIMPs) via their elastic-scattering interactions with nuclei while discriminating against interactions of background particles. For recoil energies above 10 keV, events due to background photons are rejected with >99.9% efficiency, and surface events are rejected with >95% efficiency. The estimate of the background due to neutrons is based primarily on the observation of multiple-scatter events that should all be neutrons. Data selection is determined primarily by examining calibration data and vetoed events. Resulting efficiencies should be accurate to ˜10%. Results of CDMS data from 1998 and 1999 with a relaxed fiducial-volume cut (resulting in 15.8 kg days exposure on Ge) are consistent with an earlier analysis with a more restrictive fiducial-volume cut. Twenty-three WIMP candidate events are observed, but these events are consistent with a background from neutrons in all ways tested. Resulting limits on the spin-independent WIMP-nucleon elastic-scattering cross section exclude unexplored parameter space for WIMPs with masses between 10 70 GeV/c2. These limits border, but do not exclude, parameter space allowed by supersymmetry models and accelerator constraints. Results are compatible with some regions reported as allowed at 3? by the annual-modulation measurement of the DAMA Collaboration. However, under the assumptions of standard WIMP interactions and a standard halo, the results are incompatible with the DAMA most likely value at >99.9% confidence level (C.L.), and are incompatible with the model-independent annual-modulation signal of DAMA at 99.99% C.L. in the asymptotic limit.

Abrams, D.; Akerib, D. S.; Armel-Funkhouser, M. S.; Baudis, L.; Bauer, D. A.; Bolozdynya, A.; Brink, P. L.; Bunker, R.; Cabrera, B.; Caldwell, D. O.; Castle, J. P.; Chang, C. L.; Clarke, R. M.; Crisler, M. B.; Dixon, R.; Driscoll, D.; Eichblatt, S.; Gaitskell, R. J.; Golwala, S. R.; Haller, E. E.; Hellmig, J.; Holmgren, D.; Huber, M. E.; Kamat, S.; Lu, A.; Mandic, V.; Martinis, J. M.; Meunier, P.; Nam, S. W.; Nelson, H.; Perera, T. A.; Perillo Isaac, M. C.; Rau, W.; Ross, R. R.; Saab, T.; Sadoulet, B.; Sander, J.; Schnee, R. W.; Shutt, T.; Smith, A.; Sonnenschein, A. H.; Spadafora, A. L.; Wang, G.; Yellin, S.; Young, B. A.

2002-12-01

99

Neutrinos from WIMP annihilations obtained using a full three-flavor Monte Carlo approach  

NASA Astrophysics Data System (ADS)

Weakly interacting massive particles (WIMPs) are one of the main candidates for making up the dark matter in the Universe. If these particles make up the dark matter, then they can be captured by the Sun or the Earth, sink to the respective cores, annihilate, and produce neutrinos. Thus, these neutrinos can be a striking dark matter signature at neutrino telescopes looking towards the Sun and/or the Earth. Here, we improve previous analyses on computing the neutrino yields from WIMP annihilations in several respects. We include neutrino oscillations in a full three-flavor framework as well as all effects from neutrino interactions on the way through the Sun (absorption, energy loss, and regeneration from tau decays). In addition, we study the effects of non-zero values of the mixing angle ?13 as well as the normal and inverted neutrino mass hierarchies. Our study is performed in an event-based setting which makes these results very useful both for theoretical analyses and for building a neutrino telescope Monte Carlo code. All our results for the neutrino yields, as well as our Monte Carlo code, are publicly available. We find that the yield of muon-type neutrinos from WIMP annihilations in the Sun is enhanced or suppressed, depending on the dominant WIMP annihilation channel. This effect is due to an effective flavor mixing caused by neutrino oscillations. For WIMP annihilations inside the Earth, the distance from source to detector is too small to allow for any significant amount of oscillations at the neutrino energies relevant for neutrino telescopes.

Blennow, Mattias; Edsjö, Joakim; Ohlsson, Tommy

2008-01-01

100

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

SciTech Connect

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. (Princeton Plasma Physics Laboratory, Princeton University, Princeton, New Jersey 08543 (USA))

1990-10-01

101

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

102

The relationship between intrinsic thymidylate synthase expression and sensitivity to THYMITAQ in human leukaemia and colorectal carcinoma cell lines.  

PubMed Central

Thymidylate synthase (TS) expression has been characterized for a panel of eight human colorectal carcinoma and five human leukaemia cell lines, to relate differences in intrinsic TS activity, protein and mRNA levels to growth inhibition caused by continuous exposure to THYMITAQ, a specific non-classical antifolate TS inhibitor. Although a 20-fold variation in sensitivity to THYMITAQ was found within the colorectal cell line panel (IC50 0.12-2.7 microM), sensitivity was not related to TS activity, TS protein or TS mRNA levels. For the leukaemic cell lines, only a twofold range in sensitivity to THYMITAQ was observed (IC50 0.87-2.3 microM), and this did not correlate with TS activity, TS protein or TS mRNA levels. Across all of the cell lines, TS activity was linearly related to TS protein levels (r2 = 0.87, P < 0.0001). However, for both the colorectal and leukaemia cell line panels, no relationship was found between TS mRNA/18S rRNA ratios and either TS activity or TS protein, consistent with the importance of post-transcriptional mechanisms in regulating TS activity. Two of the colorectal cell lines (BE and HCT116) and one of the human leukaemic cell lines (HL60), were intrinsically resistant to THYMITAQ (IC50 > 2 microM) in the absence of TS overexpression, suggesting that, subsequent to TS inhibition, events such as DNA repair and tolerance to apoptotic stimuli are also important determinants of sensitivity to THYMITAQ. Images Figure 1 Figure 2

Estlin, E. J.; Balmanno, K.; Calvert, A. H.; Hall, A. G.; Lunec, J.; Newell, D. R.; Pearson, A. D.; Taylor, G. A.

1997-01-01

103

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

PubMed

Hexadecylphosphocholine (HePC, Miltefosine) is a representative of the group of alkyl-lysophosphocholines showing remarkable antitumoral activity in in vitro experiments and in experimental animal tumour models. The epidermoid tumour cell line KB, which is highly sensitive to HePC (half-maximal growth inhibiting concentration, IC50: 1.2 microM; half lethal concentration, LC50: 2.8 microM), was slowly adapted to increasing concentrations of HePC. After 14 months, the adaptation process was stopped at a concentration of 10 micrograms/ml (23.5 microM). At this point, the KB cells tolerated high doses of HePC (IC50: 41.2 microM; LC50: 87.1 microM). The resistant cells (KBr) also showed crossresistance to the other well studied ether-lysophospholipids, Edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine, OMG-3PC; ET18OCH3) and Ilmofosine (1 S-hexadecyl-2-methoxymethyl-rac-(1-thio-3-hydroxy)propyl-3-phosphocho lin e, BM 41.440). Comparison of the KB and KBr cells showed that total lipid phosphate, ether-lipid content, vinyl-ether-lipid content, protein content as well as cholesterol content were unchanged. Furthermore, no changes were observed in the lipid composition between KB and KBr cells. Uptake of choline was also unchanged in both cells, but the uptake of D-myo-inositol was lower by a factor of two in the KBr cells. However, in KB cells, the addition of HePC induced a 50% reduction of D-myo-inositol-uptake, whereas in KBr cells inositol uptake was unchanged. Differences in HePC uptake and HePC metabolism were apparent between the KB and KBr cell lines. KBr cells showed a 3-fold lower uptake for HePC and a 3- to 4-fold faster metabolism of HePC than KB cells. However, the amount of non-metabolised HePC after 2 days of incubation with 1 microgram/ml HePC (LC50: 1.2 microgram/ml) in KB cells was 3- to 4-fold lower than the amount of HePC in KBR cells at 10 micrograms/ml (LC50: 37 micrograms/ml), indicating that KBr cells can incorporate higher amounts of HePC than KB cells without adverse effects for cell growth and viability. This seems to indicate that mechanisms other than slower uptake and faster metabolism are involved in the induction of resistance to HePC in KBr cells. PMID:8814699

Fleer, E A; Berkovic, D; Grunwald, U; Hiddemann, W

1996-03-01

104

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

Microsoft Academic Search

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

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

1991-01-01

105

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

PubMed Central

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

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

1995-01-01

106

The CDF and its sensitivity analysis of stochastic structure with stochastic excitation by advanced stratified line sampling  

NASA Astrophysics Data System (ADS)

For the stochastic structure with stochastic excitation, an advanced stratified line sampling (SLS) method is presented to obtain the cumulative distribution function (CDF) of the structural response and its sensitivity. The advanced stratified line sampling method introduces a set of middle failure subsets firstly. And for each subset, the conventional line sampling can be used to obtain the corresponding value of the response's CDF. At the same time, the sensitivity estimations of each failure subset can also be computed by modifying the important direction and corresponding reliability coefficients. The properties of CDF sensitivity are proved while the performance function is linear with normal random variables. After two simple examples are used to demonstrate the properties of CDF sensitivity and the feasibility of the presented method, the method employed to analyze the CDF and corresponding sensitivity of root bending moment (RBM) responses for the stochastic BAH is wing with gust excitation to a square-edged gust and to a Dryden gust. The results show that the parameters of the second and the fifth order modals exert more influence on the CDF of response than the other ones, and the presented SLS method can more significantly reduce the computational cost compared with Monte Carlo simulation (MCS).

Song, ShuFang; Lu, ZhenZhou; Zhang, WeiWei; Ye, ZhengYin

2013-08-01

107

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

PubMed

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

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

2010-08-16

108

Drug Resistant Breast Cancer Cell Line Displays Cancer Stem Cell Phenotype and Responds Sensitively to Epigenetic Drug SAHA  

PubMed Central

Cancer stem cell (CSC) population in solid human breast tumor was identified by CD44+/CD24? phenotype, characterized by high tumorigenicity, invasiveness and drug resistance. In this study, we characterized drug resistant breast cancer cell line-MCF-7/Adr and a number of breast cancer cell lines using flow cytometry, immunofluorescence, mammosphere formation assay and migration assay, examining their CSC immunophenotypes, presence of CSC proteins, tumorigenicity in vitro and migratory rates, respectively. Our results show that MCF-7/Adr cells uniformly display CSC characteristics yet retain low migratory rate. They are also able to self-renew and differentiate under floating culture conditions. Furthermore, MCF-7/Adr is selectively sensitive to epigenetic drug, suberoylanilide hydroxamic acid (SAHA), losing drug resistance and changes morphology yet retaining CSC immunophenotypes. In conclusion, we show that resistant breast cancer cell line MCF-7/Adr demonstrates uniform CSC like characteristics and are sensitive to epigenetic drug treatment.

Lu, Shan; Labhasetwar, Vinod

2012-01-01

109

Preliminary Results for Fermi-LAT Milky Way High Energy Gamma Line Limits  

NASA Astrophysics Data System (ADS)

The FGST Large Array Telescope (Fermi-LAT) Collaboration Dark Matter and New Physics Working group has been developing approaches for the indirect astrophysical detection of dark matter by its annihilation or decay products. Our work is motivated by the hypothesis that a significant component of dark matter is Weakly Interacting Massive Particles (WIMPs). The annihilation of two WIMPs or WIMP decay usually results in the production of many ? rays that if present, can be well measured in the LAT. There is also the possibility to observe ? lines from annihilation or decay into ?? and/or ?Z final states. Detection of these high energy ? lines would give convincing evidence for the existence of WIMPs and a measurement of the WIMP mass. We present preliminary work that will ultimately lead to 1-year upper limits on ? lines. The 1-year analysis will be a ``blind'' analysis developed on the first two months of Fermi-LAT data and Monte Carlos simulations. Limits will be given independent of the WIMP and dark matter structure models.

Edmonds, Yvonne; Bloom, Elliott

2009-05-01

110

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

SciTech Connect

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

Labadi, Karim [EPMI-ECS, 13 Bld de l'Hautil, 95092 Cergy-Pontoise Cedex (France); Saggadi, Samira [INRIA Rennes, DIONYSOS, Bretagne Atlantique, Campus Universitaire de Beaulieu, 35042 Rennes (France); Amodeo, Lionel [UTT-ICD, Universite de Technologie de Troyes, 12 rue Marie Curie, BP2060, 10010 Troyes (France)

2009-03-05

111

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

PubMed Central

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

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

2009-01-01

112

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

PubMed Central

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

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

2009-01-01

113

Effects of residue background events in direct dark matter detection experiments on the determination of the WIMP mass  

NASA Astrophysics Data System (ADS)

In the earlier work on the development of a model-independent data analysis method for determining the mass of Weakly Interacting Massive Particles (WIMPs) by using measured recoil energies from direct Dark Matter detection experiments directly, it was assumed that the analyzed data sets are background-free, i.e., all events are WIMP signals. In this article, as a more realistic study, we take into account a fraction of possible residue background events, which pass all discrimination criteria and then mix with other real WIMP-induced events in our data sets. Our simulations show that, for the determination of the WIMP mass, the maximal acceptable fraction of residue background events in the analyzed data sets of Script O(50) total events is ~ 20%, for background windows of the entire experimental possible energy ranges, or in low energy ranges; while, for background windows in relatively higher energy ranges, this maximal acceptable fraction of residue background events can not be larger than ~ 10%. For a WIMP mass of 100 GeV with 20% background events in the windows of the entire experimental possible energy ranges, the reconstructed WIMP mass and the 1? statistical uncertainty are ~ 97GeV+61%-35% ( ~ 94GeV+55%-33% for background-free data sets).

Chou, Yu-Ting; Shan, Chung-Lin

2010-08-01

114

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

115

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

116

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

Microsoft Academic Search

Most of the matter of the universe is ``dark''. Based on the Schwarz viscous and turbulence self-gravitational condensation scales, most dark matter has two forms: ``primordial fog particles'' (PFPs---now moon-mass black dwarfs in galaxy halos) which condensed when the plasma universe neutralized to an inviscid, weakly-turbulent gas about 0.3 By (billion years after the big bang); plus WIMP fluids whose

Carl H. Gibson

1996-01-01

117

Clinical drug response can be predicted using baseline gene expression levels and in vitro drug sensitivity in cell lines  

PubMed Central

We demonstrate a method for the prediction of chemotherapeutic response in patients using only before-treatment baseline tumor gene expression data. First, we fitted models for whole-genome gene expression against drug sensitivity in a large panel of cell lines, using a method that allows every gene to influence the prediction. Following data homogenization and filtering, these models were applied to baseline expression levels from primary tumor biopsies, yielding an in vivo drug sensitivity prediction. We validated this approach in three independent clinical trial datasets, and obtained predictions equally good, or better than, gene signatures derived directly from clinical data.

2014-01-01

118

A DNA repair defect in a radiation-sensitive clone of a human bladder carcinoma cell line.  

PubMed Central

DNA repair was measured in an ionising radiation-sensitive mutant of a human bladder carcinoma cell line. No difference in the rate or extent of double-strand break rejoining was found using the techniques of neutral filter elution and pulsed-field gel electrophoresis. In contrast, significant differences in repair fidelity, measured by plasmid reconstitution, were found. The parent line had a repair fidelity of 84.7% compared with 58.9% for S40b (P = 0.0003). It is suggested that repair fidelity can be an important determinant of radiosensitivity in human tumour cells.

Powell, S. N.; Whitaker, S. J.; Edwards, S. M.; McMillan, T. J.

1992-01-01

119

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

National Technical Information Service (NTIS)

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 h...

Y. Wang W. K. Tao J. Simpson S. Lang

1999-01-01

120

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

PubMed Central

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

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

2013-01-01

121

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

NASA Astrophysics Data System (ADS)

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]. These contributions arise from meson-exchange currents (MECs) and potentially modify the impulse approximation estimates of these interactions by 10%-60%. We point out that these MECs also contribute to the quark mass dependence of nuclear binding energies, that is, nuclear ? terms. In this work, we use recent lattice QCD calculations of the binding energies of the deuteron, He3 and He4 at pion masses near 500 and 800 MeV, combined with the experimentally determined binding energies at the physical point, to provide approximate determinations of the ? terms for these light nuclei. For each nucleus, we find that the deviation of the corresponding nuclear ? term from the single-nucleon estimate is at the few-percent level, in conflict with the conjectured enhancement. As a consequence, lattice QCD calculations currently indicate that the cross sections for scalar-isoscalar WIMP-nucleus interactions arising from fundamental WIMP interactions with quarks do not suffer from significant uncertainties due to enhanced MECs.

Beane, S. R.; Cohen, S. D.; Detmold, W.; Lin, H.-W.; Savage, M. J.

2014-04-01

122

Establishment of a feline T-lymphoblastoid cell line highly sensitive for replication of feline immunodeficiency virus  

Microsoft Academic Search

Summary Interleukin-2 dependent feline T-lymphoblastoid cells designated as MYA-1 cells were established. The cells were free from exogenous retroviruses and sensitive for replication of feline immunodeficiency virus (FIV). FIV can grow more efficiently in MYA-1 cells than in feline primary peripheral blood mononuclear cells. This line of cells will be useful not only for isolation and propagation of FIV, but

Takayuki Miyazawa; Tetsuya Furuya I; Shin-ichi Itagaki; Yukinobu Tohya; Eiji Takahashi; Takeshi Mikami I

1989-01-01

123

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

Microsoft Academic Search

The XRCC1 gene (X-ray repair cross complementing) complements the DNA repair deficiency of the radiation sensitive Chinese hamster ovary (CHO) mutant cell line EM9 but the mechanism of the correction is not elucidated yet. XRCC1 shows substantial homology to the RAG2 gene (recombination activating gene) and we therefore tried to answer question, whether structural similarities (sequence of a putative recombination

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

1997-01-01

124

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.

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

2013-01-01

125

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

PubMed

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; Gerhard, Markus

2013-11-01

126

miR-101 sensitizes A549 NSCLC cell line to CDDP by activating caspase 3-dependent apoptosis  

PubMed Central

MicroRNA-101 (miR-101) is evidently downregulated in several types of cancer, including non-small cell lung cancer (NSCLC), and is crucial in sensitizing cells to chemotherapy drugs. The aim of the present study was to investigate the correlation between miR-101 and chemosensitivity in the A549 NSCLC cell line. Here, we used the human A549 cell line for transfection with an miR-101 overexpressing vector and detected the cytotoxic acticity, proliferation and apoptosis of cis-diaminedichloroplatinum (CDDP) in A549-miR-101 and A549-mock cells. We demonstrated that overexpression of miR-101 sensitized A549 cells to CDDP, one of the most frequently used agents in curing or controlling NSCLC and enhanced CDDP-induced cell death and caspase 3-dependent apoptosis. In addition, miR-101 facilitated the inhibitory role of CDDP in A549 cell colony formation. Overall, the results of the present study demonstrated that miR-101 sensitizes the A549 NSCLC cell line to CDDP via the activation of caspase 3-dependent apoptosis.

YIN, JIQING; WANG, MINGGUO; JIN, CUIXIANG; QI, QINGGUO

2014-01-01

127

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

2014-07-01

128

Improved phase sensitivity in spectral domain phase microscopy using line-field illumination and self phase-referencing  

PubMed Central

We report a quantitative phase microscope based on spectral domain optical coherence tomography and line-field illumination. The line illumination allows self phase-referencing method to reject common-mode phase noise. The quantitative phase microscope also features a separate reference arm, permitting the use of high numerical aperture (NA > 1) microscope objectives for high resolution phase measurement at multiple points along the line of illumination. We demonstrate that the path-length sensitivity of the instrument can be as good as 41 pm/Hz, which makes it suitable for nanometer scale study of cell motility. We present the detection of natural motions of cell surface and two-dimensional surface profiling of a HeLa cell.

Yaqoob, Zahid; Choi, Wonshik; Oh, Seungeun; Lue, Niyom; Park, Yongkeun; Fang-Yen, Christopher; Dasari, Ramachandra R.; Badizadegan, Kamran; Feld, Michael S.

2010-01-01

129

Reply to: “Critical revision of the ZEPLIN-I sensitivity to WIMP interactions”  

NASA Astrophysics Data System (ADS)

Recent objections [A. Benoit et al., Phys. Lett. B 637 (2006) 156] to the published ZEPLIN I limit [G.J. Alner et al., Astropart. Phys. 23 (2005) 444] are shown to arise from misunderstandings of the calibration data and procedure, and a misreading of the data in one of the referenced papers.

Smith, N. J. T.; Murphy, A. S.; Sumner, T. J.

2006-11-01

130

NAIAD: an advanced sodium iodide scintillation detector with improved sensitivity to WIMP dark matter  

Microsoft Academic Search

A novel bulk NaI detector, NAIAD, developed by the UK Dark Matter Collaboration (UKDMC), combines improved light collection from suspending an unencapsulated crystal viewed by photomultipliers (PMTs) in mineral oil with background reduction from a liquid scintillator Compton veto. Low background NaI(Tl) detectors, which use pulse shape analysis (PSA) to distinguish scintillation from background electron recoils from nuclear recoils, currently

C. D. Peak; J. E. McMillan; N. J. C. Spooner; J. W. Roberts

1998-01-01

131

Characterization of a new trabectedin-resistant myxoid liposarcoma cell line that shows collateral sensitivity to methylating agents.  

PubMed

Myxoid Liposarcomas (MLS), characterized by the expression of FUS-CHOP fusion gene are clinically very sensitive to the DNA binding antitumor agent, trabectedin. However, resistance eventually occurs, preventing disease eradication. To investigate the mechanisms of resistance, a trabectedin resistant cell line, 402-91/ET, was developed. The resistance to trabectedin was not related to the expression of MDR related proteins, uptake/efflux of trabectedin or GSH levels that were similar in parental and resistant cells. The 402-91/ET cells were hypersensitive to UV light because of a nucleotide excision repair defect: XPG complementation decreased sensitivity to UV rays, but only partially to trabectedin. 402-91/ET cells showed collateral sensitivity to temozolomide due to the lack of O(6) -methylguanine-DNA-methyltransferase (MGMT) activity, related to the hypermethylation of MGMT promoter. In 402-91 cells chromatin immunoprecipitation (ChIP) assays showed that FUS-CHOP was bound to the PTX3 and FN1 gene promoters, as previously described, and trabectedin caused FUS-CHOP detachment from DNA. Here we report that, in contrast, in 402-91/ET cells, FUS-CHOP was not bound to these promoters. Differences in the modulation of transcription of genes involved in different pathways including signal transduction, apoptosis and stress response between the two cell lines were found. Trabectedin activates the transcription of genes involved in the adipogenic-program such as c/EBP? and ?, in 402-91 but not in 402-91/ET cell lines. The collateral sensitivity of 402-91/ET to temozolomide provides the rationale to investigate the potential use of methylating agents in MLS patients resistant to trabectedin. PMID:21805478

Uboldi, S; Bernasconi, S; Romano, M; Marchini, S; Fuso Nerini, I; Damia, G; Ganzinelli, M; Marangon, E; Sala, F; Clivio, L; Chiorino, G; Di Giandomenico, S; Rocchi, M; Capozzi, O; Margison, G P; Watson, A J; Caccuri, A M; Pastore, A; Fossati, A; Mantovani, R; Grosso, F; Tercero, J C; Erba, E; D'Incalci, M

2012-07-01

132

Pentacyclic triterpenes from Chrysobalanaceae species: cytotoxicity on multidrug resistant and sensitive leukemia cell lines.  

PubMed

Plants are known as important source in the search for new anti-cancer agents. Cytotoxicity-guided fractionation of leaves and fruits from Licania tomentosa Bench and leaves from Chrysobalanus icaco L. resulted in the isolation of betulinic, oleanolic and pomolic acids. These triterpenoids inhibited the growth and induced apoptosis of K562, an erythroleukemia cell line. Most importantly, they also inhibited the proliferation of Lucena 1, a vincristine-resistant derivative of K562 that displays several multidrug resistance (MDR) characteristics. Taken together, our findings emphasize the anti-tumor activity of these triterpenes on leukemia cell lines and call attention to their potential as anti MDR agents. PMID:12565171

Fernandes, Janaina; Castilho, Rachel Oliveira; da Costa, Mariana Rangel; Wagner-Souza, Karen; Coelho Kaplan, Maria Auxiliadora; Gattass, Cerli Rocha

2003-02-20

133

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

NASA Astrophysics Data System (ADS)

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

Rao, Gottipaty N.; Karpf, Andreas

2011-05-01

134

The Sensitivity of Two-Dimensional Simulations of Tropical Squall Lines to Environmental Profiles  

Microsoft Academic Search

Two dimensional experiments are carried out to determine the effect of various wind and thermodynamic structure on squall line characteristics. Two ideas concerning the effect of shear are found useful in explaining many of the outcomes of the numerical experiments. First, in two dimensions, shear in the absence of vorticity sources and sinks is detrimental to convection (Kuo, Asai). Second,

Melville E. Nicholls; Richard H. Johnson; William R. Cotton

1988-01-01

135

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

National Technical Information Service (NTIS)

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 lan...

K. I. Mohr R. D. Baker W. K. Tao J. S. Famiglietti

2001-01-01

136

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...

137

Effect of Berry Extracts and Bioactive Compounds on Fulvestrant (ICI 182,780) Sensitive and Resistant Cell Lines  

PubMed Central

Fulvestrant (ICI 182,780; ICI) is approved for the treatment of advanced metastatic breast cancer that is unresponsive to other endocrine therapies. Berries are frequently consumed for their antioxidant, anti-inflammatory, and anticancer potential. In this study, we tested the efficacy of two berry extracts (Jamun-EJAE and red raspberry-RRE) and their bioactive compounds (Delphinidin-Del and Ellagic acid-EA) to inhibit cell proliferation with or without a sublethal dose of ICI in various breast cancer cell lines. ICI-sensitive (LCC1, ZR75-1, and BT474) and -resistant (LCC9, ZR75-1R) cells were subjected to treatment with berry extracts alone (0.1–100??g/mL) or with a sub-lethal dose of ICI (sensitive; 1??M for resistant cells). Extracts and Del enhanced the effect of ICI in sensitive ZR75-1 and BT474 cells primarily in an additive fashion (measured by relative index (RI)~1). In ZR75-1R cells, both EJAE and RRE synergistically enhanced the effects of ICI (15–50%; P < 0.05; RI > 1). EA, in doses tested, did not have any significant effects on any of the cell lines. Finally, we found that the extracts were more effective at lower, physiologically relevant concentrations than at higher experimental doses.

Woode, Denzel R.; Aiyer, Harini S.; Sie, Nicole; Zwart, Alan L.; Li, Liya; Seeram, Navindra P.; Clarke, Robert

2012-01-01

138

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

NASA Technical Reports Server (NTRS)

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

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

1992-01-01

139

Activity of Dendrimer?Methotrexate Conjugates on Methotrexate-Sensitive and Resistant Cell Lines  

Microsoft Academic Search

Dendritic nanostructures can play a key role in drug delivery, due to the high density and variety of surface functional groups that can facilitate and modulate the delivery process. We have investigated the effect of dendrimer end-functionality on the activity of polyamido amine (PAMAM) dendrimer-methotrexate (MTX) conjugates in MTX-sensitive and MTX-resistant human acute lymphoblastoid leukemia (CCRF-CEM) and Chinese hamster ovary

Sezen Gurdag; Jayant Khandare; Sarah Stapels; Larry H. Matherly; Rangaramanujam M. Kannan

2006-01-01

140

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

NASA Astrophysics Data System (ADS)

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

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

2008-07-01

141

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

142

Integrated cantilever-based flow sensors with tunable sensitivity for in-line monitoring of flow fluctuations in microfluidic systems.  

PubMed

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

2013-01-01

143

A very sensitive nonintercepting beam average velocity monitoring system for the TRIUMF 300-keV injection line  

SciTech Connect

A nonintercepting beam velocity monitoring system has been installed in the 300-keV injection line of the TRIUMF cyclotron to reproduce the injection energy for beam from different ion sources and to monitor any beam energy fluctuations. By using a programmable beam signal leveling method the system can work with a beam current dynamic range of 50 dB. Using synchronous detection, the system can detect 0.5 eV peak-to-peak energy modulation of the beam, sensitivity is 1.7{times}10{sup {minus}6}. The paper will describe the principle and beam measurement results. {copyright} {ital 1997 American Institute of Physics.}

Yin, Y.; Laxdal, R.E.; Zelenski, A. [TRIUMF, 4004 Wesbrook Mall, Vancouver, B.C., V6T 2A3 (CANADA); Ostroumov, P. [INR, 117312 Moscow (Russia)

1997-01-01

144

cis -Diamminedichloroplatinum(II)-induced cell death through apoptosis in sensitive and resistant human ovarian carcinoma cell lines  

Microsoft Academic Search

We have studied the effects of the chemotherapeutic drug cis-diamminedichloroplatinum(II) (cisplatin) on three human ovarian carcinoma cell lines one sensitive to the drug (CHI), one\\u000a with acquired resistance (CHlcisR) and one with intrinsic resistance (SKOV-3). Previous work has shown that the 50% inhibitory\\u000a concentrations (IC50 values) after a 2-h exposure to the drug are: CHI, 2.5 (µM; CHlcisR, 7.5 µM;

Michael G. Ormerod; Ciaran O’Neill; David Robertson; Lloyd R. Kelland; Kenneth R. Harrap

1996-01-01

145

GeV WIMPs scattering off of OH impurities cannot explain the DAMA signal  

NASA Astrophysics Data System (ADS)

In the presence of OH impurities in the DAMA crystals, GeV-scale WIMPs elastically scattering off of hydrogen nuclei with a spin independent cross section of ~10?33cm2 might explain the annual modulation observed by the DAMA experiment, while being consistent with other direct dark matter searches, as scattering would occur at energies below the energy threshold of other detectors. In this work we examine this possibility and show that, independent of the level of OH impurities in the DAMA crystals, for several reasons this scenario does not provide a viable explanation to the DAMA signal.

Profumo, Stefano; Queiroz, Farinaldo S.

2014-05-01

146

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

PubMed

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

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

2012-10-01

147

Temperature-sensitive transport of glycoproteins to the surface of a variant mouse lymphoma cell line.  

PubMed Central

The expression of mouse mammary tumor virus (MMTV) glycoproteins on the surface of stably infected mouse lymphoma cell line W7MG1 is dramatically increased by glucocorticoid hormones. A variant cell line, W7M.TS1, was selected from W7MG1 for its lack of expression of MMTV glycoproteins on the cell surface in response to treatment with glucocorticoid. Hormonal stimulation of MMTV RNA levels and hormone-induced cytolysis occurred normally in the variant cells. Furthermore, the rates of production of the precursor and mature forms of MMTV glycoproteins in the presence of glucocorticoid were similar in variant and wild-type cells. However, the accumulation of MMTV glycoproteins on the cell surface after hormone treatment was delayed by about 8 h in the variant relative to wild-type cells. The steady-state level of a constitutively expressed cellular protein, T200, on the variant cell surface was comparable to that on wild-type cells. However, in pulse-chase experiments, the appearance of newly synthesized T200 on the cell surface was delayed in the variant compared with wild-type cells. Another glucocorticoid hormone response, removal of H-2 class I antigens from the cell surface, was also delayed in the variant relative to wild-type cells, suggesting that turnover or internalization of cell surface glycoproteins may also be affected in the variant. The defects in the variant cell line were observed at 37 degrees C, but not at 31 degrees C; the variant cells grew normally at both temperatures. This variant phenotype defines a new genetic entity that is important for transport of glycoproteins between internal microsomal compartments and the cell surface. Images

Nori, M; Stallcup, M R

1988-01-01

148

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

149

Blockade of ataxia telangiectasia mutated sensitizes hepatoma cell lines to sorafenib by interfering with Akt signaling.  

PubMed

Sorafenib is a multi-kinase inhibitor applicable to hepatocellular carcinoma (HCC), but its limited therapeutic effects are a major problem to be solved. Here, we show that blockade of ataxia telangiectasia mutated (ATM) improves the antitumor effects of sorafenib. When hepatoma cell lines HepG2 and PLC/PRF/5 were treated with sorafenib plus ATM small inhibitory RNAs, ATM inhibitor KU55933 or caffeine, Akt signaling was suppressed and the cytotoxic effects were significantly potentiated. Moreover, ATM inhibition effectively suppressed the sorafenib-induced cell migration. Taken together, manipulation of ATM activity might be a useful strategy for improving sorafenib treatment of HCC. PMID:22265862

Fujimaki, Shun; Matsuda, Yasunobu; Wakai, Toshifumi; Sanpei, Ayumi; Kubota, Masayuki; Takamura, Masaaki; Yamagiwa, Satoshi; Yano, Masahiko; Ohkoshi, Shogo; Aoyagi, Yutaka

2012-06-01

150

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

151

Sensitivity of Tropical West Pacific Oceanic Squall Lines to Tropospheric Wind and Moisture Profiles.  

NASA Astrophysics Data System (ADS)

Two-dimensional experiments using the Goddard Cumulus Ensemble model are performed in order to examine the influence of environmental profiles of wind and humidity on the dynamical and microphysical structure of mesoscale convective systems (MCSs) over the tropical oceans. The initial environments used in this study are derived from the results of a cluster analysis of the TOGA COARE sounding data. The model data are analyzed with methods and measurements similar to those used in observational studies.Experiments to test the sensitivity of MCSs to the thermodynamic profile focus on the role of humidity in the free troposphere. In the experiments, a constant amount of relative humidity is added to every level above the boundary layer. As humidity is increased, model storms transition from weak, unsteady systems with little precipitation to strong, upshear-tilted systems with copious rainfall. This behavior is hypothesized to be the result of the entrainment of environmental air into the updraft cores.Experiments to test the sensitivity of MCSs to the kinematic profile focus on the amount of vertical wind shear in the midlevels, between approximately 2 and 10 km. Five kinematic profiles are used. The dynamical and microphysical characteristics of the runs changed dramatically in different shear environments. Shear in the midlevels affects the convective systems by altering the perturbation pressure field. Stronger shear results in a broader and deeper mesolow below the updraft and a more intense dynamic high above the leading edge.

Lucas, Christopher; Zipser, Edward J.; Ferrier, Brad S.

2000-08-01

152

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

PubMed

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

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

2009-09-01

153

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

NASA Technical Reports Server (NTRS)

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

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

1988-01-01

154

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

155

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

NASA Astrophysics Data System (ADS)

Data from the operation of a bubble chamber filled with 3.5 kg of CF3I in a shallow underground site are reported. An analysis of ultrasound signals accompanying bubble nucleations confirms that alpha decays generate a significantly louder acoustic emission than single nuclear recoils, leading to an efficient background discrimination. Three dark matter candidate events were observed during an effective exposure of 28.1kgday, consistent with a neutron background. This observation provides strong direct detection constraints on weakly interacting massive particle (WIMP)-proton spin-dependent scattering for WIMP masses >20GeV/c2.

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

2011-01-01

156

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

SciTech Connect

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

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

2010-08-01

157

Large-scale and high-sensitivity multi-line CO surveys toward the Galactic center  

NASA Astrophysics Data System (ADS)

We carried out large-scale (4 × 2 degree) CO multi-line observations toward the central molecular zone (CMZ) in the Galactic center (GC) with the NANTEN2 4m telescope and mapped several diffuse molecular features located at relatively high Galactic latitudes above 0°.6. These high-latitude features are composed of diffuse molecular halo gas and molecular filaments according to their morphological aspects. Their high velocities and high intensity ratios between 12CO J = (2-1) and J = (1-0) clearly indicate their location in the GC, and their total mass amount to ˜10% of that of the CMZ. We discuss that magnetic field is a possible mechanism of these high-latitude molecular features lifting up toward high galactic latitude.

Enokiya, R.; Torii, K.; Schultheis, M.; Asahina, Y.; Matsumoto, R.; Yamamoto, H.; Tachihara, K.; Okuda, T.; Morris, M. R.; Fukui, Y.

2014-05-01

158

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

PubMed Central

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

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

1995-01-01

159

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

160

Patterns Prediction of Chemotherapy Sensitivity in Cancer Cell lines Using FTIR Spectrum, Neural Network and Principal Components Analysis  

PubMed Central

Drug resistance enables cancer cells to break away from cytotoxic effect of anticancer drugs. Identification of resistant phenotype is very important because it can lead to effective treatment plan. There is an interest in developing classifying models of resistance phenotype based on the multivariate data. We have investigated a vibrational spectroscopic approach in order to characterize a sensitive human ovarian cell line, A2780, and its cisplatin-resistant derivative, A2780-cp. In this study FTIR method have been evaluated via the use of principal components analysis (PCA), ANN (artificial neuronal network) and LDA (linear discriminate analysis). FTIR spectroscopy on these cells in the range of 400-4000 cm-1 showed alteration in the secondary structure of proteins and a CH stretching vibration. We have found that the ANN models correctly classified more than 95% of the cell lines, while the LDA models with the same data sets could classify 85% of cases. In the process of different ranges of spectra, the best classification of data set in the range of 1000-2000 cm-1 was done using ANN model, while the data set between 2500-3000 cm-1 was more correctly classified with the LDA model. PCA of the spectral data also provide a good separation for representing the variety of cell line spectra. Our work supports the promise of ANN analysis of FTIR spectrum as a supervised powerful approach and PCA as unsupervised modeling for the development of automated methods to determine the resistant phenotype of cancer classification.

Zendehdel, Rezvan; Masoudi-Nejad, Ali; H. Shirazi, Farshad

2012-01-01

161

Contribution of reactive oxygen species to the regulation of Glut1 in two hemopoietic cell lines differing in cytokine sensitivity.  

PubMed

Glucose transport activity and its possible regulation by reactive oxygen species in two Glut1-expressing megakaryocytic cell lines, MO7e and B1647, differing in cytokine sensitivity were compared. Results show that: (1) In MO7e cells, glucose transport rate increased in response to thrombopoietin, granulocyte-macrophage colony-stimulating factor, or stem cell factor, due to a decreased Km. (2) A higher Vmax value was determined in B1647 cells, owing to the relative higher abundance of Glut1 on the plasmalemma; in these cells no change in glucose transport rate was observed on cytokine treatment. (3) The basal level of intracellular ROS was higher in B1647 than in M07e cells, where ROS production was enhanced upon cytokine exposure. (4) Basal or stimulated ROS production and Glut1 activity were significantly reduced by pretreating both cell lines with EUK-134, a superoxide dismutase and catalase mimetic. (5) In MO7e cells, EUK-134 brought back to control levels the Km values obtained on cytokine treatment, whereas in B1647 cells the antioxidant drastically reduced Vmax by decreasing the Glut1 content of the plasma membrane. Our data suggest that differences in acute regulation of glucose transport activity in the two cell lines may be related to differences in amplitude and spatial organization of ROS production. PMID:15454279

Fiorentini, Diana; Prata, Cecilia; Maraldi, Tullia; Zambonin, Laura; Bonsi, Laura; Hakim, Gabriele; Landi, Laura

2004-11-01

162

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

PubMed

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

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

2012-11-20

163

Differential sensitivity of telomerase from human hematopoietic stem cells and leukemic cell lines to mild hyperthermia.  

PubMed

We have investigated the effects of hyperthermia (HT) on cell proliferation and telomerase activity of human hematopoietic stem cells (HSCs) and compared with human leukemic cell lines (TF-1, K562 and HL-60). The cells were exposed to HT at 42 and 43 °C up to 120 min. The cells were incubated at 37 °C for 96 h. Then the cells were collected and assayed for cell proliferation, viability, telomerase activity, and terminal restriction fragment (TRF) lengths. The enzyme activity from HSCs was decreased up to 68.6 at 42 and 85.1 % at 43 °C for 120 min. This inhibition in leukemic cells was up to 28.9 and 53.6 % in TF-1; 53 and 63.9 % in K562; 45.2 and 61.1 % in HL-60 cells. The treated cells showed TRF lengths about 5.3 kb for control HL-60 cells, 5.0 kb for HL-60 cells treated at 42 and 4.5 kb at 43 °C for 120 min. In HSCs, the TRF length was about 4.5 kb for untreated cells and 4.0-4.5 kb for treated cells at 42 and 43 °C for 120 min. The time response curves indicated that, inhibition of the enzyme activity in leukemic cells was dependent to the time of exposure to HT. But in HSCs, the inhibition was reached to steady state at 15 min exposure to 43 °C heat stress. TRF length was constant at treated two types of cells, which implies that in cells subjected to mild HT no telomere shortening was observed. PMID:24590263

Deezagi, Abdolkhaleg

2014-07-01

164

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

165

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

PubMed Central

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

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

2012-01-01

166

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

PubMed

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

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

2006-04-01

167

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

PubMed Central

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

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

2009-01-01

168

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

169

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

170

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

Microsoft Academic Search

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

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

2009-01-01

171

Variation in dehydration tolerance, ABA sensitivity and related gene expression patterns in D-genome progenitor and synthetic hexaploid wheat lines.  

PubMed

The wild wheat Aegilops tauschii Coss. has extensive natural variation available for breeding of common wheat. Drought stress tolerance is closely related to abscisic acid (ABA) sensitivity. In this study, 17 synthetic hexaploid wheat lines, produced by crossing the tetraploid wheat cultivar Langdon with 17 accessions of Ae. tauschii, were used for comparative analysis of natural variation in drought tolerance and ABA sensitivity. Ae. tauschii showed wide natural variation, with weak association between the traits. Drought-sensitive accessions of Ae. tauschii exhibited significantly less ABA sensitivity. D-genome variations observed at the diploid genome level were not necessarily reflected in synthetic wheats. However, synthetic wheats derived from the parental Ae. tauschii accessions with high drought tolerance were significantly more tolerant to drought stress than those from drought-sensitive accessions. Moreover, synthetic wheats with high drought tolerance showed significantly higher ABA sensitivity than drought-sensitive synthetic lines. In the hexaploid genetic background, therefore, weak association of ABA sensitivity with drought tolerance was observed. To study differences in gene expression patterns between stress-tolerant and -sensitive lines, levels of two Cor/Lea and three transcription factor gene transcripts were compared. The more tolerant accession of Ae. tauschii tended to accumulate more abundant transcripts of the examined genes than the sensitive accession under stress conditions. The expression patterns in the synthetic wheats seemed to be additive for parental lines exposed to drought and ABA treatments. However, the transcript levels of transcription factor genes in the synthetic wheats did not necessarily correspond to the postulated levels based on expression in parental lines. Allopolyploidization altered the expression levels of the stress-responsive genes in synthetic wheats. PMID:19582226

Kurahashi, Yumeto; Terashima, Akihiro; Takumi, Shigeo

2009-06-01

172

Density sensitive X-ray line ratios in the Be I, B I, and Ne I isoelectronic sequences  

NASA Technical Reports Server (NTRS)

The intensities of X-ray transitions in highly charged ions in the Be I, B I, and Ne I isoelectronic sequences have been calculated as functions of electron density. The intensities of the transitions from the 2s(n)2p(m)3p configuration, relative to the intensities from the 2s(n)2p(m)3s and 2s(n)p(m)3d configurations, are strong functions of electron density in high-density plasmas. The density sensitivity occurs at electron densities between 10 to the 16th/cu cm (for Si ions) and 10 to the 22nd/cu cm (for Kr ions). Opacity is unimportant for plasma dimensions that are characteristic of dense laser-produced plasmas. These X-ray line ratios represent a promising new density diagnostic for high-density plasmas.

Feldman, U.; Seely, J. F.; Bhatia, A. K.

1985-01-01

173

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

NASA Astrophysics Data System (ADS)

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

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

2010-06-01

174

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.

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

2014-01-01

175

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

PubMed

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

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

2014-07-15

176

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

PubMed Central

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

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

2013-01-01

177

Elevated expression of Dickkopf-1 increases the sensitivity of human glioma cell line SHG44 to BCNU  

PubMed Central

Background Studies have shown that Dickkopf-1 (DKK-1) is involved in tumorigenesis. Recently, we found that 9 out of 12 human glioma cell lines had high level of DKK-1 protein while the other 3 had very low or non-detectable level of DKK-1. The aim of this study is to further examine the function of DKK-1 in glioma cells. Materials and methods The glioma cell line SHG44 was obtained from a patient with grade II-III astrocytoma. SHG44 cells were transfected with a human DKK-1 gene. Transfection of the empty vector pcDNA3.1 was used as negative control. Sensitivity to BCNU was measured by Annexin-V staining. Expression of bax, bcl-2 and caspase-3 of three groups was determined by immunohistochemistry. Results The tranfection was confirmed by PCR, RT-PCR and Western blot. More apoptotic cell death was observed in the DKK-1 transfected cells, comparing to the non-transfected cells, or cells with empty vector. The expression of bax and caspase-3 of the SHG44 -DDK-1 increased, whereas the expression of bcl-2 decreased Conclusion Our results indicated that DKK-1 has a pro-apoptotic function of in glioma.

2010-01-01

178

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

PubMed

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

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

2008-06-01

179

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

PubMed Central

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

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

2013-01-01

180

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

PubMed

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

Kova?evi?, Tomislav; Skelin, Ivan; Minuzzi, Luciano; Rosa-Neto, Pedro; Diksic, Mirko

2012-03-10

181

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

NASA Astrophysics Data System (ADS)

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

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

2012-07-01

182

CMB constraints on WIMP annihilation: Energy absorption during the recombination epoch  

SciTech Connect

We compute in detail the rate at which energy injected by dark matter (DM) annihilation heats and ionizes the photon-baryon plasma at z{approx}1000, and provide accurate fitting functions over the relevant redshift range for a broad array of annihilation channels and DM masses. The resulting perturbations to the ionization history can be constrained by measurements of the CMB temperature and polarization angular power spectra. We show that models which fit recently measured excesses in 10-1000 GeV electron and positron cosmic rays are already close to the 95% confidence limits from WMAP. The recently launched Planck satellite will be capable of ruling out a wide range of DM explanations for these excesses. In models of dark matter with Sommerfeld-enhanced annihilation, where <{sigma}v> rises with decreasing WIMP velocity until some saturation point, the WMAP5 constraints imply that the enhancement must be close to saturation in the neighborhood of the Earth.

Slatyer, Tracy R. [Physics Department, Harvard University, Cambridge, Massachusetts 02138 (United States); Padmanabhan, Nikhil [Physics Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, California 94720 (United States); Finkbeiner, Douglas P. [Physics Department, Harvard University, Cambridge, Massachusetts 02138 (United States); Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, Massachusetts 02138 (United States)

2009-08-15

183

DNA microarray reveals ZNF195 and SBF1 are potential biomarkers for gemcitabine sensitivity in head and neck squamous cell carcinoma cell lines  

PubMed Central

Gemcitabine is a potential chemotherapy drug for treatment of head and neck squamous cell carcinoma (HNSCC), however, the poor or partial response of HNSCC patients to gemcitabine demonstrated the urgent need for gemcitabine biomarkers to improve the therapy. In present work, 10 HNSCC cell lines were employed to figure out the biomarkers for gemcitabine sensitivity. The sensitivities of these 10 cell lines to gemcitabine and the basal expression of these cell lines was investigated, the correlation between gemcitabine response (IC50 dose) and gene expression was investigated by Pearson correlation and FDR estimation. The top seven positive genes responsible for gemcitabine sensitivity were validated by qPCR in these 10 HNSCC cell lines, while only two genes (SBF1 and ZNF195) were expression-correlated to gemcitabine response. Furthermore, ZNF195 expression was closely associated with gemcitabine sensitivity in the subsequent independent validation in cell lines from various types of cancer. Our work might provide potential biomarkers for gemcitabine sensitivity in HNSCC and various type of cancer.

Zhu, Min-Hui; Ji, Shun-Long; Zhang, Cai-Yun; Cui, Long; Xiong, Lei; Zheng, Hong-Liang

2014-01-01

184

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

PubMed

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

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

2014-03-01

185

Sensitivities of Uterine Adenocarcinoma, Mixed Mullerian Tumor (MMT) and Sarcoma Cell Lines to Chemotherapeutic Agents and a Flex-Het Drug  

PubMed Central

The administration and combination of a variety of chemotherapeutic agents for treatment of advanced or recurrent uterine cancer of different histologies is under current debate. Mixed Mullerian Tumors (MMTs), which contain both adenocarcinoma and sarcoma components, are the most rate histologic type and it is therefore difficult to conduct clinical trials to determine if they should be treated like endometrial adenocarinomas or like sarcomas. Flexible Heteroarotionoids (Flex-Hets) are a promising class of anti-cancer drugs with low toxicity that have demonstrated activity against a wide variety of cancer types, but their efficacy in uterine cancers is unknown. The objective of this study was to determine if cell lines established from endometrial carcinoma (HEC-1-A), uterine sarcoma (SK-UT-1) and MMT (MES-SA) cancers exhibit differential sensitivities to cisplatin, carboplatin, paclitaxel, docetaxel, doxorubicin and SHetA2, if SHetA2 can enhance sensitivity to the chemotherapeutic drugs and if SHetA2 exhibits a differential effect on uterine cancer cells in comparison to normal endometrial cells using a cytotoxicity assay. These cell lines did not differ in their sensitivities to platinum or taxel drugs. Doxorubicin was active against the sarcoma but not the adenocarcinoma or MMT cell lines. SHetA2 decreased the survival of all three cell lines, but did not enhance their sensitivities to the chemotherapeutic agents. Two of the three uterine cancer cell lines were more sensitive to SHetA2 in comparison to normal endometrial cells. In conclusion, doxorubicin appears to have a greater effect against sarcoma than other uterine histology types. SHetA2 is affective against uterine cancer cell lines, but does not enhance their sensitivities to chemotherapeutic agents.

Hyde, Johnny; Benbrook, Doris M.

2009-01-01

186

Sensitivities of Uterine Adenocarcinoma, Mixed Mullerian Tumor (MMT) and Sarcoma Cell Lines to Chemotherapeutic Agents and a Flex-Het Drug.  

PubMed

The administration and combination of a variety of chemotherapeutic agents for treatment of advanced or recurrent uterine cancer of different histologies is under current debate. Mixed Mullerian Tumors (MMTs), which contain both adenocarcinoma and sarcoma components, are the most rate histologic type and it is therefore difficult to conduct clinical trials to determine if they should be treated like endometrial adenocarinomas or like sarcomas. Flexible Heteroarotionoids (Flex-Hets) are a promising class of anti-cancer drugs with low toxicity that have demonstrated activity against a wide variety of cancer types, but their efficacy in uterine cancers is unknown. The objective of this study was to determine if cell lines established from endometrial carcinoma (HEC-1-A), uterine sarcoma (SK-UT-1) and MMT (MES-SA) cancers exhibit differential sensitivities to cisplatin, carboplatin, paclitaxel, docetaxel, doxorubicin and SHetA2, if SHetA2 can enhance sensitivity to the chemotherapeutic drugs and if SHetA2 exhibits a differential effect on uterine cancer cells in comparison to normal endometrial cells using a cytotoxicity assay. These cell lines did not differ in their sensitivities to platinum or taxel drugs. Doxorubicin was active against the sarcoma but not the adenocarcinoma or MMT cell lines. SHetA2 decreased the survival of all three cell lines, but did not enhance their sensitivities to the chemotherapeutic agents. Two of the three uterine cancer cell lines were more sensitive to SHetA2 in comparison to normal endometrial cells. In conclusion, doxorubicin appears to have a greater effect against sarcoma than other uterine histology types. SHetA2 is affective against uterine cancer cell lines, but does not enhance their sensitivities to chemotherapeutic agents. PMID:19890461

Hyde, Johnny; Benbrook, Doris M

2006-01-01

187

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

NASA Astrophysics Data System (ADS)

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

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

188

Defining Ploidy-Specific Thresholds in Array Comparative Genomic Hybridization to Improve the Sensitivity of Detection of Single Copy Alterations in Cell Lines  

PubMed Central

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

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

2006-01-01

189

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

Microsoft Academic Search

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

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

2010-01-01

190

Establishment and drug sensitivity evaluation of murine ascites hepatocarcinoma cell line with high lymphatic metastatic potential (Hca-P\\/L 6 )  

Microsoft Academic Search

In order to provide a sensitive cell line model for investigating the mechanisms underlying the lymphatic metastasis of tumors\\u000a and the effect of medicine against cells, a new murine ascites hepatocarcinoma cell line with high lymphatic metastatic potential\\u000a (Hca-P\\/L6) was established and the effect of curcumin on biological behavior of Hca-P\\/L6 was observed. Murine ascites hepatocarcinoma cell strain with low

Hongying Zhang; Jianwu Tang; Wenting Zhu; Chunxiu Hu; Guowang Xu

2009-01-01

191

Overexpression of miR-145 increases the sensitivity of vemurafenib in drug-resistant colo205 cell line.  

PubMed

Vemurafenib is a selective and potent small molecule inhibitor of the V600 mutant form of the BRAF protein used in the treatment of melanoma and colorectal cancer. However, vemurafenib has less effect in BRAF mutant colorectal cancer due to the resistance of tumor cell to vemurafenib. To verify whether or not miR-145, a short RNA molecule of microRNA which has been supposed to be a tumor suppressor, is involved in this process, we established vemurafenib-resistant cell line colo205/V and found that the miR-145 expression was significantly downregulated in colo205/V cells compared to normal colo205 cells. Moreover, the overexpression of miR-145 could increase the sensitivity of colo205/V cells to vemurafenib both in vitro and in vivo. In conclusion, miR-145 might be used as a therapeutic target in the treatment of colorectal cancer patients with BRAF V600E mutation. PMID:24248543

Peng, Wei; Hu, Jian; Zhu, Xiao-dong; Liu, Xin; Wang, Chen-chen; Li, Wen-hua; Chen, Zhi-yu

2014-04-01

192

The REST Gene Signature Predicts Drug Sensitivity in Neuroblastoma Cell Lines and Is Significantly Associated with Neuroblastoma Tumor Stage.  

PubMed

Neuroblastoma is the most common and deadly solid tumor in children, and there is currently no effective treatment available for neuroblastoma patients. The repressor element-1 silencing transcription (REST) factor has been found to play important roles in the regulation of neural differentiation and tumorigenesis. Recently, a REST signature consisting of downstream targets of REST has been reported to have clinical relevance in both breast cancer and glioblastoma. However it remains unclear how the REST signature works in neuroblastoma. Publicly available datasets were mined and bioinformatic approaches were used to investigate the utility of the REST signature in neuroblastoma with both preclinical and real patient data. The REST signature was found to be associated with drug sensitivity in neuroblastoma cell lines. Further, neuroblastoma patients with enhanced REST activity are significantly associated with higher clinical stages. Loss of heterozygosity on chromosome 11q23, which occurs in a large subset of high-risk neuroblastomas, tends to be correlated with high REST activity, with marginal significance. In conclusion, the REST signature has important implications for targeted therapy, and it is a prognostic factor in neuroblastoma patients. PMID:24968265

Liang, Jianfeng; Tong, Pan; Zhao, Wanni; Li, Yaqiao; Zhang, Li; Xia, Ying; Yu, Yanbing

2014-01-01

193

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

SciTech Connect

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

Linnarsson, M. K.; Hallen, A. [KTH Royal Institute of Technology, School of Information and Communication Technology, Integrated Circuits and Devices, P.O. Box E229, SE-16440 Kista-Stockhom (Sweden); Astroem, J.; Primetzhofer, D.; Legendre, S.; Possnert, G. [Uppsala University, Angstroem Laboratory, Department of Physics, Ion Physics, P.O. Box 534, SE-751 21 Uppsala (Sweden)

2012-09-15

194

Improving Blast Resistance of a ThermoSensitive Genic Male Sterile Rice Line GD8S by Molecular Marker-Assisted Selection  

Microsoft Academic Search

The broad-spectrum blast resistance gene Pi-1, from donor line BL122, was introduced into a thermo-sensitive genic male sterile rice line GD-8S, which possessed good grain quality but high susceptibility to rice blast, by using backcross breeding and molecular marker-assisted selection. Five elite improved male sterile lines, RGD8S-1, RGD8S-2, RGD8S-3, RGD8S-4 and RGD8S-5, were selected based on the results of molecular

Wu-ge LIU; Su-juan JIN; Xiao-yuan ZHU; Feng WANG; Jin-hua LI; Zhen-rong LIU; Yi-long LIAO; Man-shan ZHU; Hui-jun HUANG; Yi-bai LIU

2008-01-01

195

First results on low-mass WIMPs from the CDEX-1 experiment at the China Jinping underground laboratory  

NASA Astrophysics Data System (ADS)

The China Dark Matter Experiment Collaboration reports the first experimental limit on weakly interacting massive particles (WIMPs) dark matter from 14.6 kg-days of data taken with a 994 g p-type point-contact germanium detector at the China Jinping underground laboratory where the rock overburden is more than 2400 m. The energy threshold achieved was 400 eVee. According to the 14.6 kg-day live data, we placed the limit of ??N=1.75×10-40cm2 at a 90% confidence level on the spin-independent cross section at a WIMP mass of 7 GeV before differentiating bulk signals from the surface backgrounds.

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

2013-09-01

196

Search for inelastic WIMP nucleus scattering on 129Xe in data from the XMASS-I experiment  

NASA Astrophysics Data System (ADS)

A search for inelastic scattering of weakly interacting massive particles (WIMPs) on the isotope ^{129}Xe was done in data taken with the single-phase liquid-xenon detector XMASS at the Kamioka Observatory. Using a restricted volume containing 41 kg of liquid xenon at the very center of our detector, we observed no significant excess of events in 165.9 live days of data. Our background reduction allowed us to derive our limits without explicitly subtracting the remaining events that are compatible with background expectations. As an example, we derive for a 50 GeV WIMP an upper limit of 3.2 pb at the 90% confidence level for its inelastic cross section on ^{129}Xe nuclei.

Uchida, H.; Abe, K.; Hieda, K.; Hiraide, K.; Hirano, S.; Ichimura, K.; Kishimoto, Y.; Kobayashi, K.; Moriyama, S.; Nakagawa, K.; Nakahata, M.; Ogawa, H.; Oka, N.; Sekiya, H.; Shinozaki, A.; Suzuki, Y.; Takeda, A.; Takachio, O.; Umemoto, D.; Yamashita, M.; Yang, B. S.; Tasaka, S.; Liu, J.; Martens, K.; Hosokawa, K.; Miuchi, K.; Murata, A.; Onishi, Y.; Otsuka, Y.; Takeuchi, Y.; Kim, Y. H.; Lee, K. B.; Lee, M. K.; Lee, J. S.; Fukuda, Y.; Itow, Y.; Masuda, K.; Nishitani, Y.; Takiya, H.; Kim, N. Y.; Kim, Y. D.; Kusaba, F.; Nishijima, K.; Fujii, K.; Murayama, I.; Nakamura, S.

2014-06-01

197

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

198

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

NASA Astrophysics Data System (ADS)

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.

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

2013-06-01

199

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

200

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

SciTech Connect

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

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

1993-03-01

201

Gene profiles of a human alveolar epithelial cell line after in vitro exposure to respiratory (non-)sensitizing chemicals: identification of discriminating genetic markers and pathway analysis.  

PubMed

There are currently no accepted biological prediction models for assessing the potential of a substance to cause respiratory sensitization. New tests should be based on mechanistic understanding and should be preferentially restricted to in vitro assays. The major goal of this study was to investigate the alterations in gene expression of human alveolar epithelial (A549) cells after exposure to respiratory sensitizing and non-respiratory sensitizing chemicals, and to identify genes that are able to discriminate between both groups of chemicals. A549 cells were exposed during 6, 10, and 24 h to the respiratory sensitizers ammonium hexachloroplatinate IV, hexamethylene diisocyanate, and trimellitic anhydride, the irritants acrolein and methyl salicylate, and the skin sensitizer 1-chloro-2,4-dinitrobenzene. Overall changes in gene expression were evaluated using Agilent Whole Human Genome 4x44K oligonucleotide arrays. A Fisher linear discriminant analysis was used to obtain a ranking of genes that reflects their potential to discriminate between respiratory sensitizing and respiratory non-sensitizing chemicals. Among the 20 most discriminating genes, which were categorized into molecular and biological gene ontology (GO) terms, CTLA4 could be associated with asthma and/or respiratory sensitization. When categorizing the top-1000 genes into biological GO terms, 22 genes were associated with immune function. Using a pathway analysis tool to identify possible underlying mechanisms of respiratory sensitization, no known canonical signaling pathway was observed to be activated in the A549 cell line. PMID:19110044

Verstraelen, Sandra; Nelissen, Inge; Hooyberghs, Jef; Witters, Hilda; Schoeters, Greet; Van Cauwenberge, Paul; Van Den Heuvel, Rosette

2009-02-25

202

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

203

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

PubMed Central

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

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

2013-01-01

204

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

205

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.

Hindle, Allyson G.; Martin, Sandra L.

2013-01-01

206

Characterization of conditionally expressed mutants affecting age-specific survival in inbred lines of Drosophila melanogaster: lethal conditions and temperature-sensitive periods.  

PubMed Central

The specific genetic basis of inbreeding depression is poorly understood. To address this question, two conditionally expressed lethal effects that were found to cause line-specific life span reductions in two separate inbred lines of Drosophila melanogaster were characterized phenotypically and genetically in terms of whether the accelerated mortality effects are dominant or recessive. The mortality effect in one line (I4) is potentially a temperature-sensitive semilethal that expresses in adult males only and is partially dominant. The other line (I10) responds as one would expect for a recessive lethal. It requires a cold shock for expression and is cold sensitive. Flies exhibiting this lethal condition responded as pupae and freshly eclosed imagoes. The effect is recessive in both males and females. The expression of the lethal effects in both lines is highly dependent upon environmental conditions. These results will serve as a basis for more detailed and mechanistic genetic research on inbreeding depression and are relevant to sex- and environment-specific effects on life span observed in quantitative trait loci studies using inbred lines.

Vermeulen, C J; Bijlsma, R

2004-01-01

207

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

NASA Astrophysics Data System (ADS)

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

Gibson, Carl H.

1996-11-01

208

Study of a WIMP dark matter model with the updated results of CDMS II  

NASA Astrophysics Data System (ADS)

The new observation of CDMS II favors low mass WIMPs. Taking the CDMS II new results as input, we consider a standard model (SM) singlet: the darkon as the dark matter (DM) candidate, which can be either a scalar, fermion, or vector. It is found that the simplest scenario of DM +SM conflicts with the stringent constraint set by the LHC data. New physics beyond the SM is needed, and in this work, we discuss an extended standard model SUL(2)?UY(1)?U(1)' where U(1)' only couples to the darkon. The new gauge symmetry is broken into Uem(1) and two neutral bosons Z0 and Z', which results in mixtures of W?3, B?, and X?. Following the literature and based on the CDMS data, we conduct a complete analysis to verify the validity of the model. The cross section of the elastic scattering between the darkon and nucleon is calculated, and the DM relic density is evaluated in the extended scenario. It is found that by considering the constraints from both the cosmology and collider experiments, one can reconcile all the presently available data only if Z ' is lighter than Z0.

Jia, Lian-Bao; Li, Xue-Qian

2014-02-01

209

Gene profiles of a human bronchial epithelial cell line after in vitro exposure to respiratory (non-)sensitizing chemicals: identification of discriminating genetic markers and pathway analysis.  

PubMed

Respiratory sensitization is a concern for occupational and environmental health in consumer product development. Despite international regulatory requirements there is no established protocol for the identification of chemical respiratory sensitizers. New tests should be based on mechanistic understanding and should be preferentially restricted to in vitro assays. The major goal of this study was to investigate the alterations in gene expression of human bronchial epithelial (BEAS-2B) cells after exposure to respiratory sensitizers and respiratory non-sensitizing chemicals, and to identify genes that are able to discriminate between both groups of chemicals. BEAS-2B cells were exposed during 6, 10, and 24h to the respiratory sensitizers ammonium hexachloroplatinate IV, hexamethylene diisocyanate, and trimellitic anhydride, the irritants acrolein and methyl salicylate, and the skin sensitizer 1-chloro-2,4-dinitrobenzene. Overall changes in gene expression were evaluated using Agilent Whole Human Genome 4x 44K oligonucleotide arrays. Fisher Linear Discriminant Analysis was used to obtain a ranking of genes that reflects their potential to discriminate between respiratory sensitizing and respiratory non-sensitizing chemicals. The 10 most discriminative genes were BC042064, A_24_P229834, DOCK11, THC2544911, DLGAP4, NINJ1, PFKM, FLJ10986, IL28RA, and CASP9. Based on the differentially expressed genes, pathway analysis was used to identify possible underlying mechanisms of respiratory sensitization. We demonstrated that in bronchial epithelial cells the canonical PTEN signaling pathway is probably the most specific pathway in the context of respiratory sensitization. Results are indicative that the BEAS-2B cell line can be used as an alternative cell model to screen chemical compounds for their respiratory sensitizing potential. PMID:19041681

Verstraelen, Sandra; Nelissen, Inge; Hooyberghs, Jef; Witters, Hilda; Schoeters, Greet; Van Cauwenberge, Paul; Van Den Heuvel, Rosette

2009-01-31

210

Chemo-sensitivity in a panel of B-cell precursor acute lymphoblastic leukemia cell lines, YCUB series, derived from children.  

PubMed

Sensitivity to 10 anticancer drugs was evaluated in 6 childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cell lines. Authenticity of newly established cell lines was confirmed by genomic fingerprinting. The line YCUB-5R established at relapse was more resistant to 4-hydroperoxy-cyclophosphamide, cytarabine, L-asparaginase, topotecan, fludarabine, and etoposide than YCUB-5 from the same patient at diagnosis. Of the drugs tested, etoposide and SN-38 (irinotecan) showed highest efficacy in the panel, with 50% growth inhibition at 0.22-1.8 microg/ml and 0.57-3.6 ng/ml, respectively. This cell line panel offers an in vitro model for the development of new therapies for childhood BCP-ALL. PMID:19157546

Goto, Hiroaki; Naruto, Takuya; Tanoshima, Reo; Kato, Hiromi; Yokosuka, Tomoko; Yanagimachi, Masakatsu; Fujii, Hisaki; Yokota, Shumpei; Komine, Hiromi

2009-10-01

211

Omega 3 fatty acids increase the chemo-sensitivity of B-CLL-derived cell lines EHEB and MEC-2 and of B-PLL-derived cell line JVM-2 to anti-cancer drugs doxorubicin, vincristine and fludarabine  

PubMed Central

Background B-Cell chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the United States. Clinical treatment of CLL is often limited due to drug resistance and severe therapy-induced toxicities. We hypothesized that the omega 3 (n-3) fatty acids, eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA), would increase the sensitivity of malignant B-lymphocytes to anti-cancer drugs doxorubicin, vincristine and/or fludarabine in vitro and that increased sensitivity is achieved by alterations in cell-cycle progression leading to growth inhibition and/or enhanced cell death. We further postulate that enhanced sensitivity is dependent on the formation of lipid peroxides and to the generation of reactive oxygen species (ROS). Methods In the present study, B-CLL-derived leukemic cell lines EHEB and MEC-2 and the B-Prolymphocytic leukemic-derived (PLL) cell line JVM-2 were tested for in vitro sensitivity against doxorubicin, vincristine or fludarabine in the presence or absence of vehicle, arachidonic acid (omega 6), EPA or DHA. Cell cycle analysis and Annexin-V assays were performed to determine cell cycle progression and % apoptotic cells, respectively. Assays for malondialdehyde, a measure of lipid peroxidation, and DCF fluorescence assays, a measure of intracellular ROS, were performed to determine if enhanced sensitivity of cells to the drugs by n-3 was dependent on the formation of ROS. Results Our results indicated that: 1) EPA and DHA differentially sensitized B-leukemic cell lines EHEB, JVM-2 and MEC-2 to doxorubicin, vincristine and fludarabine in vitro; 2) n-3 alone and with drug treatment increased cell death and induced G2/M arrest in a cell-type specific manner; 3) lipid peroxidation increased in the presence of n-3; 4) there was higher lipid peroxidation in MEC-2 cells in presence of DHA and doxorubicin than with either alone; 5) n-3 increased generation of ROS in MEC-2, and 6) the addition of vitamin-E abrogated the increase in ROS generation and chemo-sensitivity of MEC-2 to doxorubicin by DHA. Conclusion N-3’s are promising chemo-sensitizing agents for the treatment of CLL. Selective enhancement of chemo-sensitivity of EHEB, JVM-2 and MEC-2 to drugs by n-3 that is not dependent on increased lipid peroxidation and ROS generation indicates alternative mechanisms by which n-3 enhances chemo-sensitivity.

2013-01-01

212

Ofatumumab demonstrates activity against rituximab-sensitive and -resistant cell lines, lymphoma xenografts and primary tumour cells from patients with B-cell lymphoma.  

PubMed

Ofatumumab is a new monoclonal antibody (mAb) targeting a novel membrane-proximal epitope on CD20. To better define ofatumumab's activity, we conducted pre-clinical studies in rituximab-sensitive cell lines (RSCL), rituximab-resistant cell lines (RRCL), ofatumumab-exposed cell lines (OECLs), primary lymphoma cells, and a lymphoma xenograft model. RRCL and OECL were generated by repeated exposure of sensitive cells to escalating doses of rituximab or ofatumumab?±?human serum. Antibody-dependent cellular cytotoxicity (ADCC) and complement-mediated cytotoxicity (CMC) assays were performed to assess cellular sensitivity to rituximab or ofatumumab. Ofatumumab elicited a higher rate of CMC in RSCL, RRCL and primary tumour cells. The chronic exposure of lymphoma cells to ofatumumab resulted in rituximab resistance but less ofatumumab resistance. In an in vivo severe combined immunodeficiency mouse model of human lymphoma, ofatumumab prolonged median survival compared to rituximab. While rituximab CMC diminished with CD20 down-regulation in RRCL passages, ofatumumab activity in vitro diminished to a lesser degree. Our data suggest that ofatumumab is more potent than rituximab in rituximab-sensitive or rituximab-resistant models and has the potential to decrease the development of biological resistance in patients with repeated exposure to anti-CD20 mAbs. PMID:22150234

Barth, Matthew J; Hernandez-Ilizaliturri, Francisco J; Mavis, Cory; Tsai, Ping-Chiao; Gibbs, John F; Deeb, George; Czuczman, Myron S

2012-02-01

213

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

214

Gene expression changes induced by skin sensitizers in the KeratinoSens™ cell line: Discriminating Nrf2-dependent and Nrf2-independent events.  

PubMed

The KeratinoSens™ assay is an in vitro screen for the skin sensitization potential of chemicals. It is based on a luciferase reporter gene under the control of the antioxidant response element of the aldoketoreductase gene AKR1C2. The transferability, reproducibility, and predictivity of the KeratinoSens™ assay have been investigated in detail and it is currently under assessment at the European Center for Validation of Alternatives to animal testing (ECVAM). Here we investigate the sensitizer-induced gene expression in the KeratinoSens™ cell line at the mRNA level and discriminate Nrf2-dependent and Nrf2-independent events by using siRNA to better characterize this test system at the molecular level. The results show that (i) the sensitizer-induced luciferase signal in KeratinoSens™ cells is completely dependent on Nrf2. The same holds true for the luciferase induction observed for the false positive chemical Tween80, indicating that the false positive result is not due to recruitment of an alternative transcription factor. (ii) Luciferase induction parallels the induction of endogenous Nrf2-dependent genes, indicating that the luciferase signal is representative for the sensitizer-induced Nrf2-response. (iii) The induction by sensitizers of additional genetic markers related to heat shock proteins and cellular stress could be reproduced in the KeratinoSens™ cell line and they were shown to be Nrf2-independent. These results confirm that the KeratinoSens™ cell line is a rapid and adequate screening tool to assess the sensitizer-induced Nrf2-response in keratinocytes. PMID:24055896

Emter, Roger; van der Veen, Jochem W; Adamson, Greg; Ezendam, Janine; van Loveren, Henk; Natsch, Andreas

2013-12-01

215

ErbB3 expression predicts sensitivity to elisidepsin treatment: in vitro synergism with cisplatin, paclitaxel and gemcitabine in lung, breast and colon cancer cell lines.  

PubMed

Irvalec® (elisidepsin trifluoroacetate, PM02734) is a novel marine-derived cyclic peptide belonging to the Kahaladide family of compounds, currently in clinical trials with preliminary evidence of antitumor activity. Previous studies have shown a correlation between elisidepsin sensitivity and expression of the ErbB3 receptor in a panel of NSCLC cell lines. We have studied the effect of elisidepsin on the ErbB3 pathway, characterizing the expression of all members of the ErbB (HER) family of receptors and their main downstream signaling effectors, such as Akt and MAPK. Interestingly, we observed a downregulation of ErbB3 upon elisidepsin treatment that correlates with a reduction in the Akt phosphorylation levels in the most sensitive cell lines, whereas ErbB3 levels are not affected in the less sensitive ones. Also, we observed that the basal levels of ErbB3 protein expression show a significant correlation with cell viability response against elisidepsin treatment in 14 different cell lines. Furthermore, we analyzed the combination of elisidepsin with different chemotherapeutics agents, such as cisplatin, paclitaxel and gemcitabine, in a panel of different breast (MDA-MB-435, MDA-MB-231 and MCF7), lung (HOP62, DV90 and A549) and colorectal cancer cell lines (DLD1 and HT29). IC50 values for the different drugs were tested. We observed a synergistic effect in all cell lines tested with any chemotherapeutic agent. More importantly, the two in vitro elisidepsin-resistant cell lines (MDA-MB-231 and HOP62) presented a synergistic effect in combination with cisplatin and paclitaxel, respectively. These results provide a rationale for further development of these combinations in an ongoing clinical trial. PMID:22485250

Teixidó, Cristina; Arguelaguet, Elisabet; Pons, Berta; Aracil, Miguel; Jimeno, Jose; Somoza, Rosa; Marés, Roso; Ramón Y Cajal, Santiago; Hernández-Losa, Javier

2012-07-01

216

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

217

Effects of residue background events in direct dark matter detection experiments on the reconstruction of the velocity distribution function of halo WIMPs  

NASA Astrophysics Data System (ADS)

In our earlier work on the development of a model-independent data analysis method for reconstructing the (moments of the) time-averaged one-dimensional velocity distribution function of Weakly Interacting Massive Particles (WIMPs) by using measured recoil energies from direct Dark Matter detection experiments directly, it was assumed that the analyzed data sets are background-free, i.e., all events are WIMP signals. In this article, as a more realistic study, we take into account a fraction of possible residue background events, which pass all discrimination criteria and then mix with other real WIMP-induced events in our data sets. Our simulations show that, for the reconstruction of the one-dimensional WIMP velocity distribution, the maximal acceptable fraction of residue background events in the analyzed data set(s) of Script O(500) total events is ~ 10%-20%. For a WIMP mass of 50 GeV with a negligible uncertainty and 20% residue background events, the deviation of the reconstructed velocity distribution would in principle be ~ 7.5% with a statistical uncertainty of ~ 18% ( ~ 19% for a background-free data set).

Shan, Chung-Lin

2010-06-01

218

Effects of the herbicide isopropyl-N-phenyl carbamate on microtubules and MTOCs in lines of Nicotiana sylvestris resistant and sensitive to its action.  

PubMed

To clarify the mechanism of isopropyl-N-phenyl carbamate (IPC) action on higher plant cells the sensitivity of microtubules (cortical network and mitotic arrays) and microtubule organizing centers to IPC treatment (30 microM) in IPC-resistant and sensitive Nicotiana sylvestris lines was studied. It was clearly demonstrated that IPC does not depolymerize plant MTs but causes the MTOC damage in cells, which results in MTOC fragmentation, splitting of the spindle poles and in abnormal division spindle formation. It was also found that IPC-resistance of mutant N. sylvestris line correlates not with tubulin resistance to IPC action but possibly with resistance of one of the proteins involved in MTOC composition. PMID:18343166

Yemets, Alla; Stelmakh, Oksana; Blume, Yaroslav B

2008-06-01

219

Exogenous cell-permeable C6 ceramide sensitizes multiple cancer cell lines to Doxorubicin-induced apoptosis by promoting AMPK activation and mTORC1 inhibition  

Microsoft Academic Search

New chemotherapy-enhancing strategies are needed for better cancer therapy. Previous studies suggest that exogenous cell-permeable C6 ceramide may be a useful adjunct to the anti-tumor effects of chemotherapeutic agents (such as Taxol) against multiple cancers. Here we demonstrate that exogenous cell-permeable C6 ceramide largely sensitizes multiple progressive cancer cell lines to Doxorubicin-induced cell death and apoptosis. We found for the

C Ji; B Yang; Y-L Yang; S-H He; D-S Miao; L He; Z-G Bi

2010-01-01

220

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

Microsoft Academic Search

We have measured polarized resonance Raman spectra of nickel(II)octaethylporphyrin in CSâ and CHâClâ solution at different excitation wavelengths (430-580nm) and temperatures (190-130 K). The analysis of the spectra revealed that the structure-sensitive Raman lines vââ and vââ can be decomposed consistently into two sublines for all excitation wavelengths and temperatures. In the resonance region of the Q{sub O} and Q{sub

Walter Jentzen; Esko Unger; Gerasimos Karvounis; W. Dreybrodt; R. Schweitzer-Stenner; J. A. Shelnutt

1996-01-01

221

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

Microsoft Academic Search

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

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

2007-01-01

222

Genome-wide transcriptomic analysis of response to low temperature reveals candidate genes determining divergent cold-sensitivity of maize inbred lines.  

PubMed

Maize, despite being thermophyllic due to its tropical origin, demonstrates high intraspecific diversity in cold-tolerance. To search for molecular mechanisms of this diversity, transcriptomic response to cold was studied in two inbred lines of contrasting cold-tolerance. Microarray analysis was followed by extensive statistical elaboration of data, literature data mining, and gene ontology-based classification. The lines used had been bred earlier specifically for determination of QTLs for cold-performance of photosynthesis. This allowed direct comparison of present transcriptomic data with the earlier QTL mapping results. Cold-treated (14 h at 8/6 °C) maize seedlings of cold-tolerant ETH-DH7 and cold-sensitive ETH-DL3 lines at V3 stage showed strong, consistent response of the third leaf transcriptome: several thousand probes showed similar, statistically significant change in both lines, while only tens responded differently in the two lines. The most striking difference between the responses of the two lines to cold was the induction of expression of ca. twenty genes encoding membrane/cell wall proteins exclusively in the cold-tolerant ETH-DH7 line. The common response comprised mainly repression of numerous genes related to photosynthesis and induction of genes related to basic biological activity: transcription, regulation of gene expression, protein phosphorylation, cell wall organization. Among the genes showing differential response, several were close to the QTL regions identified in earlier studies with the same inbred lines and associated with biometrical, physiological or biochemical parameters. These transcripts, including two apparently non-protein-coding ones, are particularly attractive candidates for future studies on mechanisms determining divergent cold-tolerance of inbred maize lines. PMID:24623520

Sobkowiak, Alicja; Jo?czyk, Maciej; Jarochowska, Emilia; Biecek, Przemys?aw; Trzcinska-Danielewicz, Joanna; Leipner, Jörg; Fronk, Jan; Sowi?ski, Pawe?

2014-06-01

223

High IGF-IR activity in triple-negative breast cancer cell lines and tumorgrafts correlates with sensitivity to anti-IGF-IR therapy  

PubMed Central

Purpose We previously reported an IGF gene expression signature, based upon genes induced or repressed by IGF-I, which correlated with poor prognosis in breast cancer. We tested if the IGF signature was affected by anti-IGF-IR inhibitors, and if the IGF signature correlated with response to a dual anti-IGF-IR/InsR inhibitor BMS-754807. Experimental Design An IGF gene expression signature was examined in human breast tumors and cell lines, and changes noted following treatment of cell lines or xenografts with anti-IGF-IR antibodies or tyrosine kinase inhibitors. Sensitivity of cells to BMS-754807 was correlated with levels of the IGF signature. Human primary tumorgrafts were analyzed for the IGF signature and IGF-IR levels and activity, and MC1 tumorgrafts treated with BMS-754807 and chemotherapy. Results The IGF gene expression signature was reversed in three different models (cancer cell lines or xenografts) treated with three different anti-IGF-IR therapies. The IGF signature was present in triple-negative breast cancers (TNBC) and TNBC cell lines. TNBC cell lines were especially sensitive to BMS-754807, and sensitivity was significantly correlated to expression of the IGF gene signature. The TNBC primary human tumorgraft MC1 showed high levels of both IGF-IR expression and activity, and IGF gene signature score. Treatment of MC1 with BMS-754807 showed growth inhibition and in combination with docetaxel tumor regression occurred until no tumor was palpable. Regression was associated with reduced proliferation, increased apoptosis, and mitotic catastrophe. Conclusion These studies provide a clear biological rationale to test anti-IGF-IR/InsR therapy in combination with chemotherapy in patients with TNBC.

Litzenburger, Beate C.; Creighton, Chad J.; Tsimelzon, Anna; Chan, Bonita T.; Hilsenbeck, Susan G.; Wang, Tao; Carboni, Joan M.; Gottardis, Marco M.; Huang, Fei; Chang, Jenny C.; Lewis, Michael T.; Rimawi, Mothaffar F.; Lee, Adrian V.

2010-01-01

224

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

PubMed Central

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

2012-01-01

225

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

SciTech Connect

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

Wu Mei [Department of Environmental Health, Sichuan University, West China School of Public Health, Chengdu (China); Zhang Zunzhen [Department of Environmental Health, Sichuan University, West China School of Public Health, Chengdu (China)], E-mail: zhangzunzhen@163.com; Che Wangjun [Department of Environmental Health, Sichuan University, West China School of Public Health, Chengdu (China)

2008-05-01

226

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

National Technical Information Service (NTIS)

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

C. A. Bigelow

1986-01-01

227

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

NASA Technical Reports Server (NTRS)

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

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

1991-01-01

228

In-line highly sensitive hydrogen sensor based on palladium-coated single-mode tapered fibers  

Microsoft Academic Search

We report a fiber-optic sensor for detecting low concentrations of hydrogen. The sensor is based on the absorption change of the evanescent fields in a Pd-coated, single-mode tapered fiber. We fabricated a collection of polarization-sensitive and polarization-insensitive devices and we studied the effect of the different parameters on the sensitivity of the device. We found that the sensor's response is

Joel Villatoro; Antonio Díez; José L. Cruz; Miguel V. Andrés

2003-01-01

229

Sensitivity of Non-Small-Cell Lung Cancer Cell Lines Established from Patients Treated with Prolonged Infusions of Paclitaxel  

Microsoft Academic Search

Objective: Regimens with prolonged infusions of taxanes have been developed for patients with cancer to overcome drug resistance. Our objective of the present study was to examine the impact of prolonged exposure on the cytotoxicity of taxanes against non-small-cell lung carcinoma (NSCLC) cell lines and the clinical response and outcome of the patients. Methods: Five cell lines (NCI-H2882, -H2887, -H2973,

Takashi Fujishita; Massimo Loda; Ross E. Turner; Marinshine Gentler; Tatsuhiko Kashii; Oscar S. Breathnach; Bruce E. Johnson

2003-01-01

230

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

Microsoft Academic Search

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

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

2004-01-01

231

The histone deacetylase inhibitor valproic acid sensitizes diffuse large B-cell lymphoma cell lines to CHOP-induced cell death  

PubMed Central

Epigenetic code modifications by histone deacetylase inhibitors (HDACis) have recently been proposed as potential new therapies for hematological malignancies. Diffuse large B-cell lymphoma (DLBCL) is the most common form of aggressive lymphoma. At present, standard first line treatment for DLBCL patients is the antracycline-based chemotherapy regimen CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) combined with the monoclonal anti-CD20 antibody rituximab (R-CHOP). Since only 50-60% of patients reach a long-time cure by this treatment, there is an urgent need for novel treatment strategies to increase the response and long-term remission to initial R-CHOP therapy. In this study, we investigated the effect of the HDAC inhibitor valproic acid (VPA) on DLBCL cell lines. To elucidate the effects of VPA on chemo-sensitivity, we used a cell-line based model of CHOP-refractory DLBCL. All five DLBCL cell lines treated with VPA alone or in combination with CHOP showed decreased viability and proliferation. The VPA-induced sensitization of DLBCL cells to cytotoxic treatment resulted in increased number of apoptotic cell as judged by annexin V-positivity and the presence of cleaved caspase-3. In addition, pretreatment with VPA resulted in a significantly increased DNA-damage as compared to CHOP alone. In summary, HDAC inhibitors such as VPA, are promising therapeutic agents in combination with R-CHOP for patients with DLBCL.

Ageberg, Malin; Rydstrom, Karin; Relander, Thomas; Drott, Kristina

2013-01-01

232

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

SciTech Connect

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

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

2005-07-01

233

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

SciTech Connect

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

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

2011-01-14

234

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

235

Inherent Sensitivity and Induced Resistance to Chemotherapeutic Drugs and Irradiation in Human Cancer Cell Lines: Relationship to Mutation Frequencies  

Microsoft Academic Search

Metastatic nonseminomatous testicular germ cell tumors are curable using combination chemotherapy in approximately 80% of patients. In contrast, most other patients with other types of cancer either present with or acquire drug-resistant disease followingchemotherapy. Cell lines derived from testis tumors retain hypersensitivity to both drugs and radiation in vitro, thus providinga model system with which to investigate the genetic basis

Christopher N. Harris; M. Claire Walker; John R. VV; Colin F. Arlett

1990-01-01

236

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

PubMed Central

High-risk neuroblastoma (NB) has a poor prognosis. Even with intensive myeloablative chemotherapy, relapse is common and almost uniformly fatal, and new treatments are needed. Translocator protein 18kDa (TSPO) ligands have been studied as potential new therapeutic agents in many cancers, but not in NB. We studied the effects of TSPO ligands on cell proliferation, cell cycle progression and apoptosis using paired cell lines derived from the same patient at the time of initial surgery and again after development of progressive disease or relapse post-chemotherapy. We found that TSPO expression was significantly increased 2- to 10-fold in post-relapse cell lines compared with pre-treatment lines derived from the same individual. Subsequently, these cell lines were treated with the specific TSPO ligand 1-(2-chlorophenyl-N-methylpropyl)-3-isoquinolinecarboxamide (PK11195) (0–160µM) as a single agent, with cytotoxic chemotherapy agents alone (carboplatin, etoposide or melphalan), or with combinations of PK11195 and chemotherapy drugs. We found that PK11195 inhibited proliferation in a dose-dependent manner, induced apoptosis and caused G1/S cell cycle arrest in all tested NB cell lines at micromolar concentrations. In addition, PK11195 significantly decreased mRNA expression of the chemotherapy resistance efflux pumps ABCA3, ABCB1 and ABCC1 in two post-relapse NB cell lines. We also found that pre-treatment with PK11195 sensitized these cell lines to treatment with cytotoxic chemotherapy agents. These results suggest that PK11195 alone or in combination with standard chemotherapeutic drugs warrants further study for the treatment of neuroblastoma.

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

2013-01-01

237

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

NASA Astrophysics Data System (ADS)

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

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

2013-10-01

238

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

Microsoft Academic Search

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

Scott M. Stoeger; Kenneth H. Cowan

2009-01-01

239

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

Microsoft Academic Search

Increased expression of manganese superoxide dismutase (Mn-SOD), one of the mitochondrial enzymes involved in the redox system, has been shown to diminish the cytotoxic effects of several anti-cancer modalities, including tumour necrosis factor-?, ionizing radiation, certain chemotherapeutic agents and hyperthermia. We asked if Mn-SOD is a potential target to augment the sensitivity of cancer cells to various anti-cancer treatments and

S Kuninaka; Y Ichinose; K Koja; Y Toh

2000-01-01

240

Elevated expression of Dickkopf-1 increases the sensitivity of human glioma cell line SHG44 to BCNU  

Microsoft Academic Search

BACKGROUND: Studies have shown that Dickkopf-1 (DKK-1) is involved in tumorigenesis. Recently, we found that 9 out of 12 human glioma cell lines had high level of DKK-1 protein while the other 3 had very low or non-detectable level of DKK-1. The aim of this study is to further examine the function of DKK-1 in glioma cells. MATERIALS AND METHODS:

Youxin Zhou; Wenshuai Li; Qinian Xu; Yulun Huang

2010-01-01

241

Heating, Moisture, and Water Budgets of Tropical and Midlatitude Squall Lines: Comparisons and Sensitivity to Longwave Radiation  

Microsoft Academic Search

A two-dimensional, time-dependent, nonhydrostatic numerical cloud model is used to estimate the heating (Q[sub 1]), moisture (Q[sub 2]), and water budgets in the convective and stratiform regions for a tropical and a midlatitude squall line (EMEX and PRE-STORM). The model is anelastic and includes a parameterized three-class ice-phase microphysical scheme and longwave radiative transfer processes. A quantitative estimate of the

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

1993-01-01

242

Patterns of intermediate filaments, VLA integrins and HLA antigens in a new human biliary epithelial cell line sensitive to interferon-?  

Microsoft Academic Search

Background\\/Aims: Intra-hepatic bile ducts are the primary site of damage in several immunologically mediated liver diseaes. However, immunological processes underlying biliary epithelial cell recognition by T lymphocytes are poorly understood. Therefore, a convenient in vitro model that could mimic these immunologic disorders would be of great interest.Methods: A human cell line (HuGB) was established from a metastasis of gallbladder adenocarcinoma

Sylvie Rumin; Olivier Loréal; Bernard Drénou; Bruno Turlin; Maryvonne Rissel; Jean-Pierre Campion; Philippe Gripon; Alastair J. Strain; Bruno Clément; Cristiane Guguen-Gauillouzo

1997-01-01

243

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

244

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

245

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

PubMed Central

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

Laurencon, A.; Bregliano, J. C.

1995-01-01

246

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

247

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

PubMed

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

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

2009-08-01

248

Increased sensitivity of human lymphoid lines to natural killer cells after induction of the Epstein-Barr viral cycle by superinfection or sodium butyrate  

PubMed Central

Superinfection of latently Epstein-Barr virus (EBV)-carrying Raji cells with the P3HR-1 substrain EBV, known to induce the entry of a substantial fraction of cells into an abortively lytic cycle, increased the susceptibility of the cells to natural killer (NK) effect of human blood lymphocytes. Reciprocal cold-target competition tests with known NK-cell sensitive and -resistant lymphoid cell ines showed that the increased susceptibility is a result of the appearance of an NK- sensitive target, rather than to a general increase in membrane fragility. Lymphocytes of EBV-seropositive and -negative donors were equally effective killers against P3HR-1 virus-superinfected targets. EBV-induced NK sensitivity increased with time. It was a result of some event associated with the intracellular viral cycle, and not to the adherence of viral particles to the cell surface. Induction of EBV- carrying P3HR-1 cells to entry into the viral cycle with n-butyrate also increased their NK sensitivity. A transforming, noncytopathic prototype strain of EBV, B95-8, failed to increase the susceptibility of theRaji cells to NK-lysis, although it had some effect on the Daudi line. Because NK cells can kill virus-producing cells at an early stage of the cycle, before the virus particles are assembled, they may restrict, in vivo, the spread of the virus from latently infected cells.

1980-01-01

249

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

SciTech Connect

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

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

1982-03-01

250

Different vimentin expression in two clones derived from a human colocarcinoma cell line (LoVo) showing different sensitivity to doxorubicin.  

PubMed Central

We selected two clones, isolated from the human colocarcinoma cell line LoVo, showing a sensitivity to doxorubicin similar to (LoVo clone 5) or three times lower than (LoVo clone 7) the parental cell line. Since vimentin was atypically expressed in a human breast carcinoma cell line made resistant to doxorubicin, we looked at vimentin expression in these two clones with spontaneously different sensitivity to the drug. For comparison we used the parental cell line LoVo WT and LoVo/DX made resistant pharmacologically. mRNA for vimentin was undetectable by Northern blot analysis in LoVo WT and in LoVo clone 5, while expression of this gene was high in LoVo clone 7 and in LoVo/DX. This increase in mRNA levels was not related to an amplification of DNA, as suggested by Southern blot analysis. Immunofluorescence and immunocytochemistry findings confirmed, at protein level, the mRNA data. In LoVo clones 5 and 7, there were respectively 8.6% and 71% vimentin-positive cells, although the two clones showed similar expression of multidrug resistance gene 1 (mdr-1) and accumulated intracellular doxorubicin at similar levels. Similarly, drug efflux was the same for both clones. Our results show for the first time that cells resistant to doxorubicin express vimentin independently of the mdr glycoprotein. However when cells from clone 5 were transfected with human vimentin cDNA, they did not become resistant, indicating that vimentin can be considered as a marker of resistance in these cells but does not give rise to a resistant phenotype by itself. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5

Conforti, G.; Codegoni, A. M.; Scanziani, E.; Dolfini, E.; Dasdia, T.; Calza, M.; Caniatti, M.; Broggini, M.

1995-01-01

251

Lymphoblastoid Cell lines: a Continuous in Vitro Source of Cells to Study Carcinogen Sensitivity and DNA Repair  

PubMed Central

Obtaining a continuous source of normal cells or DNA from a single individual has always been a rate limiting step in biomedical research. Availability of Lymphoblastoid cell lines (LCLs) as a surrogate for isolated or cryopreserved peripheral blood lymphocytes has substantially accelerated the process of biological investigations. LCLs can be established by in vitro infection of resting B cells from peripheral blood with Epstein Barr Virus (EBV) resulting in a continuous source, bearing negligible genetic and phenotypic alterations. Being a spontaneous replicating source, LCLs fulfil the requirement of constant supply of starting material for variety of assays, sparing the need of re-sampling. There is a reason to believe that LCLs are in close resemblance with the parent lymphocytes based on the ample supporting observations from a variety of studies showing significant level of correlation at molecular and functional level. LCLs, which carry the complete set of germ line genetic material, have been instrumental in general as a source of biomolecules and a system to carry out various immunological and epidemiological studies. Furthermore, in recent times their utility for analysing the whole human genome has extensively been documented. This proves the usefulness of LCLs in various genetic and functional studies. There are a few contradictory reports that have questioned the employment of LCLs as parent surrogate. Regardless of some inherent limitations LCLs are increasingly being considered as an important resource for genetic and functional research.

Hussain, Tabish; Mulherkar, Rita

2012-01-01

252

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

253

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.

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

2013-01-01

254

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

NASA Technical Reports Server (NTRS)

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

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

1993-01-01

255

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

256

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

PubMed

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

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

2008-10-31

257

Activation of the simian virus 40 (SV40) genome abrogates sensitivity to AVP in a rabbit collecting tubule cell line by repressing membrane expression of AVP receptors  

PubMed Central

To analyze the role of SV40 genome in the phenotypic alterations previously observed in SV40-transformed cell lines, we infected rabbit renal cortical cells with a temperature-sensitive SV40 mutant strain (tsA58) and compared the cell phenotypes at temperatures permissive (33 degrees C) and restrictive (39.5 degrees C) for SV40 genome expression. At both temperatures, the resulting cell line (RC.SVtsA58) expresses cytokeratin and uvomorulin, but epithelial differentiation is more elaborate at 39.5 degrees C as shown by the formation of a well- organized cuboidal monolayer with numerous tight junctions and desmosomes. Functional characteristics are also markedly influenced by the culture temperature: cells grown at 33 degrees C respond only to isoproterenol (ISO, 10(-6) M) by a sevenfold increase in cAMP cell content above basal values; in contrast, when transferred to 39.5 degrees C, they exhibit increased sensitivity to ISO (ISO/basal: 19.1) and a dramatic response to 10(-7) M dDarginine vasopressin (dDAVP/basal: 18.2, apparent Ka: 5 X 10(-9) M) which peaks 48 h after the temperature shift. The latter is associated with membrane expression of V2-type AVP receptors (approximately 50 fmol/10(6) cells) which are undetectable when SV40 genome is activated (33 degrees C). Clonal analysis, additivity studies, and desensitization experiments argue for the presence of a single cell type responsive to both AVP and ISO. The characteristics of the RC. SVtsA58 cell line at 39.5 degrees C (effector-stimulated cAMP profile, lack of expression of brush-border hydrolases and Tamm-Horsfall protein) suggest that it originates from the cortical collecting tubule, and probably from principal cells.

1991-01-01

258

The proliferative effect of "anti-androgens" on the androgen-sensitive human prostate tumor cell line LNCaP.  

PubMed

The effect of steroidal and nonsteroidal "anti-androgens" on the proliferative capacity of androgen-sensitive LNCaP-FGC human prostate tumor cells in culture was studied using charcoal-dextran stripped human serum-supplemented media. Cyproterone and medroxyprogesterone acetates, flutamide, hydroxyflutamide, and anandron (R23908) were administered alone at concentrations between 3 X 10(-12) and 3 X 10(-6) M. Results indicated that although medroxyprogesterone induced maximal proliferation at 3 X 10(-9) M, the other "anti-androgens" (with the exception of flutamide that was ineffective) were effective at 3 X 10(-8) M and higher concentrations; the amplitude of the proliferative response by these compounds was comparable to that elicited by estradiol-17 beta (3 to 5-fold over control). None of the anti-androgens tested triggered the shutoff effect characteristic of androgen action. When 3 X 10(-10) M DHT and the above mentioned anti-androgens were administered simultaneously, a synergistic pattern was seen; on the contrary, 3 X 10(-8) M DHT cancelled the proliferative effect of each of the anti-androgens when administered simultaneously. The relative binding affinity of these anti-androgens to androgen receptors present in LNCaP-FGC cells did not correlate well with their proliferative efficiency. The data collected were interpreted within the premises of the negative control hypotheses for the regulation of cell proliferation in metazoans. Within those premises, results became compatible with the notion that first, "anti-androgens" elicited the proliferation of androgen-sensitive cells by neutralizing the effect of a serum-borne inhibitor (androcolyone-I); this event seems not to be mediated by androgens receptors. Second, anti-androgens did not trigger a proliferative shutoff response like androgens do, i.e. the proliferative pattern induced by anti-androgens was comparable to that elicited by estrogens and progestins. Third, when administered simultaneously with 3 X 10(-10) M DHT, anti-androgens behaved synergistically. Fourth, the DHT-induced shutoff effect consistently overrode the proliferative effect generated by anti-androgens and estrogens when added alone. Finally, taken together these results raise important questions regarding the therapeutic role of anti-androgens in prostate cancer. PMID:2307113

Olea, N; Sakabe, K; Soto, A M; Sonnenschein, C

1990-03-01

259

Altered p53 status correlates with differences in sensitivity to radiation-induced mutation and apoptosis in two closely related human lymphoblast lines.  

PubMed

Previous work identified TK6 and WTK1 as human lymphoblast cell lines from one donor that have different capacities to catalyze recombination and that vary significantly in their response to ionizing radiation. WTK1 cells are more resistant to the toxic effects of X-rays yet more sensitive to induced mutation. We demonstrate here that although both cell lines contain equal levels of p53 mRNA, baseline protein levels are 4 times higher in WTK1. Irradiation leads to higher levels of p53 protein in both lines but to a greater extent in TK6. TK6 contains a wild-type p53 sequence, while WTK1 has a homozygous mutation in codon 237 of exon 7. We also observed a significant difference in the kinetics but not the overall degree of apoptosis induced by X-rays in these cells; apoptotic death is delayed for 3 days in WTK1. We hypothesize that this p53 mutation is responsible for the difference in apoptosis as well as for the differences in mutability and mutational spectra reported previously. PMID:7805021

Xia, F; Wang, X; Wang, Y H; Tsang, N M; Yandell, D W; Kelsey, K T; Liber, H L

1995-01-01

260

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

261

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

SciTech Connect

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

Chin, H.-N.S.

1996-04-01

262

Organosulfur derivatives of the HDAC inhibitor valproic acid sensitize human lung cancer cell lines to apoptosis and to cisplatin cytotoxicity.  

PubMed

Lung cancer is the leading cause of cancer mortality worldwide and despite efforts made to improve clinical results, continuing poor survival rates indicate that novel therapeutic approaches are needed. Valproic acid (VPA), a short-chain branched fatty acid used mainly for the treatment of epilepsy and bipolar disorder, has been shown to inhibit class I histone deacetylases (HDAC-I), a group of enzymes involved in chromatin remodeling and which are thought to play a role in tumor development. Although evidence of VPA's therapeutic efficacy has also been observed in patients with solid tumors, the very high concentration required to induce antitumor activity limits its clinical usefulness. We used a panel of NSCLC cell lines to evaluate the activity and mechanisms of action of organosulfur valproic acid derivatives, a promising new class of compounds designed to improve the safety and efficacy of the valproic acid molecule and created by coupling it with a hydrogen sulfide (H(2) S)-releasing moiety. Our results highlighted the increased cytotoxic activity of the novel organosulfur derivatives, ACS33 and ACS2, with respect to VPA, starting from low concentrations. In particular, ACS2 exhibited important pro-apoptotic activity triggered by the mitochondrial pathway and also showed anti-invasion potential. Furthermore, our in vitro results identified a highly effective combination schedule of ACS2 and cisplatin capable of inducing a synergistic interaction even when the two drugs were used at low concentrations, which could prove a valid alternative to traditional chemotherapeutic regimens used for advanced lung cancer. Further studies are needed to confirm these preliminary findings. PMID:22212895

Tesei, Anna; Brigliadori, Giovanni; Carloni, Silvia; Fabbri, Francesco; Ulivi, Paola; Arienti, Chiara; Sparatore, Anna; Del Soldato, Piero; Pasini, Alice; Amadori, Dino; Silvestrini, Rosella; Zoli, Wainer

2012-10-01

263

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

PubMed

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

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

2013-10-01

264

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

PubMed Central

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

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

2013-01-01

265

Gene-specific repair of Pt\\/DNA lesions and induction of apoptosis by the oral platinum drug JM216 in three human ovarian carcinoma cell lines sensitive and resistant to cisplatin  

Microsoft Academic Search

JM216, an oral platinum drug entering into phase III clinical trial, exhibited comparable cytotoxicity to cisplatin in three human ovarian carcinoma cell lines: the sensitive (CH1), acquired resistant (CH1cisR) and intrinsically resistant (SKOV-3). Platinum accumulation and binding to DNA were similar in each of the three cell lines at equimolar doses, indicating that the resistant cell lines could tolerate higher

C F O'Neill; B Koberle; J R W Masters; L R Kelland

1999-01-01

266

Establishment and characterization of UM-EC-2, a tamoxifen-sensitive, estrogen receptor-negative human endometrial carcinoma cell line.  

PubMed

UM-EC-2 was established from a patient with poorly differentiated stage IB endometrial carcinoma. This cell line produces tumors in nude mice that have the same histological features as the patient's tumor. UM-EC-2 cells express b2-microglobulin, the epidermal growth factor receptor (EGF), and the H blood group antigen. This membrane antigen phenotype is consistent with cells of human endometrial origin. The karyotype of UM-EC-2 is fairly complex, with rearrangements affecting all chromosomes except 3, 10, 14, 19, and 20. There were two populations of cells, a hyperdiploid population with a modal number of 53-55 and a hypertetraploid population with a modal number of 109. A postulated sequence of events before and after tetraploidization is suggested based on the number of copies of individual chromosomes and rearrangements. Comparison of the UM-EC-2 karyotype to that of UM-EC-1 (a previously described line from a different patient with endometrial carcinoma) revealed that the two lines share eight very similar chromosome changes, which include loss of most of chromosome 4, breakpoints affecting proximal bands on 8p, loss of most of 9q, a breakpoint at 12q22, loss of 13q, breakpoints in proximal bands on 18q, and a breakpoint at 22p11. These changes may represent nonrandom chromosome abnormalities in poorly differentiated endometrial cancer. Estrogen (ER) and progesterone (PgR) receptors were not detected in either the primary tumor or the cell line. Nevertheless, UM-EC-2 cells were very sensitive to growth inhibition by tamoxifen (TAM) in vitro. One micromolar TAM caused 50% inhibition of cell growth, 2.5 microM caused cytostasis, and 5 microM TAM was cytotoxic, killing all cells after 5-7 days of exposure to the drug. Paradoxically, 100 nM estradiol (E2) caused a moderate increase in the growth of the cells but it did not prevent or reverse growth inhibitory effects of TAM. These findings support the concept that in some tumors TAM causes growth inhibition by an ER-independent mechanism. UM-EC-2 cells were also sensitive to growth regulation by EGF. Thus, these cells provide a new in vitro model of human endometrial cancer in which the roles of both TAM and EGF as growth regulatory substances can be investigated. PMID:2344964

Grenman, S E; Worsham, M J; Van Dyke, D L; England, B; McClatchey, K D; Babu, V R; Roberts, J A; Mäenpää, J; Carey, T E

1990-05-01

267

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

PubMed

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

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

2013-11-22

268

[Glutathione levels in human colon cancer cell line M7609 following culture in a low sulfur amino acid medium and its sensitivity to various anticancer drugs].  

PubMed

Glutathione levels in human colon cancer cell line M7609 and its sensitivity to anticancer drugs were investigated in a complete medium RPMI-1640 (medium A) and an incomplete medium (medium B), which was prepared by removing glutathione and sulfur amino acids from medium A. Four different medium conditions were prepared by combining a medium A and a medium B; a medium of 100% medium A (Control), a 50:50 mixture medium of medium A and medium B (Condition 2), a 20:80 mixture medium of medium A and medium B (Condition 3), and a 10:90 mixture medium of medium A and medium B (Condition 4). The cells were cultured in each medium for 14 days, and intracellular levels of glutathione were determined to estimate the cell sensitivity to anticancer drugs. There were no significant differences in glutathione levels among the cancer agents in condition 2, as compared to those in the control. In condition 3, the reduced glutathione levels were decreased to 23.1%, where CDDP, ADM, MMC and melphalane showed 2.5, 2.2, 1.8 and 1.5 times greater antitumor activity than in the control, respectively. In condition 4, cell proliferation was too low to collect adequate cells for glutathione determination. These results demonstrated that the decrease in cellular glutathione concentration with this method might enhance the cytotoxic effects of anticancer drugs. PMID:9170520

Saito, T; Ikeda, S; Hisai, H; Katahira, T; Kondo, H; Takahashi, Y; Takayama, T

1997-05-01

269

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

PubMed Central

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

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

2012-01-01

270

Downregulation of BRCA1 in A375 melanoma cell line increases radio-sensitivity and modifies metastatic and angiogenic gene expression.  

PubMed

The participation of BRCA1 (breast cancer 1) in DNA repair is well established, especially in mammary and ovarian cells. Our purpose was to develop a new in vivo radio-sensitizing therapy for melanoma. We therefore investigated the effect of downregulation of BRCA1 on irradiated melanoma cells using an anti-BRCA1 ribozyme. Our results show that BRCA1 downregulation increased radio-sensitivity of the A375 cell line, suggesting that BRCA1 could act as a caretaker in melanoma; however, as BRCA1 functions are not limited to maintaining genomic integrity but also regulate transcription and the cell cycle, we confirmed that the proliferative rate of BRCA1 downregulated clones did not change. We also demonstrate that: (1) among the major pro-angiogenic genes, FGF-2 was not increased before or after irradiation and vascular endothelial growth factor strongly inhibited after irradiation; (2) expression of two important metalloproteinases, matrix metalloproteinase 2 and 9, involved in melanoma metastasis were decreased before and after irradiation; (3) expression of their major inhibitor, tissue inhibitor of metalloproteinase, was mainly upregulated; and (4) that invasion of BRCA1 downregulated cells was modified. Together these data suggest that BRCA1 downregulation in melanoma cells did not make them more aggressive and could lead to new therapeutic strategies for this tumor, which is so difficult to control once metastasized. PMID:15009718

Hesling, Cédric; D'Incan, Michel; D'Incan, Chantal; Souteyrand, Pierre; Monboisse, Jean-Claude; Pasco, Sylvie; Madelmont, Jean-Claude; Bignon, Yves Jean

2004-02-01

271

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

PubMed

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

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

2012-01-01

272

Exogenous cell-permeable C6 ceramide sensitizes multiple cancer cell lines to Doxorubicin-induced apoptosis by promoting AMPK activation and mTORC1 inhibition.  

PubMed

New chemotherapy-enhancing strategies are needed for better cancer therapy. Previous studies suggest that exogenous cell-permeable C6 ceramide may be a useful adjunct to the anti-tumor effects of chemotherapeutic agents (such as Taxol) against multiple cancers. Here we demonstrate that exogenous cell-permeable C6 ceramide largely sensitizes multiple progressive cancer cell lines to Doxorubicin-induced cell death and apoptosis. We found for the first time that Doxorubicin induces AMP-activated protein kinase (AMPK) activation in a reactive oxygen species-dependent manner. Activation of AMPK contributes to Doxorubicin-induced cancer cell death and apoptosis. Inhibition of AMPK by small interfering RNA knockdown or a pharmacological inhibitor reduces Doxorubicin-induced cancer cell apoptosis, whereas AMPK activator AICAR enhances it. Importantly, we found that C6 ceramide largely enhances Doxorubicin-induced activation of AMPK, which leads to mTOR complex 1 inhibition and chemo-sensitization. Our data suggest that the combination of C6 ceramide with traditional chemotherapy drugs such as Doxorubicin may have the potential to be used as a new therapeutic intervention against multiple cancers. PMID:20802518

Ji, C; Yang, B; Yang, Y-L; He, S-H; Miao, D-S; He, L; Bi, Z-G

2010-12-16

273

Development of oral epithelial cell line ROE2 with differentiation potential from transgenic rats harboring temperature-sensitive simian virus40 large T-antigen gene.  

PubMed

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

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

2014-01-01

274

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

PubMed

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

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

2007-02-01

275

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

PubMed

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

Hindmarsh, Richard C A

2006-07-15

276

Influence of vitamin D on cisplatin sensitivity in testicular germ cell cancer-derived cell lines and in a NTera2 xenograft model.  

PubMed

The active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has anti-proliferative, pro-apoptotic, and pro-differentiating effects in somatic cancer cells in vitro and in vivo. 1,25(OH)2D3 also augments the anti-tumor effects of several chemotherapeutic agents, including cisplatin, which may have clinical relevance. Given the pro-differentiation effect of vitamin D recently demonstrated in testicular germ cell tumors (TGCTs), we hypothesized that 1,25(OH)2D3 could be a beneficial adjunctive to existing chemotherapy regime used to treat these tumors. In this study, cell survival effects of 1,25(OH)2D3, another pro-differentiation compound, retinoic acid and cisplatin were investigated in TGCT-derived cell lines in vitro. 1,25(OH)2D3 augmented the effect of cisplatin in an embryonal carcinoma-derived cell line (NTera2), possibly through downregulation of pluripotency genes and simultaneous upregulation of the cell cycle regulators p21, p27, p53, p73 and FOXO1, while no significant effects were found in TCam-2 and 2102Ep cell lines (derived from seminoma and embryonal carcinoma, respectively). Anti-tumor effects of cholecalciferol, 1,25(OH)2D3, and cisplatin were subsequently tested in vivo, in a NTera2 xenograft tumor model in nude mice. In xenograft tumors, co-treatment with 1,25(OH)2D3 and cisplatin resulted in downregulation of OCT4 and simultaneous upregulation of p21 and p73, but did not reduce tumor growth significantly more than cisplatin alone. Also, cholecalciferol supplemented diet (1100IU daily) after tumor formation did not increase cisplatin sensitivity in vivo. In conclusion, addition of 1,25(OH)2D3 augmented the antitumor effect of cisplatin monotherapy in vitro, but not in this in vivo testicular germ cell cancer model. Future studies are needed to investigate potential beneficial effects of vitamin D with lower cisplatin doses, and to determine whether 1,25(OH)2D3 may increase cisplatin sensitivity in chemotherapy-resistant TGCTs. This article is part of a Special Issue entitled 'Vitamin D Workshop'. PMID:23098692

Jørgensen, Anne; Blomberg Jensen, Martin; Nielsen, John Erik; Juul, Anders; Rajpert-De Meyts, Ewa

2013-07-01

277

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

SciTech Connect

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

Baltz, E.A.; Berenji, B.; /SLAC /KIPAC, Menlo Park; Bertone, G.; /Paris, Inst. Astrophys.; Bergstrom, L.; /Stockholm U.; Bloom, E.; /SLAC /KIPAC, Menlo Park; Bringmann, T.; /Stockholm U.; Chiang, J.; Cohen-Tanugi, J.; /SLAC /KIPAC, Menlo Park; Conrad, J.; /Stockholm U.; Edmonds, Y.; /SLAC /KIPAC, Menlo Park; Edsjo, J.; /Stockholm U.; Godfrey, G.; /SLAC /KIPAC, Menlo Park; Hughes, R.E.; /Ohio State U.; Johnson, R.P.; /UC, Santa Cruz; Lionetto, A.; /Rome U.,Tor Vergata /INFN, Rome2; Moiseev, A.A.; /CRESST; Morselli, A.; /Rome U.,Tor Vergata /INFN, Rome2; Moskalenko, I.V.; /Stanford U., HEPL /KIPAC, Menlo Park; Nuss, E.; /Montpellier U.; Ormes, J.F.; /Denver U.; Rando, R.; /INFN, Padua /Ohio State U. /Stockholm U. /Ohio State U. /Garching, Max Planck Inst., MPE /SLAC /KIPAC, Menlo Park /Ohio State U.

2009-05-15

278

Growth sensitivity of a recombinant simian virus 5 P/V mutant to type I interferon differs between tumor cell lines and normal primary cells.  

PubMed

A paramyxovirus SV5 mutant (rSV5-P/V-CPI-) that encodes 6 naturally-occurring P/V gene substitutions is a potent inducer of type I interferon (IFN) and is restricted for low moi growth, two phenotypes not seen with WT SV5. In this study, we have compared the IFN sensitivity of WT SV5 and the rSV5-P/V-CPI- mutant in tumor cell lines and in cultures of normal primary cells. We have tested the hypothesis that differences in IFN induction elicited by WT rSV5 and rSV5-P/V-CPI- are responsible for differences in low moi growth and spread. In contrast to WT SV5, low moi infection of A549 lung carcinoma cells with rSV5-P/V-CPI- resulted in a plateau of virus production by 24-48 h pi when secreted IFN levels were between approximately 100 and 1000 U/ml. Gene microarray and RT-PCR analyses identified IFN genes and IFN-stimulated genes whose expression were increased by infection of A549 cells with WT and P/V mutant viruses. Restricted low moi growth and spread of rSV5-P/V-CPI- in A549 cells was relieved in the presence of neutralizing antibodies to IFN-beta but not TNF-alpha. When A549 or MDA-MB-435 breast tumor cells were pretreated with IFN, both WT and P/V mutant viruses showed delayed spread and approximately 10-fold reduction in virus yield, but infections were not eliminated. Using normal primary human epithelial cells that have undergone limited passage in culture, WT rSV5 and rSV5-P/V-CPI- displayed high moi growth properties that were similar to that seen in A549 cells. However, IFN pretreatment of these primary cells as well as normal human lung cells eliminated low moi spread of both mutant and WT rSV5 infections. Together, these data demonstrate that SV5 growth in normal primary human cells is highly sensitive to IFN compared to growth in some tumor cell lines, regardless of whether the P/V gene is WT or mutant. These results suggest a model in which spread of WT SV5 in normal human cells is dependent on the ability of the virus to prevent IFN synthesis. The implications of these results for the use of recombinant paramyxoviruses as vectors are discussed. PMID:15823612

Wansley, Elizabeth K; Dillon, Patrick J; Gainey, Maria D; Tam, James; Cramer, Scott D; Parks, Griffith D

2005-04-25

279

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

PubMed Central

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

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

2013-01-01

280

Human mast cell line-1 (HMC-1) cells transfected with Fc?RI? are sensitive to IgE/antigen-mediated stimulation demonstrating selectivity towards cytokine production.  

PubMed

Mast cells play important roles in allergic and inflammatory diseases. Efforts to better understand human mast cell activation and develop novel inhibitory agents have been hampered by the lack of suitable human mast cell lines. The HMC-1 mast cell line has been extensively used, but lacks native expression of the human high-affinity IgE receptor Fc?RI limiting its applications. We have stably transfected HMC-1 cells with the IgE-binding ?-subunit of Fc?RI to generate HMC? cells that are antigen-responsive. We have used flow cytometry, cell signaling assays, pharmacological pathway inhibitors and cell functional assays to characterize the properties of HMC? cells. IgE/antigen responses were compared with those of the adenosine receptor agonist NECA. Surface expression of Fc?RI in HMC? cells was demonstrated and was enhanced by prior sensitization with IgE. Activation of HMC? cells with IgE/antigen did not produce degranulation, but did lead to release of numerous cytokines. Whilst there was no measurable increase of intracellular Ca(2+) or marked general changes in protein tyrosine phosphorylation, IgE/antigen stimulation of HMC? cells enhanced phosphorylation of p38(MAPK) and Erk. Inhibitors of these pathways, as well as the src kinase inhibitor PP2, attenuated IgE/antigen-induced cytokine release. In summary, we have generated and characterized HMC? cells and show that they are a useful and relevant human mast cell model to examine Fc?RI stabilization, signaling and mediator release. We envisage that HMC? cells will have utility in understanding the importance of mast cells in human allergic disease and in assessing the activity of novel anti-allergic compounds. PMID:21356342

Xia, YuXiu C; Sun, ShanShan; Kuek, Li Eon; Lopata, Andreas L; Hulett, Mark D; Mackay, Graham A

2011-08-01

281

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

SciTech Connect

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

Jentzen, W. [Universitaet Bremen (Germany)] [Universitaet Bremen (Germany); [Sandia National Lab., Albuquerque, NM (United States); Unger, E.; Karvounis, G.; Dreybrodt, W.; Schweitzer-Stenner, R. [Universitaet Bremen (Germany)] [Universitaet Bremen (Germany); Shelnutt, J.A. [Sandia National Lab., Albuquerque, NM (United States)] [Sandia National Lab., Albuquerque, NM (United States); [Univ. of New Mexico, Albuquerque, NM (United States)

1996-08-15

282

4-Oxo-Fenretinide, a Recently Identified Fenretinide Metabolite, Induces Marked G2-M Cell Cycle Arrest and Apoptosis in Fenretinide-Sensitive and Fenretinide-Resistant Cell Lines  

Microsoft Academic Search

Oxo-N-(4-hydroxyphenyl)retinamide (4-oxo-4-HPR) is a re- cently identified metabolite of fenretinide (4-HPR). We explored the effectiveness of 4-oxo-4-HPR in inducing cell growth inhibition in ovarian, breast, and neuroblastoma tumor cell lines; moreover, we investigated the molecular events mediating this effect in two ovarian carcinoma cell lines, one sensitive (A2780) and one resistant (A2780\\/HPR) to 4-HPR. 4-Oxo-4-HPR was two to four times

Maria Grazia Villani; Valentina Appierto; Elena Cavadini; Arianna Bettiga; Alessandro Prinetti; Margaret Clagett-Dame; Robert W. Curley; Franca Formelli

283

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

PubMed

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

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

2011-11-01

284

Novel second mitochondria-derived activator of caspases (Smac) mimetic compounds sensitize human leukemic cell lines to conventional chemotherapeutic drug-induced and death receptor-mediated apoptosis.  

PubMed

The Inhibitor of Apoptosis Proteins (IAPs) are important regulators of programmed cell death. XIAP is the most potent among them and is over-expressed in several hematological malignancies. Its activity is endogenously antagonized by SMAC/DIABLO, and also by small molecules mimicking Smac that can induce apoptosis in tumor cells. Here we describe the activity of 56 newly synthesized Smac-mimetics in human leukemic cell lines and normal CD34(+) progenitor cells. Our compounds bind to XIAP with high affinity, reduce the levels of cIAP1 and are cytotoxic at nanomolar or low micromolar concentrations. Furthermore, the Smac-mimetics synergize with Cytarabine, Etoposide and especially with TRAIL in combination treatments. Apoptosis activation was clearly detectable by the occurrence of sub G(1) apoptotic peak and the accumulation of cleaved PARP, caspase 8 and caspase 3. Interestingly, the down-regulation of XIAP sensitized Jurkat cells to drugs too, confirming the role of this protein in drug-resistance. In conclusion, while being very active in leukemic cells, our Smac-mimetics have modest effects on normal hematopoietic progenitors, suggesting their promising therapeutic potential as a new class of anticancer drugs in onco-hematology, particularly when combined with TRAIL, to overcome the resistance of cancer cells. PMID:20614162

Servida, Federica; Lecis, Daniele; Scavullo, Cinzia; Drago, Carmelo; Seneci, Pierfausto; Carlo-Stella, Carmelo; Manzoni, Leonardo; Polli, Elio; Lambertenghi Deliliers, Giorgio; Delia, Domenico; Onida, Francesco

2011-12-01

285

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.

286

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

SciTech Connect

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

Connett, M.B.; Hanson, M.R. (Cornell Univ., Ithaca, NY (USA))

1990-08-01

287

The effect of dexamethasone on human mucin 1 expression and antibody-dependent complement sensitivity in a prostate cancer cell line in vitro and in vivo  

PubMed Central

Dexamethasone has been shown to up-regulate human mucin 1 (MUC1) expression in certain types of cancer cell lines in vitro, suggesting that this gluocorticoid may enhance MUC1-based immunotherapies. Here we investigated the effect of dexamethasone on MUC1 expression in the DU145 human prostate cancer cell line in terms of antibody-mediated complement-dependent cell lysis. Cells treated with 1 × 10?8 m dexamethasone in vitro expressed maximal levels of MUC1 after 6 days, with an approximately 3-fold increase over MUC1 levels on untreated cells. DU145 cells were highly resistant to lysis by anti-MUC1 antibody and complement, and their susceptibility to antibody and complement was unaffected by dexamethasone treatment. However, dexamethasone also induced expression of the complement inhibitor decay accelerating factor (DAF) on DU145 cells. Blocking or overcoming the function of DAF resulted in enhanced complement-dependent lysis of dexamethasone-treated cells with anti-MUC1 antibodies, indicating that the failure of dexamethasone to enhance the complement susceptibility of DU145 cells was caused by the up-regulated expression of DAF. We also investigated MUC1 expression in vivo and found that MUC1 expression was significantly up-regulated on tumour cells isolated from immune-deficient mice that had been injected with dexamethasone. However, in contrast to in vitro data, there was no difference between the levels of DAF expressed on tumour-derived DU145 cells isolated from either phosphate buffered saline (PBS)-treated or dexamethasone-treated mice, and tumour cells isolated from dexamethasone-treated mice were more sensitive to complement-mediated lysis. In the broad context of immunotherapy, the in vivo data support the use of dexamethasone as an adjunct treatment. Up-regulated DAF expression would not be a favourable outcome of dexamethasone treatment in terms of complement-dependent antibody therapy, but the in vivo data caution against extrapolation of in vitro data with regard to the modulation of complement inhibitors reported here and elsewhere.

Imai, Masaki; Hwang, Hee-Young; Norris, James S; Tomlinson, Stephen

2004-01-01

288

Both acute and chronic buspirone treatments have different effects on regional 5-HT synthesis in Flinders Sensitive Line rats (a rat model of depression) than in control rats  

PubMed Central

The main objective of this investigation was to evaluate the effects of buspirone, a 5-HT1A agonist with some partial agonist properties and also an antidepressant, on regional 5-HT synthesis in Flinders Sensitive Line (FSL) rats (“depressed”), and to compare the effects to the Flinders Resistant Line (FRL) control rats (not “depressed”). In addition results were compared to those previously reported in normal Sprague-Dawley (SPD) rats (normal control). Serotonin synthesis in both FSL and FRL rats was measured following acute and chronic treatments with buspirone. Both of these strains were derived from the SPD rats. No direct comparison was done between the FSL saline and FRL saline groups, or the FSL buspirone and FRL buspirone groups, because the objective of the studies was to evaluate effects of buspirone in these two strains. The results show that acute treatment with buspirone elevates 5-HT synthesis throughout the brain in the FRL rats. In the FSL rats, there were reductions in some brain regions (e.g., dorsal and median raphe, amygdala, anterior olfactory nucleus, substantia nigra reticulate), while in other regions, there were increases in the synthesis observed (e.g., frontal, parietal, visual and somatosensory cortices, ventral hippocampus). In twenty out of the thirty brain regions investigated in the FSL rats, there was no significant change in the synthesis following acute buspirone treatment. During the chronic treatment, buspirone produced a significant reduction of 5-HT synthesis in fifteen out of thirty brain regions in the FRL rats. In the FSL rats, buspirone produced a significant elevation of the synthesis in ten out of thirty brain regions. In both the FSL and FRL rats, buspirone produced rather different effects than those reported previously for SPD (normal) rats. The acute effect in the FSL rats was somewhat similar to the effect reported previously for the SPD rats, while in the FRL rats, the acute buspirone treatment produced an effect observed previously in treatments with 5-HT1A antagonists suggesting an action of buspirone as partial agonist in FRL rats. The data suggest that with respect to 5-HT synthesis, FRL rats differ from SPD rats (a natural control; normal rats) and, as such, indicate that when the effects related to the serotonergic system (e.g., influence of serotonergic drugs) are studied in the FSL rats and compared to those in the FRL rats, any conclusions drawn may not reflect differences relative to a normal rat.

Nishi, Kyoko; Kanemaru, Kazuya; Hasegawa, Shu; Watanabe, Arata; Diksic, Mirko

2009-01-01

289

Arctic land hydrothermal sensitivity under warming: Idealized off-line evaluation of a physical terrestrial scheme in a global climate model  

NASA Astrophysics Data System (ADS)

A series of idealized one-dimensional off-line sensitivity experiments for the Arctic hydroclimate under a transitional warming environment were conducted to investigate the impact of different internal mechanisms and external forcing (excessive water input) in a physical terrestrial scheme, Minimal Advanced Treatments of Surface Interaction and Runoff (MATSIRO), used in a global climate model. The scheme has freeze/thaw processes and was run with the column depth greater than 50 m. The inclusion of the top organic layers and the physically based parameterization of soil hydrothermal properties led to a realistic seasonal amplitude of a subsurface thermal regime and mitigated the warming and deepening of the maximum active layer thickness (ALT). After a 6-K warming over 100 years, ALT increases by 67% (from 9.6 to 16 cm) with the top organic layers and increases by more than a factor of 2 for the default mineral layers (122% from 45 cm to 1.0 m). With the more realistic thermal property profile, the physically based parameterizations projected ALT after the 100-year warming to be about a half of what the original parameterization did (2.0 against 3.5 m). Finer soil layer thickness near the surface had impacts on the near-surface wetness and the energy and water exchange between the atmosphere and also showed greater tolerance to the misconfiguration of porosity profile, whose global-scale distribution is poorly known for global climate model applications. With much wetter forcing, water infiltration kept the soil close to the saturation, degradation of the frozen state proceeded faster, and the adaptation back to a drier condition occurred on a decadal time scale.

Saito, Kazuyuki

2008-11-01

290

Chronic citalopram treatment elevates serotonin synthesis in Flinders Sensitive and Flinders Resistant Lines of rats, with no significant effect on Sprague-Dawley rats  

PubMed Central

The influence of citalopram on regional 5-hydroxytryptamine (serotonin, 5-HT) synthesis, one of the most important pre-synaptic parameters of serotonergic neurotransmission, was studied. Sprague-Dawley (SPD) rats were used as the controls, and Flinders Resistant Line (FRL) rats were used as auxiliary controls, to hopefully obtain a better understanding of the effects of citalopram on Flinders Sensitive Line (FSL; “depressed”) rats. Regional 5-HT synthesis was evaluated using a radiographic method with a labelled tryptophan analog tracer. In each strain of rats, the animals were treated with citalopram (10 mg/kg/day) or saline for fourteen days. The groups consisted of between fourteen and twenty rats. There were six groups of rats with citalopram (CIT) and saline (SAL) groups in each of the strains (SPD-SAL, SPD-CIT, FRLSAL, FRL-CIT, FSL-SAL and FSL-CIT). A two-factor analysis of variance was used to evaluate the effect of the treatment (e.g., SPD-SAL relative to SPD-CIT) followed by planned comparisons to evaluate the effect in each brain region. In addition, the planned comparison with appropriate contrast was used to evaluate a relative effects in SPD relative to FSL and FRL, and FSL relative to FRL groups. A statistical analysis was first performed in the apriori selected regions, because we had learned, from previous work, that it was possible to select the brain regions in which neurochemical variables had been altered by the disorder and subsequent antidepressant treatments. The results clearly show that citalopram treatment does not have an overall effect on synthesis in the control SPD rats; there was no significant (p>0.05) difference between the SPD-SAL and SPD-CIT rats. In “depressed” FSL rats, citalopram produced a significant (p<0.05) elevation of synthesis in seventeen out of thirty four regions, with a significant (p<0.05) reduction in the dorsal and median raphe. In the FRL rats, there was a significant (p<0.05) elevation in the synthesis in twenty-two out of thirty-four brain regions, with a reduction in the dorsal raphe. In addition to these regions magnus raphe was different in the SPD and FSL groups, but it was on the statistical grounds identified as an outlier. There were significant changes produced in the FSL and FRL rats in thirteen out of seventeen apriori selected brain regions, while in the SPD rats, citalopram produced significant changes in only four out of seventeen apriori selected regions. The statistical evaluation also revealed that changes produced by citalopram in the FSL and FRL rats were significantly greater than those in the SPD rats and that there was no significant difference between the effect produced in the FSL and FRL rats. The presented results suggest that in “depressed” FSL rats, the antidepressant citalopram elevates 5-HT synthesis, which probably in part relates to the reported improved in behaviour with citalopram.

Kanemaru, Kazuya; Nishi, Kyoko; Hasegawa, Shu; Diksic, Mirko

2009-01-01

291

Use of the human monocytic leukemia THP1 cell line and co-incubation with microsomes to identify and differentiate hapten and prohapten sensitizers  

Microsoft Academic Search

Consumer and medical products can contain leachable chemical allergens which can cause skin sensitization. Recent efforts have been directed at the development of non-animal based tests such as in vitro cell activation assays for the identification of skin sensitizers. Prohapten identification by in vitro assays is still problematic due to the lack of prohapten bioactivation. The present study evaluated the

Itai Chipinda; Tinashe B. Ruwona; Steven P. Templeton; Paul D. Siegel

2011-01-01

292

Dark matter sensitivities of the Majorana Demonstrator  

NASA Astrophysics Data System (ADS)

The Majorana Demonstrator is an array of natural and enriched high purity germanium detectors that will search for the neutrinoless double-beta decay of Germanium-76 and perform a search for weakly interacting massive particles with masses below 10 GeV. To reach the background rate goal in the neutrinoless double-beta decay region of interest of 4 counts/keV/t/y, the DEMONSTRATOR will utilize a number of background reduction strategies, including a time-correlated event cut for 68Ge that requires a sub-keV energy threshold. This low energy threshold allows the DEMONSTRATOR to extend its physics reach to include a search for light WIMPs. We will discuss the detector systems and data analysis techniques required to achieve sub-keV thresholds as well as present the projected dark matter sensitivities of the Majorana Demonstrator.

Giovanetti, G. K.; Aguayo, E.; Avignone, F. T., Iii; Back, H. O.; Barabash, A. S.; Beene, J. R.; Bergevin, M.; Bertrand, F. E.; Boswell, M.; Brudanin, V.; Busch, M.; Chan, Y.-D.; Christofferson, C. D.; Collar, J. I.; Combs, D. C.; Cooper, R. J.; Detwiler, J. A.; Doe, P. J.; Efremenko, Yu; Egorov, V.; Ejiri, H.; Elliott, S. R.; Esterline, J.; Fast, J. E.; Fields, N.; Finnerty, P.; Fraenkle, F. M.; Gehman, V. M.; Green, M. P.; Guiseppe, V. E.; Gusey, K.; Hallin, A. L.; Hazama, R.; Henning, R.; Hoppe, E. W.; Horton, M.; Howard, S.; Howe, M. A.; Johnson, R. A.; Keeter, K. J.; Keller, C.; Kidd, M. F.; Knecht, A.; Kochetov, O.; Konovalov, S. I.; Kouzes, R. T.; LaFerriere, B. D.; LaRoque, B. H.; Leon, J.; Leviner, L. E.; Loach, J. C.; MacMullin, S.; Marino, M. G.; Martin, R. D.; Mei, D.-M.; Merriman, J. H.; Miller, M. L.; Mizouni, L.; Nomachi, M.; Orrell, J. L.; Overman, N. R.; Phillips, D. G., Ii; Poon, A. W. P.; Perumpilly, G.; Prior, G.; Radford, D. C.; Rielage, K.; Robertson, R. G. H.; Ronquest, M. C.; Schubert, A. G.; Shima, T.; Shirchenko, M.; Snavely, K. J.; Steele, D.; Strain, J.; Thomas, K.; Timkin, V.; Tornow, W.; Vanyushin, I.; Varner, R. L.; Vetter, K.; Vorren, K.; Wilkerson, J. F.; Yakushev, E.; Young, A. R.; Yu, C.-H.; Yumatov, V.; Zhang, C.

2012-07-01

293

rIFN-?-mediated growth suppression of platinum-sensitive and -resistant ovarian tumor cell lines not dependent upon arginase inhibition  

PubMed Central

Background Arginine metabolism in tumor cell lines can be influenced by various cytokines, including recombinant human interferon-? (rIFN-?), a cytokine that shows promising clinical activity in epithelial ovarian cancer (EOC). Methods We examined EOC cell lines for the expression of arginase in an enzymatic assay and for transcripts of arginase I and II, inducible nitric oxide synthase (iNOS), and indoleamine 2,3-dioxygenase (IDO) by reverse transcription-polymerase chain reaction. The effects of rIFN-? on arginase activity and on tumor cell growth inhibition were determined by measuring [3H]thymidine uptake. Results Elevated arginase activity was detected in 5 of 8 tumor cell lines, and analysis at the transcriptional level showed that arginase II was involved but arginase I was not. rIFN-? reduced arginase activity in 3 EOC cell lines but increased activity in the 2008 cell line and its platinum-resistant subline, 2008.C13. iNOS transcripts were not detected in rIFN-?-treated or untreated cell lines. In contrast, IDO activity was induced or increased by rIFN-?. Suppression of arginase activity by rIFN-? in certain cell lines suggested that such inhibition might contribute to its antiproliferative effects. However, supplementation of the medium with polyamine pathway products did not interfere with the growth-inhibitory effects of rIFN-? EOC cells. Conclusions Increased arginase activity, specifically identified with arginase II, is present in most of the tested EOC cell lines. rIFN-? inhibits or stimulates arginase activity in certain EOC cell lines, though the decrease in arginase activity does not appear to be associated with the in vitro antiproliferative activity of rIFN-?. Since cells within the stroma of EOC tissues could also contribute to arginine metabolism following treatment with rIFN-? or rIFN-?-inducers, it would be helpful to examine these effects in vivo.

Melichar, Bohuslav; Hu, Wei; Patenia, Rebecca; Melicharova, Karolina; Gallardo, Stacie T; Freedman, Ralph

2003-01-01

294

Phospholipid-sensitive Ca2+-dependent Protein Phosphorylation System in Various Types of Leukemic Cells from Human Patients and in Human Leukemic Cell Lines HL60 and K562, and Its Inhibition by Alkyl-lysophospholipid1  

Microsoft Academic Search

Phospholipid-sensitive Ca2+-dependent protein kinase (PL-Ca- PK), its endogenous substrate proteins, and regulation of the enzyme system by an antitumor agent alkyl-lysophospholipid were investigated in various types of leukemic cells (chronic myelocytic, acute myelocytic, and acute monocytic)from patients and in two cultured human leukemic cell lines (HL60 and K562). Exceedingly high levels of PL-Ca-PK, largely localized in the paniculate fraction, were

David M. Helfman; Katherine C. Barnes; Joseph M. Kinkade; William R. Vogler; Mamoru Shoji; J. F. Kuo

295

The relationship between CD86/CD54 expression and THP-1 cell viability in an in vitro skin sensitization test--human cell line activation test (h-CLAT).  

PubMed

Recent regulations for cosmetics in Europe prohibit animal testing for evaluating the sensitization potential of chemicals to improve animal welfare. Yet, there is not an acceptable Organization for Economic Co-operation and Development non-animal skin sensitization test method. Several in vitro skin sensitization methods that focus on the activation of Langerhans cells, including human cell lines, are being evaluated as possible alternatives. In our previous study, we optimized our human cell line activation test (h-CLAT) using THP-1 cells (monocytic leukemia cell line) and conducted an inter-laboratory study. We found that measuring CD86/CD54 expression may be useful for predicting skin sensitization. The aim of this study was to confirm the relationship between CD86/CD54 expression and THP-1 cell viability in the h-CLAT. In this study, 21 allergens (e.g., dinitrochlorobenzene, p-phenylenediamine, Ni) and 8 non-allergens (e.g., SLS, lactic acid) were evaluated. For each chemical, more than 10 concentrations that gave a predicted cell viability range of 20-95% were used. The data showed that expression patterns of CD86/CD54 differed depending on chemical. For most allergens, cytotoxicity (65-90% cell viability) was needed for enhancement of CD86/CD54 expression. The criteria of "CD86 > or = 150 or CD54 > or = 200" resulted in an accuracy of 93%, which confirms appropriate cut-off criteria for h-CLAT. Furthermore, a good correlation was observed between EC3 of local lymph node assay and EC150(CD86) or EC200(CD54) of h-CLAT (12 or 16 chemicals, respectively), which would provide a useful estimate of allergic potency. These findings suggest that h-CLAT would be a good robust in vitro skin sensitization test. PMID:18204907

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

2009-04-01

296

Increased Production of IL4 by Gut T-Cell Lines from Patients with Dermatitis Herpetiformis Compared to Patients with Isolated Gluten-Sensitive Enteropathy  

Microsoft Academic Search

Dermatitis herpetiformis (DH) and isolated gluten-sensitive enteropathy (GSE) are gluten-sensitive diseases in which ingestion of dietary gluten results in the development of clinical disease. Patients with DH develop cutaneous IgA deposits and a severe skin disease, but rarely develop gastrointestinal symptoms. Patients with isolated GSE develop clinically significant gastrointestinal symptoms, but not skin disease or cutaneous IgA deposits. The aim

RUSSELL P. HALL III; Alastair D. Smith; Robert D. Streilein

2000-01-01

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

Behavioral, Physiological, and Neuroendocrine Stress Responses and Differential Sensitivity to Diazepam in Two Wistar Rat Lines Selectively Bred for High and Low-Anxiety–Related Behavior  

Microsoft Academic Search

Two Wistar rat lines, selectively bred for high-anxiety–related behavior (HAB) and low-anxiety–related behavior (LAB) in the elevated plus-maze test, were tested for the susceptibility of their behavioral characteristics to anxiolytic treatment and for their endocrine and physiological reactivity to different stressors. Injection of 1mg\\/kg diazepam failed to affect line differences in coping strategy but resulted in a marked (20-fold) decrease

Gudrun Liebsch; Astrid CE Linthorst; Inga D Neumann; Johannes MHM Reul; Florian Holsboer; Rainer Landgraf

1998-01-01

299

Interferon-alpha conditioned sensitivity to an anti-epidermal growth factor receptor monoclonal antibody in a human lung cancer cell line with intermediate expression of the receptor.  

PubMed

Targeted therapy to the epidermal growth factor receptor (EGFR) seems to be related to its expression level on tumor cells. Interferon-alpha (IFN-alpha) induces growth inhibition but also may up-regulate the EGFR expression in some cancer cell lines. We aimed to determine whether the IFN-alpha combined with an EGFR-specific monoclonal antibody (nimotuzumab) may affect the growth of human tumor epithelial cell lines with different EGFR expression levels. H125, a lung adenosquamous carcinoma, and A431, a vulvar epidermoid carcinoma, cell lines express intermediate and high levels of EGFR, respectively, whereas MDA MB231, a breast adenocarcinoma cell line expresses undetectable levels of EGFR measured by flow cytometry/FACS. We found that IFN-alpha alone inhibited in a dose-dependent fashion the growth of all cell lines, but only up-regulated the EGFR expression in the lung carcinoma-derived cell line. Noteworthy, the combined treatment did not modify the complement-mediated cytotoxicity of the antibody although the antiproliferative activity of nimotuzumab in H125 cells in vitro increased when an IFN-alpha-conditioning treatment was used. In conclusion, this study may provide insights about the rational use of EGFR inhibitors into the immunopharmacological management of targeted therapies including the IFN-alpha for lung cancer. PMID:19514842

Diaz, Arlhee; Batista, Ana E; Montero, Enrique

2009-08-01

300

Pattern of male reproductive system effects after in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure in three differentially TCDD-sensitive rat lines.  

PubMed

Male reproductive effects induced by in utero and lactational exposure to TCDD were analyzed in three rat lines that are differently sensitive to TCDD. Rats from lines A, B, and C were selectively bred from TCDD-resistant Han/Wistar (Kuopio, H/W) and TCDD-sensitive Long-Evans (Turku/AB, L-E) rats and exhibited very different LD50 values for TCDD: >10,000, 830, and 40 microg/kg in males, respectively. The resistance in line A rats was linked to a mutated H/W-type aryl hydrocarbon receptor (Ahr(hw)) and in line B rats to a H/W-type unknown allele B (B(hw)). Line C rats had no resistance alleles. Influence of the resistance alleles on developmentally induced male reproductive effects of TCDD was studied by exposing pregnant females to TCDD (0.03, 0.1, 0.3, or 1 microg/kg) on gestation day (GD) 15. Male progeny were sacrificed on postnatal day (PND) 70. Next, the dams were given 1 microg/kg TCDD on GD 15 and male progeny were sacrificed on PND 14, 21, 28, 35, or 49. Serum testosterone concentration, male sex organ weights, and testicular and cauda epididymal sperm numbers were analyzed; the most sensitive end point was decreased sperm numbers. The dose of 1 microg/kg TCDD reduced daily sperm production by 9.3, 25, and 36%, and cauda epididymal sperm reserves by 18, 42, and 49% in rat lines A, B, and C when measured on PND 70, respectively. The most consistent and significant effect was decreased weight of prostate lobes. The growth of the male reproductive organs was not markedly affected by the resistance alleles Ahr(hw) and B(hw). In contrast, the effects on sperm parameters appeared to be slightly modified by the resistance alleles. Thus, the intraspecies genetic differences in C-terminal transactivation domain of AHR appear to modify the sensitivity to only certain dioxin-induced male reproductive effects. PMID:15084753

Simanainen, Ulla; Haavisto, Tapio; Tuomisto, Jouni T; Paranko, Jorma; Toppari, Jorma; Tuomisto, Jouko; Peterson, Richard E; Viluksela, Matti

2004-07-01

301

Topoisomerase I Levels in the NCI-60 Cancer Cell line Panel Determined by Validated ELISA and Microarray Analysis and Correlation with Indenoisoquinoline Sensitivity  

PubMed Central

Topoisomerase I (Top1) is a proven target for cancer therapeutics, and the level of Top1 in tumors has been employed as a biomarker for chemotherapeutic efficacy. In this study, we report the development and validation of a two-site enzyme chemiluminescent immunoassay for Top1, which we used to measure Top1 levels in the NCI-60 cancer cell line panel. Top1 levels ranged from 0.9 to 9.8 ng/mL/?g protein extract in these cell lines. Levels varied both within and between cancer types but were generally highest in colon cancer and leukemia cell lines and lowest in central nervous system and renal cancer cell lines. Top1 mRNA levels in the NCI-60 cell lines were also measured by microarray; mRNA values generally demonstrated a good correlation with protein levels (Pearson correlation = 0.8). When these expression levels were compared with the activity of the indenoisoquinoline class of Top1 inhibitors across the NCI-60 cell panel, low levels of Top1 were associated with increased resistance to these drugs. The results of our studies indicate that our Top1 assay can be used to quantify Top1 levels in untreated cells as well as cells treated with Top1 inhibitors, and that the assay has the potential to be adapted for use in predicting clinical response to Top1-active antineoplastic agents.

Pfister, Thomas D.; Reinhold, William; Agama, Keli; Gupta, Shalu; Khin, Sonny A.; Kinders, Robert J.; Parchment, Ralph E.; Tomaszewski, Joseph E.; Doroshow, James H.; Pommier, Yves

2009-01-01

302

The physics of background discrimination in liquid xenon, and first results from Xenon10 in the hunt for WIMP dark matter  

NASA Astrophysics Data System (ADS)

The WIMP limit set by the Xenon10 experiment in 2007 signals a new era in direct detection of dark matter, with several large-scale liquid target detectors now under construction. A major challenge in these detectors will be to understand backgrounds at the level necessary to claim a positive WIMP signal. In liquid xenon, these backgrounds are dominated by electron recoils, which may be distinguished from the WIMP signal (nuclear recoils) by their higher charge-to-light ratio. During the construction and operation of Xenon10, the prototype detector Xed probed the physics of this discrimination. Particle interactions in liquid xenon both ionize and excite xenon atoms, giving charge and scintillation signals, respectively. Some fraction of ions recombine, reducing the charge signal and creating additional scintillation. The charge-to-light ratio, determined by the initial exciton-ion ratio and the ion recombination fraction, provides the basis for discrimination between electron and nuclear recoils. Intrinsic fluctuations in the recombination fraction limit discrimination. Changes in recombination induce an exact anti-correlation between charge and light, and when calibrated this anti-correlation distinguishes recombination fluctuations from uncorrelated fluctuations in the measured signals. We determine the mean recombination and recombination fluctuations as a function of energy and applied field for electron and nuclear recoils, finding that recombination fluctuations are already the limiting factor for discrimination above ~12 keVr (nuclear recoil energy). Below 12 keVr statistical fluctuations in the number of scintillation photons counted dominate, and we project a x6 improvement in background rejection with a x2 increase in light collection efficiency. We also build a simple recombination model that successfully reproduces the mean recombination in electron and nuclear recoils, including the surprising reversal of the expected trend for recombination with ionization density in low energy electron recoils. The model also reproduces the measured recombination fluctuations to within a factor of two at high energies. Surprisingly, the model suggests that recombination at low energies is independent of ionization density, and our observed discrimination is due not to the different stopping powers of electrons and nuclei as was thought, but rather to a different initial exciton-ion ratio. We suggest two possible physical models for this new result.

Dahl, Carl Eric

2009-06-01

303

Repair analysis of 4-hydroperoxycyclophosphamide-induced DNA interstrand crosslinking in the c- myc gene in 4-hydroperoxycyclophosphamide-sensitive and-resistant medulloblastoma cell lines  

Microsoft Academic Search

Cyclophosphamide is one of the most active agents in the treatment of medulloblastoma. However, development of resistance to this alkylator frequently occurs and is the harbinger of tumor progression and death. In order to understand the biochemical basis of this resistance, we generated a panel of medulloblastoma cell lines in our laboratory that were resistant to 4-hydroperoxycyclophosphamide (4-HC). Previously, we

Qing Dong; Nancy Bullock; Francis Ali-Osman; O. Michael Colvin; Darell D. Bigner; Henry S. Friedman

1995-01-01

304

Epithelial to Mesenchymal Transition Is a Determinant of Sensitivity of Non-Small-Cell Lung Carcinoma Cell Lines and Xenografts to Epidermal Growth Factor Receptor Inhibition  

Microsoft Academic Search

Treatment of second- and third-line patients with non-small- cell lung carcinoma (NSCLC) with the epidermal growth factor receptor (EGFR) kinase inhibitor erlotinib significantly in- creased survival relative to placebo. Whereas patient tumors with EGFR mutations have shown responses to EGFR inhi- bitors, an exclusive role for mutations in patient survival benefit from EGFR inhibition is unclear. Here we show that

Stuart Thomson; Elizabeth Buck; Filippo Petti; Graeme Griffin; Eric Brown; Nishal Ramnarine; Kenneth K. Iwata; Neil Gibson; John D. Haley

2005-01-01

305

Improved calculations for the C III 1907,1909 and Si III 1883,1892 electron density sensitive emission-line ratios, and a comparison with IUE observations  

NASA Astrophysics Data System (ADS)

Atomic data are used in conjunction with the statistical equilibrium code of Dufton (1977) to calculate relative C III and Si III level populations, and hence emission-line strengths for a range of electron temperatures and densities. It is assumed that photoexcitation and deexcitaton rates are negligible in comparison with the corresponding collisional rates, that ionization to and recombination from other ionic levels are slow compared with bound-bound rates, and that all transitions are optically thin. The observed values of R1 and R2 for several planetary nebulae and a symbiotic star, measured from high-resolution spectra obtained with the IUE satellite, lead to electron densities that are compatible, and are also in good agreement with those deduced from line ratios in other species.

Keenan, F. P.; Feibelman, W. A.; Berrington, K. A.

1992-04-01

306

Improved calculations for the C III 1907,1909 and Si III 1883,1892 electron density sensitive emission-line ratios, and a comparison with IUE observations  

NASA Technical Reports Server (NTRS)

Atomic data are used in conjunction with the statistical equilibrium code of Dufton (1977) to calculate relative C III and Si III level populations, and hence emission-line strengths for a range of electron temperatures and densities. It is assumed that photoexcitation and deexcitaton rates are negligible in comparison with the corresponding collisional rates, that ionization to and recombination from other ionic levels are slow compared with bound-bound rates, and that all transitions are optically thin. The observed values of R1 and R2 for several planetary nebulae and a symbiotic star, measured from high-resolution spectra obtained with the IUE satellite, lead to electron densities that are compatible, and are also in good agreement with those deduced from line ratios in other species.

Keenan, F. P.; Feibelman, W. A.; Berrington, K. A.

1992-01-01

307

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

Microsoft Academic Search

INTRODUCTION: Our goal was to generate xenograft mouse models of human breast cancer based on luciferase-expressing MDA-MB-231 tumor cells that would provide rapid mammary tumor growth; produce metastasis to clinically relevant tissues such as lymph nodes, lung, and bone; and permit sensitive in vivo detection of both primary and secondary tumor sites by bioluminescent imaging. METHOD: Two clonal cell sublines

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

2005-01-01

308

Retrovirus-Mediated Herpes Simplex Virus Thymidine Kinase Gene Transduction Renders Human Thyroid Carcinoma Cell Lines Sensitive to Ganciclovir and Radiation in Vitro and in Vivo  

Microsoft Academic Search

In an attempt to develop gene therapy for thyroid carcinomas, the present studies were undertaken to evaluate in vitro and in vivo therapeutic efficacy and toxicity of herpes simplex virus thymidine kinase (HSV-tk) gene and ganciclovir (GCV) treatment, a widely used prodrug\\/suicide gene therapy, in human thyroid carcinoma cell lines, FRO and WRO cells, using a means of retrovirus-mediated gene

EIJUN NISHIHARA; YUJI NAGAYAMA; FUMIHIRO MAWATARI; KUNIHIKO TANAKA; HIROYUKI NAMBA; MASAMI NIWA; SHUNICHI YAMASHITA

1997-01-01

309

A Robust Digital Delay Line Architecture in a 0.13µm CMOS Technology Node for Reduced Design and Process Sensitivities  

Microsoft Academic Search

The combination of high operating frequencies and low-power requirements for DSP cores targeted towards mobile applications makes clock synthesis and phase synchronization for these devices very challenging. These constraints make all-digital solutions (digital PLLs and DLLs) an attractive option (Dunning et al, 1995; Fried, 1996; Minami et al, 2000). This paper describes a digital delay-line architecture that can be used

Prasun Raha; Scott Randall; Richard Jennings; Bob Helmick; Ajith Amerasekera; Baher Haroun

2002-01-01

310

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

NASA Astrophysics Data System (ADS)

The absorption spectrum of nitrous oxide, N2O, has been recorded by CW-Cavity Ring Down Spectroscopy between 6950 and 7653 cm-1. The spectra were obtained at Doppler limited resolution using a CW-CRDS spectrometer based on a series of fibered DFB laser diodes. The typical noise equivalent absorption, in the order of ?min?1×10-10 cm-1, allowed for the detection of lines with intensity as small as 1×10-29 cm/molecule.The positions of 7203 lines of four isotopologues (14N216O, 14N15N16O, 15N14N16O and 14N218O) were measured with a typical accuracy of 1.0×10-3 cm-1. The transitions were rovibrationally assigned on the basis of the global effective Hamiltonian models developed for each isotopologue. The band by band analysis allowed for the determination of the rovibrational parameters of more than 95 bands, most of them being newly reported while new rotational transitions are measured for the others. The measured line positions of the main isotopologue are found to be in good agreement with the predictions of the effective Hamiltonian model but a few deviations up to 0.20 cm-1 are observed. Local rovibrational perturbations were evidenced for several bands. The interaction mechanisms and the perturbers were univocally assigned on the basis of the effective Hamiltonian models.

Lu, Y.; Mondelain, D.; Liu, A. W.; Perevalov, V. I.; Kassi, S.; Campargue, A.

2012-07-01

311

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

PubMed

Pathophysiological conditions challenge cell volume homeostasis and perturb cell volume regulatory mechanisms leading to alterations of cell metabolism, active transepithelial transport, cell migration, and death. We report that inhibition of the 5-lipoxygenase (5-LO) with AA861 or ETH 615-139, the cysteinyl leukotriene 1 receptor (CysLT?) with the antiasthmatic drug Zafirlukast, or the volume-sensitive organic anion channel (VSOAC) with DIDS blocks the release of organic osmolytes (taurine, meAIB) and the concomitant cell volume restoration following hypoosmotic swelling of human type II-like lung epithelial cells (A549). Reactive oxygen species (ROS) are produced in A549 cells upon hypotonic cell swelling by a diphenylene iodonium-sensitive NADPH oxidase. The swelling-induced taurine release is suppressed by ROS scavenging (butylated hydroxytoluene, N-acetyl cysteine) and potentiated by H?O?. Ca²? mobilization with ionomycin or ATP stimulates the swelling-induced taurine release whereas calmodulin inhibition (W7) inhibits the release. Chelation of the extracellular Ca²? (EGTA) had no effect on swelling-induced taurine release but prevented ATP-induced stimulation. H?O?, ATP, and ionomycin were unable to stimulate the taurine release in the presence of AA861 or Zafirlukast, placing 5-LO and CysLT? as essential elements in the swelling-induced activation of VSOAC with ROS and Ca²? as potent modulators. Inhibition of tyrosine kinases (genistein, cucurbitacin) reduces volume-sensitive taurine release, adding tyrosine kinases (Janus kinase) as regulators of VSOAC activity. Caspase-3 activity during hypoxia is unaffected by inhibition of 5-LO/CysLT? but reduced when swelling-induced taurine loss via VSOAC is prevented by DIDS excess extracellular taurine, indicating a beneficial role of taurine under hypoxia. PMID:23485709

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

2013-07-01

312

Use of a lethally irradiated major histocompatibility complex nonrestricted cytotoxic T-cell line for effective purging of marrows containing lysis-sensitive or -resistant leukemic targets.  

PubMed

Improved marrow purging protocols are needed in autologous bone marrow transplantation (BMT) to achieve complete eradication of minimal residual disease. This study investigates the potential of a human major histocompatibility complex (MHC) nonrestricted killer T-cell line (TALL-104) as a new marrow purging agent in a clinical setting. TALL-104 cells can be irradiated without losing cytotoxic activity against tumor targets in vitro. In vivo, the irradiated killers can be adoptively transferred into immunodeficient and immunocompetent leukemia-bearing mice, and reverse their disease even in advanced stages. The present study shows that gamma-irradiated TALL-104 cells, cultured for 18 hours with marrows from healthy donors, do not impair the viability and long-term growth of committed and pluripotent hematopoietic progenitors. However, as determined by polymerase chain reaction (PCR) and colony assays, TALL-104 cells could completely purge marrows containing up to 50% lysis-susceptible myelomonocytic leukemia cells (U937). When marrows were admixed with a pre-B leukemia cell line (ALL-1), which is fairly resistant to TALL-104 cell lysis in longterm 51Cr-release assays but can be totally growth inhibited by TALL-104 cells in proliferation assays, residual ALL-1 cells were detectable by PCR after TALL-104 purging. However, importantly, these PCR+ marrows were devoid of tumorigenic activity when transplanted into the human hematopoietic microenvironment of human severe combined immunodeficient (SCID) chimeras. These data indicate the strong potential of the TALL-104 cell line in future marrow purging strategies against lysis-susceptible and -resistant leukemias. PMID:8547668

Cesano, A; Pierson, G; Visonneau, S; Migliaccio, A R; Santoli, D

1996-01-01

313

Repair analysis of 4-hydroperoxycyclophosphamide-induced DNA interstrand crosslinking in the c-myc gene in 4-hydroperoxycyclophosphamide-sensitive and -resistant medulloblastoma cell lines.  

PubMed

Cyclophosphamide is one of the most active agents in the treatment of medulloblastoma. However, development of resistance to this alkylator frequently occurs and is the harbinger of tumor progression and death. In order to understand the biochemical basis of this resistance, we generated a panel of medulloblastoma cell lines in our laboratory that were resistant to 4-hydroperoxycyclophosphamide (4-HC). Previously, we have shown that elevated levels of aldehyde dehydrogenase and glutathione mediate cellular resistance to 4-HC. The present study was conducted to identify the third unknown mechanism mediating the resistance of cell line D283 Med (4-HCR) to 4-HC, testing the hypothesis that this resistance is mediated by an increased repair of DNA interstrand crosslinks (ICLs). The doses of 4-HC that produced a one- and two-log cell kill of D283 Med cells were 25 and 50 microM, respectively, compared with values of 125 and 165 microM in D283 Med (4-HCR), the resistant cell line. The formation and disappearance of 4-HC-induced DNA ICLs at the c-myc gene were subsequently studied by DNA denaturing/renaturing gel electrophoresis and Southern blot analysis. 4-HC-induced DNA ICLs in the c-myc gene exhibited a dose-dependent relationship. The percentage of the c-myc gene that was crosslinked was approximately 1-3% at a dose of 100 microM. More than 50% of the DNA crosslinking in D283 Med (4-HCR) cells was removed by 6 h after drug treatment, whereas, in D283 Med cells, more than 90% of the DNA crosslinking was still present at 6 h. These findings suggest that the increased repair of DNA ICLs in D283 Med (4-HCR) may contribute significantly to its resistance to 4-HC. PMID:8529284

Dong, Q; Bullock, N; Ali-Osman, F; Colvin, O M; Bigner, D D; Friedman, H S

1996-01-01

314

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

NASA Astrophysics Data System (ADS)

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

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

2007-07-01

315

Study of light detection and sensitivity for a ton-scale liquid xenon dark matter detector  

NASA Astrophysics Data System (ADS)

Ton-scale liquid xenon detectors operated in two-phase mode are proposed and being constructed recently to explore the favored parameter space for the Weakly Interacting Massive Particles (WIMPs) dark matter. To achieve a better light collection efficiency while limiting the number of electronics channels compared to the previous generation detectors, large-size photo-multiplier tubes (PMTs) such as the 3-inch-diameter R11410 from Hamamatsu are suggested to replace the 1-inch-square R8520 PMTs. In a two-phase xenon dark matter detector, two PMT arrays on the top and bottom are usually used. In this study, we compare the performance of two different ton-scale liquid xenon detector configurations with the same number of either R11410 (config.1) or R8520 (config.2) for the top PMT array, while both using R11410 PMTs for the bottom array. The self-shielding of liquid xenon suppresses the background from the PMTs and the dominant background is from the pp solar neutrinos in the central fiducial volume. The light collection efficiency for the primary scintillation light is largely affected by the xenon purity and the reflectivity of the reflectors. In the optimistic situation with a 10 m light absorption length and a 95% reflectivity, the light collection efficiency is 43%(34%) for config.1(config.2). In the conservative situation with a 2.5 m light absorption length and a 85% reflectivity, the value is only 18%(13%) for config.1(config.2). The difference between the two configurations is due to the larger PMT coverage on the top for config.1. The slightly different position resolutions for the two configurations have a negligible effect on the sensitivity. Based on the above considerations, we estimate the sensitivity reach of the two detector configurations. Both configurations can reach a sensitivity of 2 ~ 3 × 10-47cm2 for spin-independent WIMP-nucleon cross section for 100 GeV/c2 WIMPs after two live-years of operation. The one with R8520 PMTs for the top PMT array is more cost-effective, while the one with R11410 PMTs on the top has a factor of two better sensitivity for light WIMPs at 10 GeV/c2.

Wei, Y.; Lin, Q.; Xiao, X.; Ni, K.

2013-06-01

316

The A-line ARX index may be a more sensitive detector of arousal than the bispectral index during propofol-fentanyl-nitrous oxide anesthesia: A preliminary investigation  

Microsoft Academic Search

Purpose  To compare changes in the A-line ARX index (AAI) by the Alaris AEP monitor™ with those of the bispectral index (BIS) during\\u000a propofol-fentanyl-nitrous oxide anesthesia.\\u000a \\u000a \\u000a \\u000a Methods  Eighty female patients undergoing partial mastectomy were randomly allocated to AAI or BIS (40 per group). Anesthesia was\\u000a induced with propofol 2 mg·kg?1 and fentanyl 3 ?g·kg?1 during the inhalation of oxygen. A laryngeal mask

Tomoki Nishiyama; Kazuo Hanaoka

2004-01-01

317

Genetic heterogeneity of the epidermal growth factor receptor in non-small cell lung cancer cell lines revealed by a rapid and sensitive detection system, the peptide nucleic acid-locked nucleic acid PCR clamp.  

PubMed

Lung cancer is one of the leading causes of the cancer death worldwide. Gefitinib is an inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) and has been introduced in the treatment of advanced lung cancers. The responsiveness to gefitinib has been linked to the presence of EGFR mutations. Clinical samples contain many normal cells in addition to cancer cells. A method capable of detecting EGFR mutations in a large background of wild-type EGFR genes could provide a superior clinical test. We developed a rapid and sensitive detection system for EGFR mutations named the peptide nucleic acid-locked nucleic acid (PNA-LNA) PCR clamp that can detect EGFR mutations in the presence of 100-to 1,000-fold background of wild-type EGFR. We used this method to screen 30 non-small cell lung cancer cell lines established from Japanese patients. In addition to 11 cell lines that have mutations, we found 12 cell lines in which specific mutations are observed only in the subpopulation(s) of the cells. Genetic heterogeneity of EGFR suggests that the EGFR gene is unstable in established cancers and the heterogeneity may explain variable clinical responses of lung cancers to gefitinib. PMID:16105816

Nagai, Yoshiaki; Miyazawa, Hitoshi; Huqun; Tanaka, Tomoaki; Udagawa, Kiyoshi; Kato, Motoyasu; Fukuyama, Shunichiro; Yokote, Akemi; Kobayashi, Kunihiko; Kanazawa, Minoru; Hagiwara, Koichi

2005-08-15

318

Sensitivity of grounding line dynamics to viscoelastic deformation of the solid Earth: Inferences from a fully coupled ice sheet - solid Earth model  

NASA Astrophysics Data System (ADS)

The interactions of ice sheets with the sea level and the solid Earth are important factors for the stability of the ice shelves and the tributary inland ice (e.g. Thomas and Bentley, 1978; Gomez et al, 2012). First, changes in ice extent and ice thickness induce viscoelastic deformation of the Earth surface and Earth's gravity field. In turn, global and local changes in sea level and bathymetry affect the grounding line and, subsequently, alter the ice dynamic behaviour. Here, we investigate these feedbacks for a synthetic ice sheet configuration as well as for the Antarctic ice sheet using a three-dimensional thermomechanical ice sheet and shelf model, coupled to a viscoelastic solid-Earth and gravitationally self-consistent sea-level model. The respective ice sheet undergoes a forcing from rising sea level, warming ocean, and/or changing surface mass balance. The coupling is realized by exchanging ice thickness, Earth surface deformation, and sea level periodically. We apply several sets of viscoelastic Earth parameters to our coupled model, e.g. simulating a low-viscous upper mantle present at the Antarctic Peninsula (Ivins et al., 2011). Special focus of our study lies on the evolution of Earth surface deformation and local sea level changes, as well as on the accompanying grounding line evolution. N. Gomez, D. Pollard, J. X. Mitrovica, P. Huybers, and P. U. Clark 2012. Evolution of a coupled marine ice sheet-sea level model, J. Geophys. Res., 117, F01013, doi:10.1029/2011JF002128. E. R. Ivins, M. M. Watkins, D.-N. Yuan, R. Dietrich, G. Casassa, and A. Rülke 2011. On-land ice loss and glacial isostatic adjustment at the Drake Passage: 2003-2009, J. Geophys. Res. 116, B02403, doi: 10.1029/2010JB007607 R. H. Thomas and C. R. Bentley 1978. A model for Holocene retreat of the West Antarctic Ice Sheet, Quaternary Research, 10 (2), pages 150-170, doi: 10.1016/0033-5894(78)90098-4.

Konrad, H.; Sasgen, I.; Thoma, M.; Klemann, V.; Grosfeld, K.; Martinec, Z.

2013-12-01

319

Differential sensitivity of melanoma cell lines with differing B-Raf mutational status to the new oncogenic B-Raf kinase inhibitor UI-152.  

PubMed

Activating mutations in B-Raf kinase are common in malignant melanoma, an aggressive tumor of neuroectodermal origin. In the present study, the antiproliferative effect of the new oncogenic B-Raf targeting drug UI-152 on two types of melanoma cell lines with differing B-Raf mutational status was examined, and the underlying mechanisms were investigated. In cellular assays, UI-152 displayed high selectivity for tumor cells bearing B-Raf(V600E), showing more than 1000-fold higher inhibition of their proliferation than wild-type B-Raf-bearing cells. As expected, UI-152 completely abolished MEK-ERK phosphorylation in A375P cells harboring B-Raf(V600E). In SK-MEL-2 cells expressing B-Raf(WT), UI-152 caused the paradoxical activation of the MAPK pathway but to a much lesser extent than that observed of other oncogenic B-Raf inhibitors. These data suggest that UI-152 may be a more ideal B-Raf inhibitor capable of preserving potency against oncogenic B-Raf while minimizing the paradoxical activation of MAPK signaling. In addition, we showed that UI-152 treatment of A375P cells simultaneously induced cellular autophagy and apoptosis. However, autophagy inhibition with 3-methyladenine and inhibition of apoptosis by overexpression of the X-linked inhibitor of apoptosis failed to rescue melanoma cells from UI-152-induced cell death, implying that apoptosis and autophagy may cooperate in the induction of cell death in UI-152-treated cells. Collectively, our data suggest that UI-152 may be an effective B-Raf inhibitor and a potential therapeutic strategy for B-Raf(WT) and Ras mutant melanoma. PMID:22425959

Kim, Yun-Ki; Ahn, Soon Kil; Lee, Michael

2012-07-28

320

The seminoma cell line TCam-2 is sensitive to HDAC inhibitor depsipeptide but tolerates various other chemotherapeutic drugs and loss of NANOG expression.  

PubMed

Seminomas and embryonal carcinomas (EC) are both type II germ cell tumor (GCT) entities and develop from the same precursor lesion (carcinoma-in situ, CIS). However, they show significant differences in growth behavior, differentiation potential, and gene expression. Although ECs are prone to differentiate into all three germ layers and give rise to the non-seminomatous GCT entities teratoma, choriocarcinoma, and yolk-sac tumor, differentiation of seminomas to these entities is only rarely observed. This might reflect the ability of seminomas to actively inhibit differentiation processes evoked by environmental cues. Also, it is not known why CIS gives rise to seminoma in some patients and to non-seminoma in the others. Here, we treated the seminoma-like cell line TCam-2 with the HDAC-inhibitor Depsipeptide, the global demethylating agent 5-aza-2'-deocycytidine, all-trans retinoic acid and the monaminooxidase inhibitor Tranylcipromine and also used knock down approaches to reduce expression of the pluripotency marker NANOG and/or the inhibitor of primordial germ cell differentiation TFAP2C. We found that TCam-2 cells induce apoptosis when treated with Depsipeptide (> 10 nM) but are resistant to treatments with 5-aza-2'-deocycytidine, all-trans retinoic acid and Tranylcipromine, highlighting Depsi as a treatment option for seminomas. We show that TCam-2 cells up-regulate endoderm- and throphectoderm-associated genes after down-regulation of NANOG expression; however, morphologically no indications of differentiation could be found. Instead, we observed up-regulation of OCT3/4 and SOX17 in TCam-2-NANOG knockdown and speculate that this compensates for the loss of the NANOG protein. Hence, NANOG is not a primary target gene responsible for the inhibition of differentiation in seminomas. PMID:21987446

Nettersheim, Daniel; Gillis, Ad; Biermann, Katharina; Looijenga, Leendert H J; Schorle, Hubert

2011-12-01

321

Dama/libra Findings Urge Replacement of the WIMP Hypotheses by the Daemon Paradigm as a Basis for Experimental Studies of DM Objects  

NASA Astrophysics Data System (ADS)

The simplest version of the daemon paradigm suggests the modulated 2-6-keV range events in DAMA/NaI and DAMA/LIBRA detectors are caused by the iodine ions knocked out elastically by the electrically neutral c-daemons moving with V = 30-50 km/s (c-daemon is a complex of negative daemon located in a remainder of formerly captured nucleus where the daemon decomposes nucleons one by one with ~ 10-6 s mean interval). Furthermore, after the 2-6 keV event occurred, in subsequent ~ 10-6 s, the c-daemon (which becomes negative during this time) recaptures new nucleus with resulting scintillations in ~ 10 MeV range! The last possibility was so far overlooked in the experiments as it did not stem from WIMP hypotheses. A modification of the NaI(Tl) experiments is suggested for revealing the effect described. Independently of the outcome, any obtained result will be important for refining the daemon paradigm further on.

Drobyshevski, E. M.

322

An enhanced and sensitive autocrine stimulation by transforming growth factor-alpha is acquired in the brain metastatic variant of a human non-small-cell lung cancer cell line.  

PubMed Central

Transforming growth factor-alpha (TGF-alpha)-mediated autocrine regulation in human non-small-cell lung cancer (NSCLC) cells NCI-H226 and its brain metastatic variant H226Br were compared. An enhanced TGF-alpha-induced dose-dependent mitogenic responsiveness in H226Br cells was observed. Neutralising antibody that binds TGF-alpha inhibits H226Br cell growth more effectively than NCI-H226 cell growth. Binding assay with 125I-labelled epidermal growth factor (EGF) revealed that H226Br has two types of EGF receptors (EGFRs), whereas the parental cell line, NCI-H226, has only one. H226Br cells contain twice as many EGFRs as H226 cells, as proved by Scatchard analysis and immune kinase assay. Northern analysis indicated that there is more EGFR transcript in H226Br than in NCI-H226, indicating a transcriptional EGFR gene elevation during metastasis progression. The level of accumulated immunoactive TGF-alpha is lower in the conditioned medium of H226Br than in that of NCI-H226. demonstrating down-regulation of TGF-alpha transcript. The accumulated data suggest an elevated and sensitive autocrine modulation by TGF-alpha and EGFR in immortalising the brain metastatic variant cells that were derived from a human NSCLC squamous cell line. Images Figure 4 Figure 5 Figure 6 Figure 7

Fang, K.

1996-01-01

323

Topiramate normalizes hippocampal NPY-LI in flinders sensitive line 'depressed' rats and upregulates NPY, galanin, and CRH-LI in the hypothalamus: implications for mood-stabilizing and weight loss-inducing effects.  

PubMed

Topiramate is currently used in the treatment of epilepsy, but this anticonvulsant drug has also been reported to exert mood-stabilizing effects and induce weight loss in patients. Neuropeptide Y (NPY) is abundantly and widely distributed in the mammalian central nervous system and centrally administered NPY markedly reduces pharmacologically induced seizures and induces antidepressant-like activity as well as feeding behavior. Two other peptides, galanin and corticotropin-releasing hormone (CRH), have also been proposed to play a modulatory role in mood, appetite, and seizure regulation. Consequently, we investigated the effects of single and repeated topiramate (10 days, once daily: 40 mg/kg i.p.) or vehicle treatment in 'depressed' flinders sensitive line (FSL) and control Flinders resistant line (FRL) rats on brain regional peptide concentrations of NPY, galanin, and CRH. The handling associated with repeated injections reduced hippocampal levels of NPY- and galanin-like immunoreactivities (LI) while NPY- and CRH-LI levels were increased in the hypothalamus, regardless of strain or treatment. In the hippocampus, concentrations of NPY-LI, galanin-LI, and CRH-LI were lower in FSL than FRL animals. Repeated topiramate treatment selectively normalized NPY-LI in this region in the FSL animals. In the hypothalamus, galanin-LI was reduced in FSL compared to FRL animals. Topiramate elevated the hypothalamic concentrations of NPY-LI, CRH-LI, and galanin-LI in both strains. Furthermore, topiramate elevated serum leptin but not corticosterone levels. The present findings show that topiramate has distinct effects on abnormal hippocampal levels of NPY, with possible implications for its anticonvulsant and mood-stabilizing effects. Furthermore, stimulating hypothalamic NPY-LI, CRH-LI and galanin-LI as well as serum leptin levels may be associated with the weight loss-inducing effects of topiramate. PMID:12700690

Husum, Henriette; Van Kammen, Daniel; Termeer, Evelien; Bolwig, G; Mathé, A

2003-07-01

324

Loss of CDKN2A expression is a frequent event in primary invasive melanoma and correlates with sensitivity to the CDK4/6 inhibitor PD0332991 in melanoma cell lines.  

PubMed

We have investigated the potential for the p16-cyclin D-CDK4/6-retinoblastoma protein pathway to be exploited as a therapeutic target in melanoma. In a cohort of 143 patients with primary invasive melanoma, we used fluorescence in situ hybridization to detect gene copy number variations (CNVs) in CDK4, CCND1, and CDKN2A and immunohistochemistry to determine protein expression. CNVs were common in melanoma, with gain of CDK4 or CCND1 in 37 and 18% of cases, respectively, and hemizygous or homozygous loss of CDKN2A in 56%. Three-quarters of all patients demonstrated a CNV in at least one of the three genes. The combination of CCND1 gain with either a gain of CDK4 and/or loss of CDKN2A was associated with poorer melanoma-specific survival. In 47 melanoma cell lines homozygous loss, methylation or mutation of CDKN2A gene or loss of protein (p16(INK) (4A) ) predicted sensitivity to the CDK4/6 inhibitor PD0332991, while RB1 loss predicted resistance. PMID:24495407

Young, Richard J; Waldeck, Kelly; Martin, Claire; Foo, Jung H; Cameron, Donald P; Kirby, Laura; Do, Hongdo; Mitchell, Catherine; Cullinane, Carleen; Liu, Wendy; Fox, Stephen B; Dutton-Regester, Ken; Hayward, Nicholas K; Jene, Nicholas; Dobrovic, Alexander; Pearson, Richard B; Christensen, James G; Randolph, Sophia; McArthur, Grant A; Sheppard, Karen E

2014-07-01

325

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

326

Beau's Lines  

MedlinePLUS

... for adults A A A Beau's lines (crosswise nail plate grooves) are due to severe illness or ... Beau's lines are horizontal (transverse) depressions in the nail plate that run parallel to the shape of ...

327

Measure Lines  

ERIC Educational Resources Information Center

One tool for enhancing students' work with data in the science classroom is the measure line. As a coteacher and curriculum developer for The Inquiry Project, the author has seen how measure lines--a number line in which the numbers refer to units of measure--help students not only represent data but also analyze it in ways that generate…

Crissman, Sally

2011-01-01

328

Farnesyltransferase inhibitor (L-744,832) restores TGF-beta type II receptor expression and enhances radiation sensitivity in K-ras mutant pancreatic cancer cell line MIA PaCa-2.  

PubMed

Activated ras is known to dysregulate TGF-beta signaling by altering the expression of TGF-beta type II receptor (RII). It is well documented that tumor cells harboring mutant ras are more resistant to radiation than cells with wild-type ras. In this study, we hypothesized that the use of farnesyltransferase inhibitor (FTI, L-744,832) may directly restore TGF-beta signaling through RII expression via ras dependent or independent pathway leading to induction of radiation sensitivity. Two pancreatic cancer cell lines, BxPC-3 and MIA PaCa-2 were used in this study. FTI inhibited farnesylation of Ras protein more significantly in MIA PaCa-2 than BxPC-3 cells. In contrast, MIA PaCa-2 cells were resistant to radiation when compared to BxPC-3 cells. BxPC-3 cells were more resistant to FTI than MIA PaCa-2 cells. In combination treatment, no significant radiosensitizing effect of FTI was observed in BxPC-3 cells at 5 or 10 microM. However, in MIA PaCa-2 cells, a significant radiosensitizing effect was observed at both 5 and 10 microM concentrations (P>0.004). The TGF-beta effector gene p21(waf1/cip1) was elevated in combination treatment in MIA PaCa-2 but not in BxPC-3 cells. In MIA PaCa-2 cells, FTI induced TGF-beta responsive promoter activity as assessed by 3TP-luciferase activity. A further induction of luciferase activity was observed in MIA PaCa-2 cells treated with radiation and FTI. Induction of TGF-beta signaling by FTI was mediated through restoration of the RII expression, as demonstrated by RT-PCR analysis. In addition, re-expression of RII by FTI was associated with a decrease in DNA methyltransferase 1 (DNMT1) levels. Thus, these findings suggest that the L-744,832 treatment restores the RII expression through inhibition of DNMT1 levels causing induction of TGF-beta signaling by radiation and this forms a novel molecular mechanism of radiosensitization by FTI. PMID:12420225

Alcock, Rachael A; Dey, Swatee; Chendil, Damodaran; Inayat, Mohammed S; Mohiuddin, Mohammed; Hartman, George; Chatfield, Lee K; Gallicchio, Vincent S; Ahmed, Mansoor M

2002-11-01

329

Keratoplasty sensitivity.  

PubMed Central

Analysis of graft sensitivity showed a return to normal after 3 years in only one-third of the eyes. It is not known whether this is due to regeneration of abnormal or superficial nerve fibres. Contact lens wearers showed less sensitivity than spectacle wearers.

Ruben, M; Colebrook, E

1979-01-01

330

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

331

Sensitive Teeth  

MedlinePLUS

... people who have tooth roots that already are exposed Frequently eating acidic foods or drinking acidic liquids Pulpal sensitivity is a reaction of the tooth's pulp. The pulp is a mass of blood vessels ...

332

Climate Sensitivity  

NASA Astrophysics Data System (ADS)

Discussion of climate sensitivity requires careful definition of forcings, feedbacks and response times, indeed, foggy definitions have produced flawed assessments of climate sensitivity. The best information available on climate sensitivity comes from insightful interpretation of the Earth's history aided by quantitative information from climate models and understanding of climate processes. Climate sensitivity is a strong function of time scale, in part because of the nature of climate feedbacks. Unfortunately for humanity, the preponderance of feedbacks on the century time scale appears to be positive. The chief implication is the need for a sharp reversal in the trend of human-made climate forcing, if we are to avoid creating a planet that is dramatically different than the one on which civilization developed.

Hansen, J.

2007-12-01

333

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

334

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

335

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

336

Shapely Lines  

NSDL National Science Digital Library

This activity gives students practice drawing straight lines with a ruler and looking for and categorizing shapes, for example, by the number of sides in polygons. The Teachers' Notes page includes suggestions for implementation, discussion questions and ideas for extension.

2010-06-01

337

Pi Line  

NSDL National Science Digital Library

This lesson from Illuminations asks students to measure the diameter and circumference of various circular objects, plot the measurements on a graph, and relate the slope of the line to ÃÂ, the ratio of circumference to diameter. A student activity sheet is included. The material is appropriate for grades 9-12 and should require 1 class period to complete.

2011-01-19

338

Sensitivity of discrete systems  

NASA Technical Reports Server (NTRS)

Sensitivity techniques are examined for structures discretized by finite element analysis. The discussion covers finite difference sensitivities, sensitivity of static response, sensitivity of eigenvalues and eigenvectors, sensitivity of linear transient response, and an example of use of transient sensitivity.

Haftka, Raphael T.; Adelman, Howard M.

1993-01-01

339

Suppressive subtractive hybridisation reveals differential expression of serglycin, sorcin, bone marrow proteoglycan and prostate-tumour-inducing gene I (PTI-1) in drug-resistant and sensitive tumour cell lines of haematopoetic origin  

Microsoft Academic Search

The development of therapy-induced drug resistance is still one of the most important therapeutic limitations. Nevertheless, an integrating view of the molecular mechanisms underlying resistance development in general is missing. In order to shed some light on the network of this resistance development, we established drug-resistant (doxorubicin (DX), methotrexate (MTX), cisplatin (cisPt), vincristine (Vin)) derivatives of six tumour cell lines

G. Beyer-Sehlmeyer; W. Hiddemann; B. Wörmann; J. Bertram

1999-01-01

340

Relationship between constitutive nuclear factor-kappaB (NF-?B) and inhibitor kappaB-alpha (I?B-?) in an interferon-?-sensitive human Burkitt lymphoma cell line  

Microsoft Academic Search

The human Burkitt lymphoma Daudi cell line expresses constitutively active nuclear factor kappaB (NF-?B) in the nucleus in spite of high levels of inhibitor kappaB-alpha (I?B-?) in the cytoplasm. The antiproliferative response of these cells to interferon-? (IFN-?) correlated with the inhibition of the constitutive NF-?B activity by the cytokine. The present study shows that IFN-? caused an increase in

Pramod C. Rath

2005-01-01

341

Real-time in vivo monitoring of circadian E-box enhancer activity: a robust and sensitive zebrafish reporter line for developmental, chemical and neural biology of the circadian clock.  

PubMed

The circadian clock co-ordinates physiology and behavior with the day/night cycle. It consists of a transcriptional-translational feedback loop that generates self-sustained oscillations in transcriptional activity with a roughly 24h period via E-box enhancer elements. Numerous in vivo aspects of core clock feedback loop function are still incompletely understood, including its maturation during development, tissue-specific activity and perturbation in disease states. Zebrafish are promising models for biomedical research due to their high regenerative capacity and suitability for in vivo drug screens, and transgenic zebrafish lines are valuable tools to study transcriptional activity in vivo during development. To monitor the activity of the core clock feedback loop in vivo, we created a transgenic zebrafish line expressing a luciferase reporter gene under the regulation of a minimal promoter and four E-boxes. This Tg(4xE-box:Luc) line shows robust oscillating reporter gene expression both under light-dark cycles and upon release into constant darkness. Luciferase activity starts to oscillate during the first days of development, indicating that the core clock loop is already functional at an early stage. To test whether the Tg(4xE-box:Luc) line could be used in drug screens aimed at identifying compounds that target the circadian clock in vivo, we examined drug effects on circadian period. We were readily able to detect period changes as low as 0.7h upon treatment with the period-lengthening drugs lithium chloride and longdaysin in an assay set-up suitable for large-scale screens. Reporter gene mRNA expression is also detected in the adult brain and reveals differential clock activity across the brain, overlapping with endogenous clock gene expression. Notably, core clock activity is strongly correlated with brain regions where neurogenesis takes place and can be detected in several types of neural progenitors. Our results demonstrate that the Tg(4xE-box:Luc) line is an excellent tool for studying the regulation of the circadian clock and its maturation in vivo and in real time. Furthermore, it is highly suitable for in vivo screens targeting the core clock mechanism that take into account the complexity of an intact organism. Finally, it allows mapping of clock activity in the brain of a vertebrate model organism with prominent adult neurogenesis and high regeneration capacity. PMID:23665472

Weger, Meltem; Weger, Benjamin D; Diotel, Nicolas; Rastegar, Sepand; Hirota, Tsuyoshi; Kay, Steve A; Strähle, Uwe; Dickmeis, Thomas

2013-08-15

342

Transmission Lines  

NSDL National Science Digital Library

All About Circuits is a website that âÂÂprovides a series of online textbooks covering electricity and electronics.â Written by Tony R. Kuphaldt, the textbooks available here are wonderful resources for students, teachers, and anyone who is interested in learning more about electronics. This specific section, Transmission Lines, is the fourteenth chapter in Volume II â Alternating Current. A few of the topics covered in this chapter include: Circuits and the speed of light; Finite-length transmission lines; and Waveguides. Diagrams and detailed descriptions of concepts are included throughout the chapter to provide users with a comprehensive lesson. Visitors to the site are also encouraged to discuss concepts and topics using the All About Circuits discussion forums (registration with the site is required to post materials).

Kuphaldt, Tony R.

2008-07-03

343

Washing Line  

NSDL National Science Digital Library

Children can use this interactive applet to practice counting and ordering numbers up to 24 in groups of 10 at a time. An empty clothesline appears along with 9 number cards and a mystery card. Students drag the numbers onto the line in the correct sequence and then determine the mystery number. After the first round, 1 - 10, users may select from three ranges, starting at 1, 7, or 15.

2009-01-01

344

Sensitive determination of a pharmaceutical compound and its metabolites in human plasma by ultra-high performance liquid chromatography-tandem mass spectrometry with on-line solid-phase extraction.  

PubMed

This paper describes the determination of a drug candidate and two metabolites in human plasma by column-switching LC-MS/MS after protein precipitation. Starting from a standard method with a quantitation limit of 0.5 ng/mL, a highly sensitive assay was developed, employing UHPLC separation and detection on an API 5000 mass spectrometer. The injected plasma equivalent was increased from 6 to 20 ?L; conventional column trapping for compound enrichment and removal of matrix constituents was combined with high-pressure analytical separation using small particle columns to improve resolution and signal-to-noise ratio. Quantitation limits were thus lowered to between 5 and 20 pg/mL, offering the possibility to provide bioanalytical support for microdosing studies in humans. Excellent assay quality and robustness were achieved by both methods. PMID:21051172

Heinig, K; Wirz, T; Bucheli, F; Monin, V; Gloge, A

2011-03-25

345

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

346

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

347

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

348

A phase II evaluation of Irofulven (IND#55804, NSC#683863) as second-line treatment of recurrent or persistent intermediately platinum-sensitive ovarian or primary peritoneal cancer: A Gynecologic Oncology Group trial  

PubMed Central

This multi-center phase II trial was conducted by the Gynecologic Oncology Group to evaluate the activity and safety of irofulven in patients with recurrent epithelial ovarian cancer. Eligible patients had documented recurrent ovarian cancer 6-12 months after receiving a front-line platinum-based regimen and no other chemotherapy. Patients were required to have measurable disease, performance status of 0-2, and adequate bone marrow, hepatic, and renal function prior to study entry. The dose of irofulven was 0.45 mg/kg IV on days 1 and 8 every 21 days. Responses were defined by RECIST. Fifty-five of 61 enrolled patients were evaluable for response and toxicity. There were seven partial responses (12.7%) and 30 patients (54.6%) had stable disease. Median progression-free and overall survival were 6.4 mo (1.3-37.5) and 22.1+ mo (2.8-57.8+), respectively. Patients received a median of three cycles (range 1-21) of protocol therapy. Grade 4 hematologic toxicity was limited to reversible neutropenia and thrombocytopenia. Grade 4 non-hematologic toxicity was limited to one patient with anorexia and another with hypomagnesemia. Irofulven administered at this dose and schedule was well tolerated but had modest activity as a single agent.

Schilder, Russell J.; Blessing, John A.; Shahin, Mark S.; Miller, David S; Tewari, Krishnansu Sujata; Muller, Carolyn Y.; Warshal, David; McMeekin, D. Scott; Rotmensch, Jacob

2010-01-01

349

Gamma-ray line transients  

SciTech Connect

Early interpretations of the variability of the narrow 0.511 MeV annihilation line from the Galactic center (GC) were confused by the unrecognized presence of a very extended component (mid 70s-mid 80s). Transient behavior was suggested by comparisons of measurements made by instruments with comparable fields of view, and by detection of other lines which could be interpreted as broadened and Doppler-shifted versions of the line. A new generation of instruments (late 80s-early 90s) provided more compelling evidence, by improved imaging capability (identifying a known transient high-energy candidate source, 1E 1740.7-2942), and by improved sensitivity. Additional broadened, shifted, and Compton-scattered derivatives of the annihilation line were detected from this and other sources. At the same time, theoretical developments suggested exciting new physics which might arise in the accretion regimes around black holes, of which these features would be important diagnostics. In the GRO era the existence of such transient lines has been brought into question by the failure of long-term monitoring to detect them. A seemingly critical observation of the GC by three different instruments simultaneously, in which transient emission was detected only by one, provides the strongest evidence that the earlier results were in error. Recent developments in accretion disk theory have weakened the theoretical case for the lines. I draw conclusions concerning the nature of scientific inquiry and public outreach efforts in science.

Harris, Michael J. [USRA/GVSP, Code 661, NASA/Goddard Spaceflight Center, Greenbelt, Maryland 20771 (United States)

1997-05-10

350

Impact of Optical Comb Stability on Waveforms Generated via Spectral Line-by-Line Pulse Shaping.  

National Technical Information Service (NTIS)

Optical arbitrary waveform generation using the line-by-line pulse shaping technique has been shown to be sensitive to variations in the offset frequency of the input frequency comb due to time-domain waveform interference. Here we present a frequency-dom...

A. M. Weiner C. Huang D. E. Leaird Z. Jiang

2007-01-01

351

Poison Help Line  

MedlinePLUS

... section: The Poison Help Line Partners Contact Us The Poison Help Line The toll-free Poison Help line, 1- ... is available in 161 languages. People usually get the help they need over the phone . Most people do ...

352

Veterans Crisis Line  

MedlinePLUS

... Enter ZIP code here Enter ZIP code here Suicide Prevention Veterans Crisis Line Warning Signs Suicide Prevention Resources ... at www.VeteransCrisisLine.net , or text 838255 today. Suicide Prevention Resources Veterans Chat - Veterans Crisis Line : Veterans Chat ...

353

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

354

How Sensitively Timed Are Sensitive Periods?  

ERIC Educational Resources Information Center

Reviews Maria Montessori's view of sensitive periods and examines the kinds of help needed from adults: an open mind, specific help from a prepared learning environment, and challenges presented at the right time. Stresses the universality of sensitive periods and their connection to brain development. Focuses on the unconscious nature and…

Zener, Rita Schaefer

2003-01-01

355

The WIMP of a Minimal Technicolor Theory  

Microsoft Academic Search

We consider the possibility that a massive fourth family neutrino, predicted\\u000aby a recently proposed minimal technicolor theory, could be the source of the\\u000adark matter in the universe. The model has two techniflavors in the adjoint\\u000arepresentation of an SU(2) techicolor gauge group and its consistency requires\\u000athe existence of a fourth family of leptons. By a suitable hypercharge

Kimmo Kainulainen; Kimmo Tuominen; Jussi Virkajarvi

2006-01-01

356

Transmission line capacitance measurement  

Microsoft Academic Search

The capacitance of coplanar lines is measured with two new techniques, one utilizing the resistance of the line and the other that of a resistor embedded in the line. The results of both measurements agree closely with calculations. A technique for directly comparing the capacitances of two similar transmission lines is also demonstrated. The relevance of these measurements to the

Dylan F. Williams; Roger B. Marks

1991-01-01

357

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

358

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

359

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

360

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

361

Superconducting microwave transmission lines  

SciTech Connect

Superconducting microwave transmission lines can be designed to have lower loss, lower dispersion, and lower phase velocity than conventional metal lines. These properties make superconducting transmission lines attractive for use in many devices and systems such as filters and analog to digital converters. The problem with designing microwave circuits which utilizes these lines is that accurate circuit models do not exist. This paper present models for the microwave transmission line parameters (phase velocity, attenuation, and characteristic impedance) of superconducting lines as a function of temperature and geometry. An experiment to verify these models is also presented.

McClay, C.P.; Soares, S.; Weitzman, P.S.

1991-10-01

362

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

363

Intruder Detector System Having Improved Uniformity of Detection Sensitivity.  

National Technical Information Service (NTIS)

Uniform detection sensitivity along the periphery of an r.f. loop intruder detector system is realized by periodically electronically interchanging the input and termination ends of the system's leaky transmission line transmitting element. The intruder d...

J. L. Poirier

1979-01-01

364

Transmission Lines - Resonant Sections.  

National Technical Information Service (NTIS)

Explains use of resonant sections as a metallic insulator harmonic filter matching transformers, quarter and half waves, line balance converter, and capacitive coupled joint. Lecher line oscillator and a typical duplexer are also discussed.

1994-01-01

365

Peripheral intravenous line - infants  

MedlinePLUS

PIV - infants; Peripheral IV - infants; Peripheral line - infants ... A peripheral intravenous line (PIV) is a small, short plastic tube, called a catheter. It is placed through the skin into a vein, usually in ...

366

Tick Cell Lines.  

National Technical Information Service (NTIS)

This invention relates to new continuous cell lines from embryonic tissues of ticks (Acari Ixodidae); the use of such cell lines for replicating selected microorganisms; and the use of the replicated microorganisms for diagnosis, prophylaxis and control o...

C. E. Yunker J. C. Cory H. R. Meibos

1981-01-01

367

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 ...

368

Near infrared hydrogen emission line ratios as diagnostics of the broad emission line region  

NASA Astrophysics Data System (ADS)

Broad emission line flux ratios are a powerful diagnostic of the physical conditions of the broad-line region gas in Active Galactic Nuclei. With recent advances in infrared spectroscopy, previously unstudied emission lines provide a new means to investigate the physical nature of the BELR gas. The hydrogen emission lines are particularly sensitive to the upper limits of both the radius from the central ionising source and the number density of the gas. Using an existing subset of near-infrared quasar spectra from the Glikman et al. (2006) sample [1] together with Cloudy photoionization simulations, we confirm the Locally Optimally emitting Cloud (LOC) model's ability to reproduce observed emission line flux ratios. The model is then used to constrain physical conditions for individual sources. The photoionization models show that high number density, low incident flux gas is required to reproduce observed near-infrared hydrogen emission line ratios. We also find that comparison to individual sources, rather than composites, is vital.

Ruff, Andrea J.; Floyd, David J. E.; Korista, Kirk T.; Webster, Rachel L.; Porter, Ryan L.; Ferland, Gary J.

2012-07-01

369

Points, Lines, and Planes  

NSDL National Science Digital Library

This lesson will define the important basics of Geometry: Points, Lines, and Planes Let's take notes on our first lesson! Click on the link below to get started: Points, Lines, and Planes Now, here is an activity to check your understanding: Points, Lines and Planes Activity OK! Now, here is a quiz to really see if you got it: Points, Lines, and Planes Quiz! Good Job! Now, your homework can be found on your Canvas account or my website calendar on ...

Neubert, Mrs.

2011-08-18

370

Emission and Absorption Lines  

NSDL National Science Digital Library

This webpage from the University of California, Riverside offers an explanation of emission and absorption lines. A diagram, with descriptive text, shows how light from a star can produce each type of line. Also, an image of solar absorption lines is provided.

Wudka, Jose

2007-12-20

371

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

372

Line Blot and Western Blot Immunoassays for Diagnosis of Mediterranean Spotted Fever.  

National Technical Information Service (NTIS)

The line blot, a new immunoassay in which antigens are placed on nitrocellulose as narrow lines, was evaluated for its sensitivity and specificity relative to the microimmunofluorescence assay for the diagnosis of Mediterranean spotted fever (MSF). The li...

D. Raoult G. A. Dasch

1989-01-01

373

Tunable-Laser Derivative Spectroscopy on Spectral Lines with Combined Doppler and Collision Broadening.  

National Technical Information Service (NTIS)

In derivative spectroscopy, the authors optimize the measurement sensitivity by using the maximum excursion of the derivative of the spectral absorption coefficient as a single spectral line is scanned. Results for lines with pure Doppler or Lorentz conto...

H. K. Chen K. G. P. Sulzmann S. S. Penner

1973-01-01

374

RF Transmission Lines  

NSDL National Science Digital Library

This is a description for a learning module from Maricopa Advanced Technology Education Center. This PDF describes the module; access may be purchased by visiting the MATEC website. After completing this module, learners will be able to describe the type of transmission lines needed in RF systems and how transmission lines work together with other RF system components to deliver maximum power while maintaining reflected power. They also learn how to interpret transmission line specifications, select a transmission line for a given application, calculate transmission line power losses, and measure standing wave ratio. Finally, this module will use visual examples and present industry best practices for identifying type of connectors used with transmission lines and procedures for transmission line testing and troubleshooting.

2012-12-07

375

The pulmonary extracellular lining.  

PubMed Central

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

George, G; Hook, G E

1984-01-01

376

STP Sensitivity to Initial Conditions Program  

NSDL National Science Digital Library

The STP Sensitivity to Initial Conditions program shows 11 particles in a line with the same velocity. You can perturb the system slightly and observe how sensitive the trajectory is to a small change. The default perturbation strength is 1.00001. STP SensitivityToInitialConditions is part of a suite of Open Source Physics programs that model aspects of Statistical and Thermal Physics (STP). The program is distributed as a ready-to-run (compiled) Java archive. Double-clicking the stp_SensitivityToInitialConditions.jar file will run the program if Java is installed on your computer. Additional programs can be found by searching ComPADRE for Open Source Physics, STP, or Statistical and Thermal Physics.

Gould, Harvey; Tobochnik, Jan; Christian, Wolfgang; Cox, Anne

2009-03-13

377

Lining avoids tank bottom replacement  

SciTech Connect

Steel petroleum storage tanks are susceptible to corrosion. The average corrosion rate of a carbon steel storage tank in crude oil service (at ambient temperatures) is more than 1 mil per year. Corrosion rates can accelerate quickly when a layer of water containing corrosive compounds, such as salt and sediment, settle to the bottom of a crude oil tank. Chlorides and other soluble salts in the water also generate a strong electrolyte that can further speed corrosion. External corrosion is another problem. For example, the bottom plates of an above-ground storage tank are vulnerable, especially if the tank is located close to the ocean or exposed to stray electrical currents in the soil. Some tanks have developed leaks in as little as five years. Faced with a quickly corroding tank bottom, tank maintenance engineers have two choices: replace it or reline it. Replacing a tank bottom can be a costly and time-consuming process. Relining the tank with a fiberglass-reinforced plastic (FRP) coating system is the least-cost alternative. A properly applied FRP lining is likely to prevent tank bottom corrosion for up to 20 years. This article describes how thick-film linings (ranging from 60 to 65 mils thick) can control internal corrosion and leaks. Such linings have sufficient strength to bridge over small perforations and are not sensitive to internal pits and other surface irregularities.

LeBleu, J.B.; Hummel, B.

1993-11-01

378

Visual Contrast Sensitivity  

Microsoft Academic Search

Like the modulation transfer function of man-made imaging devices, the contrast sensitivity of the human eye can be measured with sinusoidal grating targets of various spatial frequencies. Criterion-free psychophysical methods permit us to regard the contrast sensitivity as a direct measure of the subject's visual performance, independent of subjective factors. Under these conditions, not only the shape of the contrast-sensitivity

D. H. KELLY

1977-01-01

379

Fatigue sensitivity determination procedure  

US Patent & Trademark Office Database

A method for determining the sensitivity of the fatigue life of a structural component with respect to specific design parameters includes obtaining the stress profile for a structural component under random process establishing a relationship between the stress profile and the fatigue life of the structural component, developing the sensitivity of the fatigue life with respect to design parameters, optimizing the design of the structural component based upon the design parameters to which the fatigue life is most sensitive.

2004-03-09

380

Fuel delivery system sensitivity based adaptive pressure control  

Microsoft Academic Search

Fast micro processors have enabled, if not on line, than still off line implementation of computationally more intensive methodologies. Because of that it is of interest to revisit some of earlier adaptive control methods and investigate them in original or modified forms and compare the performance with some newer methodologies. In this paper Sensitivity Based Adaptive Control has been challenged

Vladimir V. Kokotovic

2011-01-01

381

Rig Evaluation of the On-Line Ferrograph.  

National Technical Information Service (NTIS)

An on-line ferrograph has been rig evaluated using the dynamic foam apparatus. The on-line ferrograph appears to be operational based upon determination of the effect of operational temperature and pressures. The unit has the required sensitivity as indic...

P. W. Centers

1980-01-01

382

Selective Pressure Broadening of Si and F Spectral Lines  

Microsoft Academic Search

The behaviour of the Si I, II, III and IV and F II and III spectral lines in highly condensed discharges, in the range 2900-6000 Å, at pressures varying from 3 mm to 35 cm, is given. The lines originating from the higher energy levels are found to be more sensitive to pressure.

M B K Sarma

1961-01-01

383

Vaginal erotic sensitivity  

Microsoft Academic Search

Vaginal erotic sensitivity was investigated in a group of 48 coitally experienced volunteers by means of systematic digital stimulation of both vaginal walls. It was found that 45 subjects reported erotic sensitivity located in most cases on the upper anterior wall, and of those, 30 (66. 7%) either reached orgasm or requested to stop stimulation short of orgasm. This study

Heli Alzate; Maria Ladi Londono

1984-01-01

384

Tuned cavity magnetometer sensitivity.  

SciTech Connect

We have developed a high sensitivity (sensitivity levels.

Okandan, Murat; Schwindt, Peter

2009-09-01

385

Are Psychopaths Morally Sensitive?  

ERIC Educational Resources Information Center

Philosophical and psychological opinion is divided over whether moral sensitivity, understood as the ability to pick out a situation's morally salient features, necessarily involves emotional engagement. This paper seeks to offer insight into this question. It reasons that if moral sensitivity does draw significantly on affective capacities of…

Maxwell, Bruce; Le Sage, Leonie

2009-01-01

386

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

387

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.

Green, Michael

2012-05-25

388

Monopoles and Wilson lines  

NASA Astrophysics Data System (ADS)

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 = 2 SU(2) gauge theory to count the number of framed BPS states of a single monopole bound to Wilson lines in different representations.

Tong, David; Wong, Kenny

2014-06-01

389

Waiting Line Models  

Microsoft Academic Search

\\u000a Waiting line or queuing system are pervasive. Many of us remember the long lineups in front of stores in the Soviet Union\\u000a and Vietnam, and we have all experienced lineups in banks and supermarkets, but there are many more instances with waiting\\u000a lines: think, for instance, about traffic lights, where drivers line up and wait, files that wait for processing

H. A. Eiselt; C.-L. Sandblom

390

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

391

Expanding the Interaction Lexicon For 3D Graphics Thesis Proposal  

Microsoft Academic Search

In their first 30 years user interfaces went through at least three significant paradigm changes: batch processing, command lines, and WIMP interfaces. Yet for the past 30 years we have been stuck on the WIMP plateau; the predominant user interfaces still draw mainly from the WIMP paradigm. Interactive 3D graphics may be the next step in the evolution of user

Jeff Pierce

392

Interplanetary Magnetic Field Lines  

NSDL National Science Digital Library

This web page provides information and a graphical exercise for students regarding the interaction between magnetic field lines and a plasma. The activity involves tracing a typical interplanetary magnetic field line, dragged out of a location on the Sun by the radial flow of the solar wind. This illustrates the way magnetic field lines are "frozen to the plasma" and the wrapping of field lines due to the rotation of the sun. This is part of the work "The Exploration of the Earth's Magnetosphere". A Spanish translation is available.

Stern, David

2005-04-27

393

I-line negative resist (INR): a negative-tone I-line chemically amplified photoresist  

NASA Astrophysics Data System (ADS)

INR, an I-line negative photoresist, is described. Acid catalyzed cross-linking of phenolic resins using a non-metallic photoacid generator, 2,6-bishydroxymethyl-p-cresol as a cross- linker, and 9-anthracene methanol as an I-line sensitizer results in a very high photospeed aqueous TMAH developable photoresist. Poly(p-hydroxystyrene) was found to have advantages over novolac resins for formulation of high performance negative I-line photoresist. Advantages obtained by using PHS rather than novolac include higher thermal stability, elimination of undercut on nuleophilic surfaces and compatibility with 2.38 percent TMAH puddle develop processes. A high resolution version, INR-X, is described. Resolution to 0.30 micrometers and linearity to 0.35 micrometers was obtained using a 0.54NA ASML I-line stepper. 0.35 micrometers line-spaces arrays had 1.2 micrometers depth of focus and 0.40 micrometers line-space arrays had a depth of focus greater than 1.6 micrometers . An unusual characteristic found in INR-X is a very low sensitivity to variation in PEB temperature. A 3nm/ degree(s)C line-width dependency was found.

Linehan, Leo L.; Spinillo, Gary T.; Smith, Randolph S.; Moreau, Wayne M.; McCormick, Barry C.; Wood, Robert L.; Puttlitz, Erik A.; Collins, James P.; Miller, William J.

1994-05-01

394

Line Orientation Adaptation: Local or Global?  

PubMed Central

Prolonged exposure to an oriented line shifts the perceived orientation of a subsequently observed line in the opposite direction, a phenomenon known as the tilt aftereffect (TAE). Here we consider whether the TAE for line stimuli is mediated by a mechanism that integrates the local parts of the line into a single global entity prior to the site of adaptation, or the result of the sum of local TAEs acting separately on the parts of the line. To test between these two alternatives we used the fact the TAE transfers almost completely across luminance contrast polarity [1]. We measured the TAE using adaptor and test lines that (1) either alternated in luminance polarity or were of a single polarity, and (2) either alternated in local orientation or were of a single orientation. We reasoned that if the TAE was agnostic to luminance polarity and was parts-based, we should obtain large TAEs using alternating-polarity adaptors with single-polarity tests. However we found that (i) TAEs using one-alternating-polarity adaptors with all-white tests were relatively small, increased slightly for two-alternating-polarity adaptors, and were largest with all-white or all-black adaptors. (ii) however TAEs were relatively large when the test was one-alternating polarity, irrespective of the adaptor type. (iii) The results with orientation closely mirrored those obtained with polarity with the difference that the TAE transfer across orthogonal orientations was weak. Taken together, our results demonstrate that the TAE for lines is mediated by a global shape mechanism that integrates the parts of lines into whole prior to the site of orientation adaptation. The asymmetry in the magnitude of TAE depending on whether the alternating-polarity lines was the adaptor or test can be explained by an imbalance in the population of neurons sensitive to 1st-and 2nd-order lines, with the 2nd-order lines being encoded by a subset of the mechanisms sensitive to 1st-order lines.

Gheorghiu, Elena; Bell, Jason; Kingdom, Frederick A. A.

2013-01-01

395

Background reduction and spin-dependent limits using DRIFT - a directionally sensitive dark matter detector  

NASA Astrophysics Data System (ADS)

The DRIFT (Directional Recoil Identification From Tracks) collaboration operates a 1m3 low pressure gaseous negative ion time projection chamber (NI-TPC) WIMP dark matter search experiment in the Boulby Underground Laboratory. Recent progress from the DRIFT collaboration is presented that includes a series of background reduction work and the addition of CF4 to the target volume. A preliminary limit on the spin-dependent WIMP-proton interaction cross-section is presented from a non-blind analysis of 47.2 days live time with a 0.8 m3 30 Torr CS2 - 10Torr CF4 target. The preliminary limit has a minimum of 1.1 pb for a 100 GeV WIMP.

Pipe, Mark; DRIFT Collaboration

2011-08-01

396

Parenteral nutrition line sepsis: the difficulty in diagnosis.  

PubMed

Parenteral nutrition (PN) line sepsis is a common and yet poorly managed complication in hospitalised patients receiving PN. Making a clinical diagnosis is difficult as the clinical picture can be very non-specific and definitions of what constitutes line infection can vary. Once there is clinical suspicion, proving it with microbiological techniques is not an exact science. Traditional techniques have required the removal of the PN line to allow microbiologists to perform analysis of it for infection. This has obvious drawbacks as it is often not easy to replace the line in these patients and the line is often later proven not to be the source of the sepsis. Although the gold-standard technique still requires removal of the line, there has been development in the field of diagnosis line infection while conserving the line. These include intra-luminal brushings of the line, differential blood cultures and simple swabs of the line hub. These techniques are not as sensitive but reduce the problems caused by removing and re-inserting the line in these patients. The definition of PN line sepsis varies between institutions. Rates can be expressed as a true number of cases, or can be expressed correctly as a number of cases per 1000 line days to standardise rates between units of differi