Search for WIMP inelastic scattering off xenon nuclei with XENON100

NASA Astrophysics Data System (ADS)

Aprile, E.; Aalbers, J.; Agostini, F.; Alfonsi, M.; Amaro, F. D.; Anthony, M.; Arneodo, F.; Barrow, P.; Baudis, L.; Bauermeister, B.; Benabderrahmane, M. L.; Berger, T.; Breur, P. A.; Brown, A.; Brown, E.; Bruenner, S.; Bruno, G.; Budnik, R.; Bütikofer, L.; Calvén, J.; Cardoso, J. M. R.; Cervantes, M.; Cichon, D.; Coderre, D.; Colijn, A. P.; Conrad, J.; Cussonneau, J. P.; Decowski, M. P.; de Perio, P.; di Gangi, P.; di Giovanni, A.; Diglio, S.; Eurin, G.; Fei, J.; Ferella, A. D.; Fieguth, A.; Fulgione, W.; Gallo Rosso, A.; Galloway, M.; Gao, F.; Garbini, M.; Geis, C.; Goetzke, L. W.; Greene, Z.; Grignon, C.; Hasterok, C.; Hogenbirk, E.; Itay, R.; Kaminsky, B.; Kazama, S.; Kessler, G.; Kish, A.; Landsman, H.; Lang, R. F.; Lellouch, D.; Levinson, L.; Lin, Q.; Lindemann, S.; Lindner, M.; Lombardi, F.; Lopes, J. A. M.; Manfredini, A.; Maris, I.; Marrodán Undagoitia, T.; Masbou, J.; Massoli, F. V.; Masson, D.; Mayani, D.; Messina, M.; Micheneau, K.; Molinario, A.; Mora, K.; Murra, M.; Naganoma, J.; Ni, K.; Oberlack, U.; Pakarha, P.; Pelssers, B.; Persiani, R.; Piastra, F.; Pienaar, J.; Pizzella, V.; Piro, M.-C.; Plante, G.; Priel, N.; Rauch, L.; Reichard, S.; Reuter, C.; Rizzo, A.; Rosendahl, S.; Rupp, N.; Dos Santos, J. M. F.; Sartorelli, G.; Scheibelhut, M.; Schindler, S.; Schreiner, J.; Schumann, M.; Scotto Lavina, L.; Selvi, M.; Shagin, P.; Silva, M.; Simgen, H.; Sivers, M. V.; Stein, A.; Thers, D.; Tiseni, A.; Trinchero, G.; Tunnell, C.; Vargas, M.; Wang, H.; Wang, Z.; Wei, Y.; Weinheimer, C.; Wulf, J.; Ye, J.; Zhang, Y.; Xenon Collaboration

2017-07-01

We present the first constraints on the spin-dependent, inelastic scattering cross section of weakly interacting massive particles (WIMPs) on nucleons from XENON100 data with an exposure of 7.64 ×103 kg .days . XENON100 is a dual-phase xenon time projection chamber with 62 kg of active mass, operated at the Laboratori Nazionali del Gran Sasso (LNGS) in Italy and designed to search for nuclear recoils from WIMP-nucleus interactions. Here we explore inelastic scattering, where a transition to a low-lying excited nuclear state of Xe 129 is induced. The experimental signature is a nuclear recoil observed together with the prompt deexcitation photon. We see no evidence for such inelastic WIMP-Xe 129 interactions. A profile likelihood analysis allows us to set a 90% C.L. upper limit on the inelastic, spin-dependent WIMP-nucleon cross section of 3.3 ×10-38 cm2 at 100 GeV /c2 . This is the most constraining result to date, and sets the pathway for an analysis of this interaction channel in upcoming, larger dual-phase xenon detectors.

Limits on spin-dependent WIMP-nucleon cross section obtained from the complete LUX exposure

DOE PAGES

Akerib, D. S.; Alsum, S.; Araújo, H. M.; ...

2017-06-23

We present experimental constraints on the spin-dependent WIMP-nucleon elastic cross sections from the total 129.5 kg yr exposure acquired by the Large Underground Xenon experiment (LUX), operating at the Sanford Underground Research Facility in Lead, South Dakota (USA). A profile likelihood ratio analysis allows 90% C.L. upper limits to be set on the WIMP-neutron (WIMP-proton) cross section of σ n = 1.6 × 10 –41 cm 2 (σ p = 5 × 10 –40 cm 2) at 35 GeV c –2, almost a sixfold improvement over the previous LUX spin-dependent results. Finally, the spin-dependent WIMP-neutron limit is the most sensitivemore » constraint to date.« less

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

NASA Astrophysics Data System (ADS)

Maisonobe, R.

2018-04-01

The EDELWEISS collaboration is performing a direct search for WIMP dark matter using an array of up to twenty-four 820-890 g cryogenic germanium detectors equipped with a full charge and thermal signal readout. The experiment is located in the ultra-low-radioactivity background environment of the Modane underground laboratory, in the French-Italian Fréjus tunnel. We present the analysis of data obtained in extended data taking periods. WIMP limits, background rejection factors and measurements of cosmogenic activation are used to assess the performance of the third generation of EDELWEISS detectors in view of the search for WIMPs in the mass range from 1 to 20 GeV/c2 . The developments in progress to pursue this goal in the coming years are also presented.

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

NASA Astrophysics Data System (ADS)

Ambrosio, M.; Antolini, R.; Aramo, C.; Auriemma, G.; Baldini, A.; Barbarino, G. C.; Barish, B. C.; Battistoni, G.; Bellotti, R.; Bemporad, C.; Bernardini, E.; Bernardini, P.; Bilokon, H.; Bisi, V.; Bloise, C.; Bower, C.; Bussino, S.; Cafagna, F.; Calicchio, M.; Campana, D.; Carboni, M.; Castellano, M.; Cecchini, S.; Cei, F.; Chiarella, V.; Choudhary, B. C.; Coutu, S.; de Benedictis, L.; de Cataldo, G.; Dekhissi, H.; de Marzo, C.; de Mitri, I.; Derkaoui, J.; de Vincenzi, M.; di Credico, A.; Diehl, E.; Erriquez, O.; Favuzzi, C.; Forti, C.; Fusco, P.; Giacomelli, G.; Giannini, G.; Giglietto, N.; Giorgini, M.; Grassi, M.; Gray, L.; Grillo, A.; Guarino, F.; Guarnaccia, P.; Gustavino, C.; Habig, A.; Hanson, K.; Heinz, R.; Huang, Y.; Iarocci, E.; Katsavounidis, E.; Katsavounidis, I.; Kearns, E.; Kim, H.; Kyriazopoulou, S.; Lamanna, E.; Lane, C.; Lari, T.; Levin, D. S.; Lipari, P.; Longley, N. P.; Longo, M. J.; Maaroufi, F.; Mancarella, G.; Mandrioli, G.; Manzoor, S.; Margiotta Neri, A.; Marini, A.; Martello, D.; Marzari-Chiesa, A.; Mazziotta, M. N.; Mazzotta, C.; Michael, D. G.; Mikheyev, S.; Miller, L.; Monacelli, P.; Montaruli, T.; Monteno, M.; Mufson, S.; Musser, J.; Nicoló, D.; Orth, C.; Osteria, G.; Ouchrif, M.; Palamara, O.; Patera, V.; Patrizii, L.; Pazzi, R.; Peck, C. W.; Petrera, S.; Pistilli, P.; Popa, V.; Rainò, A.; Rastelli, A.; Reynoldson, J.; Ronga, F.; Sanzgiri, A.; Satriano, C.; Satta, L.; Scapparone, E.; Scholberg, K.; Sciubba, A.; Serra-Lugaresi, P.; Severi, M.; Sioli, M.; Sitta, M.; Spinelli, P.; Spinetti, M.; Spurio, M.; Steinberg, R.; Stone, J. L.; Sulak, L. R.; Surdo, A.; Tarlè, G.; Togo, V.; Ugolotti, D.; Vakili, M.; Walter, C. W.; Webb, R.

1999-10-01

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

Search for bosonic super-WIMP interactions with the XENON100 experiment

NASA Astrophysics Data System (ADS)

Aprile, E.; Aalbers, J.; Agostini, F.; Alfonsi, M.; Althueser, L.; Amaro, F. D.; Anthony, M.; Arneodo, F.; Barrow, P.; Baudis, L.; Bauermeister, B.; Benabderrahmane, M. L.; Berger, T.; Breur, P. A.; Brown, A.; Brown, A.; Brown, E.; Bruenner, S.; Bruno, G.; Budnik, R.; Bütikofer, L.; Calvén, J.; Capelli, C.; Cardoso, J. M. R.; Cichon, D.; Coderre, D.; Colijn, A. P.; Conrad, J.; Cussonneau, J. P.; Decowski, M. P.; de Perio, P.; di Gangi, P.; di Giovanni, A.; Diglio, S.; Eurin, G.; Fei, J.; Ferella, A. D.; Fieguth, A.; Fulgione, W.; Gallo Rosso, A.; Galloway, M.; Gao, F.; Garbini, M.; Geis, C.; Goetzke, L. W.; Greene, Z.; Grignon, C.; Hasterok, C.; Hogenbirk, E.; Howlett, J.; Itay, R.; Kaminsky, B.; Kazama, S.; Kessler, G.; Kish, A.; Landsman, H.; Lang, R. F.; Lellouch, D.; Levinson, L.; Lin, Q.; Lindemann, S.; Lindner, M.; Lombardi, F.; Lopes, J. A. M.; Manfredini, A.; Maris, I.; Marrodán Undagoitia, T.; Masbou, J.; Massoli, F. V.; Masson, D.; Mayani, D.; Messina, M.; Micheneau, K.; Molinario, A.; Morâ, K.; Murra, M.; Naganoma, J.; Ni, K.; Oberlack, U.; Pakarha, P.; Pelssers, B.; Persiani, R.; Piastra, F.; Pienaar, J.; Pizzella, V.; Piro, M.-C.; Plante, G.; Priel, N.; Ramírez García, D.; Rauch, L.; Reichard, S.; Reuter, C.; Rizzo, A.; Rupp, N.; Dos Santos, J. M. F.; Sartorelli, G.; Scheibelhut, M.; Schindler, S.; Schreiner, J.; Schumann, M.; Scotto Lavina, L.; Selvi, M.; Shagin, P.; Silva, M.; Simgen, H.; Sivers, M. V.; Stein, A.; Thers, D.; Tiseni, A.; Trinchero, G.; Tunnell, C.; Vargas, M.; Wang, H.; Wang, Z.; Wei, Y.; Weinheimer, C.; Wittweg, C.; Wulf, J.; Ye, J.; Zhang, Y.; Zhu, T.; Xenon Collaboration

2017-12-01

We present results of searches for vector and pseudoscalar bosonic super-weakly interacting massive particles (WIMPs), which are dark matter candidates with masses at the keV-scale, with the XENON100 experiment. XENON100 is a dual-phase xenon time projection chamber operated at the Laboratori Nazionali del Gran Sasso. A profile likelihood analysis of data with an exposure of 224.6 live days ×34 kg showed no evidence for a signal above the expected background. We thus obtain new and stringent upper limits in the (8 - 125 ) keV /c2 mass range, excluding couplings to electrons with coupling constants of ga e>3 ×10-13 for pseudo-scalar and α'/α >2 ×10-28 for vector super-WIMPs, respectively. These limits are derived under the assumption that super-WIMPs constitute all of the dark matter in our galaxy.

WIMPs at the galactic center

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

2015-05-07

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

WIMPs at the galactic center

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

2015-05-01

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

WIMPs at the galactic center

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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

WIMPs at the galactic center

DOE PAGES

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

2015-05-07

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

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)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manungu Kiveni, Joseph

2012-12-01

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

WIMP capture by the Sun in the effective theory of dark matter self-interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Catena, Riccardo; Widmark, Axel, E-mail: catena@chalmers.se, E-mail: axel.widmark@fysik.su.se

We study the capture of WIMP dark matter by the Sun in the non-relativistic effective theory of dark matter self-interactions. The aim is to assess how self-interactions affect the expected neutrino flux coming from WIMP annihilation in the Sun, and to do so in a model independent manner. We consider all non-relativistic Galilean invariant self-interaction operators that can arise from the exchange of a heavy particle of spin less than or equal to 1 for WIMPs of spin equal to 0, 1/2 and 1. We show that for interaction operators depending at most linearly on the momentum transfer, the WIMP-inducedmore » neutrino flux can be enhanced by several orders of magnitude compared to the same flux in absence of self-interactions. This is true even for standard values of the thermally averaged annihilation cross-section. This conclusion impacts the analysis of present and future observations performed at neutrino telescopes.« less

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Golwala, Sunil Ramanlal

2000-01-01

Extensive evidence indicates that a large fraction of the matter in the universe is nonluminous, nonbaryonic, and “cold” — nonrelativistic at the time matter began to dominate the energy density of the universe. Weakly Interacting Massive Particles (WIMPs) are an excellent candidate for nonbaryonic, cold dark matter. Minimal supersymmetry provides a natural WIMP candidate in the form of the lightest superpartner, with a typical mass Mδ ~ 100 GeV c-2 . WIMPs are expected to have collapsed into a roughly isothermal, spherical halo within which the visible portion of our galaxy resides. They would scatter off nuclei via the weakmore » interaction, potentially allowingtheir direct detection. The Cryogenic Dark Matter Search (CDMS) employs Ge and Si detectors to search for WIMPs via their elastic-scatteringinteractions with nuclei while discriminatingagainst interactions of background particles. The former yield nuclear recoils while the latter produce electron recoils. The ionization yield (the ratio of ionization production to recoil energy in a semiconductor) of a particle interaction differs greatly for nuclear and electron recoils. CDMS detectors measure phonon and electron-hole-pair production to determine recoil energy and ionization yield for each event and thereby discriminate nuclear recoils from electron recoils. This dissertation reports new limits on the spin-independent WIMP-nucleon elastic-scattering cross section that exclude unexplored parameter space above 10 GeV c-2 WIMP mass and, at > 75% CL, the entire 3σ allowed region for the WIMP signal reported by the DAMA experiment. The experimental apparatus, detector performance, and data analysis are fully described.« less

The zero age main sequence of WIMP burners

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fairbairn, Malcolm; Scott, Pat; Edsjoe, Joakim

2008-02-15

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

Oh to Be Rid of Administrative Wimps!

ERIC Educational Resources Information Center

Weissberg, Robert

2007-01-01

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…

Dark matter sensitivity of multi-ton liquid xenon detectors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schumann, Marc; Bütikofer, Lukas; Baudis, Laura

2015-10-01

We study the sensitivity of multi ton-scale time projection chambers using a liquid xenon target, e.g., the proposed DARWIN instrument, to spin-independent and spin-dependent WIMP-nucleon scattering interactions. Taking into account realistic backgrounds from the detector itself as well as from neutrinos, we examine the impact of exposure, energy threshold, background rejection efficiency and energy resolution on the dark matter sensitivity. With an exposure of 200 t × y and assuming detector parameters which have been already demonstrated experimentally, spin-independent cross sections as low as 2.5 × 10{sup −49} cm{sup 2} can be probed for WIMP masses around 40 GeV/c{sup 2}. Additional improvementsmore » in terms of background rejection and exposure will further increase the sensitivity, while the ultimate WIMP science reach will be limited by neutrinos scattering coherently off the xenon nuclei.« less

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

PubMed

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

2008-08-29

XENON10 is an experiment to directly detect weakly interacting massive particles (WIMPs), which may comprise the bulk of the nonbaryonic dark matter in our Universe. We report new results for spin-dependent WIMP-nucleon interactions with 129Xe and 131Xe from 58.6 live days of operation at the Laboratori Nazionali del Gran Sasso. Based on the nonobservation of a WIMP signal in 5.4 kg of fiducial liquid xenon mass, we exclude previously unexplored regions in the theoretically allowed parameter space for neutralinos. We also exclude a heavy Majorana neutrino with a mass in the range of approximately 10 GeV/c2-2 TeV/c2 as a dark matter candidate under standard assumptions for its density and distribution in the galactic halo.

Secluded WIMPs, Dark QED with Massive Photons, and the Galactic Center Gamma-Ray Excess

NASA Technical Reports Server (NTRS)

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

2015-01-01

We discuss a particular secluded WIMP dark matter model consisting of neutral fermions as the dark matter candidate and a Proca-Wentzel (PW) field as a mediator. In the model that we consider here, dark matter WIMPs interact with standard model (SM) particles only through the PW field of approximately MeV-multi-GeV mass particles. The interactions occur via a U(1)' mediator, V'(sub mu), which couples to the SM by kinetic mixing with U(1) hypercharge bosons, B'(sub mu). One important difference between our model and other such models in the literature is the absence of an extra singlet scalar, so that the parameter with dimension of mass M(sup 2, sub V) is not related to a spontaneous symmetry breaking. This QED based model is also renormalizable. The mass scale of the mediator and the absence of the singlet scalar can lead to interesting astrophysical signatures. The dominant annihilation channels are different from those usually considered in previous work. We show that the GeV energy gamma-ray excess in the galactic center region, as derived from Fermi-LAT Gamma-ray Space Telescope data, can be attributed to such secluded dark matter WIMPs, given parameters of the model that are consistent with both the cosmological dark matter density and the upper limits on WIMP spin-independent elastic scattering. Secluded WIMP models are also consistent with suggested upper limits on a DM contribution to the cosmic-ray antiproton flux.

Deformed shell model study of event rates for WIMP-73Ge scattering

NASA Astrophysics Data System (ADS)

Sahu, R.; Kota, V. K. B.

2017-12-01

The event detection rates for the Weakly Interacting Massive Particles (WIMP) (a dark matter candidate) are calculated with 73Ge as the detector. The calculations are performed within the deformed shell model (DSM) based on Hartree-Fock states. First, the energy levels and magnetic moment for the ground state and two low-lying positive parity states for this nucleus are calculated and compared with experiment. The agreement is quite satisfactory. Then the nuclear wave functions are used to investigate the elastic and inelastic scattering of WIMP from 73Ge; inelastic scattering, especially for the 9/2+ → 5/2+ transition, is studied for the first time. The nuclear structure factors which are independent of supersymmetric model are also calculated as a function of WIMP mass. The event rates are calculated for a given set of nucleonic current parameters. The calculation shows that 73Ge is a good detector for detecting dark matter.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCarthy, Kevin

2013-06-01

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

A Bio-Inspired Model-Based Approach for Context-Aware Post-WIMP Tele-Rehabilitation.

PubMed

López-Jaquero, Víctor; Rodríguez, Arturo C; Teruel, Miguel A; Montero, Francisco; Navarro, Elena; Gonzalez, Pascual

2016-10-13

Tele-rehabilitation is one of the main domains where Information and Communication Technologies (ICT) have been proven useful to move healthcare from care centers to patients' home. Moreover, patients, especially those carrying out a physical therapy, cannot use a traditional Window, Icon, Menu, Pointer (WIMP) system, but they need to interact in a natural way, that is, there is a need to move from WIMP systems to Post-WIMP ones. Moreover, tele-rehabilitation systems should be developed following the context-aware approach, so that they are able to adapt to the patients' context to provide them with usable and effective therapies. In this work a model-based approach is presented to assist stakeholders in the development of context-aware Post-WIMP tele-rehabilitation systems. It entails three different models: (i) a task model for designing the rehabilitation tasks; (ii) a context model to facilitate the adaptation of these tasks to the context; and (iii) a bio-inspired presentation model to specify thoroughly how such tasks should be performed by the patients. Our proposal overcomes one of the limitations of the model-based approach for the development of context-aware systems supporting the specification of non-functional requirements. Finally, a case study is used to illustrate how this proposal can be put into practice to design a real world rehabilitation task.

The waning of the WIMP? A review of models, searches, and constraints

NASA Astrophysics Data System (ADS)

Arcadi, Giorgio; Dutra, Maíra; Ghosh, Pradipta; Lindner, Manfred; Mambrini, Yann; Pierre, Mathias; Profumo, Stefano; Queiroz, Farinaldo S.

2018-03-01

Weakly Interacting Massive Particles (WIMPs) are among the best-motivated dark matter candidates. No conclusive signal, despite an extensive search program that combines, often in a complementary way, direct, indirect, and collider probes, has been detected so far. This situation might change in near future due to the advent of one/multi-TON Direct Detection experiments. We thus, find it timely to provide a review of the WIMP paradigm with focus on a few models which can be probed at best by these facilities. Collider and Indirect Detection, nevertheless, will not be neglected when they represent a complementary probe.

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

NASA Astrophysics Data System (ADS)

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

2016-08-01

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roszkowski, Leszek; Sessolo, Enrico Maria; Trojanowski, Sebastian

2016-08-01

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

Direct detection of WIMPs: implications of a self-consistent truncated isothermal model of the Milky Way's dark matter halo

NASA Astrophysics Data System (ADS)

Chaudhury, Soumini; Bhattacharjee, Pijushpani; Cowsik, Ramanath

2010-09-01

Direct detection of Weakly Interacting Massive Particle (WIMP) candidates of Dark Matter (DM) is studied within the context of a self-consistent truncated isothermal model of the finite-size dark halo of the Galaxy. The halo model, based on the ``King model'' of the phase space distribution function of collisionless DM particles, takes into account the modifications of the phase-space structure of the halo due to the gravitational influence of the observed visible matter in a self-consistent manner. The parameters of the halo model are determined by a fit to a recently determined circular rotation curve of the Galaxy that extends up to ~ 60 kpc. Unlike in the Standard Halo Model (SHM) customarily used in the analysis of the results of WIMP direct detection experiments, the velocity distribution of the WIMPs in our model is non-Maxwellian with a cut-off at a maximum velocity that is self-consistently determined by the model itself. For our halo model that provides the best fit to the rotation curve data, the 90% C.L. upper limit on the WIMP-nucleon spin-independent cross section from the recent results of the CDMS-II experiment, for example, is ~ 5.3 × 10-8 pb at a WIMP mass of ~ 71 GeV. We also find, using the original 2-bin annual modulation amplitude data on the nuclear recoil event rate seen in the DAMA experiment, that there exists a range of small WIMP masses, typically ~ 2-16 GeV, within which DAMA collaboration's claimed annual modulation signal purportedly due to WIMPs is compatible with the null results of other experiments. These results, based as they are on a self-consistent model of the dark matter halo of the Galaxy, strengthen the possibility of low-mass (lsim10 GeV) WIMPs as a candidate for dark matter as indicated by several earlier studies performed within the context of the SHM. A more rigorous analysis using DAMA bins over smaller intervals should be able to better constrain the ``DAMA regions'' in the WIMP parameter space within the context of

Annual modulation experiments, galactic models and WIMPs

NASA Astrophysics Data System (ADS)

Hudson, Robert G.

Our task in the paper is to examine some recent experiments (in the period 1996-2002) bearing on the issue of whether there is dark matter in the universe in the form of neutralino WIMPs (weakly interacting massive particles). Our main focus is an experiment performed by the DAMA group that claims to have found an 'annual modulation signature' for the WIMP. DAMA's result has been hotly contested by two other groups, EDELWEISS and CDMS, and we study the details of the experiments performed by all three groups. Our goal is to investigate the philosophic and sociological implications of this controversy. Particularly, using an innovative theoretical strategy suggested by (Copi, C. and L. M. Krauss (2003). Comparing interaction rate detectors for weakly interacting massive particles with annual modulation detectors. Physical Review D, 67, 103 507), we suggest a new way of resolving discordant experimental data (extending a previous analysis by (Franklin, A. (2002). Selectivity and discord. Pittsburgh: University of Pittsburgh Press). In addition, we are in a position to contribute substantively to the debate between realists and constructive empiricists. Finally, from a sociological standpoint, we remark that DAMA's work has been valuable in mobilizing other research teams and providing them with a critical focus.

Solar atmospheric neutrinos and the sensitivity floor for solar dark matter annihilation searches

DOE Office of Scientific and Technical Information (OSTI.GOV)

Argüelles, C.A.; De Wasseige, G.; Fedynitch, A.

Cosmic rays interacting in the solar atmosphere produce showers that result in a flux of high-energy neutrinos from the Sun. These form an irreducible background to indirect solar WIMP self-annihilation searches, which look for heavy dark matter particles annihilating into final states containing neutrinos in the Solar core. This background will eventually create a sensitivity floor for indirect WIMP self-annihilation searches analogous to that imposed by low-energy solar neutrino interactions for direct dark matter detection experiments. We present a new calculation of the flux of solar atmospheric neutrinos with a detailed treatment of systematic uncertainties inherent in solar atmospheric showermore » evolution, and we use this to derive the sensitivity floor for indirect solar WIMP annihilation analyses. We find that the floor lies less than one order of magnitude beyond the present experimental limits on spin-dependent WIMP-proton cross sections for some mass points, and that the high-energy solar atmospheric neutrino flux may be observable with running and future neutrino telescopes.« less

WIMP dark matter candidates and searches-current status and future prospects.

PubMed

Roszkowski, Leszek; Sessolo, Enrico Maria; Trojanowski, Sebastian

2018-06-01

We review several current aspects of dark matter theory and experiment. We overview the present experimental status, which includes current bounds and recent claims and hints of a possible signal in a wide range of experiments: direct detection in underground laboratories, gamma-ray, cosmic ray, x-ray, neutrino telescopes, and the LHC. We briefly review several possible particle candidates for a weakly interactive massive particle (WIMP) and dark matter that have recently been considered in the literature. We pay particular attention to the lightest neutralino of supersymmetry as it remains the best motivated candidate for dark matter and also shows excellent detection prospects. Finally we briefly review some alternative scenarios that can considerably alter properties and prospects for the detection of dark matter obtained within the standard thermal WIMP paradigm.

WIMP dark matter candidates and searches—current status and future prospects

NASA Astrophysics Data System (ADS)

Roszkowski, Leszek; Sessolo, Enrico Maria; Trojanowski, Sebastian

2018-06-01

We review several current aspects of dark matter theory and experiment. We overview the present experimental status, which includes current bounds and recent claims and hints of a possible signal in a wide range of experiments: direct detection in underground laboratories, gamma-ray, cosmic ray, x-ray, neutrino telescopes, and the LHC. We briefly review several possible particle candidates for a weakly interactive massive particle (WIMP) and dark matter that have recently been considered in the literature. We pay particular attention to the lightest neutralino of supersymmetry as it remains the best motivated candidate for dark matter and also shows excellent detection prospects. Finally we briefly review some alternative scenarios that can considerably alter properties and prospects for the detection of dark matter obtained within the standard thermal WIMP paradigm.

New class of biological detectors for WIMPs

NASA Astrophysics Data System (ADS)

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

2014-07-01

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

No WIMP mini-spikes in dwarf spheroidal galaxies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wanders, Mark; Bertone, Gianfranco; Weniger, Christoph

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

Calculated WIMP signals at the ANDES laboratory: comparison with northern and southern located dark matter detectors

NASA Astrophysics Data System (ADS)

Civitarese, O.; Fushimi, K. J.; Mosquera, M. E.

2016-12-01

Weakly interacting massive particles (WIMPs) are possible components of the Universe’s dark matter (DM). The detection of WIMPs is signaled by the recoil of the atomic nuclei which form a detector. CoGeNT at the Soudan Underground Laboratory (SUL) and DAMA at the Laboratori Nazionali del Gran Sasso (LNGS) have reported data on annual modulation of signals attributed to WIMPs. Both experiments are located in laboratories in the Northern Hemisphere. DM detectors are planned to operate (or already operate) in laboratories in the Southern Hemisphere, including SABRE at Stawell Underground Physics Laboratory (SUPL) in Australia, and DM-ICE in Antarctica. In this work we have analyzed the dependence of diurnal and annual modulation of signals, pertaining to the detection of WIMP, on the coordinates of the laboratory, for experiments which may be performed in the planned new Agua Negra Deep Experimental Site (ANDES) underground facility, to be built in San Juan, Argentina. We made predictions for NaI and Ge-type detectors placed in ANDES, to compare with DAMA, CoGeNT, SABRE and DM-ICE arrays, and found that the diurnal modulation of the signals, at the ANDES site, is amplified at its maximum value, both for NaI (Ge)-type detectors, while the annual modulation remains unaffected by the change in coordinates from north to south.

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

NASA Astrophysics Data System (ADS)

Nygren, David

2013-04-01

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

SABRE: WIMP modulation detection in the northern and southern hemisphere

NASA Astrophysics Data System (ADS)

Froborg, F.; SABRE Collaboration

2016-05-01

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

The fraternal WIMP miracle

DOE PAGES

Craig, Nathaniel; Katz, Andrey

2015-10-27

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

Looking for the WIMP next door

NASA Astrophysics Data System (ADS)

Evans, Jared A.; Gori, Stefania; Shelton, Jessie

2018-02-01

We comprehensively study experimental constraints and prospects for a class of minimal hidden sector dark matter (DM) models, highlighting how the cosmological history of these models informs the experimental signals. We study simple `secluded' models, where the DM freezes out into unstable dark mediator states, and consider the minimal cosmic history of this dark sector, where coupling of the dark mediator to the SM was sufficient to keep the two sectors in thermal equilibrium at early times. In the well-motivated case where the dark mediators couple to the Standard Model (SM) via renormalizable interactions, the requirement of thermal equilibrium provides a minimal, UV-insensitive, and predictive cosmology for hidden sector dark matter. We call DM that freezes out of a dark radiation bath in thermal equilibrium with the SM a WIMP next door, and demonstrate that the parameter space for such WIMPs next door is sharply defined, bounded, and in large part potentially accessible. This parameter space, and the corresponding signals, depend on the leading interaction between the SM and the dark mediator; we establish it for both Higgs and vector portal interactions. In particular, there is a cosmological lower bound on the portal coupling strength necessary to thermalize the two sectors in the early universe. We determine this thermalization floor as a function of equilibration temperature for the first time. We demonstrate that direct detection experiments are currently probing this cosmological lower bound in some regions of parameter space, while indirect detection signals and terrestrial searches for the mediator cut further into the viable parameter space. We present regions of interest for both direct detection and dark mediator searches, including motivated parameter space for the direct detection of sub-GeV DM.

On WIMP detection rates in constrained SUSY

NASA Astrophysics Data System (ADS)

Roszkowski, Leszek

Cosmological and experimental restrictions provide tight constraints on the mass spectra in the Constrained MSSM. For tan β <~ 45-50 relatively little room remains, mostly in the neutralino-slepton coannihilation region and also close to theoretially excluded regions. For larger values of tan β the decreasing mass of the pseudoscalar Higgs gives rise to a wide resonance in the neutralino WIMP pair-annihilation, whose position depends on the ratio of top and bottom quark masses. As a consequence, the cosmologically expected regions consistent with other constraints often grow significantly and generally shift towards allowing superpartner masses in the TeV range.

Radiation sensitivity of Merkel cell carcinoma cell lines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leonard, J.H.; Ramsay, J.R.; Birrell, G.W.

1995-07-30

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)more » 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.« less

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cao, Huajie

2014-11-01

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

Pre-launch estimates for GLAST sensitivity to dark matter annihilation signals

DOE PAGES

Baltz, E. A.; Berenji, B.; Bertone, G.; ...

2008-07-17

Here, we investigate the sensitivity of the Gamma-ray Large Area Space Telescope (GLAST) to indirectly detect weakly interacting massive particles (WIMPs) through the γ-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 themore » 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. Lastly, 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.« less

Limits on light WIMPs with a 1 kg-scale germanium detector at 160 eVee physics threshold at the China Jinping Underground Laboratory

NASA Astrophysics Data System (ADS)

Yang, Li-Tao; Li, Hau-Bin; Yue, Qian; Kang, Ke-Jun; Cheng, Jian-Ping; Li, Yuan-Jing; Tsz-King Wong, Henry; Aǧartioǧlu, M.; An, Hai-Peng; Chang, Jian-Ping; Chen, Jing-Han; Chen, Yun-Hua; Deng, Zhi; Du, Qiang; Gong, Hui; He, Li; Hu, Jin-Wei; Hu, Qing-Dong; Huang, Han-Xiong; Jia, Li-Ping; Jiang, Hao; Li, Hong; Li, Jian-Min; Li, Jin; Li, Xia; Li, Xue-Qian; Li, Yu-Lan; Lin, Fong-Kay; Lin, Shin-Ted; Liu, Shu-Kui; Liu, Zhong-Zhi; Ma, Hao; Ma, Jing-Lu; Pan, Hui; Ren, Jie; Ruan, Xi-Chao; Sevda, B.; Sharma, Vivek; Shen, Man-Bin; Singh, Lakhwinder; Singh, Manoj Kumar; Tang, Chang-Jian; Tang, Wei-You; Tian, Yang; Wang, Ji-Min; Wang, Li; Wang, Qing; Wang, Yi; Wu, Shi-Yong; Wu, Yu-Cheng; Xing, Hao-Yang; Xu, Yin; Xue, Tao; Yang, Song-Wei; Yi, Nan; Yu, Chun-Xu; Yu, Hai-Jun; Yue, Jian-Feng; Zeng, Xiong-Hui; Zeng, Ming; Zeng, Zhi; Zhang, Yun-Hua; Zhao, Ming-Gang; Zhao, Wei; Zhou, Ji-Fang; Zhou, Zu-Ying; Zhu, Jing-Jun; Zhu, Zhong-Hua; CDEX Collaboration

2018-01-01

We report results of a search for light weakly interacting massive particle (WIMP) dark matter from the CDEX-1 experiment at the China Jinping Underground Laboratory (CJPL). Constraints on WIMP-nucleon spin-independent (SI) and spin-dependent (SD) couplings are derived with a physics threshold of 160 eVee, from an exposure of 737.1 kg-days. The SI and SD limits extend the lower reach of light WIMPs to 2 GeV and improve over our earlier bounds at WIMP mass less than 6 GeV. Supported by the National Key Research and Development Program of China (2017YFA0402200, 2017YFA0402201), the National Natural Science Foundation of China (11175099, 11275107, 11475117, 11475099, 11475092, 11675088), the National Basic Research Program of China (973 Program) (2010CB833006). We thank the support of grants from the Tsinghua University Initiative Scientific Research Program (20121088494, 20151080354) and the Academia Sinica Investigator Award 2011-15, contracts 103-2112-M-001-024 and 104-2112-M-001-038-MY3 from the Ministry of Science and Technology of Taiwan.

Readout technologies for directional WIMP Dark Matter detection

NASA Astrophysics Data System (ADS)

Battat, J. B. R.; Irastorza, I. G.; Aleksandrov, A.; Asada, T.; Baracchini, E.; Billard, J.; Bosson, G.; Bourrion, O.; Bouvier, J.; Buonaura, A.; Burdge, K.; Cebrián, S.; Colas, P.; Consiglio, L.; Dafni, T.; D'Ambrosio, N.; Deaconu, C.; De Lellis, G.; Descombes, T.; Di Crescenzo, A.; Di Marco, N.; Druitt, G.; Eggleston, R.; Ferrer-Ribas, E.; Fusayasu, T.; Galán, J.; Galati, G.; García, J. A.; Garza, J. G.; Gentile, V.; Garcia-Sciveres, M.; Giomataris, Y.; Guerrero, N.; Guillaudin, O.; Guler, A. M.; Harton, J.; Hashimoto, T.; Hedges, M. T.; Iguaz, F. J.; Ikeda, T.; Jaegle, I.; Kadyk, J. A.; Katsuragawa, T.; Komura, S.; Kubo, H.; Kuge, K.; Lamblin, J.; Lauria, A.; Lee, E. R.; Lewis, P.; Leyton, M.; Loomba, D.; Lopez, J. P.; Luzón, G.; Mayet, F.; Mirallas, H.; Miuchi, K.; Mizumoto, T.; Mizumura, Y.; Monacelli, P.; Monroe, J.; Montesi, M. C.; Naka, T.; Nakamura, K.; Nishimura, H.; Ochi, A.; Papevangelou, T.; Parker, J. D.; Phan, N. S.; Pupilli, F.; Richer, J. P.; Riffard, Q.; Rosa, G.; Santos, D.; Sawano, T.; Sekiya, H.; Seong, I. S.; Snowden-Ifft, D. P.; Spooner, N. J. C.; Sugiyama, A.; Taishaku, R.; Takada, A.; Takeda, A.; Tanaka, M.; Tanimori, T.; Thorpe, T. N.; Tioukov, V.; Tomita, H.; Umemoto, A.; Vahsen, S. E.; Yamaguchi, Y.; Yoshimoto, M.; Zayas, E.

2016-11-01

The measurement of the direction of WIMP-induced nuclear recoils is a compelling but technologically challenging strategy to provide an unambiguous signature of the detection of Galactic dark matter. Most directional detectors aim to reconstruct the dark-matter-induced nuclear recoil tracks, either in gas or solid targets. The main challenge with directional detection is the need for high spatial resolution over large volumes, which puts strong requirements on the readout technologies. In this paper we review the various detector readout technologies used by directional detectors. In particular, we summarize the challenges, advantages and drawbacks of each approach, and discuss future prospects for these technologies.

The use of twin-screen-based WIMPS in spacecraft control

NASA Astrophysics Data System (ADS)

Klim, R. D.

1990-10-01

The ergonomic problems of designing a sophisticated Windows Icons Mouse Pop-up (WIMP) based twin screen workstation are outlined. These same problems will be encountered by future spacecraft controllers. The design of a modern, advanced workstation for use on a distributed multicontrol center in a multisatellite control system is outlined. The system uses access control mechanisms to ensure that only authorized personnel can undertake certain operations on the workstation. Rules governing the use of windowing features, screen attributes, icons, keyboard and mouse in spacecraft control are discussed.

WIMP-less dark matter and meson decays with missing energy

DOE Office of Scientific and Technical Information (OSTI.GOV)

McKeen, David

2009-06-01

WIMP-less dark matter [J. L. Feng and J. Kumar, Phys. Rev. Lett. 101, 231301 (2008).] offers an attractive framework in which dark matter can be very light. We investigate the implications of such scenarios on invisible decays of bottomonium states for dark matter with a mass less than around 5 GeV. We relate these decays to measurements of nucleon-dark matter elastic scattering. We also investigate the effect that a coupling to s quarks has on flavor changing b{yields}s processes involving missing energy.

High-sensitivity supercontinuum-based parallel line-field optical coherence tomography with 1 million A-lines/s (Conference Presentation)

NASA Astrophysics Data System (ADS)

Barrick, Jessica; Doblas, Ana; Sears, Patrick R.; Ostrowski, Lawrence E.; Oldenburg, Amy L.

2017-02-01

While traditional, flying-spot, spectral domain OCT systems can achieve MHz linerates, they are limited by the need for mechanical scanning to produce a B-mode image. Line-field OCT (LF OCT) removes the need for mechanical scanning by simultaneously recording all A-lines on a 2D CMOS sensor. Our LF OCT system operates at the highest A-line rate of any spectral domain (SD) LF OCT system reported to date (1,024,000 A-lines/s). This is comparable with the fastest flying-spot SDOCT system reported. Additionally, all OCT systems face a tradeoff between imaging speed and sensitivity. Long exposure times improve sensitivity but can lead to undesirable motion artifacts. LF OCT has the potential to relax this tradeoff between sensitivity and imaging speed because all A-lines are exposed during the entire frame acquisition time. However, this advantage has not yet been realized due to the loss of power-per-A-line by spreading the illumination light across all A-lines on the sample. Here we use a supercontinuum source to illuminate the sample with 500mW of light in the 605-950 nm wavelength band, effectively providing 480 µW of power-per-A-line, with axial and lateral resolutions of 1.8 µm and 14 µm, respectively. With this system we achieve the highest reported sensitivity (113 dB) of any LF OCT system. We then demonstrate the capability of this system by capturing the rapidly beating cilia of human bronchial-epithelial cells in vitro. The combination of high speed and high sensitivity offered by supercontinuum-based LF SD OCT offers new opportunities for studying cell and tissue dynamics.

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

PubMed

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

2010-05-28

Clinicians successfully utilize high uptake of radiolabeled glucose via PET scanning to localize metastases in melanoma patients. To take advantage of this altered metabolome, 3-bromopyruvate (BrPA) was used to overcome the notorious resistance of melanoma to cell death. Using four melanoma cell lines, BrPA triggered caspase independent necrosis in two lines, whilst the other two lines were resistant to killing. Mechanistically, sensitive cells differed from resistant cells by; constitutively lower levels of glutathione, reduction of glutathione by BrPA only in sensitive cells; increased superoxide anion reactive oxygen species, loss of outer mitochondrial membrane permeability, and rapid ATP depletion. Sensitive cell killing was blocked by N-acetylcysteine or glutathione. When glutathione levels were reduced in resistant cell lines, they became sensitive to killing by BrPA. Taken together, these results identify a metabolic-based Achilles' heel in melanoma cells to be exploited by use of BrPA. Future pre-clinical and clinical trials are warranted to translate these results into improved patient care for individuals suffering from metastatic melanoma. Copyright (c) 2010 Elsevier Inc. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qin, J.-Z.; Xin, H.; Nickoloff, B.J., E-mail: bnickol@lumc.edu

2010-05-28

Clinicians successfully utilize high uptake of radiolabeled glucose via PET scanning to localize metastases in melanoma patients. To take advantage of this altered metabolome, 3-bromopyruvate (BrPA) was used to overcome the notorious resistance of melanoma to cell death. Using four melanoma cell lines, BrPA triggered caspase independent necrosis in two lines, whilst the other two lines were resistant to killing. Mechanistically, sensitive cells differed from resistant cells by; constitutively lower levels of glutathione, reduction of glutathione by BrPA only in sensitive cells; increased superoxide anion reactive oxygen species, loss of outer mitochondrial membrane permeability, and rapid ATP depletion. Sensitive cellmore » 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.« less

Search for low-mass WIMPs in a 0.6 kg day exposure of the DAMIC experiment at SNOLAB

NASA Astrophysics Data System (ADS)

Aguilar-Arevalo, A.; Amidei, D.; Bertou, X.; Butner, M.; Cancelo, G.; Castañeda Vázquez, A.; Cervantes Vergara, B. A.; Chavarria, A. E.; Chavez, C. R.; de Mello Neto, J. R. T.; D'Olivo, J. C.; Estrada, J.; Fernandez Moroni, G.; Gaïor, R.; Guardincerri, Y.; Hernández Torres, K. P.; Izraelevitch, F.; Kavner, A.; Kilminster, B.; Lawson, I.; Letessier-Selvon, A.; Liao, J.; Mello, V. B. B.; Molina, J.; Peña, J. R.; Privitera, P.; Ramanathan, K.; Sarkis, Y.; Schwarz, T.; Sengul, C.; Settimo, M.; Sofo Haro, M.; Thomas, R.; Tiffenberg, J.; Tiouchichine, E.; Torres Machado, D.; Trillaud, F.; You, X.; Zhou, J.; Damic Collaboration

2016-10-01

We present results of a dark matter search performed with a 0.6 kg d exposure of the DAMIC experiment at the SNOLAB underground laboratory. We measure the energy spectrum of ionization events in the bulk silicon of charge-coupled devices down to a signal of 60 eV electron equivalent. The data are consistent with radiogenic backgrounds, and constraints on the spin-independent WIMP-nucleon elastic-scattering cross section are accordingly placed. A region of parameter space relevant to the potential signal from the CDMS-II Si experiment is excluded using the same target for the first time. This result obtained with a limited exposure demonstrates the potential to explore the low-mass WIMP region (<10 GeV c-2 ) with the upcoming DAMIC100, a 100 g detector currently being installed in SNOLAB.

Sites of ozone sensitivity in diverse maize inbred lines

USDA-ARS?s Scientific Manuscript database

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nobile, Eugenio Del; Gelmini, Graciela B.; Georgescu, Andreea

2015-08-25

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

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

NASA Astrophysics Data System (ADS)

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

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

Isolated Flinders Sensitive Line rats have decreased dopamine D2 receptor mRNA.

PubMed

Bjørnebekk, Astrid; Mathé, Aleksander A; Brené, Stefan

2007-07-02

Social isolation has profound effects on animal behavior and dopamine systems. We investigated the effect of social isolation on the dopamine receptor and neuropeptide mRNAs in the brain reward system in an animal model of depression, the Flinders Sensitive Line rats and Sprague-Dawley controls. We demonstrate that socially isolated but not group housed Flinders sensitive line rats had lower dopamine D2 receptor mRNA levels compared with Sprague-Dawley rats. Isolated and group housed Flinders Sensitive Line rats had higher levels of dopamine D1 receptor and substance P and enkephalin but not dynorphin mRNAs when compared with Sprague-Dawley rats. Our findings of decreased dopamine D2 receptor levels in socially isolated Flinders Sensitive Line rats suggest that low D2 receptor expression may play a role in pathophysiology of depression.

Last electroweak WIMP standing: pseudo-dirac higgsino status and compact stars as future probes

NASA Astrophysics Data System (ADS)

Krall, Rebecca; Reece, Matthew

2018-04-01

Electroweak WIMPs are under intense scrutiny from direct detection, indirect detection, and collider experiments. Nonetheless the pure (pseudo-Dirac) higgsino, one of the simplest such WIMPs, remains elusive. We present an up-to-date assessment of current experimental constraints on neutralino dark matter. The strongest bound on pure higgsino dark matter currently may arise from AMS-02 measurements of antiprotons, though the interpretation of these results has sizable uncertainty. We discuss whether future astrophysical observations could offer novel ways to test higgsino dark matter, especially in the challenging regime with order MeV mass splitting between the two neutral higgsinos. We find that heating of white dwarfs by annihilation of higgsinos captured via inelastic scattering could be one useful probe, although it will require challenging observations of distant dwarf galaxies or a convincing case to be made for substantial dark matter content in ω Cen, a globular cluster that may be a remnant of a disrupted dwarf galaxy. White dwarfs and neutron stars give a target for astronomical observations that could eventually help to close the last, most difficult corner of parameter space for dark matter with weak interactions. Supported by NSF (PHY-1415548) and NASA ATP (NNX16AI12G)

The neuroendocrine phenotype, genomic profile and therapeutic sensitivity of GEPNET cell lines

PubMed Central

Hofving, Tobias; Arvidsson, Yvonne; Almobarak, Bilal; Inge, Linda; Pfragner, Roswitha; Persson, Marta; Stenman, Göran; Kristiansson, Erik; Johanson, Viktor; Nilsson, Ola

2018-01-01

Experimental models of neuroendocrine tumour disease are scarce, and no comprehensive characterisation of existing gastroenteropancreatic neuroendocrine tumour (GEPNET) cell lines has been reported. In this study, we aimed to define the molecular characteristics and therapeutic sensitivity of these cell lines. We therefore performed immunophenotyping, copy number profiling, whole-exome sequencing and a large-scale inhibitor screening of seven GEPNET cell lines. Four cell lines, GOT1, P-STS, BON-1 and QGP-1, displayed a neuroendocrine phenotype while three others, KRJ-I, L-STS and H-STS, did not. Instead, these three cell lines were identified as lymphoblastoid. Characterisation of remaining authentic GEPNET cell lines by copy number profiling showed that GOT1, among other chromosomal alterations, harboured losses on chromosome 18 encompassing the SMAD4 gene, while P-STS had a loss on 11q. BON-1 had a homozygous loss of CDKN2A and CDKN2B, and QGP-1 harboured amplifications of MDM2 and HMGA2. Whole-exome sequencing revealed both disease-characteristic mutations (e.g. ATRX mutation in QGP-1) and, for patient tumours, rare genetic events (e.g. TP53 mutation in P-STS, BON-1 and QGP-1). A large-scale inhibitor screening showed that cell lines from pancreatic NETs to a greater extent, when compared to small intestinal NETs, were sensitive to inhibitors of MEK. Similarly, neuroendocrine NET cells originating from the small intestine were considerably more sensitive to a group of HDAC inhibitors. Taken together, our results provide a comprehensive characterisation of GEPNET cell lines, demonstrate their relevance as neuroendocrine tumour models and explore their therapeutic sensitivity to a broad range of inhibitors. PMID:29444910

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

PubMed Central

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

2012-01-01

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

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

PubMed

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

2012-03-28

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

Sensitivity of grounding line dynamics to basal conditions

NASA Astrophysics Data System (ADS)

Gagliardini, O.; Brondex, J.; Chauveau, G.; Gillet-chaulet, F.; Durand, G.

2017-12-01

In the context of a warming climate, the dynamical contribution of Antarctica to future sea level rise is still tainted by high uncertainties. Among the processes entering these uncertainties is the link between basal hydrology, friction and grounding line dynamics. Recent works have shown how sensitive is the response of the grounding line retreat to the choice of the form of the friction law. Indeed, starting from the same initial state, grounding line retreat rates can range over almost two orders of magnitude depending on the friction law formulation.Here, we use a phenomenological law that depends on the water pressure and allows a continuous transition from a Weertman-type friction at low water pressure to a Coulomb-type friction at high water pressure. This friction law depends on two main parameters that control the Weertman and Coulomb regimes. The range of values for these two parameters is only weakly physically constrained, and it can be shown that, for a given basal shear stress, different couples of parameters can conduct to the same sliding velocity. In addition, we show that close to the grounding line where basal water pressure is high, determining these two parameters might conduct to an ill-posed inverse problem with no solution.The aim of this presentation is to discuss a methodology to guide the choice of the two friction parameters and explore the sensitivity of the grounding line dynamics to this initial choice. We present results obtained both on a synthetic configuration used by the Marine Ice Sheet Model Intercomparison exercise and for the Amundsen sea sector using the experiments proposed by InitMIP-Antarctica, the first exercise in a series of ISMIP6 ice-sheet model intercomparison activities.

Search for low-mass WIMPs in a 0.6 kg day exposure of the DAMIC experiment at SNOLAB

DOE PAGES

Aguilar-Arevalo, A.

2016-10-27

In this paper, we present results of a dark matter search performed with a 0.6 kg d exposure of the DAMIC experiment at the SNOLAB underground laboratory. We measure the energy spectrum of ionization events in the bulk silicon of charge-coupled devices down to a signal of 60 eV electron equivalent. The data are consistent with radiogenic backgrounds, and constraints on the spin-independent WIMP-nucleon elastic-scattering cross section are accordingly placed. A region of parameter space relevant to the potential signal from the CDMS-II Si experiment is excluded using the same target for the first time. This result obtained with a limited exposure demonstratesmore » the potential to explore the low-mass WIMP region (<10 GeV c -2) with the upcoming DAMIC100, a 100 g detector currently being installed in SNOLAB.« less

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

NASA Astrophysics Data System (ADS)

Hill, Richard J.; Solon, Mikhail P.

2015-02-01

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

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

PubMed Central

2010-01-01

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

Increasing the sensitivity of LXe TPCs to dark matter by doping with helium or neon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lippincott, W. Hugh; Alexander, Thomas R.; Hime, Andrew

Next generation liquid xenon TPCs are poised to increase our sensitivity to dark matter by two orders of magnitude over a wide range of possible dark matter candidates. This proceedings describes an idea to expand the reach and flexibility of such detectors even further, by adding helium and neon to the xenon to enable searches for very light dark matter and combining high and low Z targets in the same detector. Adding helium or neon to LXe-TPCs has many advantages. First, the helium or neon target benefits from the excellent self-shielding provided by a large liquid xenon detector. Second, themore » same instrumentation, PMTs, and data acquisition can be used. Third, light nuclei are more robust to the systematic uncertainties that affect light WIMP searches. Fourth, helium and neon recoils will likely produce larger signals in liquid xenon than xenon recoils, achieving lower energy thresholds, and further increasing the sensitivity to light WIMPs. Finally, by adding He/Ne in sequence after a Xe-only run, the source of any observed signal can be isolated.« less

Increasing the sensitivity of LXe TPCs to dark matter by doping with helium or neon

DOE PAGES

Lippincott, W. Hugh; Alexander, Thomas R.; Hime, Andrew

2017-02-03

Next generation liquid xenon TPCs are poised to increase our sensitivity to dark matter by two orders of magnitude over a wide range of possible dark matter candidates. This proceedings describes an idea to expand the reach and flexibility of such detectors even further, by adding helium and neon to the xenon to enable searches for very light dark matter and combining high and low Z targets in the same detector. Adding helium or neon to LXe-TPCs has many advantages. First, the helium or neon target benefits from the excellent self-shielding provided by a large liquid xenon detector. Second, themore » same instrumentation, PMTs, and data acquisition can be used. Third, light nuclei are more robust to the systematic uncertainties that affect light WIMP searches. Fourth, helium and neon recoils will likely produce larger signals in liquid xenon than xenon recoils, achieving lower energy thresholds, and further increasing the sensitivity to light WIMPs. Finally, by adding He/Ne in sequence after a Xe-only run, the source of any observed signal can be isolated.« less

Identifying WIMP dark matter from particle and astroparticle data

NASA Astrophysics Data System (ADS)

Bertone, Gianfranco; Bozorgnia, Nassim; Kim, Jong Soo; Liem, Sebastian; McCabe, Christopher; Otten, Sydney; Ruiz de Austri, Roberto

2018-03-01

One of the most promising strategies to identify the nature of dark matter consists in the search for new particles at accelerators and with so-called direct detection experiments. Working within the framework of simplified models, and making use of machine learning tools to speed up statistical inference, we address the question of what we can learn about dark matter from a detection at the LHC and a forthcoming direct detection experiment. We show that with a combination of accelerator and direct detection data, it is possible to identify newly discovered particles as dark matter, by reconstructing their relic density assuming they are weakly interacting massive particles (WIMPs) thermally produced in the early Universe, and demonstrating that it is consistent with the measured dark matter abundance. An inconsistency between these two quantities would instead point either towards additional physics in the dark sector, or towards a non-standard cosmology, with a thermal history substantially different from that of the standard cosmological model.

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

PubMed

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

2014-01-01

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

High Sensitivity Absorption Spectroscopy on Ti II VUV Resonance Lines of Astrophysical Interest

NASA Astrophysics Data System (ADS)

Wiese, Lm; Fedchak, Ja; Lawler, Je

2000-06-01

The neutral hydrogen regions of the Interstellar Medium (ISM) of our Galaxy and distant galaxies produce simple absorption spectra because most metals are singly ionized and in their ground fine structure level. Elemental abundance measurements and other studies of the ISM rely on accurate atomic oscillator strengths (f-values) for a few key lines in the second spectra of Ti and other metals. The Ti II VUV resonance lines at 1910.6 and 1910.9 Åare important in absorption line systems in which quasars provide the continuum and the ISM of intervening galaxies is observed. Some of these absorption line systems are redshifted to the visible and observed with ground based telescopes. We report the first laboratory measurement of these Ti II VUV resonance lines. Using High Sensitivity Absorption Spectroscopy, we determined f-values for the 1910 Ålines relative to well-known Ti II resonance lines at 3067 and 3384 ÅContinuum radiation from an Aladdin Storage Ring bending magnet at the Synchrotron Radiation Center (SRC) is passed through a discharge plasma containing Ti^+. The transmitted light is analyzed by our 3m vacuum echelle spectrometer equipped with VUV sensitive CCD array. The resolving power of our spectrometer/detector array is 300,000. F-values are determined to within 10%.

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

DOE PAGES

Gómez-Vargas, Germán A.; Sánchez-Conde, Miguel A.; Huh, Ji -Haeng; ...

2013-10-16

Here, we derive constraints on parameters of generic dark matter candidates by comparing theoretical predictions with the gamma-ray emission observed by the Fermi-LAT from the region around the Galactic Center. Our analysis is conservative since it simply requires that the expected dark matter signal does not exceed the observed emission. The constraints obtained in the likely case that the collapse of baryons to the Galactic Center is accompanied by the contraction of the dark matter are strong. In particular, we find that for b b¯ and τ +τ – or W +W – dark matter annihilation channels, the upper limitsmore » on the annihilation cross section imply that the thermal cross section is excluded for a Weakly Interacting Massive Particle (WIMP) mass smaller than about 700 and 500 GeV, respectively. For the μ +μ – 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.« less

Delay-Line Three-Dimensional Position Sensitive Radiation Detection

NASA Astrophysics Data System (ADS)

Jeong, Manhee

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

Cytological characterization of a thermo-sensitive cytoplasmic male-sterile wheat line having K-type cytoplasm of Aegilops kotschyi.

PubMed

Meng, Liying; Liu, Zihan; Zhang, Lingli; Hu, Gan; Song, Xiyue

2016-12-01

Male sterility is an important tool for obtaining crop heterosis. A thermo-sensitive cytoplasmic male-sterile (TCMS) line was developed recently using a new method based on tiller regeneration. In the present study, we explored the critical growth stages required to maintain thermo-sensitive male sterility in TCMS lines and found that fertility is associated with abnormal tapetal and microspore development. We investigated the fertility and cytology of temperature-treated plant anthers at various developmental stages. TCMS line KTM3315A exhibited thermo-sensitive male sterility in Zadoks growth stages 41-49 and 58-59. Morphologically, the line exhibited thermo-sensitive male sterility at 3-9 days before heading and at 3-6 days before flowering, and it was partially restored in three locations during spring and summer. TCMS line KTM3315A plants exhibited premature tapetal programmed cell death (PCD) from the early uninucleate stage of microspore development until the tapetal cells degraded completely. Microspore development was then blocked and the pollen abortion type was stainable abortion. Thus, male fertility in the line KTM3315A is sensitive to temperature and premature tapetal PCD is the main cause of pollen abortion, where it determines the starting period and affects male fertility conversion in K-type TCMS lines at certain temperatures.

Azelaic acid was sensitizing effect in the chemotherapeutic treatment of several melanoma cell lines.

PubMed

Rodriguez-Vicente, J; Vicente-Ortega, V; Canteras-Jordana

1996-12-01

Chemotherapy for melanoma results in low response and must be reinforced with sensitizer compounds. We believed that azelaic acid (AZA) could modulate melanomas' resistance to antineoplastics. Therefore we tried to compare in vitro treatment with antineoplastics alone versus AZA treatment followed by antineoplastics. We carried out MTT assays to evaluate the cytotoxicity of melphalan, lomustine (CCNU), fotemustine, and 4-Hydroxyanisole (4-HA) on three melanoma lines (B16F10, SK-MEL-28, and SK-MEL-1), and the modulating effect of pretreatment with AZA (1 mM). AZA showed a dose-dependent antineoplastic activity on the three lines. Melphalan was the most active drug followed by CCNU, fotemustine, and 4-HA. The most sensitive line was B16F10 and the least sensitive was SK-meL-1. Previous treatment with AZA of B16F10 reinforced the effect of melphalan (2.5 times), CCNU (10 times), and fotemustine (14 times); whereas for SK-MEL-28 and SK-MEL-1, only the cytotoxicity of CCNU and fotemustine increased. An antagonist effect was produced by 4-HA on all three lines. We concluded that AZA enhances in vitro cytotoxicity of CCNU and fotemustine.

Raman spectroscopy differentiates between sensitive and resistant multiple myeloma cell lines

NASA Astrophysics Data System (ADS)

Franco, Domenico; Trusso, Sebastiano; Fazio, Enza; Allegra, Alessandro; Musolino, Caterina; Speciale, Antonio; Cimino, Francesco; Saija, Antonella; Neri, Fortunato; Nicolò, Marco S.; Guglielmino, Salvatore P. P.

2017-12-01

Current methods for identifying neoplastic cells and discerning them from their normal counterparts are often nonspecific and biologically perturbing. Here, we show that single-cell micro-Raman spectroscopy can be used to discriminate between resistant and sensitive multiple myeloma cell lines based on their highly reproducible biomolecular spectral signatures. In order to demonstrate robustness of the proposed approach, we used two different cell lines of multiple myeloma, namely MM.1S and U266B1, and their counterparts MM.1R and U266/BTZ-R subtypes, resistant to dexamethasone and bortezomib, respectively. Then, micro-Raman spectroscopy provides an easily accurate and noninvasive method for cancer detection for both research and clinical environments. Characteristic peaks, mostly due to different DNA/RNA ratio, nucleic acids, lipids and protein concentrations, allow for discerning the sensitive and resistant subtypes. We also explored principal component analysis (PCA) for resistant cell identification and classification. Sensitive and resistant cells form distinct clusters that can be defined using just two principal components. The identification of drug-resistant cells by confocal micro-Raman spectroscopy is thus proposed as a clinical tool to assess the development of resistance to glucocorticoids and proteasome inhibitors in myeloma cells.

Cytological characterization of a thermo-sensitive cytoplasmic male-sterile wheat line having K-type cytoplasm of Aegilops kotschyi

PubMed Central

Meng, Liying; Liu, Zihan; Zhang, Lingli; Hu, Gan; Song, Xiyue

2016-01-01

Male sterility is an important tool for obtaining crop heterosis. A thermo-sensitive cytoplasmic male-sterile (TCMS) line was developed recently using a new method based on tiller regeneration. In the present study, we explored the critical growth stages required to maintain thermo-sensitive male sterility in TCMS lines and found that fertility is associated with abnormal tapetal and microspore development. We investigated the fertility and cytology of temperature-treated plant anthers at various developmental stages. TCMS line KTM3315A exhibited thermo-sensitive male sterility in Zadoks growth stages 41–49 and 58–59. Morphologically, the line exhibited thermo-sensitive male sterility at 3–9 days before heading and at 3–6 days before flowering, and it was partially restored in three locations during spring and summer. TCMS line KTM3315A plants exhibited premature tapetal programmed cell death (PCD) from the early uninucleate stage of microspore development until the tapetal cells degraded completely. Microspore development was then blocked and the pollen abortion type was stainable abortion. Thus, male fertility in the line KTM3315A is sensitive to temperature and premature tapetal PCD is the main cause of pollen abortion, where it determines the starting period and affects male fertility conversion in K-type TCMS lines at certain temperatures. PMID:28163591

γ-radiation induces cellular sensitivity and aberrant methylation in human tumor cell lines.

PubMed

Kumar, Ashok; Rai, Padmalatha S; Upadhya, Raghavendra; Vishwanatha; Prasada, K Shama; Rao, B S Satish; Satyamoorthy, Kapettu

2011-11-01

Ionizing radiation induces cellular damage through both direct and indirect mechanisms, which may include effects from epigenetic changes. The purpose of this study was to determine the effect of ionizing radiation on DNA methylation patterns that may be associated with altered gene expression. Sixteen human tumor cell lines originating from various cancers were initially tested for radiation sensitivity by irradiating them with γ-radiation in vitro and subsequently, radiation sensitive and resistant cell lines were treated with different doses of a demethylating agent, 5-Aza-2'-Deoxycytidine (5-aza-dC) and a chromatin modifier, Trichostatin-A (TSA). Survival of these cell lines was measured using 3-(4, 5-Dimethylthiazol- 2-yl)-2, 5-diphenyltetrazolium (MTT) and clonogenic assays. The effect of radiation on global DNA methylation was measured using reverse phase high performance liquid chromatography (RP-HPLC). The transcription response of methylated gene promoters, from cyclin-dependent kinase inhibitor 2A (p16(INK4a)) and ataxia telangiectasia mutated (ATM) genes, to radiation was measured using a luciferase reporter assay. γ-radiation resistant (SiHa and MDAMB453) and sensitive (SaOS2 and WM115) tumor cell lines were examined for the relationship between radiation sensitivity and DNA methylation. Treatment of cells with 5-aza-dC and TSA prior to irradiation enhanced DNA strand breaks, G2/M phase arrest, apoptosis and cell death. Exposure to γ-radiation led to global demethylation in a time-dependent manner in tumor cells in relation to resistance and sensitivity to radiation with concomitant activation of p16(INK4a) and ATM gene promoters. These results provide important information on alterations in DNA methylation as one of the determinants of radiation effects, which may be associated with altered gene expression. Our results may help in delineating the mechanisms of radiation resistance in tumor cells, which can influence diagnosis, prognosis and

Dark matter experiment using Argon pulse-shape discrimination: DEAP-3600. Design and assembly

NASA Astrophysics Data System (ADS)

Jillings, C. J.; DEAP Collaboration

2016-12-01

DEAP-3600 is a single-phase liquid-argon dark matter detector that at time of writing is cooling down in preparation for filling at the SNOLAB facility near Sudbury, Ontario, Canada. DEAP-3600 is designed and constructed to achieve a sensitivity of 10-46cm2 for a WIMP-nucleon cross section for a 100 GeV WIMP. The steps taken in design and construction to achieve the ultra-low backgrounds required for such a sensitive WIMP search are reviewed.

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

PubMed

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

2015-02-01

Photodynamic therapy (PDT) with photosensitizer is one of the promising modalities for cancer treatment. For clinical use of PDT, screening process should be preceded to enhance sensitivity to PDT. Thus, we investigated a molecular biomarker to determine the sensitivity to pheophorbide a (Pa)-PDT in immortalized human oral keratinocytes (IHOK) and oral squamous cell carcinoma (OSCC) cell lines. Two IHOK and several OSCC cell lines were used. After Pa-PDT, cell viability was reduced by more than 50%, and reactive oxygen species were generated in IHOK and OSCC cell lines. Additionally, apoptosis occurred in PDT-treated cells. IHOK(S) and IHOK(P), the two IHOK cell lines derived from the same source, showed a difference in cytotoxicity after Pa-PDT. To explain this difference in cytotoxicity, we looked at the expression of Wnt signaling-related genes in these two cell lines, for the morphology of IHOK(S) which was spindle like and elongated and distinct from IHOK(P) and the parent cell. Among the relevant genes, runt-related transcription factor 3 (RUNX3), an apoptosis-related gene, was selected as a potential marker that confers sensitivity to PDT. We found that the cytotoxicity by Pa-PDT was proportional to RUNX3 expression in OSCC cell lines. Additionally, knockdown of RUNX3 expression reduced cytotoxicity by Pa-PDT, suggesting that RUNX3 might be a biomarker to determine sensitivity to Pa-PDT. This was the first study to find a new target molecule that enhances Pa-PDT effects in IHOK and OSCC cell lines. Hence, the development of a PDT-dependent biomarker could provide a novel approach to improve the effects of PDT on oral precancerous and cancerous lesions.

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

PubMed

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

2012-11-01

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

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

PubMed

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

2009-09-01

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

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

NASA Technical Reports Server (NTRS)

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

1985-01-01

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

Highly sensitive fetal goat tongue cell line for detection and isolation of foot-and-mouth disease virus.

PubMed

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

2009-10-01

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.

Social isolation increases number of newly proliferated cells in hippocampus in female flinders sensitive line rats.

PubMed

Bjørnebekk, Astrid; Mathé, Aleksander A; Gruber, Susanne H M; Brené, Stefan

2007-01-01

Genetic background influences the responsiveness to stress and plays a crucial role in the pathophysiology of depression. In an animal model of depression, Flinders Sensitive Line rats, and Sprague Dawley controls we analyzed if 7 weeks of social isolation of adult animals affect the number of newly proliferated cells in the dentate gyrus or mRNAs of Neuropeptide Y (NPY), the NPY-Y1 receptor, nociceptin, BDNF, and the serotonin 5HT1A and 5HT2A receptors, which are molecules involved in hippocampal plasticity. Since depressive illness more frequently affects women than men, and females seem to respond differently to stressful experiences than males, female rats were used in this study. Bromodeoxyuridine, which is a thymidin analogue that is incorporated into the DNA of newly formed cells, was administered during 9 days to even out the effects of hormonal fluctuations. Social isolation increased the number of newly proliferated Bromodeoxyuridine-immunoreactive cells in the Flinders Sensitive Line rats, whereas it had no impact on the number of cells in the Sprague Dawley strain. Group housed Sprague Dawley rats had a higher expression of BDNF, NPY, and the serotonin 5HT2A receptor mRNA than "depressed" Flinders Sensitive Line. Social isolation downregulated these molecules in Sprague Dawley but not in Flinders Sensitive Line rats thereby eliminating the differences between the two strains. We demonstrate strain and gender specific responses to stress induced regulation of factors important for hippocampal plasticity. (c) 2007 Wiley-Liss, Inc.

[Analysis of photoperiod-sensitivity genes in Minghui63, an restorer line of indica rice(Oryza sativa L.)].

PubMed

Luo, Lin-Guang; Xu, Jun-Feng; Zhai, Hu-Qu; Wan, Jian-Min

2003-09-01

Hybrid rice is very important in agriculture production in China. Its selecting property makes it significant to study the genetic performance of F1's date to heading (DH). Minghui63, an indica rice restorer line, has been widdly applied to hybrid rice seed production in China, but the photoperiod-sensitivity gene of heading date in this restorer line is still unknown. This definitely limited the further use of this restorer line in breeding practice and re-production of hybrid seeds. To solve this problem, using heading time nearly isogenic lines EGO-EG7, ER-LR and two heading date QTL-isogenic lines, NIL (Hd1) and NIL (Hd4), with the genes of Nipponbare but Hd1 (Se-1) and Hd4 (E1) genes from Kasalath, respectively, we performed a genetic analysis of Minghui63 with special reference to photoperiod-sensitivity loci, using natural long days in Nanjing(32 degrees N) and natural short days in Linshui county, Hainan province (18 degrees 29'N), where the average day-length is about 14 h and 11.6 h during the course of rice growing, respectively. The F1 and F2 generations from the crosses "heading time nearly isogenic lines x Minghui63" were subjected to genetic analyses. Experimental results showed that Minghui63 carries photoperiod-sensitivity allele gene E1 and E3 in E1 and E3 loci, respectly, and a photoperiod insensitivity allele Se-1e in Se-1 locus, and it also carries a recessive inhibitor for photoperiod-sensitivity gene E1. Meanwhile, the photoperiod-sensitive genes, E1 and the photoperiod-insensitive genes, Se-1e, in Minghui63 were also identified by crossing with the nearly isogenic lines for heading time QTLs, NIL (Hd1) and NIL(Hd4). The results indicated that Minghui63's genotype of heading date was: E1E1e2e2E3E3Se-1eSe-1e. The result from this research indicated that Minghui63 carries a major dominant photoperiod-sensitive gene E1 in E1 locus, and our previous researches indicated that Zhenshan97A carried a major dominant photoperiod-sensitive gene Se-1n in

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

PubMed Central

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

2015-01-01

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

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

PubMed

Asada, Hajime; Tomiyasu, Hirotaka; Goto-Koshino, Yuko; Fujino, Yasuhito; Ohno, Koichi; Tsujimoto, Hajime

2015-06-01

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Katsumi, Yoshiki; Iehara, Tomoko; Miyachi, Mitsuru

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

Mutation and repair in an ultraviolet-sensitive Chinese hamster ovary cell line

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wood, R.D.

1981-11-01

An ultraviolet (UV) light-sensitive mutant of Chinese hamster ovary cells (CHO) has been isolated and characterized with respect to a number of post-irradiation responses. The UV-sensitive mutant, termed 43-3B, has the same growth rate and chromosome number as the wild-type CHO-9. 43-3B is hypersensitive to the lethal effects of UV light (D/sub 0/ of 0.3 J/m/sup 2/ as compared to 3.2 J/m/sup 2/ for the wild-type). A marked UV-hypermutability is observed in 43-3B as compared to the wild-type, as measured with markers for induced resistance to 6-thioguanine, ouabain, and diphtheria toxin. A factor of 38 to 65 more mutations aremore » induced per unit fluence in 43-3B than in CHO-9. The UV-sensitive mutant is also sensitive to killing by simulated solar light, although the D/sub 0/ ratio is not as great as for germicidal UV. 43-3B exhibits only about 17% of the wild-type level of UV-stimulated DNA repair synthesis, as measured by autoradiography of G/sub 1/ phase cells. A much reduced ability to recover control rates of semiconservative DNA synthesis after UV irradiation was observed in the repair-deficient 43-3B cell line. Recovery of colony-forming ability between fractionated UV exposures was observed in the wild-type CHO-9, but little recovery was seen in 43-3B. The present investigation demonstrates that a sensitive/wild-type pair of CHO cell lines can be used in comparative studies to determine the involvement of repair in a wide range of post-irradiation phenomena.« less

Electron-density-sensitive Line Ratios of Fe XIII– XVI from Laboratory Sources Compared to CHIANTI

NASA Astrophysics Data System (ADS)

Weller, M. E.; Beiersdorfer, P.; Soukhanovskii, V. A.; Scotti, F.; LeBlanc, B. P.

2018-02-01

We present electron-density-sensitive line ratios for Fe XIII– XVI measured in the spectral wavelength range of 200–440 Å and an electron density range of (1–4) × 1013 cm‑3. The results provide a test at the high-density limit of density-sensitive line ratios useful for astrophysical studies. The measurements were performed on the National Spherical Torus Experiment-Upgrade, where electron densities were measured independently by the laser Thomson scattering diagnostic. Spectra were collected with a flat-field grazing-incidence spectrometer, which provided a spectral resolution of up to 0.3 Å, i.e., high resolution across the broad wavelength range. The response of the instrument was relatively calibrated using spectroscopic techniques in order to improve accuracy. The line ratios are compared to other laboratory sources and the latest version of CHIANTI (8.0.2), and an agreement within 30% is found.

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

NASA Astrophysics Data System (ADS)

Dahl, Carl Eric

2009-06-01

The WIMP limit set by the Xenon10 experiment in 2007 signals a new era in direct detection of dark matter, with several large-scale liquid target detectors now under construction. A major challenge in these detectors will be to understand backgrounds at the level necessary to claim a positive WIMP signal. In liquid xenon, these backgrounds are dominated by electron recoils, which may be distinguished from the WIMP signal (nuclear recoils) by their higher charge-to-light ratio. During the construction and operation of Xenon10, the prototype detector Xed probed the physics of this discrimination. Particle interactions in liquid xenon both ionize and excite xenon atoms, giving charge and scintillation signals, respectively. Some fraction of ions recombine, reducing the charge signal and creating additional scintillation. The charge-to-light ratio, determined by the initial exciton-ion ratio and the ion recombination fraction, provides the basis for discrimination between electron and nuclear recoils. Intrinsic fluctuations in the recombination fraction limit discrimination. Changes in recombination induce an exact anti-correlation between charge and light, and when calibrated this anti-correlation distinguishes recombination fluctuations from uncorrelated fluctuations in the measured signals. We determine the mean recombination and recombination fluctuations as a function of energy and applied field for electron and nuclear recoils, finding that recombination fluctuations are already the limiting factor for discrimination above ~12 keVr (nuclear recoil energy). Below 12 keVr statistical fluctuations in the number of scintillation photons counted dominate, and we project a x6 improvement in background rejection with a x2 increase in light collection efficiency. We also build a simple recombination model that successfully reproduces the mean recombination in electron and nuclear recoils, including the surprising reversal of the expected trend for recombination with

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

NASA Astrophysics Data System (ADS)

Wang, Lu; Mei, Dongming

2014-03-01

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

Electron-density-sensitive Line Ratios of Fe xiii– xvi from Laboratory Sources Compared to CHIANTI

DOE PAGES

Weller, M. E.; Beiersdorfer, P.; Soukhanovskii, V. A.; ...

2018-02-15

We present electron-density-sensitive line ratios for Fe xiii– xvi measured in the spectral wavelength range of 200–440 Å and an electron density range of (1-4) × 10 13 cm -3. The results provide a test at the high-density limit of density-sensitive line ratios useful for astrophysical studies. The measurements were performed on the National Spherical Torus Experiment-Upgrade, where electron densities were measured independently by the laser Thomson scattering diagnostic. Spectra were collected with a flat-field grazing-incidence spectrometer, which provided a spectral resolution of up to 0.3 Å, i.e., high resolution across the broad wavelength range. The response of the instrumentmore » was relatively calibrated using spectroscopic techniques in order to improve accuracy. Lastly, the line ratios are compared to other laboratory sources and the latest version of CHIANTI (8.0.2), and an agreement within 30% is found.« less

Electron-density-sensitive Line Ratios of Fe xiii– xvi from Laboratory Sources Compared to CHIANTI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weller, M. E.; Beiersdorfer, P.; Soukhanovskii, V. A.

We present electron-density-sensitive line ratios for Fe xiii– xvi measured in the spectral wavelength range of 200–440 Å and an electron density range of (1-4) × 10 13 cm -3. The results provide a test at the high-density limit of density-sensitive line ratios useful for astrophysical studies. The measurements were performed on the National Spherical Torus Experiment-Upgrade, where electron densities were measured independently by the laser Thomson scattering diagnostic. Spectra were collected with a flat-field grazing-incidence spectrometer, which provided a spectral resolution of up to 0.3 Å, i.e., high resolution across the broad wavelength range. The response of the instrumentmore » was relatively calibrated using spectroscopic techniques in order to improve accuracy. Lastly, the line ratios are compared to other laboratory sources and the latest version of CHIANTI (8.0.2), and an agreement within 30% is found.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Collaboration: ANTARES Collaboration

A search for high-energy neutrinos coming from the direction of the Galactic Centre is performed using the data recorded by the ANTARES neutrino telescope from 2007 to 2012. The event selection criteria are chosen to maximise the sensitivity to possible signals produced by the self-annihilation of weakly interacting massive particles accumulated around the centre of the Milky Way with respect to the atmospheric background. After data unblinding, the number of neutrinos observed in the line of sight of the Galactic Centre is found to be compatible with background expectations. The 90% C.L. upper limits in terms of the neutrino+anti-neutrino flux,more » Φ{sub ν{sub μ+ν-bar}} {sub μ}, and the velocity averaged annihilation cross-section, (σ{sub A}v), are derived for the WIMP self-annihilation channels into b b-bar , W{sup +}W{sup −}, τ{sup +}τ{sup −}, μ{sup +}μ{sup −}, νν-bar . The ANTARES limits for (σ{sub A}v) are shown to be the most stringent for a neutrino telescope over the WIMP masses 25 GeV < M{sub WIMP} < 10 TeV.« less

A Low-threshold Analysis of Data from the Cryogenic Dark Matter Search Experiment

NASA Astrophysics Data System (ADS)

Bunker, Raymond A., III

Although dark matter appears to constitute over 80% of the matter in the Universe, its composition is a mystery. Astrophysical observations suggest that the luminous portions of the Galaxy are embedded in a halo of darkmatter particles. Weakly Interacting Massive Particles (WIMPs) are the most studied class of dark-matter candidates and arise naturally within the context of many weak-scale supersymmetric theories. Direct-detection experiments like the Cryogenic Dark Matter Search (CDMS) strive to discern the kinetic energy of recoiling nuclei resulting from WIMP interactions with terrestrial matter. This is a considerable challenge in which the low (expected) rate of WIMP interactions must be distinguished from an overwhelming rate due to known types of radiation. An incontrovertible positive detection has remained elusive. However, a few experiments have recorded data that appear consistent with a low-mass WIMP. This thesis describes an attempt to probe the favored parameter space. To increase sensitivity to low-mass WIMPs, a low-threshold technique with improved sensitivity to small energy depositions is applied to CDMS shallow-site data. Four germanium and two silicon detectors were operated between December 2001 and June 2002, yielding 118 days of exposure. By sacrificing some of the CDMS detectors' ability to discriminate signal from background, energy thresholds of ˜1 and ˜2 keV were achieved for three of the germanium and both silicon detectors, respectively. A large number of WIMP candidate events are observed, most of which can be accounted for by misidentification of background sources. No conclusive evidence for a low-mass WIMP signal is found. The observed event rates are used to set upper limits on the WIMPnucleon scattering cross section as a function of WIMP mass. Interesting parameter space is excluded for WIMPs with masses below ˜9GeV/c 2. Under standard assumptions, the parameter space favored by interpretations of other experiments' data as

Specific down-regulation of XIAP with RNA interference enhances the sensitivity of canine tumor cell-lines to TRAIL and doxorubicin

PubMed Central

Spee, Bart; Jonkers, Martijn DB; Arends, Brigitte; Rutteman, Gerard R; Rothuizen, Jan; Penning, Louis C

2006-01-01

Background Apoptosis resistance occurs in various tumors. The anti-apoptotic XIAP protein is responsible for inhibiting apoptosis by reducing caspase-3 activation. Our aim is to evaluate whether RNA inhibition against XIAP increases the sensitivity of canine cell-lines for chemotherapeutics such as TRAIL and doxorubicin. We used small interfering RNA's (siRNA) directed against XIAP in three cell-lines derived from bile-duct epithelia (BDE), mammary carcinoma (P114), and osteosarcoma (D17). These cell-lines represent frequently occurring canine cancers and are highly comparable to their human counterparts. XIAP down-regulation was measured by means of quantitative PCR (Q-PCR) and Western blotting. The XIAP depleted cells were treated with a serial dilution of TRAIL or doxorubicin and compared to mock- and nonsense-treated controls. Viability was measured with a MTT assay. Results All XIAP siRNA treated cell-lines showed a mRNA down-regulation over 80 percent. Western blot analysis confirmed mRNA measurements. No compensatory effect of IAP family members was seen in XIAP depleted cells. The sensitivity of XIAP depleted cells for TRAIL was highest in BDE cells with an increase in the ED50 of 14-fold, compared to mock- and nonsense-treated controls. The sensitivity of P114 and D17 cell-lines increased six- and five-fold, respectively. Doxorubicin treatment in XIAP depleted cells increased sensitivity in BDE cells more than eight-fold, whereas P114 and D17 cell-lines showed an increase in sensitivity of three- and five-fold, respectively. Conclusion XIAP directed siRNA's have a strong sensitizing effect on TRAIL-reduced cell-viability and a smaller but significant effect with the DNA damaging drug doxorubicin. The increase in efficacy of chemotherapeutics with XIAP depletion provides the rationale for the use of XIAP siRNA's in insensitive canine tumors. PMID:16953886

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2006-01-15

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

Results on the Spin-Dependent Scattering of Weakly Interacting Massive Particles on Nucleons from the Run 3 Data of the LUX Experiment

NASA Astrophysics Data System (ADS)

Akerib, D. S.; Araújo, H. M.; Bai, X.; Bailey, A. J.; Balajthy, J.; Beltrame, P.; Bernard, E. P.; Bernstein, A.; Biesiadzinski, T. P.; Boulton, E. M.; Bradley, A.; Bramante, R.; Cahn, S. B.; Carmona-Benitez, M. C.; Chan, C.; Chapman, J. J.; Chiller, A. A.; Chiller, C.; Currie, A.; Cutter, J. E.; Davison, T. J. R.; de Viveiros, L.; Dobi, A.; Dobson, J. E. Y.; Druszkiewicz, E.; Edwards, B. N.; Faham, C. H.; Fiorucci, S.; Gaitskell, R. J.; Gehman, V. M.; Ghag, C.; Gibson, K. R.; Gilchriese, M. G. D.; Hall, C. R.; Hanhardt, M.; Haselschwardt, S. J.; Hertel, S. A.; Hogan, D. P.; Horn, M.; Huang, D. Q.; Ignarra, C. M.; Ihm, M.; Jacobsen, R. G.; Ji, W.; Kazkaz, K.; Khaitan, D.; Knoche, R.; Larsen, N. A.; Lee, C.; Lenardo, B. G.; Lesko, K. T.; Lindote, A.; Lopes, M. I.; Malling, D. C.; Manalaysay, A.; Mannino, R. L.; Marzioni, M. F.; McKinsey, D. N.; Mei, D.-M.; Mock, J.; Moongweluwan, M.; Morad, J. A.; Murphy, A. St. J.; Nehrkorn, C.; Nelson, H. N.; Neves, F.; O'Sullivan, K.; Oliver-Mallory, K. C.; Ott, R. A.; Palladino, K. J.; Pangilinan, M.; Pease, E. K.; Phelps, P.; Reichhart, L.; Rhyne, C.; Shaw, S.; Shutt, T. A.; Silva, C.; Solovov, V. N.; Sorensen, P.; Stephenson, S.; Sumner, T. J.; Szydagis, M.; Taylor, D. J.; Taylor, W.; Tennyson, B. P.; Terman, P. A.; Tiedt, D. R.; To, W. H.; Tripathi, M.; Tvrznikova, L.; Uvarov, S.; Verbus, J. R.; Webb, R. C.; White, J. T.; Whitis, T. J.; Witherell, M. S.; Wolfs, F. L. H.; Yazdani, K.; Young, S. K.; Zhang, C.; LUX Collaboration

2016-04-01

We present experimental constraints on the spin-dependent WIMP (weakly interacting massive particle)-nucleon elastic cross sections from LUX data acquired in 2013. LUX is a dual-phase xenon time projection chamber operating at the Sanford Underground Research Facility (Lead, South Dakota), which is designed to observe the recoil signature of galactic WIMPs scattering from xenon nuclei. A profile likelihood ratio analysis of 1.4 ×104 kg day of fiducial exposure allows 90% C.L. upper limits to be set on the WIMP-neutron (WIMP-proton) cross section of σn=9.4 ×10-41 cm2 (σp=2.9 ×10-39 cm2 ) at 33 GeV /c2 . The spin-dependent WIMP-neutron limit is the most sensitive constraint to date.

Identification of biomarkers in human head and neck tumor cell lines that predict for in vitro sensitivity to gefitinib.

PubMed

Hickinson, D Mark; Marshall, Gayle B; Beran, Garry J; Varella-Garcia, Marileila; Mills, Elizabeth A; South, Marie C; Cassidy, Andrew M; Acheson, Kerry L; McWalter, Gael; McCormack, Rose M; Bunn, Paul A; French, Tim; Graham, Alex; Holloway, Brian R; Hirsch, Fred R; Speake, Georgina

2009-06-01

Potential biomarkers were identified for in vitro sensitivity to the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib in head and neck cancer. Gefitinib sensitivity was determined in cell lines, followed by transcript profiling coupled with a novel pathway analysis approach. Eleven cell lines were highly sensitive to gefitinib (inhibitor concentration required to give 50% growth inhibition [GI(50)] < 1 microM), three had intermediate sensitivity (GI(50) 1-7 microM), and six were resistant (GI(50) > 7 microM); an exploratory principal component analysis revealed a separation between the genomic profiles of sensitive and resistant cell lines. Subsequently, a hypothesis-driven analysis of Affymetrix data (Affymetrix, Inc., Santa Clara, CA, USA) revealed higher mRNA levels for E-cadherin (CDH1); transforming growth factor, alpha (TGF-alpha); amphiregulin (AREG); FLJ22662; EGFR; p21-activated kinase 6 (PAK6); glutathione S-transferase Pi (GSTP1); and ATP-binding cassette, subfamily C, member 5 (ABCC5) in sensitive versus resistant cell lines. A hypothesis-free analysis identified 46 gene transcripts that were strongly differentiated, seven of which had a known association with EGFR and head and neck cancer (human EGF receptor 3 [HER3], TGF-alpha, CDH1, EGFR, keratin 16 [KRT16], fibroblast growth factor 2 [FGF2], and cortactin [CTTN]). Polymerase chain reaction (PCR) and enzyme-linked immunoabsorbant assay analysis confirmed Affymetrix data, and EGFR gene mutation, amplification, and genomic gain correlated strongly with gefitinib sensitivity. We identified biomarkers that predict for in vitro responsiveness to gefitinib, seven of which have known association with EGFR and head and neck cancer. These in vitro predictive biomarkers may have potential utility in the clinic and warrant further investigation.

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

PubMed

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

2016-08-01

ME-344 [(3R,4S)-3,4-bis(4-hydroxyphenyl)-8-methyl-3,4-dihydro-2H-chromen-7-ol] is a second-generation derivative natural product isoflavone presently under clinical development. ME-344 effects were compared in lung cancer cell lines that are either intrinsically sensitive or resistant to the drug and in primary immortalized human lung embryonic fibroblasts (IHLEF). Cytotoxicity at low micromolar concentrations occurred only in sensitive cell lines, causing redox stress, decreased mitochondrial ATP production, and subsequent disruption of mitochondrial function. In a dose-dependent manner the drug caused instantaneous and pronounced inhibition of oxygen consumption rates (OCR) in drug-sensitive cells (quantitatively significantly less in drug-resistant cells). This was consistent with targeting of mitochondria by ME-344, with specific effects on the respiratory chain (resistance correlated with higher glycolytic indexes). OCR inhibition did not occur in primary IHLEF. ME-344 increased extracellular acidification rates in drug-resistant cells (significantly less in drug-sensitive cells), implying that ME-344 targets mitochondrial proton pumps. Only in drug-sensitive cells did ME-344 dose-dependently increase the intracellular generation of reactive oxygen species and cause oxidation of total (mainly glutathione) and protein thiols and the concomitant immediate increases in NADPH levels. We conclude that ME-344 causes complex, redox-specific, and mitochondria-targeted effects in lung cancer cells, which differ in extent from normal cells, correlate with drug sensitivity, and provide indications of a beneficial in vitro therapeutic index. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Effect of sulphur mustard on human skin cell lines with differential agent sensitivity.

PubMed

Simpson, Rachel; Lindsay, Christopher D

2005-01-01

The ability of sulphur mustard (HD) to induce DNA damage places limits on the efficacy of approaches aimed at protecting human cells from the cytotoxic effects of HD using a variety of protective agents such as thiol-containing esters and protease inhibitors. In the present study, potential alternative strategies were investigated by examining the differential effects of HD on G361, SVK14, HaCaT and NCTC 2544 human skin cells. The G361 cell line was more resistant to the cytotoxic effects of HD than the NCTC, HaCaT and SVK14 cell lines at HD doses of >3 and <100 microM HD as determined by the MTT assay. At 72 h after exposure to 60 microM HD there was up to an 8.8-fold difference (P < 0.0001) between G361 and SVK14 cell culture viability. Buthionine sulphoximine (BSO) pretreatment increased the sensitivity of all four cell lines to HD. A substantial proportion of the resistance of G361 cells to HD was attributable to BSO-mediated effects on antioxidant-mediated metabolism, although G361 cultures still retained a high degree of viability at 30 microM HD following BSO pretreatment. Cell cycle analysis confirmed that SVK14 cells were relatively more sensitive to HD, as shown by the 2.1-fold reduction (P < 0.0001) in the percentage of cells in G0/G1 phase 24 h after HD exposure compared with control cultures. This compared well with a 1.2-fold increase (P < 0.05) in the percentage of G361 cells in G0/G1 phase following HD exposure, suggesting the existence of a more efficient G0/G1 checkpoint control mechanism in this cell line. Manipulation of the cell cycle using various modulating agents did not increase the resistance of cell lines to the cytotoxic effects of HD. Crown copyright 2005

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

NASA Technical Reports Server (NTRS)

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

1986-01-01

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

Indirect searches for dark matter with the Fermi large area telescope

DOE PAGES

Albert, Andrea

2015-03-24

There is overwhelming evidence that non-baryonic dark matter constitutes ~ 27% of the energy density of the Universe. Weakly Interacting Massive Particles (WIMPs) are promising dark matter candidates that may produce γ rays via annihilation or decay detectable by the Fermi Large Area Telescope (LAT). A detection of WIMPs would also indicate the existence of physics beyond the Standard Model. We present recent results from the two cleanest indirect WIMP searches by the Fermi-LAT Collaboration: searches for γ-ray spectral lines and γ-ray emission associated with Milky Way dwarf spheroidal satellite galaxies.

Status and perspective of the DarkSide experiment at LNGS

DOE PAGES

Agnes, P.

2018-09-01

The DarkSide experiment aims to perform a background-free direct search for dark matter with a dual-phase argon TPC. The current phase of the experiment, DarkSide-50, is acquiring data at Laboratori Nazionali del Gran Sasso and produced the most sensitive limit on the WIMP-nucleon cross section ever obtained with a liquid argon target (2.0 × 10 -44 cm2 for a WIMP mass of 100 GeV/c 2). The future phase of the experiment will be a 20 t fiducial mass detector, designed to reach a sensitivity of ~1 × 10 -47 cm2 (at 1 TeV/c 2 WIMP mass) with a background-free exposuremore » of 100 ty. Here, this work contains a discussion of the current status of the DarkSide-50 WIMP search and of the results which are more relevant for the construction of the future detector.« less

Status and perspective of the DarkSide experiment at LNGS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agnes, P.

The DarkSide experiment aims to perform a background-free direct search for dark matter with a dual-phase argon TPC. The current phase of the experiment, DarkSide-50, is acquiring data at Laboratori Nazionali del Gran Sasso and produced the most sensitive limit on the WIMP-nucleon cross section ever obtained with a liquid argon target (2.0 × 10 -44 cm2 for a WIMP mass of 100 GeV/c 2). The future phase of the experiment will be a 20 t fiducial mass detector, designed to reach a sensitivity of ~1 × 10 -47 cm2 (at 1 TeV/c 2 WIMP mass) with a background-free exposuremore » of 100 ty. Here, this work contains a discussion of the current status of the DarkSide-50 WIMP search and of the results which are more relevant for the construction of the future detector.« less

Indirect detection of Particle Dark Matter with gamma rays - status and perspectives

NASA Astrophysics Data System (ADS)

Conrad, Jan

2014-03-01

In this contribution I review the present status and discuss some prospects for indirect detection of dark matter with gamma rays. Thanks mainly to the Fermi Large Area Telescope (Fermi-LAT), searches in gamma-rays have reached sensitivities that allow to probe the most interesting parameter space of the weakly interacting massive particles (WIMP) paradigm. This gain in sensitivity is naturally accompanied by a number of detection claims or indications. At WIMP masses above roughly a TeV current Imaging Air Cherenkov Telescopes (HESS, VERITAS, MAGIC) become more sensitive than the Fermi-LAT, the most promising recent development being the first light for the second phase HESS II telescope with significantly lower energy threshold. Predictions for the next generation air Cherenkov telescope, Cherenkov Telescope Array (CTA), together with forecasts on future Fermi-LAT constraints arrive at the exciting possibility that the cosmological benchmark cross-section could be probed from masses of a few GeV to a few TeV. Consequently, non-detection would pose a challenge to the WIMP paradigm, but the reached sensitivities also imply that-optimistically-a detection within the next decade is in the cards. Time allowing, I will comment on complementarity between the different approaches to WIMP detection.

The Xenon1T Dark Matter Search Experiment

NASA Astrophysics Data System (ADS)

Aprile, Elena

The worldwide race towards direct dark matter detection in the form of Weakly Interacting Massive Particles (WIMPs) has been dramatically accelerated by the remarkable progress and evolution of liquid xenon time projection chambers (LXeTPCs). With a realistic discovery potential, Xenon100 has already reached a sensitivity of 7 × 10-45 cm2, and continues to accrue data at the Laboratori Nazionali del Gran Sasso (LNGS) in Italy towards its ultimate sensitivity reach at the σ SI ˜ 2 × 10-45 cm2 level for the spin-independent WIMP-nucleon cross-section. To fully explore the favoured parameter space for WIMP dark matter in search of a first robust and statistically significant discovery, or to confirm any hint of a signal from Xenon100, the next phase of the Xenon program will be a detector at the ton scale - Xenon1T. The Xenon1T detector, based on 2.2 ton of LXe viewed by low radioactivity photomultiplier tubes and housed in a water Cherenkov muon veto at LNGS, is presented. With an experimental aim of probing WIMP interaction cross-sections above of order σ SI ˜ 2 × 10-47 cm2 within 2 years of operation, Xenon1T will provide the sensitivity to probe a particularly favourable region of electroweak physics on a timescale compatible with complementary ground and satellite based indirect searches and with accelerator dark matter searches at the LHC. Indeed, for a σ SI ˜ 10-45 cm2 and 100 GeV/c2 WIMP mass, Xenon1T could detect of order 100 events in this exposure, providing statistics for placing significant constraints on the WIMP mass.

Inelastic dark matter with spin-dependent couplings to protons and large modulation fractions in DAMA

NASA Astrophysics Data System (ADS)

Scopel, Stefano; Yoon, Kook-Hyun

2016-02-01

We discuss a scenario where the DAMA modulation effect is explained by a Weakly Interacting Massive Particle (WIMP) which upscatters inelastically to a heavier state and predominantly couples to the spin of protons. In this scenario constraints from xenon and germanium targets are evaded dynamically, due to the suppression of the WIMP coupling to neutrons, while those from fluorine targets are evaded kinematically, because the minimal WIMP incoming speed required to trigger upscatters off fluorine exceeds the maximal WIMP velocity in the Galaxy, or is very close to it. In this scenario WIMP scatterings off sodium are usually sensitive to the large-speed tail of the WIMP velocity distribution and modulated fractions of the signal close to unity arise in a natural way. On the other hand, a halo-independent analysis with more conservative assumptions about the WIMP velocity distribution allows to extend the viable parameter space to configurations where large modulated fractions are not strictly necessary. We discuss large modulated fractions in the Maxwellian case showing that they imply a departure from the usual cosine time dependence of the expected signal in DAMA. However we explicitly show that the DAMA data is not sensitive to this distortion, both in time and frequency space, even in the extreme case of a 100 % modulated fraction. Moreover the same scenario provides an explanation of the maximum in the energy spectrum of the modulation amplitude detected by DAMA in terms of WIMPs whose minimal incoming speed matches the kinematic threshold for inelastic upscatters. For the elastic case the detection of such maximum suggests an inversion of the modulation phase below the present DAMA energy threshold, while this is not expected for inelastic scattering. This may allow to discriminate between the two scenarios in a future low-threshold analysis of the DAMA data.

Inelastic dark matter with spin-dependent couplings to protons and large modulation fractions in DAMA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scopel, Stefano; Yoon, Kook-Hyun, E-mail: scopel@sogang.ac.kr, E-mail: koreasds@naver.com

2016-02-01

We discuss a scenario where the DAMA modulation effect is explained by a Weakly Interacting Massive Particle (WIMP) which upscatters inelastically to a heavier state and predominantly couples to the spin of protons. In this scenario constraints from xenon and germanium targets are evaded dynamically, due to the suppression of the WIMP coupling to neutrons, while those from fluorine targets are evaded kinematically, because the minimal WIMP incoming speed required to trigger upscatters off fluorine exceeds the maximal WIMP velocity in the Galaxy, or is very close to it. In this scenario WIMP scatterings off sodium are usually sensitive tomore » the large-speed tail of the WIMP velocity distribution and modulated fractions of the signal close to unity arise in a natural way. On the other hand, a halo-independent analysis with more conservative assumptions about the WIMP velocity distribution allows to extend the viable parameter space to configurations where large modulated fractions are not strictly necessary. We discuss large modulated fractions in the Maxwellian case showing that they imply a departure from the usual cosine time dependence of the expected signal in DAMA. However we explicitly show that the DAMA data is not sensitive to this distortion, both in time and frequency space, even in the extreme case of a 100 % modulated fraction. Moreover the same scenario provides an explanation of the maximum in the energy spectrum of the modulation amplitude detected by DAMA in terms of WIMPs whose minimal incoming speed matches the kinematic threshold for inelastic upscatters. For the elastic case the detection of such maximum suggests an inversion of the modulation phase below the present DAMA energy threshold, while this is not expected for inelastic scattering. This may allow to discriminate between the two scenarios in a future low-threshold analysis of the DAMA data.« less

Results from a Search for Dark Matter in the Complete LUX Exposure

NASA Astrophysics Data System (ADS)

Akerib, D. S.; Alsum, S.; Araújo, H. M.; Bai, X.; Bailey, A. J.; Balajthy, J.; Beltrame, P.; Bernard, E. P.; Bernstein, A.; Biesiadzinski, T. P.; Boulton, E. M.; Bramante, R.; Brás, P.; Byram, D.; Cahn, S. B.; Carmona-Benitez, M. C.; Chan, C.; Chiller, A. A.; Chiller, C.; Currie, A.; Cutter, J. E.; Davison, T. J. R.; Dobi, A.; Dobson, J. E. Y.; Druszkiewicz, E.; Edwards, B. N.; Faham, C. H.; Fiorucci, S.; Gaitskell, R. J.; Gehman, V. M.; Ghag, C.; Gibson, K. R.; Gilchriese, M. G. D.; Hall, C. R.; Hanhardt, M.; Haselschwardt, S. J.; Hertel, S. A.; Hogan, D. P.; Horn, M.; Huang, D. Q.; Ignarra, C. M.; Ihm, M.; Jacobsen, R. G.; Ji, W.; Kamdin, K.; Kazkaz, K.; Khaitan, D.; Knoche, R.; Larsen, N. A.; Lee, C.; Lenardo, B. G.; Lesko, K. T.; Lindote, A.; Lopes, M. I.; Manalaysay, A.; Mannino, R. L.; Marzioni, M. F.; McKinsey, D. N.; Mei, D.-M.; Mock, J.; Moongweluwan, M.; Morad, J. A.; Murphy, A. St. J.; Nehrkorn, C.; Nelson, H. N.; Neves, F.; O'Sullivan, K.; Oliver-Mallory, K. C.; Palladino, K. J.; Pease, E. K.; Phelps, P.; Reichhart, L.; Rhyne, C.; Shaw, S.; Shutt, T. A.; Silva, C.; Solmaz, M.; Solovov, V. N.; Sorensen, P.; Stephenson, S.; Sumner, T. J.; Szydagis, M.; Taylor, D. J.; Taylor, W. C.; Tennyson, B. P.; Terman, P. A.; Tiedt, D. R.; To, W. H.; Tripathi, M.; Tvrznikova, L.; Uvarov, S.; Verbus, J. R.; Webb, R. C.; White, J. T.; Whitis, T. J.; Witherell, M. S.; Wolfs, F. L. H.; Xu, J.; Yazdani, K.; Young, S. K.; Zhang, C.; LUX Collaboration

2017-01-01

We report constraints on spin-independent weakly interacting massive particle (WIMP)-nucleon scattering using a 3.35 ×1 04 kg day exposure of the Large Underground Xenon (LUX) experiment. A dual-phase xenon time projection chamber with 250 kg of active mass is operated at the Sanford Underground Research Facility under Lead, South Dakota (USA). With roughly fourfold improvement in sensitivity for high WIMP masses relative to our previous results, this search yields no evidence of WIMP nuclear recoils. At a WIMP mass of 50 GeV c-2 , WIMP-nucleon spin-independent cross sections above 2.2 ×10-46 cm2 are excluded at the 90% confidence level. When combined with the previously reported LUX exposure, this exclusion strengthens to 1.1 ×10-46 cm2 at 50 GeV c-2 .

Results on the Spin-Dependent Scattering of Weakly Interacting Massive Particles on Nucleons from the Run 3 Data of the LUX Experiment.

PubMed

Akerib, D S; Araújo, H M; Bai, X; Bailey, A J; Balajthy, J; Beltrame, P; Bernard, E P; Bernstein, A; Biesiadzinski, T P; Boulton, E M; Bradley, A; Bramante, R; Cahn, S B; Carmona-Benitez, M C; Chan, C; Chapman, J J; Chiller, A A; Chiller, C; Currie, A; Cutter, J E; Davison, T J R; de Viveiros, L; Dobi, A; Dobson, J E Y; Druszkiewicz, E; Edwards, B N; Faham, C H; Fiorucci, S; Gaitskell, R J; Gehman, V M; Ghag, C; Gibson, K R; Gilchriese, M G D; Hall, C R; Hanhardt, M; Haselschwardt, S J; Hertel, S A; Hogan, D P; Horn, M; Huang, D Q; Ignarra, C M; Ihm, M; Jacobsen, R G; Ji, W; Kazkaz, K; Khaitan, D; Knoche, R; Larsen, N A; Lee, C; Lenardo, B G; Lesko, K T; Lindote, A; Lopes, M I; Malling, D C; Manalaysay, A; Mannino, R L; Marzioni, M F; McKinsey, D N; Mei, D-M; Mock, J; Moongweluwan, M; Morad, J A; Murphy, A St J; Nehrkorn, C; Nelson, H N; Neves, F; O'Sullivan, K; Oliver-Mallory, K C; Ott, R A; Palladino, K J; Pangilinan, M; Pease, E K; Phelps, P; Reichhart, L; Rhyne, C; Shaw, S; Shutt, T A; Silva, C; Solovov, V N; Sorensen, P; Stephenson, S; Sumner, T J; Szydagis, M; Taylor, D J; Taylor, W; Tennyson, B P; Terman, P A; Tiedt, D R; To, W H; Tripathi, M; Tvrznikova, L; Uvarov, S; Verbus, J R; Webb, R C; White, J T; Whitis, T J; Witherell, M S; Wolfs, F L H; Yazdani, K; Young, S K; Zhang, C

2016-04-22

We present experimental constraints on the spin-dependent WIMP (weakly interacting massive particle)-nucleon elastic cross sections from LUX data acquired in 2013. LUX is a dual-phase xenon time projection chamber operating at the Sanford Underground Research Facility (Lead, South Dakota), which is designed to observe the recoil signature of galactic WIMPs scattering from xenon nuclei. A profile likelihood ratio analysis of 1.4×10^{4}  kg day of fiducial exposure allows 90% C.L. upper limits to be set on the WIMP-neutron (WIMP-proton) cross section of σ_{n}=9.4×10^{-41}  cm^{2} (σ_{p}=2.9×10^{-39}  cm^{2}) at 33  GeV/c^{2}. The spin-dependent WIMP-neutron limit is the most sensitive constraint to date.

Results on the spin-dependent scattering of weakly interacting massive particles on nucleons from the Run 3 Data of the LUX Experiment

DOE PAGES

Akerib, D. S.

2016-04-20

Here, we present experimental constraints on the spin-dependent WIMP (weakly interacting massive particle)-nucleon elastic cross sections from LUX data acquired in 2013. LUX is a dual-phase xenon time projection chamber operating at the Sanford Underground Research Facility (Lead, South Dakota), which is designed to observe the recoil signature of galactic WIMPs scattering from xenon nuclei. A profile likelihood ratio analysis of 1.4 × 10 4 kg day of fiducial exposure allows 90% C.L. upper limits to be set on the WIMP-neutron (WIMP-proton) cross section of σ n = 9.4 × 10 –41 cm 2 (σ p = 2.9 × 10more » –39 cm 2) at 33 GeV/c 2. The spin-dependent WIMP-neutron limit is the most sensitive constraint to date.« less

Efficacy and safety of cytotoxic drug chemotherapy after first-line EGFR-TKI treatment in elderly patients with non-small-cell lung cancer harboring sensitive EGFR mutations.

PubMed

Imai, Hisao; Minemura, Hiroyuki; Sugiyama, Tomohide; Yamada, Yutaka; Kaira, Kyoichi; Kanazawa, Kenya; Kasai, Takashi; Kaburagi, Takayuki; Minato, Koichi

2018-05-08

Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is effective as first-line chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC) harboring sensitive EGFR mutations. However, whether the efficacy of second-line cytotoxic drug chemotherapy after first-line EGFR-TKI treatment is similar to that of first-line cytotoxic drug chemotherapy in elderly patients aged ≥ 75 years harboring sensitive EGFR mutations is unclear. Therefore, we aimed to investigate the efficacy and safety of cytotoxic drug chemotherapy after first-line EGFR-TKI treatment in elderly patients with NSCLC harboring sensitive EGFR mutations. We retrospectively evaluated the clinical effects and safety profiles of second-line cytotoxic drug chemotherapy after first-line EGFR-TKI treatment in elderly patients with NSCLC harboring sensitive EGFR mutations (exon 19 deletion/exon 21 L858R mutation). Between April 2008 and December 2015, 78 elderly patients with advanced NSCLC harboring sensitive EGFR mutations received first-line EGFR-TKI at four Japanese institutions. Baseline characteristics, regimens, responses to first- and second-line treatments, whether or not patients received subsequent treatment, and if not, the reasons for non-administration were recorded. Overall, 20 patients with a median age of 79.5 years (range 75-85 years) were included in our analysis. The overall response, disease control, median progression-free survival, and overall survival rates were 15.0, 60.0%, 2.4, and 13.2 months, respectively. Common adverse events included leukopenia, neutropenia, anemia, thrombocytopenia, malaise, and anorexia. Major grade 3 or 4 toxicities included leukopenia (25.0%) and neutropenia (45.0%). No treatment-related deaths were noted. Second-line cytotoxic drug chemotherapy after first-line EGFR-TKI treatment among elderly patients with NSCLC harboring sensitive EGFR mutations was effective and safe and showed equivalent outcomes to first-line

A Dark Matter Search with MALBEK

NASA Astrophysics Data System (ADS)

Giovanetti, G. K.; Abgrall, N.; Aguayo, E.; Avignone, F. T.; Barabash, A. S.; Bertrand, F. E.; Boswell, M.; Brudanin, V.; Busch, M.; Byram, D.; Caldwell, A. S.; Chan, Y.-D.; Christofferson, C. D.; Combs, D. C.; Cuesta, C.; Detwiler, J. A.; Doe, P. J.; Efremenko, Yu.; Egorov, V.; Ejiri, H.; Elliott, S. R.; Fast, J. E.; Finnerty, P.; Fraenkle, F. M.; Galindo-Uribarri, A.; Goett, J.; Green, M. P.; Gruszko, J.; Guiseppe, V. E.; Gusev, K.; Hallin, A. L.; Hazama, R.; Hegai, A.; Henning, R.; Hoppe, E. W.; Howard, S.; Howe, M. A.; Keeter, K. J.; Kidd, M. F.; Kochetov, O.; Konovalov, S. I.; Kouzes, R. T.; LaFerriere, B. D.; Leon, J.; Leviner, L. E.; Loach, J. C.; MacMullin, J.; MacMullin, S.; Martin, R. D.; Meijer, S.; Mertens, S.; Nomachi, M.; Orrell, J. L.; O'Shaughnessy, C.; Overman, N. R.; Phillips, D. G.; Poon, A. W. P.; Pushkin, K.; Radford, D. C.; Rager, J.; Rielage, K.; Robertson, R. G. H.; Romero-Romero, E.; Ronquest, M. C.; Schubert, A. G.; Shanks, B.; Shima, T.; Shirchenko, M.; Snavely, K. J.; Snyder, N.; Suriano, A. M.; Thompson, J.; Timkin, V.; Tornow, W.; Trimble, J. E.; Varner, R. L.; Vasilyev, S.; Vetter, K.; Vorren, K.; White, B. R.; Wilkerson, J. F.; Wiseman, C.; Xu, W.; Yakushev, E.; Young, A. R.; Yu, C.-H.; Yumatov, V.

The Majorana Demonstrator is an array of natural and enriched high purity germanium detectors that will search for the neutrinoless double-beta decay of 76Ge and perform a search for weakly interacting massive particles (WIMPs) with masses below 10 GeV. As part of the Majorana research and development efforts, we have deployed a modified, low-background broad energy germanium detector at the Kimballton Underground Research Facility. With its sub-keV energy threshold, this detector is sensitive to potential non-Standard Model physics, including interactions with WIMPs. We discuss the backgrounds present in the WIMP region of interest and explore the impact of slow surface event contamination when searching for a WIMP signal.

Characterization of Nuclear Recoils in High Pressure Xenon Gas: Towards a Simultaneous Search for WIMP Dark Matter and Neutrinoless Double Beta Decay

DOE PAGES

Renner, J.; Gehman, V. M.; Goldschmidt, A.; ...

2015-03-24

Xenon has recently been the medium of choice in several large scale detectors searching for WIMP dark matter and neutrinoless double beta decay. Though present-day large scale experiments use liquid xenon, the gas phase offers advantages favorable to both types of searches such as improved intrinsic energy resolution and fewer fluctuations in the partition of deposited energy between scintillation and ionization channels. We recently constructed a high pressure xenon gas TPC as a prototype for the NEXT (Neutrino Experiment with a Xenon TPC) neutrinoless double beta decay experiment and have demonstrated the feasibility of 0.5% FWHM energy resolution at themore » 136Xe double beta Q-value with 3-D tracking capabilities. We now present results from this prototype on the simultaneous observation of scintillation and ionization produced by nuclear recoils at approximately 14 bar pressure. The recoils were produced by neutrons of approximately 2-6 MeV emitted from a radioisotope plutonium-beryllium source, and primary scintillation (S1) and electroluminescent photons produced by ionization (S2) were observed. We discuss the potential of gaseous xenon to distinguish between electron and nuclear recoils through the ratio of these two signals S2/S1. From these results combined with the possibility of using columnar recombination to sense nuclear recoil directionality at high pressures we envision a dual-purpose, ton-scale gaseous xenon detector capable of a combined search for WIMP dark matter and neutrinoless double beta decay. This work has been performed within the context of the NEXT collaboration.« less

Results from a search for dark matter in the complete LUX exposure

DOE PAGES

Akerib, D. S.; Alsum, S.; Araújo, H. M.; ...

2017-01-11

Here, we report constraints on spin-independent weakly interacting massive particle (WIMP)-nucleon scattering using a 3.35 ×10 4 kg day exposure of the Large Underground Xenon (LUX) experiment. A dual-phase xenon time projection chamber with 250 kg of active mass is operated at the Sanford Underground Research Facility under Lead, South Dakota (USA). With roughly fourfold improvement in sensitivity for high WIMP masses relative to our previous results, this search yields no evidence of WIMP nuclear recoils. At a WIMP mass of 50 GeV c –2, WIMP-nucleon spin-independent cross sections above 2.2 ×10 –46 cm 2 are excluded at the 90%more » confidence level. When combined with the previously reported LUX exposure, this exclusion strengthens to 1.1 × 10 –46 cm 2 at 50 GeV c –2.« less

Results from a Search for Dark Matter in the Complete LUX Exposure.

PubMed

Akerib, D S; Alsum, S; Araújo, H M; Bai, X; Bailey, A J; Balajthy, J; Beltrame, P; Bernard, E P; Bernstein, A; Biesiadzinski, T P; Boulton, E M; Bramante, R; Brás, P; Byram, D; Cahn, S B; Carmona-Benitez, M C; Chan, C; Chiller, A A; Chiller, C; Currie, A; Cutter, J E; Davison, T J R; Dobi, A; Dobson, J E Y; Druszkiewicz, E; Edwards, B N; Faham, C H; Fiorucci, S; Gaitskell, R J; Gehman, V M; Ghag, C; Gibson, K R; Gilchriese, M G D; Hall, C R; Hanhardt, M; Haselschwardt, S J; Hertel, S A; Hogan, D P; Horn, M; Huang, D Q; Ignarra, C M; Ihm, M; Jacobsen, R G; Ji, W; Kamdin, K; Kazkaz, K; Khaitan, D; Knoche, R; Larsen, N A; Lee, C; Lenardo, B G; Lesko, K T; Lindote, A; Lopes, M I; Manalaysay, A; Mannino, R L; Marzioni, M F; McKinsey, D N; Mei, D-M; Mock, J; Moongweluwan, M; Morad, J A; Murphy, A St J; Nehrkorn, C; Nelson, H N; Neves, F; O'Sullivan, K; Oliver-Mallory, K C; Palladino, K J; Pease, E K; Phelps, P; Reichhart, L; Rhyne, C; Shaw, S; Shutt, T A; Silva, C; Solmaz, M; Solovov, V N; Sorensen, P; Stephenson, S; Sumner, T J; Szydagis, M; Taylor, D J; Taylor, W C; Tennyson, B P; Terman, P A; Tiedt, D R; To, W H; Tripathi, M; Tvrznikova, L; Uvarov, S; Verbus, J R; Webb, R C; White, J T; Whitis, T J; Witherell, M S; Wolfs, F L H; Xu, J; Yazdani, K; Young, S K; Zhang, C

2017-01-13

We report constraints on spin-independent weakly interacting massive particle (WIMP)-nucleon scattering using a 3.35×10^{4}  kg day exposure of the Large Underground Xenon (LUX) experiment. A dual-phase xenon time projection chamber with 250 kg of active mass is operated at the Sanford Underground Research Facility under Lead, South Dakota (USA). With roughly fourfold improvement in sensitivity for high WIMP masses relative to our previous results, this search yields no evidence of WIMP nuclear recoils. At a WIMP mass of 50  GeV c^{-2}, WIMP-nucleon spin-independent cross sections above 2.2×10^{-46}  cm^{2} are excluded at the 90% confidence level. When combined with the previously reported LUX exposure, this exclusion strengthens to 1.1×10^{-46}  cm^{2} at 50  GeV c^{-2}.

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

PubMed

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

2015-11-13

As a population, non-Hodgkin's lymphoma (NHL) cell lines positive for the t(14;18) translocation and/or possessing elevated BCL2 copy number (CN; BCL2(High)) are exquisitely sensitive to navitoclax or the B-cell lymphoma protein-2 (BCL-2)-selective inhibitor venetoclax. Despite this, some BCL2(High) cell lines remain resistant to either agent. Here we show that the MCL-1-specific inhibitor A-1210477 sensitizes these cell lines to navitoclax. Chemical segregation of this synergy with the BCL-2-selective inhibitor venetoclax or BCL-XL-selective inhibitor A-1155463 indicated that MCL-1 and BCL-2 are the two key anti-apoptotic targets for sensitization. Similarly, the CDK inhibitor flavopiridol downregulated MCL-1 expression and synergized with venetoclax in BCL2(High) NHL cell lines to a similar extent as A-1210477. A-1210477 also synergized with navitoclax in the majority of BCL2(Low) NHL cell lines. However, chemical segregation with venetoclax or A-1155463 revealed that synergy was driven by BCL-XL inhibition in this population. Collectively these data emphasize that BCL2 status is predictive of venetoclax potency in NHL not only as a single agent, but also in the adjuvant setting with anti-tumorigenic agents that inhibit MCL-1 function. These studies also potentially identify a patient population (BCL2(Low)) that could benefit from BCL-XL (navitoclax)-driven combination therapy.

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

PubMed Central

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

2010-01-01

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. PMID:19550464

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

PubMed

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

2014-03-01

pH-responsive polymers produce liposomes with pH-sensitive property which can release their encapsulated drug under mild acidic conditions found inside the cellular endosomes, inflammatory tissues and cancerous cells. The aim of this study was preparing pH-sensitive and plasma stable liposomes in order to enhance the selectivity and antiproliferative effect of Rapamycin. In the present study we used PEG-poly (monomethylitaconate)-CholC6 (PEG-PMMI-CholC6) copolymer and Oleic acid (OA) to induce pH-sensitive property in Rapamycin liposomes. pH-sensitive liposomal formulations bearing copolymer PEG-PMMI-CholC6 and OA were characterized in regard to physicochemical stability, pH-responsiveness and stability in human plasma. The ability of pH-sensitive liposomes in enhancing the cytotoxicity of Rapamycin was evaluated in vitro by using colon cancer cell line (HT-29) and compared with its cytotoxicity on human umbilical vein endothelial cell (HUVEC) line. Both formulations were found to release their contents under mild acidic conditions rapidly. However, unlike OA-based liposomes, the PEG-PMMI-CholC6 bearing liposomes preserved their pH-sensitivity in plasma. Both types of pH-sensitive Rapamycin-loaded liposomes exhibited high physicochemical stability and could deliver antiproliferative agent into HT-29 cells much more efficiently in comparison with conventional liposomes. Conversely, the antiproliferative effect of pH-sensitive liposomes on HUVEC cell line was less than conventional liposomes. This study showed that both OA and PEG-PMMI-CholC6-based vesicles could submit pH-sensitive property, however, only PEG-PMMI-CholC6-based liposomes could preserve pH-sensitive property after incubation in plasma. As a result pH-sensitive PEG-PMMI-CholC6-based liposomal formulation can improve the selectivity, stability and antiproliferative effect of Rapamycin. Copyright © 2014 Elsevier B.V. All rights reserved.

A dark matter search with MALBEK

DOE PAGES

Giovanetti, G. K.; Abgrall, N.; Aguayo, E.; ...

2015-01-01

The Majorana Demonstrator is an array of natural and enriched high purity germanium detectors that will search for the neutrinoless double-beta decay of ⁷⁶Ge and perform a search for weakly interacting massive particles (WIMPs) with masses below 10 GeV. As part of the Majorana research and development efforts, we have deployed a modified, low-background broad energy germanium detector at the Kimballton Underground Research Facility. With its sub-keV energy threshold, this detector is sensitive to potential non-Standard Model physics, including interactions with WIMPs. We discuss the backgrounds present in the WIMP region of interest and explore the impact of slow surfacemore » event contamination when searching for a WIMP signal.« less

A Dark Matter Search with MALBEK

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giovanetti, G. K.; Abgrall, N.; Aguayo, Estanislao

2015-06-01

The Majorana Demonstrator is an array of natural and enriched high purity germanium detectors that will search for the neutrinoless double-beta decay of 76Ge and perform a search for weakly interacting massive particles (WIMPs) with masses below 10 GeV. As part of the Majorana research and development efforts, we have deployed a modified, low-background broad energy germanium detector at the Kimballton Underground Research Facility. With its sub-keV energy threshold, this detector is potentially sensitive to non-Standard Model physics, including interactions with WIMPs. We discuss the backgrounds present in the WIMP region of interest and present results from a WIMP searchmore » with 221.49 live days of data from this detector.« less

First Results of the LUX Dark Matter Experiment

NASA Astrophysics Data System (ADS)

Carmona-Benitez, M. C.; Akerib, D. S.; Araújo, H. M.; Bai, X.; Bailey, A. J.; Balajthy, J.; Beltrame, P.; Bernard, E.; Bernstein, A.; Bradley, A.; Byram, D.; Cahn, S. B.; Chan, C.; Chapman, J. J.; Chiller, A. A.; Chiller, C.; Currie, A.; de Viveiros, L.; Dobi, A.; Dobson, J.; Druszkiewicz, E.; Edwards, B.; Faham, C. H.; Fiorucci, S.; Flores, C.; Gaitskell, R. J.; Gehman, V. M.; Ghag, C.; Gibson, K. R.; Gilchriese, M. G. D.; Hall, C.; Hanhardt, M.; Haselschwardt, S.; Hertel, S. A.; Horn, M.; Huang, D. Q.; Ihm, M.; Jacobsen, R. G.; Kazkaz, K.; Knoche, R.; Larsen, N. A.; Lee, C.; Lenardo, B.; Lesko, K. T.; Lindote, A.; Lopes, M. I.; Malling, D. C.; Manalaysay, A.; Mannino, R.; McKinsey, D. N.; Mei, D.-M.; Mock, J.; Moongweluwan, M.; Morad, J.; Murphy, A. St. J.; Nehrkorn, C.; Nelson, H.; Neves, F.; Ott, R. A.; Pangilinan, M.; Parker, P. D.; Pease, E. K.; Pech, K.; Phelps, P.; Reichhart, L.; Shutt, T.; Silva, C.; Solovov, V. N.; Sorensen, P.; O'Sullivan, K.; Sumner, T. J.; Szydagis, M.; Taylor, D.; Tennyson, B.; Tiedt, D. R.; Tripathi, M.; Tvrznikova, L.; Uvarov, S.; Verbus, J. R.; Walsh, N.; Webb, R.; White, J. T.; Witherell, M. S.; Wolfs, F. L. H.; Woods, M.; Zhang, C.; LUX Collaboration

2016-04-01

LUX (Large Underground Xenon) is a dark matter direct detection experiment deployed at the 4850' level of the Sanford Underground Research Facility (SURF) in Lead, SD, operating a 370 kg dual-phase xenon TPC. Results of the first WIMP search run were presented in late 2013, for the analysis of 85.3 live-days with a fiducial volume of 118 kg, taken during the period of April to August 2013. The experiment exhibited a sensitivity to spin-independent WIMP-nucleon elastic scattering with a minimum upper limit on the cross section of 7.6 ×10-46cm2 at a WIMP mass of 33 GeV/c2, becoming the world's leading WIMP search result, in conflict with several previous claimed hints of discovery.

Quantification of sensitivity and resistance of breast cancer cell lines to anti-cancer drugs using GR metrics

PubMed Central

Hafner, Marc; Heiser, Laura M.; Williams, Elizabeth H.; Niepel, Mario; Wang, Nicholas J.; Korkola, James E.; Gray, Joe W.; Sorger, Peter K.

2017-01-01

Traditional means for scoring the effects of anti-cancer drugs on the growth and survival of cell lines is based on relative cell number in drug-treated and control samples and is seriously confounded by unequal division rates arising from natural biological variation and differences in culture conditions. This problem can be overcome by computing drug sensitivity on a per-division basis. The normalized growth rate inhibition (GR) approach yields per-division metrics for drug potency (GR50) and efficacy (GRmax) that are analogous to the more familiar IC50 and Emax values. In this work, we report GR-based, proliferation-corrected, drug sensitivity metrics for ~4,700 pairs of breast cancer cell lines and perturbagens. Such data are broadly useful in understanding the molecular basis of therapeutic response and resistance. Here, we use them to investigate the relationship between different measures of drug sensitivity and conclude that drug potency and efficacy exhibit high variation that is only weakly correlated. To facilitate further use of these data, computed GR curves and metrics can be browsed interactively at http://www.GRbrowser.org/. PMID:29112189

THE MAGNETIC SENSITIVITY OF THE Mg ii k LINE TO THE JOINT ACTION OF HANLE, ZEEMAN, AND MAGNETO-OPTICAL EFFECTS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ballester, E. Alsina; Bueno, J. Trujillo; Belluzzi, L., E-mail: ealsina@iac.es, E-mail: jtb@iac.es, E-mail: belluzzi@irsol.ch

2016-11-10

We highlight the main results of a radiative transfer investigation on the magnetic sensitivity of the solar Mg ii k resonance line at 2795.5 Å, accounting for the joint action of the Hanle and Zeeman effects as well as partial frequency redistribution phenomena. We confirm that at the line center, the linear polarization signals produced by scattering processes are measurable, and that they are sensitive, via the Hanle effect, to magnetic fields with strengths between 5 and 50 G, approximately. We also show that the Zeeman effect produces conspicuous circular polarization signals, especially for longitudinal fields stronger than 50 G,more » which can be used to estimate the magnetization of the solar chromosphere via the familiar magnetograph formula. The most novel result is that magneto-optical effects produce, in the wings of the line, a decrease of the Q / I scattering polarization pattern and the appearance of U / I signals (i.e., a rotation of the plane of linear polarization). This sensitivity of the Q / I and U / I wing signals to both weak (∼5 G) and stronger magnetic fields expands the scientific interest of the Mg ii k line for probing the chromosphere in quiet and active regions of the Sun.« less

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

PubMed Central

Vermeulen, C J; Bijlsma, R

2004-01-01

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. PMID:15280238

Cell Penetrating Capacity and Internalization Mechanisms Used by the Synthetic Peptide CIGB-552 and Its Relationship with Tumor Cell Line Sensitivity.

PubMed

Astrada, Soledad; Fernández Massó, Julio Raúl; Vallespí, Maribel G; Bollati-Fogolín, Mariela

2018-03-30

CIGB-552 is a twenty-amino-acid novel synthetic peptide that has proven to be effective in reducing tumor size and increasing lifespan in tumor-bearing mice. Such capability is conferred by its cell-penetrating peptide character, which allows it to enter cells and elicit a pro-apoptotic effect through its major mediator, COMMD1 protein. Cell-penetrating peptides are able to use different internalization mechanisms, such as endocytosis or direct transduction through the plasma membrane. Although CIGB-552 cytotoxicity has been evaluated in several non-tumor- and tumor-derived cell lines, no data regarding the relationship between cell line sensitivity, cell penetrating capacity, the internalization mechanisms involved, COMMD1 expression levels, or its subcellular localization has yet been produced. Here, we present the results obtained from a comparative analysis of CIGB-552 sensitivity, internalization capacity and the mechanisms involved in three human tumor-derived cell lines from different origins: mammary gland, colon and lung (MCF-7, HT-29 and H460, respectively). Furthermore, cell surface markers relevant for internalization processes such as phosphatidylserine, as well as CIGB-552 target COMMD1 expression/localization, were also evaluated. We found that both endocytosis and transduction are involved in CIGB-552 internalization in the three cell lines evaluated. However, CIGB-552 incorporation efficiency and contribution of each mechanism is cell-line dependent. Finally, sensitivity was directly correlated with high internalization capacity in those cell lines where endocytosis had a major contribution on CIGB-552 internalization.

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

PubMed Central

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

2015-01-01

As a population, non-Hodgkin's lymphoma (NHL) cell lines positive for the t(14;18) translocation and/or possessing elevated BCL2 copy number (CN; BCL2High) are exquisitely sensitive to navitoclax or the B-cell lymphoma protein-2 (BCL-2)-selective inhibitor venetoclax. Despite this, some BCL2High cell lines remain resistant to either agent. Here we show that the MCL-1-specific inhibitor A-1210477 sensitizes these cell lines to navitoclax. Chemical segregation of this synergy with the BCL-2-selective inhibitor venetoclax or BCL-XL-selective inhibitor A-1155463 indicated that MCL-1 and BCL-2 are the two key anti-apoptotic targets for sensitization. Similarly, the CDK inhibitor flavopiridol downregulated MCL-1 expression and synergized with venetoclax in BCL2High NHL cell lines to a similar extent as A-1210477. A-1210477 also synergized with navitoclax in the majority of BCL2Low NHL cell lines. However, chemical segregation with venetoclax or A-1155463 revealed that synergy was driven by BCL-XL inhibition in this population. Collectively these data emphasize that BCL2 status is predictive of venetoclax potency in NHL not only as a single agent, but also in the adjuvant setting with anti-tumorigenic agents that inhibit MCL-1 function. These studies also potentially identify a patient population (BCL2Low) that could benefit from BCL-XL (navitoclax)-driven combination therapy. PMID:26565405

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Azam, Philippe; Peiffer, Jean-Luc; Chamousset, Delphine

2006-04-01

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. Onlymore » 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.« less

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)

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

2013-10-01

Xenon is an especially attractive candidate for both direct WIMP and 0νββ 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 0νββ 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 γ-rays with topological cuts. However, sensitivity goals for WIMP dark matter and 0νββ 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.

Results from the LUX dark matter experiment

NASA Astrophysics Data System (ADS)

Horn, Markus; Akerib, D. S.; Araújo, H. M.; Bai, X.; Bailey, A. J.; Balajthy, J.; Bernard, E.; Bernstein, A.; Bradley, A.; Byram, D.; Cahn, S. B.; Carmona-Benitez, M. C.; Chan, C.; Chapman, J. J.; Chiller, A. A.; Chiller, C.; Currie, A.; de Viveiros, L.; Dobi, A.; Dobson, J.; Druszkiewicz, E.; Edwards, B.; Faham, C. H.; Fiorucci, S.; Flores, C.; Gaitskell, R. J.; Gehman, V. M.; Ghag, C.; Gibson, K. R.; Gilchriese, M. G. D.; Hall, C.; Hanhardt, M.; Haselschwardt, S.; Hertel, S. A.; Huang, D. Q.; Ihm, M.; Jacobsen, R. G.; Kazkaz, K.; Knoche, R.; Larsen, N. A.; Lee, C.; Lenardo, B.; Lesko, K. T.; Lindote, A.; Lopes, M. I.; Malling, D. C.; Mannino, R.; McKinsey, D. N.; Mei, D.-M.; Mock, J.; Moongweluwan, M.; Morad, J.; Murphy, A. St. J.; Nehrkorn, C.; Nelson, H.; Neves, F.; Ott, R. A.; Pangilinan, M.; Parker, P. D.; Pease, E. K.; Pech, K.; Phelps, P.; Reichhart, L.; Shutt, T.; Silva, C.; Solovov, V. N.; Sorensen, P.; O`Sullivan, K.; Sumner, T. J.; Szydagis, M.; Taylor, D.; Tennyson, B.; Tiedt, D. R.; Tripathi, M.; Uvarov, S.; Verbus, J. R.; Walsh, N.; Webb, R.; White, J. T.; Witherell, M. S.; Wolfs, F. L. H.; Woods, M.; Zhang, C.; LUX Collaboration

2015-06-01

The LUX (Large Underground Xenon) experiment aims at the direct detection of dark matter particles via their collisions with xenon nuclei. The 370 kg two-phase liquid xenon time projection chamber measures simultaneously the scintillation and ionization from interactions in the target. The ratio of these two signals provides very good discrimination between potential nuclear recoil and electronic recoil signals to search for WIMP-nucleon scattering. The LUX detector operates at the Sanford Underground Research Facility (Lead, South Dakota, USA) since February 2013. First results were presented in late 2013 setting the world's most stringent limits on WIMP-nucleon scattering cross-sections over a wide range of WIMP masses. A 300 day run beginning in 2014 will further improve the sensitivity and new calibration techniques will reduce systematics for the WIMP signal search.

First Results of the LUX Dark Matter Experiment

DOE PAGES

Carmona-Benitez, M. C.; Akerib, D. S.; Araújo, H. M.; ...

2016-05-31

LUX (Large Underground Xenon) is a dark matter direct detection experiment deployed at the 4850' level of the Sanford Underground Research Facility (SURF) in Lead, SD, operating a 370 kg dual-phase xenon TPC. Results of the first WIMP search run were presented in late 2013, for the analysis of 85.3 live-days with a fiducial volume of 118 kg, taken during the period of April to August 2013. The experiment exhibited a sensitivity to spin-independent WIMP-nucleon elastic scattering with a minimum upper limit on the cross section of 7.6×10 -46 cm 2 at a WIMP mass of 33 GeV/c 2, thusmore » becoming the world's leading WIMP search result, in conflict with several previous claimed hints of discovery.« less

First Results of the LUX Dark Matter Experiment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carmona-Benitez, M. C.; Akerib, D. S.; Araújo, H. M.

LUX (Large Underground Xenon) is a dark matter direct detection experiment deployed at the 4850' level of the Sanford Underground Research Facility (SURF) in Lead, SD, operating a 370 kg dual-phase xenon TPC. Results of the first WIMP search run were presented in late 2013, for the analysis of 85.3 live-days with a fiducial volume of 118 kg, taken during the period of April to August 2013. The experiment exhibited a sensitivity to spin-independent WIMP-nucleon elastic scattering with a minimum upper limit on the cross section of 7.6×10 -46 cm 2 at a WIMP mass of 33 GeV/c 2, thusmore » becoming the world's leading WIMP search result, in conflict with several previous claimed hints of discovery.« less

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2006-08-01

Recent regulatory changes have placed a major emphasis on in vitro safety testing and alternative models. In regard to skin sensitization tests, dendritic cells (DCs) derived from human peripheral blood have been considered in the development of new in vitro alternatives. Human cell lines have been also reported recently. In our previous study, we suggested that measuring CD86 and/or CD54 expression on THP-1 cells (human monocytic leukemia cell line) could be used as an in vitro skin sensitization method. An inter-laboratory study among two laboratories was undertaken in Japan in order to further develop an in vitro skin sensitization model. In the present study, we used two human cell lines: THP-1 and U-937 (human histiocytic lymphoma cell line). First we optimized our test protocol (refer to the related paper entitled "optimization of the h-CLAT protocol" within this journal) and then we did an inter-laboratory validation with nine chemicals using the optimized protocol. We measured the expression of CD86 and CD54 on the above cells using flow cytometry after a 24h and 48h exposure to six known allergens (e.g., DNCB, pPD, NiSO(4)) and three non-allergens (e.g., SLS, tween 80). For the sample test concentration, four doses (0.1x, 0.5x, 1x, and 2x of the 50% inhibitory concentration (IC(50))) were evaluated. IC(50) was calculated using MTT assay. We found that allergens/non-allergens were better predicted using THP-1 cells compared to U-937 cells following a 24 h and a 48 h exposure. We also found that the 24h treatment time tended to have a better accuracy than the 48 h treatment time for THP-1 cells. Expression of CD86 and CD54 were good predictive markers for THP-1 cells, but for U-937 cells, expression of CD86 was a better predictor than CD54, at the 24h and the 48 h treatment time. The accuracy also improved when both markers (CD86 and CD54) were used as compared with a single marker for THP-1 cells. Both laboratories gave a good prediction of allergen

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

PubMed

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

2013-11-01

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

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

PubMed

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

2009-10-01

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.

Dark matter search results from the PICO-2L C$$_3$$F$$_8$$ bubble chamber

DOE PAGES

Amole, C.

2015-06-11

New data are reported from the operation of a 2 liter C 3F 8 bubble chamber in the SNOLAB underground laboratory, with a total exposure of 211.5 kg days at four different energy thresholds below 10 keV. These data show that C 3F 8 provides excellent electron-recoil and alpha rejection capabilities at very low thresholds. The chamber exhibits an electron-recoil sensitivity of < 3.5 × 10 –10 and an alpha rejection factor of > 98.2%. These data also include the first observation of a dependence of acoustic signal on alpha energy. Twelve single nuclear recoil event candidates were observed duringmore » the run. The candidate events exhibit timing characteristics that are not consistent with the hypothesis of a uniform time distribution, and no evidence for a dark matter signal is claimed. Lastly, these data provide the most sensitive direct detection constraints on WIMP-proton spin-dependent scattering to date, with significant sensitivity at low WIMP masses for spin-independent WIMP-nucleon scattering.« less

Lapatinib sensitivities of two novel trastuzumab-resistant HER2 gene-amplified gastric cancer cell lines.

PubMed

Oshima, Yukiko; Tanaka, Harunari; Murakami, Hiroki; Ito, Yuichi; Furuya, Tomomi; Kondo, Eisaku; Kodera, Yasuhiro; Nakanishi, Hayao

2014-01-01

Trastuzumab (Tmab) resistance is a major clinical problem to be resolved in patients with HER2-positive gastric cancers. However, in contrast to the situation for HER2-positive breast cancer lines, the Tmab-resistant gastric cancer preclinical models that are needed to develop a new therapy to overcome this problem are not yet available. We developed three new cell lines from HER2 gene-amplified gastric cancer cell lines (GLM-1, GLM-4, NCI N-87) by a new in vivo selection method consisting of the repeated culture of small residual peritoneal metastasis but not subcutaneous tumor after Tmab treatment. We then evaluated the anti-tumor efficacy of lapatinib for these Tmab-resistant cells. We successfully isolated two Tmab-resistant cell lines (GLM1-HerR2(3), GLM4-HerR2) among the three tested cell lines. These resistant cells differed from the parental cells in their flat morphology and rapid growth in vitro, but HER2, P95HER2 expression, and Tmab binding were essentially the same for the parental and resistant cells. MUC4 expression was up- or downregulated depending on the cell line. These resistant cells were still sensitive to lapatinib, similar to the parental cells, in vitro. This growth inhibition of the Tmab-resistant cells by lapatinib was due to both G1 cell-cycle arrest and apoptosis induction via effective blockade of the PI3K/Akt and MAPK pathways. A preclinical study confirmed that the Tmab-resistant tumors are significantly susceptible to lapatinib. These results suggest that lapatinib has antitumor activity against the Tmab-resistant gastric cancer cell lines, and that these cell lines are useful for understanding the mechanism of Tmab resistance and for developing a new molecular therapy for Tmab-resistant HER2-positive gastric cancers.

XENON100 dark matter results from a combination of 477 live days

NASA Astrophysics Data System (ADS)

Aprile, E.; Aalbers, J.; Agostini, F.; Alfonsi, M.; Amaro, F. D.; Anthony, M.; Arneodo, F.; Barrow, P.; Baudis, L.; Bauermeister, B.; Benabderrahmane, M. L.; Berger, T.; Breur, P. A.; Brown, A.; Brown, E.; Bruenner, S.; Bruno, G.; Budnik, R.; Bütikofer, L.; Calvén, J.; Cardoso, J. M. R.; Cervantes, M.; Cichon, D.; Coderre, D.; Colijn, A. P.; Conrad, J.; Cussonneau, J. P.; Decowski, M. P.; de Perio, P.; di Gangi, P.; di Giovanni, A.; Diglio, S.; Duchovni, E.; Fei, J.; Ferella, A. D.; Fieguth, A.; Franco, D.; Fulgione, W.; Gallo Rosso, A.; Galloway, M.; Gao, F.; Garbini, M.; Geis, C.; Goetzke, L. W.; Greene, Z.; Grignon, C.; Hasterok, C.; Hogenbirk, E.; Itay, R.; Kaminsky, B.; Kessler, G.; Kish, A.; Landsman, H.; Lang, R. F.; Lellouch, D.; Levinson, L.; Le Calloch, M.; Levy, C.; Lin, Q.; Lindemann, S.; Lindner, M.; Lopes, J. A. M.; Manfredini, A.; Marrodán Undagoitia, T.; Masbou, J.; Massoli, F. V.; Masson, D.; Mayani, D.; Meng, Y.; Messina, M.; Micheneau, K.; Miguez, B.; Molinario, A.; Murra, M.; Naganoma, J.; Ni, K.; Oberlack, U.; Orrigo, S. E. A.; Pakarha, P.; Pelssers, B.; Persiani, R.; Piastra, F.; Pienaar, J.; Piro, M.-C.; Plante, G.; Priel, N.; Rauch, L.; Reichard, S.; Reuter, C.; Rizzo, A.; Rosendahl, S.; Rupp, N.; Dos Santos, J. M. F.; Sartorelli, G.; Scheibelhut, M.; Schindler, S.; Schreiner, J.; Schumann, M.; Scotto Lavina, L.; Selvi, M.; Shagin, P.; Silva, M.; Simgen, H.; Sivers, M. V.; Stein, A.; Thers, D.; Tiseni, A.; Trinchero, G.; Tunnell, C. D.; Wall, R.; Wang, H.; Weber, M.; Wei, Y.; Weinheimer, C.; Wulf, J.; Zhang, Y.; Xenon Collaboration

2016-12-01

We report on WIMP search results of the XENON100 experiment, combining three runs summing up to 477 live days from January 2010 to January 2014. Data from the first two runs were already published. A blind analysis was applied to the last run recorded between April 2013 and January 2014 prior to combining the results. The ultralow electromagnetic background of the experiment, ˜5 ×10-3 events /(keVee×kg ×day ) ) before electronic recoil rejection, together with the increased exposure of 48 kg ×yr , improves the sensitivity. A profile likelihood analysis using an energy range of (6.6 - 43.3 ) keVnr sets a limit on the elastic, spin-independent WIMP-nucleon scattering cross section for WIMP masses above 8 GeV /c2 , with a minimum of 1.1 ×10-45 cm2 at 50 GeV /c2 and 90% confidence level. We also report updated constraints on the elastic, spin-dependent WIMP-nucleon cross sections obtained with the same data. We set upper limits on the WIMP-neutron (proton) cross section with a minimum of 2.0 ×10-40 cm2 (52 ×10-40 cm2 ) at a WIMP mass of 50 GeV /c2 , at 90% confidence level.

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

NASA Astrophysics Data System (ADS)

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

2007-11-01

Results are presented from the first underground data run of ZEPLIN-II, a 31 kg two-phase xenon detector developed to observe nuclear recoils from hypothetical weakly interacting massive dark matter particles. Discrimination between nuclear recoils and background electron recoils is afforded by recording both the scintillation and ionisation signals generated within the liquid xenon, with the ratio of these signals being different for the two classes of event. This ratio is calibrated for different incident species using an AmBe neutron source and 60Co γ-ray sources. From our first 31 live days of running ZEPLIN-II, the total exposure following the application of fiducial and stability cuts was 225 kg × days. A background population of radon progeny events was observed in this run, arising from radon emission in the gas purification getters, due to radon daughter ion decays on the surfaces of the walls of the chamber. An acceptance window, defined by the neutron calibration data, of 50% nuclear recoil acceptance between 5 keV ee and 20 keV ee, had an observed count of 29 events, with a summed expectation of 28.6 ± 4.3 γ-ray and radon progeny induced background events. These figures provide a 90% c.l. upper limit to the number of nuclear recoils of 10.4 events in this acceptance window, which converts to a WIMP-nucleon spin-independent cross-section with a minimum of 6.6 × 10 -7 pb following the inclusion of an energy-dependent, calibrated, efficiency. A second run is currently underway in which the radon progeny will be eliminated, thereby removing the background population, with a projected sensitivity of 2 × 10 -7 pb for similar exposures as the first run.

Low-mass dark matter search with CDMSlite

NASA Astrophysics Data System (ADS)

Agnese, R.; Anderson, A. J.; Aralis, T.; Aramaki, T.; Arnquist, I. J.; Baker, W.; Balakishiyeva, D.; Barker, D.; Basu Thakur, R.; Bauer, D. A.; Binder, T.; Bowles, M. A.; Brink, P. L.; Bunker, R.; Cabrera, B.; Caldwell, D. O.; Calkins, R.; Cartaro, C.; Cerdeño, D. G.; Chang, Y.; Chagani, H.; Chen, Y.; Cooley, J.; Cornell, B.; Cushman, P.; Daal, M.; Di Stefano, P. C. F.; Doughty, T.; Esteban, L.; Fascione, E.; Figueroa-Feliciano, E.; Fritts, M.; Gerbier, G.; Ghaith, M.; Godfrey, G. L.; Golwala, S. R.; Hall, J.; Harris, H. R.; Hong, Z.; Hoppe, E. W.; Hsu, L.; Huber, M. E.; Iyer, V.; Jardin, D.; Jastram, A.; Jena, C.; Kelsey, M. H.; Kennedy, A.; Kubik, A.; Kurinsky, N. A.; Leder, A.; Loer, B.; Lopez Asamar, E.; Lukens, P.; MacDonell, D.; Mahapatra, R.; Mandic, V.; Mast, N.; Miller, E. H.; Mirabolfathi, N.; Moffatt, R. A.; Mohanty, B.; Morales Mendoza, J. D.; Nelson, J.; Orrell, J. L.; Oser, S. M.; Page, K.; Page, W. A.; Partridge, R.; Pepin, M.; Peñalver Martinez, M.; Phipps, A.; Poudel, S.; Pyle, M.; Qiu, H.; Rau, W.; Redl, P.; Reisetter, A.; Reynolds, T.; Roberts, A.; Robinson, A. E.; Rogers, H. E.; Saab, T.; Sadoulet, B.; Sander, J.; Schneck, K.; Schnee, R. W.; Scorza, S.; Senapati, K.; Serfass, B.; Speller, D.; Stein, M.; Street, J.; Tanaka, H. A.; Toback, D.; Underwood, R.; Villano, A. N.; von Krosigk, B.; Welliver, B.; Wilson, J. S.; Wilson, M. J.; Wright, D. H.; Yellin, S.; Yen, J. J.; Young, B. A.; Zhang, X.; Zhao, X.; SuperCDMS Collaboration

2018-01-01

The SuperCDMS experiment is designed to directly detect weakly interacting massive particles (WIMPs) that may constitute the dark matter in our Galaxy. During its operation at the Soudan Underground Laboratory, germanium detectors were run in the CDMSlite mode to gather data sets with sensitivity specifically for WIMPs with masses <10 GeV /c2 . In this mode, a higher detector-bias voltage is applied to amplify the phonon signals produced by drifting charges. This paper presents studies of the experimental noise and its effect on the achievable energy threshold, which is demonstrated to be as low as 56 eVee (electron equivalent energy). The detector-biasing configuration is described in detail, with analysis corrections for voltage variations to the level of a few percent. Detailed studies of the electric-field geometry, and the resulting successful development of a fiducial parameter, eliminate poorly measured events, yielding an energy resolution ranging from ˜9 eVee at 0 keV to 101 eVee at ˜10 keVee . New results are derived for astrophysical uncertainties relevant to the WIMP-search limits, specifically examining how they are affected by variations in the most probable WIMP velocity and the Galactic escape velocity. These variations become more important for WIMP masses below 10 GeV /c2 . Finally, new limits on spin-dependent low-mass WIMP-nucleon interactions are derived, with new parameter space excluded for WIMP masses ≲3 GeV /c2.

Low-Mass Dark Matter Search Results and Radiogenic Backgrounds for the Cryogenic Dark Matter Search

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pepin, Mark David

An ever-increasing amount of evidence suggests that approximately one quarter of the energy in the universe is composed of some non-luminous, and hitherto unknown, “dark matter”. Physicists from numerous sub-fields have been working on and trying to solve the dark matter problem for decades. The common solution is the existence of some new type of elementary particle with particular focus on weakly interacting massive particles (WIMPs). One avenue of dark matter research is to create an extremely sensitive particle detector with the goal of directly observing the interaction of WIMPs with standard matter. The Cryogenic Dark Matter Search (CDMS) projectmore » operated at the Soudan Underground Laboratory from 2003–2015, under the CDMS II and SuperCDMS Soudan experiments, with this goal of directly detecting dark matter. The next installation, SuperCDMS SNOLAB, is planned for near-future operation. The reason the dark-matter particle has not yet been observed in traditional particle physics experiments is that it must have very small cross sections, thus making such interactions extremely rare. In order to identify these rare events in the presence of a background of known particles and interactions, direct detection experiments employ various types and amounts of shielding to prevent known backgrounds from reaching the instrumented detector(s). CDMS utilized various gamma and neutron shielding to such an effect that the shielding, and other experimental components, themselves were sources of background. These radiogenic backgrounds must be understood to have confidence in any WIMP-search result. For this dissertation, radiogenic background studies and estimates were performed for various analyses covering CDMS II, SuperCDMS Soudan, and SuperCDMS SNOLAB. Lower-mass dark matter t c2 inent in the past few years. The CDMS detectors can be operated in an alternative, higher-biased, mode v to decrease their energy thresholds and correspondingly increase their

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

PubMed

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

2012-01-01

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 μg/mL) or with a sub-lethal dose of ICI (sensitive; 1 μM 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.

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

PubMed Central

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

2012-01-01

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 μg/mL) or with a sub-lethal dose of ICI (sensitive; 1 μM 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. PMID:23346406

HCPCF-based in-line fiber Fabry-Perot refractometer and high sensitivity signal processing method

NASA Astrophysics Data System (ADS)

Liu, Xiaohui; Jiang, Mingshun; Sui, Qingmei; Geng, Xiangyi; Song, Furong

2017-12-01

An in-line fiber Fabry-Perot interferometer (FPI) based on the hollow-core photonic crystal fiber (HCPCF) for refractive index (RI) measurement is proposed in this paper. The FPI is formed by splicing both ends of a short section of the HCPCF to single mode fibers (SMFs) and cleaving the SMF pigtail to a proper length. The RI response of the sensor is analyzed theoretically and demonstrated experimentally. The results show that the FPI sensor has linear response to external RI and good repeatability. The sensitivity calculated from the maximum fringe contrast is -136 dB/RIU. A new spectrum differential integration (SDI) method for signal processing is also presented in this study. In this method, the RI is obtained from the integrated intensity of the absolute difference between the interference spectrum and its smoothed spectrum. The results show that the sensitivity obtained from the integrated intensity is about -1.34×105 dB/RIU. Compared with the maximum fringe contrast method, the new SDI method can provide the higher sensitivity, better linearity, improved reliability, and accuracy, and it's also convenient for automatic and fast signal processing in real-time monitoring of RI.

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

NASA Technical Reports Server (NTRS)

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

2001-01-01

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

Genetic load makes cancer cells more sensitive to common drugs: evidence from Cancer Cell Line Encyclopedia.

PubMed

Pavel, Ana B; Korolev, Kirill S

2017-05-16

Genetic alterations initiate tumors and enable the evolution of drug resistance. The pro-cancer view of mutations is however incomplete, and several studies show that mutational load can reduce tumor fitness. Given its negative effect, genetic load should make tumors more sensitive to anticancer drugs. Here, we test this hypothesis across all major types of cancer from the Cancer Cell Line Encyclopedia, which provides genetic and expression data of 496 cell lines together with their response to 24 common anticancer drugs. We found that the efficacy of 9 out of 24 drugs showed significant association with genetic load in a pan-cancer analysis. The associations for some tissue-drug combinations were remarkably strong, with genetic load explaining up to 83% of the variance in the drug response. Overall, the role of genetic load depended on both the drug and the tissue type with 10 tissues being particularly vulnerable to genetic load. We also identified changes in gene expression associated with increased genetic load, which included cell-cycle checkpoints, DNA damage and apoptosis. Our results show that genetic load is an important component of tumor fitness and can predict drug sensitivity. Beyond being a biomarker, genetic load might be a new, unexplored vulnerability of cancer.

Ultra-sensitive probe of spectral line structure and detection of isotopic oxygen

NASA Astrophysics Data System (ADS)

Garner, Richard M.; Dharamsi, A. N.; Khan, M. Amir

2018-01-01

We discuss a new method of investigating and obtaining quantitative behavior of higher harmonic (> 2f) wavelength modulation spectroscopy (WMS) based on the signal structure. It is shown that the spectral structure of higher harmonic WMS signals, quantified by the number of zero crossings and turnings points, can have increased sensitivity to ambient conditions or line-broadening effects from changes in temperature, pressure, or optical depth. The structure of WMS signals, characterized by combinations of signal magnitude and spectral locations of turning points and zero crossings, provides a unique scale that quantifies lineshape parameters and, thus, useful in optimization of measurements obtained from multi-harmonic WMS signals. We demonstrate this by detecting weaker rotational-vibrational transitions of isotopic atmospheric oxygen (16O18O) in the near-infrared region where higher harmonic WMS signals are more sensitive contrary to their signal-to-noise ratio considerations. The proposed approach based on spectral structure provides the ability to investigate and quantify signals not only at linecenter but also in the wing region of the absorption profile. This formulation is particularly useful in tunable diode laser spectroscopy and ultra-precision laser-based sensors where absorption signal profile carries information of quantities of interest, e.g., concentration, velocity, or gas collision dynamics, etc.

DARWIN: towards the ultimate dark matter detector

NASA Astrophysics Data System (ADS)

Aalbers, J.; Agostini, F.; Alfonsi, M.; Amaro, F. D.; Amsler, C.; Aprile, E.; Arazi, L.; Arneodo, F.; Barrow, P.; Baudis, L.; Benabderrahmane, M. L.; Berger, T.; Beskers, B.; Breskin, A.; Breur, P. A.; Brown, A.; Brown, E.; Bruenner, S.; Bruno, G.; Budnik, R.; Bütikofer, L.; Calvén, J.; Cardoso, J. M. R.; Cichon, D.; Coderre, D.; Colijn, A. P.; Conrad, J.; Cussonneau, J. P.; Decowski, M. P.; Diglio, S.; Drexlin, G.; Duchovni, E.; Erdal, E.; Eurin, G.; Ferella, A.; Fieguth, A.; Fulgione, W.; Gallo Rosso, A.; Di Gangi, P.; Di Giovanni, A.; Galloway, M.; Garbini, M.; Geis, C.; Glueck, F.; Grandi, L.; Greene, Z.; Grignon, C.; Hasterok, C.; Hannen, V.; Hogenbirk, E.; Howlett, J.; Hilk, D.; Hils, C.; James, A.; Kaminsky, B.; Kazama, S.; Kilminster, B.; Kish, A.; Krauss, L. M.; Landsman, H.; Lang, R. F.; Lin, Q.; Linde, F. L.; Lindemann, S.; Lindner, M.; Lopes, J. A. M.; Marrodán Undagoitia, T.; Masbou, J.; Massoli, F. V.; Mayani, D.; Messina, M.; Micheneau, K.; Molinario, A.; Morå, K. D.; Morteau, E.; Murra, M.; Naganoma, J.; Newstead, J. L.; Ni, K.; Oberlack, U.; Pakarha, P.; Pelssers, B.; de Perio, P.; Persiani, R.; Piastra, F.; Piro, M. C.; Plante, G.; Rauch, L.; Reichard, S.; Rizzo, A.; Rupp, N.; Dos Santos, J. M. F.; Sartorelli, G.; Scheibelhut, M.; Schindler, S.; Schumann, M.; Schreiner, J.; Scotto Lavina, L.; Selvi, M.; Shagin, P.; Silva, M. C.; Simgen, H.; Sissol, P.; von Sivers, M.; Thers, D.; Thurn, J.; Tiseni, A.; Trotta, R.; Tunnell, C. D.; Valerius, K.; Vargas, M. A.; Wang, H.; Wei, Y.; Weinheimer, C.; Wester, T.; Wulf, J.; Zhang, Y.; Zhu, T.; Zuber, K.

2016-11-01

DARk matter WImp search with liquid xenoN (DARWIN) will be an experiment for the direct detection of dark matter using a multi-ton liquid xenon time projection chamber at its core. Its primary goal will be to explore the experimentally accessible parameter space for Weakly Interacting Massive Particles (WIMPs) in a wide mass-range, until neutrino interactions with the target become an irreducible background. The prompt scintillation light and the charge signals induced by particle interactions in the xenon will be observed by VUV sensitive, ultra-low background photosensors. Besides its excellent sensitivity to WIMPs above a mass of 5 GeV/c2, such a detector with its large mass, low-energy threshold and ultra-low background level will also be sensitive to other rare interactions. It will search for solar axions, galactic axion-like particles and the neutrinoless double-beta decay of 136Xe, as well as measure the low-energy solar neutrino flux with < 1% precision, observe coherent neutrino-nucleus interactions, and detect galactic supernovae. We present the concept of the DARWIN detector and discuss its physics reach, the main sources of backgrounds and the ongoing detector design and R&D efforts.

A position- and time-sensitive photon-counting detector with delay- line read-out

NASA Astrophysics Data System (ADS)

Jagutzki, Ottmar; Dangendorf, Volker; Lauck, Ronald; Czasch, Achim; Milnes, James

2007-05-01

We have developed image intensifier tubes with delay-anode read-out for time- and position-sensitive photon counting. The timing precision is better than 1 ns with 1000x1000 pixels position resolution and up to one megacounts/s processing rate. Large format detectors of 40 and 75 mm active diameter with internal helical-wire delay-line anodes have been produced and specified. A different type of 40 and 25 mm tubes with semi-conducting screen for image charge read-out allow for an economic and robust tube design and for placing the read-out anodes outside the sealed housing. Two types of external delay-line anodes, i.e. pick-up electrodes for the image charge, have been tested. We present tests of the detector and anode performance. Due to the low background this technique is well suited for applications with very low light intensity and especially if a precise time tagging for each photon is required. As an example we present the application of scintillator read-out in time-of-flight (TOF) neutron radiography. Further applications so far are Fluorescence Life-time Microscopy (FLIM) and Astronomy.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agnese, R.; Anderson, A. J.; Aralis, T.

The SuperCDMS experiment is designed to directly detect weakly interacting massive particles (WIMPs) that may constitute the dark matter in our Galaxy. During its operation at the Soudan Underground Laboratory, germanium detectors were run in the CDMSlite mode to gather data sets with sensitivity specifically for WIMPs with masses < 10 GeV/c 2. In this mode, a higher detector-bias voltage is applied to amplify the phonon signals produced by drifting charges. This article presents studies of the experimental noise and its effect on the achievable energy threshold, which is demonstrated to be as low as 56 eV ee (electron equivalentmore » energy). The detector-biasing configuration is described in detail, with analysis corrections for voltage variations to the level of a few percent. Detailed studies of the electric-field geometry, and the resulting successful development of a fiducial parameter, eliminate poorly measured events, yielding an energy resolution ranging from ~ 9 eV ee at 0 keV to 101 eV ee at ~ 10 keV ee. New results are derived for astrophysical uncertainties relevant to the WIMP-search limits, specifically examining how they are affected by variations in the most probable WIMP velocity and the Galactic escape velocity. These variations become more important for WIMP masses below 10 GeV/c 2. Finally, new limits on spin-dependent low-mass WIMP-nucleon interactions are derived, with new parameter space excluded for WIMP masses ≲ 3 GeV/c 2.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agnese, R.; Anderson, A. J.; Aralis, T.

The SuperCDMS experiment is designed to directly detect WIMPs (Weakly Interacting Massive Particles) that may constitute the dark matter in our galaxy. During its operation at the Soudan Underground Laboratory, germanium detectors were run in the CDMSlite (Cryogenic Dark Matter Search low ionization threshold experiment) mode to gather data sets with sensitivity specifically for WIMPs with massesmore » $${<}10$$ GeV/$c^2$. In this mode, a large detector-bias voltage is applied to amplify the phonon signals produced by drifting charges. This paper presents studies of the experimental noise and its effect on the achievable energy threshold, which is demonstrated to be as low as 56 eV$$_{\\text{ee}}$$ (electron equivalent energy). The detector biasing configuration is described in detail, with analysis corrections for voltage variations to the level of a few percent. Detailed studies of the electric-field geometry, and the resulting successful development of a fiducial parameter, eliminate poorly measured events, yielding an energy resolution ranging from $${\\sim}$$9 eV$$_{\\text{ee}}$$ at 0 keV to 101 eV$$_{\\text{ee}}$$ at $${\\sim}$$10 keV$$_{\\text{ee}}$$. New results are derived for astrophysical uncertainties relevant to the WIMP-search limits, specifically examining how they are affected by variations in the most probable WIMP velocity and the galactic escape velocity. These variations become more important for WIMP masses below 10 GeV/$c^2$. Finally, new limits on spin-dependent low-mass WIMP-nucleon interactions are derived, with new parameter space excluded for WIMP masses $${\\lesssim}$$3 GeV/$c^2$.« less

Low-mass dark matter search with CDMSlite

DOE PAGES

Agnese, R.; Anderson, A. J.; Aralis, T.; ...

2018-01-01

The SuperCDMS experiment is designed to directly detect WIMPs (Weakly Interacting Massive Particles) that may constitute the dark matter in our galaxy. During its operation at the Soudan Underground Laboratory, germanium detectors were run in the CDMSlite (Cryogenic Dark Matter Search low ionization threshold experiment) mode to gather data sets with sensitivity specifically for WIMPs with massesmore » $${<}10$$ GeV/$c^2$. In this mode, a large detector-bias voltage is applied to amplify the phonon signals produced by drifting charges. This paper presents studies of the experimental noise and its effect on the achievable energy threshold, which is demonstrated to be as low as 56 eV$$_{\\text{ee}}$$ (electron equivalent energy). The detector biasing configuration is described in detail, with analysis corrections for voltage variations to the level of a few percent. Detailed studies of the electric-field geometry, and the resulting successful development of a fiducial parameter, eliminate poorly measured events, yielding an energy resolution ranging from $${\\sim}$$9 eV$$_{\\text{ee}}$$ at 0 keV to 101 eV$$_{\\text{ee}}$$ at $${\\sim}$$10 keV$$_{\\text{ee}}$$. New results are derived for astrophysical uncertainties relevant to the WIMP-search limits, specifically examining how they are affected by variations in the most probable WIMP velocity and the galactic escape velocity. These variations become more important for WIMP masses below 10 GeV/$c^2$. Finally, new limits on spin-dependent low-mass WIMP-nucleon interactions are derived, with new parameter space excluded for WIMP masses $${\\lesssim}$$3 GeV/$c^2$.« less

Low-mass dark matter search with CDMSlite

DOE PAGES

Agnese, R.; Anderson, A. J.; Aralis, T.; ...

2018-01-17

The SuperCDMS experiment is designed to directly detect weakly interacting massive particles (WIMPs) that may constitute the dark matter in our Galaxy. During its operation at the Soudan Underground Laboratory, germanium detectors were run in the CDMSlite mode to gather data sets with sensitivity specifically for WIMPs with masses < 10 GeV/c 2. In this mode, a higher detector-bias voltage is applied to amplify the phonon signals produced by drifting charges. This article presents studies of the experimental noise and its effect on the achievable energy threshold, which is demonstrated to be as low as 56 eV ee (electron equivalentmore » energy). The detector-biasing configuration is described in detail, with analysis corrections for voltage variations to the level of a few percent. Detailed studies of the electric-field geometry, and the resulting successful development of a fiducial parameter, eliminate poorly measured events, yielding an energy resolution ranging from ~ 9 eV ee at 0 keV to 101 eV ee at ~ 10 keV ee. New results are derived for astrophysical uncertainties relevant to the WIMP-search limits, specifically examining how they are affected by variations in the most probable WIMP velocity and the Galactic escape velocity. These variations become more important for WIMP masses below 10 GeV/c 2. Finally, new limits on spin-dependent low-mass WIMP-nucleon interactions are derived, with new parameter space excluded for WIMP masses ≲ 3 GeV/c 2.« less

Temperature sensor based on an isopropanol-sealed photonic crystal fiber in-line interferometer with enhanced refractive index sensitivity.

PubMed

Qiu, Sun-jie; Chen, Ye; Xu, Fei; Lu, Yan-qing

2012-03-01

We fabricate a simple, compact, and stable temperature sensor based on a liquid-sealed photonic crystal fiber (PCF) in-line nonpolarimetric modal interferometer. Different from other reported PCF devices, it does not need expensive polarimetric devices, and the liquid is sealed in one fiber. The device consists of a stub of isopropanol-filled PCF spliced between standard single-mode fibers. The temperature sensitivity (-166 pm/°C) increases over an order of magnitude compared with those of the previous sensors based on air-sealed PCF interferometers built via fusion splicing with the same mechanism. In addition, the refractive index sensitivity also increases. Higher temperature sensitivity can be realized by infiltrating some liquid having a higher thermo-optic coefficient into the microholes of the PCF. © 2012 Optical Society of America

Anticancer drug sensitivity prediction in cell lines from baseline gene expression through recursive feature selection.

PubMed

Dong, Zuoli; Zhang, Naiqian; Li, Chun; Wang, Haiyun; Fang, Yun; Wang, Jun; Zheng, Xiaoqi

2015-06-30

An enduring challenge in personalized medicine is to select right drug for individual patients. Testing drugs on patients in large clinical trials is one way to assess their efficacy and toxicity, but it is impractical to test hundreds of drugs currently under development. Therefore the preclinical prediction model is highly expected as it enables prediction of drug response to hundreds of cell lines in parallel. Recently, two large-scale pharmacogenomic studies screened multiple anticancer drugs on over 1000 cell lines in an effort to elucidate the response mechanism of anticancer drugs. To this aim, we here used gene expression features and drug sensitivity data in Cancer Cell Line Encyclopedia (CCLE) to build a predictor based on Support Vector Machine (SVM) and a recursive feature selection tool. Robustness of our model was validated by cross-validation and an independent dataset, the Cancer Genome Project (CGP). Our model achieved good cross validation performance for most drugs in the Cancer Cell Line Encyclopedia (≥80% accuracy for 10 drugs, ≥75% accuracy for 19 drugs). Independent tests on eleven common drugs between CCLE and CGP achieved satisfactory performance for three of them, i.e., AZD6244, Erlotinib and PD-0325901, using expression levels of only twelve, six and seven genes, respectively. These results suggest that drug response could be effectively predicted from genomic features. Our model could be applied to predict drug response for some certain drugs and potentially play a complementary role in personalized medicine.

Results from the DarkSide-50 Dark Matter Experiment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fan, Alden

2016-01-01

While there is tremendous astrophysical and cosmological evidence for dark matter, its precise nature is one of the most significant open questions in modern physics. Weakly interacting massive particles (WIMPs) are a particularly compelling class of dark matter candidates with masses of the order 100 GeV and couplings to ordinary matter at the weak scale. Direct detection experiments are aiming to observe the low energy (<100 keV) scattering of dark matter off normal matter. With the liquid noble technology leading the way in WIMP sensitivity, no conclusive signals have been observed yet. The DarkSide experiment is looking for WIMP darkmore » matter using a liquid argon target in a dual-phase time projection chamber located deep underground at Gran Sasso National Laboratory (LNGS) in Italy. Currently filled with argon obtained from underground sources, which is greatly reduced in radioactive 39Ar, DarkSide-50 recently made the most sensitive measurement of the 39Ar activity in underground argon and used it to set the strongest WIMP dark matter limit using liquid argon to date. This work describes the full chain of analysis used to produce the recent dark matter limit, from reconstruction of raw data to evaluation of the final exclusion curve. The DarkSide- 50 apparatus is described in detail, followed by discussion of the low level reconstruction algorithms. The algorithms are then used to arrive at three broad analysis results: The electroluminescence signals in DarkSide-50 are used to perform a precision measurement of ii longitudinal electron diffusion in liquid argon. A search is performed on the underground argon data to identify the delayed coincidence signature of 85Kr decays to the 85mRb state, a crucial ingredient in the measurement of the 39Ar activity in the underground argon. Finally, a full description of the WIMP search is given, including development of cuts, efficiencies, energy scale, and exclusion curve in the WIMP mass vs. spin

Similar cisplatin sensitivity of HPV-positive and -negative HNSCC cell lines

PubMed Central

Kriegs, Malte; Gatzemeier, Fruzsina; Krüger, Katharina; Möckelmann, Nikolaus; Fritz, Gerhard; Petersen, Cordula; Knecht, Rainald; Rothkamm, Kai; Rieckmann, Thorsten

2016-01-01

Patients with HPV-positive head and neck squamous cell carcinoma (HNSCC) show better survival rates than those with HPV-negative HNSCC. While an enhanced radiosensitivity of HPV-positive tumors is clearly evident from single modality treatment, cisplatin is never administered as monotherapy and therefore its contribution to the enhanced cure rates of HPV-positive HNSCC is not known. Both cisplatin and radiotherapy can cause severe irreversible side effects and therefore various clinical studies are currently testing deintensified regimes for patients with HPV-positive HNSCC. One strategy is to omit cisplatin-based chemotherapy or replace it by less toxic treatments but the risk assessment of these approaches remains difficult. In this study we have compared the cytotoxic effects of cisplatin in a panel of HPV-positive and -negative HNSCC cell lines alone and when combined with radiation. While cisplatin-treated HPV-positive strains showed a slightly stronger inhibition of proliferation, there was no difference regarding colony formation. Cellular responses to the drug, namely cell cycle distribution, apoptosis and γH2AX-induction did not differ between the two entities but assessment of cisplatin-DNA-adducts suggests differences regarding the mechanisms that determine cisplatin sensitivity. Combining cisplatin with radiation, we generally observed an additive but only in a minority of strains from both entities a clear synergistic effect on colony formation. In summary, HPV-positive and -negative HNSCC cells were equally sensitive to cisplatin. Therefore replacing cisplatin may be feasible but the substituting agent should be of similar efficacy in order not to jeopardize the high cure rates for HPV-positive HNSCC. PMID:27127883

The LZ Dark Matter Experiment

NASA Astrophysics Data System (ADS)

Bernard, Ethan; LZ Collaboration

2013-10-01

Astrophysical and cosmological observations show that dark matter is concentrated in halos around galaxies and is approximately five times more abundant than baryonic matter. Dark matter has evaded direct detection despite a series of increasingly sensitive experiments. The LZ (LUX-ZEPLIN) experiment will use a two-phase liquid-xenon time projection chamber to search for elastic scattering of xenon nuclei by WIMP (weakly interactive massive particle) dark matter. The detector will contain seven tons of liquid xenon shielded by an active organic scintillator veto and a water tank within the Sanford Underground Research Facility (SURF) in Lead, South Dakota. The LZ detector scales up the demonstrated light-sensing, cryogenic, radiopurity and shielding technologies of the LUX experiment. Active shielding, position fiducialization, radiopurity control and signal discrimination will reduce backgrounds to levels subdominant to solar neutrino scattering. This experiment will reach a sensitivity to the WIMP-nucleon spin-independent cross section approaching ~ 2 .10-48 cm2 for a 50 GeV WIMP mass, which is about three orders of magnitude smaller than current limits.

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

SLAC is helping to build and test the LUX-ZEPLIN or LZ detector, one of the biggest and most sensitive detectors ever designed to catch hypothetical dark matter particles known as WIMPs. Researchers at the Department of Energy’s SLAC National Accelerator Laboratory are on a quest to solve one of physics’ biggest mysteries: What exactly is dark matter – the invisible substance that accounts for 85 percent of all the matter in the universe but can’t be seen even with our most advanced scientific instruments? Most scientists believe it’s made of ghostly particles that rarely bump into their surroundings; that’s whymore » billions of dark matter particles might zip right through our bodies every second without us even noticing. Leading candidates for dark matter particles are WIMPs, or weakly interacting massive particles. Now SLAC is helping to build and test one of the biggest and most sensitive detectors ever designed to catch a WIMP – the LUX-ZEPLIN or LZ detector.« less

Neutrino physics with multi-ton scale liquid xenon detectors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baudis, L.; Ferella, A.; Kish, A.

2014-01-01

We study the sensitivity of large-scale xenon detectors to low-energy solar neutrinos, to coherent neutrino-nucleus scattering and to neutrinoless double beta decay. As a concrete example, we consider the xenon part of the proposed DARWIN (Dark Matter WIMP Search with Noble Liquids) experiment. We perform detailed Monte Carlo simulations of the expected backgrounds, considering realistic energy resolutions and thresholds in the detector. In a low-energy window of 2–30 keV, where the sensitivity to solar pp and {sup 7}Be-neutrinos is highest, an integrated pp-neutrino rate of 5900 events can be reached in a fiducial mass of 14 tons of natural xenon,more » after 5 years of data. The pp-neutrino flux could thus be measured with a statistical uncertainty around 1%, reaching the precision of solar model predictions. These low-energy solar neutrinos will be the limiting background to the dark matter search channel for WIMP-nucleon cross sections below ∼ 2 × 10{sup −48} cm{sup 2} and WIMP masses around 50 GeV⋅c{sup −2}, for an assumed 99.5% rejection of electronic recoils due to elastic neutrino-electron scatters. Nuclear recoils from coherent scattering of solar neutrinos will limit the sensitivity to WIMP masses below ∼ 6 GeV⋅c{sup −2} to cross sections above ∼ 4 × 10{sup −45}cm{sup 2}. DARWIN could reach a competitive half-life sensitivity of 5.6 × 10{sup 26} y to the neutrinoless double beta decay of {sup 136}Xe after 5 years of data, using 6 tons of natural xenon in the central detector region.« less

Modulators of sensitivity and resistance to inhibition of PI3K identified in a pharmacogenomic screen of the NCI-60 human tumor cell line collection.

PubMed

Kwei, Kevin A; Baker, Joffre B; Pelham, Robert J

2012-01-01

The phosphoinositide 3-kinase (PI3K) signaling pathway is significantly altered in a wide variety of human cancers, driving cancer cell growth and survival. Consequently, a large number of PI3K inhibitors are now in clinical development. To begin to improve the selection of patients for treatment with PI3K inhibitors and to identify de novo determinants of patient response, we sought to identify and characterize candidate genomic and phosphoproteomic biomarkers predictive of response to the selective PI3K inhibitor, GDC-0941, using the NCI-60 human tumor cell line collection. In this study, sixty diverse tumor cell lines were exposed to GDC-0941 and classified by GI(50) value as sensitive or resistant. The most sensitive and resistant cell lines were analyzed for their baseline levels of gene expression and phosphorylation of key signaling nodes. Phosphorylation or activation status of both the PI3K-Akt signaling axis and PARP were correlated with in vitro response to GDC-0941. A gene expression signature associated with in vitro sensitivity to GDC-0941 was also identified. Furthermore, in vitro siRNA-mediated silencing of two genes in this signature, OGT and DDN, validated their role in modulating sensitivity to GDC-0941 in numerous cell lines and begins to provide biological insights into their role as chemosensitizers. These candidate biomarkers will offer useful tools to begin a more thorough understanding of determinants of patient response to PI3K inhibitors and merit exploration in human cancer patients treated with PI3K inhibitors.

Modulators of Sensitivity and Resistance to Inhibition of PI3K Identified in a Pharmacogenomic Screen of the NCI-60 Human Tumor Cell Line Collection

PubMed Central

Kwei, Kevin A.; Baker, Joffre B.; Pelham, Robert J.

2012-01-01

The phosphoinositide 3-kinase (PI3K) signaling pathway is significantly altered in a wide variety of human cancers, driving cancer cell growth and survival. Consequently, a large number of PI3K inhibitors are now in clinical development. To begin to improve the selection of patients for treatment with PI3K inhibitors and to identify de novo determinants of patient response, we sought to identify and characterize candidate genomic and phosphoproteomic biomarkers predictive of response to the selective PI3K inhibitor, GDC-0941, using the NCI-60 human tumor cell line collection. In this study, sixty diverse tumor cell lines were exposed to GDC-0941 and classified by GI50 value as sensitive or resistant. The most sensitive and resistant cell lines were analyzed for their baseline levels of gene expression and phosphorylation of key signaling nodes. Phosphorylation or activation status of both the PI3K-Akt signaling axis and PARP were correlated with in vitro response to GDC-0941. A gene expression signature associated with in vitro sensitivity to GDC-0941 was also identified. Furthermore, in vitro siRNA-mediated silencing of two genes in this signature, OGT and DDN, validated their role in modulating sensitivity to GDC-0941 in numerous cell lines and begins to provide biological insights into their role as chemosensitizers. These candidate biomarkers will offer useful tools to begin a more thorough understanding of determinants of patient response to PI3K inhibitors and merit exploration in human cancer patients treated with PI3K inhibitors. PMID:23029544

On the DEAP-3600 resurfacing

NASA Astrophysics Data System (ADS)

Giampa, P.

2018-01-01

The DEAP-3600 experiment is a single-phase detector that can hold up to 3600 kg of liquid argon to search for dark matter at SNOLAB in Sudbury Canada, 6800 ft. underground. The projected sensitivity to the spin-independent WIMP-nucleon cross-section is 10-46 cm2 for a WIMP mass of 100 GeV/c2. One of the primary background sources to the WIMP search are alpha decays occurring on the surface of the experiment, which only deposit a tiny fraction of their energy in the argon. The work reported here focuses on the development and operation of a custom designed robot, the Resurfacer, which was used to remove 500 micrometers from the inner-most layer of the detector's acrylic cryostat, thus removing contaminations introduced during construction.

Improved Limits on Scattering of Weakly Interacting Massive Particles from Reanalysis of 2013 LUX Data.

PubMed

Akerib, D S; Araújo, H M; Bai, X; Bailey, A J; Balajthy, J; Beltrame, P; Bernard, E P; Bernstein, A; Biesiadzinski, T P; Boulton, E M; Bradley, A; Bramante, R; Cahn, S B; Carmona-Benitez, M C; Chan, C; Chapman, J J; Chiller, A A; Chiller, C; Currie, A; Cutter, J E; Davison, T J R; de Viveiros, L; Dobi, A; Dobson, J E Y; Druszkiewicz, E; Edwards, B N; Faham, C H; Fiorucci, S; Gaitskell, R J; Gehman, V M; Ghag, C; Gibson, K R; Gilchriese, M G D; Hall, C R; Hanhardt, M; Haselschwardt, S J; Hertel, S A; Hogan, D P; Horn, M; Huang, D Q; Ignarra, C M; Ihm, M; Jacobsen, R G; Ji, W; Kazkaz, K; Khaitan, D; Knoche, R; Larsen, N A; Lee, C; Lenardo, B G; Lesko, K T; Lindote, A; Lopes, M I; Malling, D C; Manalaysay, A; Mannino, R L; Marzioni, M F; McKinsey, D N; Mei, D-M; Mock, J; Moongweluwan, M; Morad, J A; Murphy, A St J; Nehrkorn, C; Nelson, H N; Neves, F; O'Sullivan, K; Oliver-Mallory, K C; Ott, R A; Palladino, K J; Pangilinan, M; Pease, E K; Phelps, P; Reichhart, L; Rhyne, C; Shaw, S; Shutt, T A; Silva, C; Solovov, V N; Sorensen, P; Stephenson, S; Sumner, T J; Szydagis, M; Taylor, D J; Taylor, W; Tennyson, B P; Terman, P A; Tiedt, D R; To, W H; Tripathi, M; Tvrznikova, L; Uvarov, S; Verbus, J R; Webb, R C; White, J T; Whitis, T J; Witherell, M S; Wolfs, F L H; Yazdani, K; Young, S K; Zhang, C

2016-04-22

We present constraints on weakly interacting massive particles (WIMP)-nucleus scattering from the 2013 data of the Large Underground Xenon dark matter experiment, including 1.4×10^{4}  kg day of search exposure. This new analysis incorporates several advances: single-photon calibration at the scintillation wavelength, improved event-reconstruction algorithms, a revised background model including events originating on the detector walls in an enlarged fiducial volume, and new calibrations from decays of an injected tritium β source and from kinematically constrained nuclear recoils down to 1.1 keV. Sensitivity, especially to low-mass WIMPs, is enhanced compared to our previous results which modeled the signal only above a 3 keV minimum energy. Under standard dark matter halo assumptions and in the mass range above 4  GeV c^{-2}, these new results give the most stringent direct limits on the spin-independent WIMP-nucleon cross section. The 90% C.L. upper limit has a minimum of 0.6 zb at 33  GeV c^{-2} WIMP mass.

Improved limits on scattering of weakly interacting massive particles from reanalysis of 2013 LUX data

DOE PAGES

Akerib, D. S.

2016-04-20

Here, we present constraints on weakly interacting massive particles (WIMP)-nucleus scattering from the 2013 data of the Large Underground Xenon dark matter experiment, including 1.4 × 10 4 kg day of search exposure. This new analysis incorporates several advances: single-photon calibration at the scintillation wavelength, improved event-reconstruction algorithms, a revised background model including events originating on the detector walls in an enlarged fiducial volume, and new calibrations from decays of an injected tritium β source and from kinematically constrained nuclear recoils down to 1.1 keV. Sensitivity, especially to low-mass WIMPs, is enhanced compared to our previous results which modeled themore » signal only above a 3 keV minimum energy. Under standard dark matter halo assumptions and in the mass range above 4 GeV c –2, these new results give the most stringent direct limits on the spin-independent WIMP-nucleon cross section. The 90% C.L. upper limit has a minimum of 0.6 zb at 33 GeV c –2 WIMP mass.« less

Improved Limits on Scattering of Weakly Interacting Massive Particles from Reanalysis of 2013 LUX Data

NASA Astrophysics Data System (ADS)

Akerib, D. S.; Araújo, H. M.; Bai, X.; Bailey, A. J.; Balajthy, J.; Beltrame, P.; Bernard, E. P.; Bernstein, A.; Biesiadzinski, T. P.; Boulton, E. M.; Bradley, A.; Bramante, R.; Cahn, S. B.; Carmona-Benitez, M. C.; Chan, C.; Chapman, J. J.; Chiller, A. A.; Chiller, C.; Currie, A.; Cutter, J. E.; Davison, T. J. R.; de Viveiros, L.; Dobi, A.; Dobson, J. E. Y.; Druszkiewicz, E.; Edwards, B. N.; Faham, C. H.; Fiorucci, S.; Gaitskell, R. J.; Gehman, V. M.; Ghag, C.; Gibson, K. R.; Gilchriese, M. G. D.; Hall, C. R.; Hanhardt, M.; Haselschwardt, S. J.; Hertel, S. A.; Hogan, D. P.; Horn, M.; Huang, D. Q.; Ignarra, C. M.; Ihm, M.; Jacobsen, R. G.; Ji, W.; Kazkaz, K.; Khaitan, D.; Knoche, R.; Larsen, N. A.; Lee, C.; Lenardo, B. G.; Lesko, K. T.; Lindote, A.; Lopes, M. I.; Malling, D. C.; Manalaysay, A.; Mannino, R. L.; Marzioni, M. F.; McKinsey, D. N.; Mei, D.-M.; Mock, J.; Moongweluwan, M.; Morad, J. A.; Murphy, A. St. J.; Nehrkorn, C.; Nelson, H. N.; Neves, F.; O'Sullivan, K.; Oliver-Mallory, K. C.; Ott, R. A.; Palladino, K. J.; Pangilinan, M.; Pease, E. K.; Phelps, P.; Reichhart, L.; Rhyne, C.; Shaw, S.; Shutt, T. A.; Silva, C.; Solovov, V. N.; Sorensen, P.; Stephenson, S.; Sumner, T. J.; Szydagis, M.; Taylor, D. J.; Taylor, W.; Tennyson, B. P.; Terman, P. A.; Tiedt, D. R.; To, W. H.; Tripathi, M.; Tvrznikova, L.; Uvarov, S.; Verbus, J. R.; Webb, R. C.; White, J. T.; Whitis, T. J.; Witherell, M. S.; Wolfs, F. L. H.; Yazdani, K.; Young, S. K.; Zhang, C.; LUX Collaboration

2016-04-01

We present constraints on weakly interacting massive particles (WIMP)-nucleus scattering from the 2013 data of the Large Underground Xenon dark matter experiment, including 1.4 ×104 kg day of search exposure. This new analysis incorporates several advances: single-photon calibration at the scintillation wavelength, improved event-reconstruction algorithms, a revised background model including events originating on the detector walls in an enlarged fiducial volume, and new calibrations from decays of an injected tritium β source and from kinematically constrained nuclear recoils down to 1.1 keV. Sensitivity, especially to low-mass WIMPs, is enhanced compared to our previous results which modeled the signal only above a 3 keV minimum energy. Under standard dark matter halo assumptions and in the mass range above 4 GeV c-2 , these new results give the most stringent direct limits on the spin-independent WIMP-nucleon cross section. The 90% C.L. upper limit has a minimum of 0.6 zb at 33 GeV c-2 WIMP mass.

DARWIN: towards the ultimate dark matter detector

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aalbers, J.; Breur, P.A.; Brown, A.

2016-11-01

DARk matter WImp search with liquid xenoN (DARWIN) will be an experiment for the direct detection of dark matter using a multi-ton liquid xenon time projection chamber at its core. Its primary goal will be to explore the experimentally accessible parameter space for Weakly Interacting Massive Particles (WIMPs) in a wide mass-range, until neutrino interactions with the target become an irreducible background. The prompt scintillation light and the charge signals induced by particle interactions in the xenon will be observed by VUV sensitive, ultra-low background photosensors. Besides its excellent sensitivity to WIMPs above a mass of 5 GeV/ c {supmore » 2}, such a detector with its large mass, low-energy threshold and ultra-low background level will also be sensitive to other rare interactions. It will search for solar axions, galactic axion-like particles and the neutrinoless double-beta decay of {sup 136}Xe, as well as measure the low-energy solar neutrino flux with < 1% precision, observe coherent neutrino-nucleus interactions, and detect galactic supernovae. We present the concept of the DARWIN detector and discuss its physics reach, the main sources of backgrounds and the ongoing detector design and R and D efforts.« less

Selective breeding of two lines of guinea pigs differing in bronchial sensitivity to acetylcholine and histamine exposure.

PubMed

Mikami, H; Nishibata, R; Kawamoto, Y; Ino, T

1991-04-01

We developed two lines of guinea pigs, one as model animals for bronchial asthma with bronchial hypersensitivity and the other with hyposensitivity as a control. In the last four years, the bronchial hypersensitive line (BHS) and hyposensitive line (BHR), both derived from Hartley strain guinea pigs, have been selected by using bronchial reactivity to acetylcholine and to histamine as parameters. Both lines have reached the F6 generation. The following results were obtained with the two lines: 1) Sib and cous in matings, and mating of selected consanguineous individuals were adopted in breeding BHS and BHR. The breeding started with six families, each, but in the F6 generation the number of families decreased to two in each line. 2) Appearance rates of hyper- or hyposensitivity to acetylcholine and histamine increased with successive generations in both lines, which had been completely separated by the F6 generation. 3) Coefficients of inbreeding in BHS and BHR in the F6 generation ranged from 42% to 45% in the former and 42% in the latter. 4) Heritabilities (h2) of BHS and BHR for the appearance rates of sensitivity to acetylcholine were presumed to be 0.54 in the former and 0.69 in the latter. 5) No difference in the body weight of 0, 20, and 40 day-old BHS was observed in any generation. On the other hand, the body weight of 20 and 40 day-old BHR tended to decrease with successive generations. 6) Mean litter sizes of BHS and BHR in each of the generations ranged from 2.24 to 3.47 animals in the former and from 2.63 to 3.38 animals in the latter.(ABSTRACT TRUNCATED AT 250 WORDS)

Chandipura virus growth kinetics in vertebrate cell lines, insect cell lines & embryonated eggs.

PubMed

Jadi, R S; Sudeep, A B; Kumar, Satyendra; Arankalle, V A; Mishra, A C

2010-08-01

Since not much information on Chandipura virus is available, an attempt was made to study the growth kinetics of the virus in certain vertebrate, invertebrate cell lines and embryonated chicken eggs. Comparative study of Chandipura virus (CHPV) growth kinetics in three vertebrate cell lines [Vero E6, Rhabdo myosarcoma (RD), Porcine stable kidney (PS) cell lines], two insect cell lines [Aedes aegypti (AA) and Phlebotomus papatasi (PP-9) cell lines] and embryonated pathogen free chicken eggs was conducted, by tissue culture infective dose 50 per cent (TCID(50)) and indirect immunofluorescence assay (IFA). All the cell lines and embryonated egg supported the growth of CHPV and yielded high virus titre. The vertebrate cell lines showed distinct cytopathic effect (CPE) within 4-6 h post infection (PI), while no CPE was observed in insect cell lines. PP-9 cell line was the most sensitive system to CHPV as viral antigen could be detected at 1 h PI by IFA. Our results demonstrated that all the systems were susceptible to CHPV and achieved high yield of virus. However, the PP-9 cell line had an edge over the others due to its high sensitivity to the virus which might be useful for detection and isolation of the virus during epidemics.

Relevance of MET activation and genetic alterations of KRAS and E-cadherin for cetuximab sensitivity of gastric cancer cell lines.

PubMed

Heindl, Stefan; Eggenstein, Evelyn; Keller, Simone; Kneissl, Julia; Keller, Gisela; Mutze, Kathrin; Rauser, Sandra; Gasteiger, Georg; Drexler, Ingo; Hapfelmeier, Alexander; Höfler, Heinz; Luber, Birgit

2012-05-01

The therapeutic activity of the epidermal growth factor receptor (EGFR)-directed monoclonal antibody cetuximab in gastric cancer is currently being investigated. Reliable biomarkers for the identification of patients who are likely to benefit from the treatment are not available. The aim of the study was to examine the drug sensitivity of five gastric cancer cell lines towards cetuximab as a single agent and to establish predictive markers for chemosensitivity in this cell culture model. The effect of a combination of cetuximab with chemotherapy was compared between a sensitive and a nonsensitive cell line. EGFR expression, activation and localisation, the presence and subcellular localisation of the cell adhesion molecule E-cadherin as well as MET activation were examined by Western blot analysis, flow cytometry and immunofluorescence staining. Cells were treated with varying concentrations of cetuximab and cisplatin and 5-fluorouracil in tumour-relevant concentrations. The biological endpoint was cell viability, which was measured by XTT cell proliferation assay. Response to treatment was evaluated using statistical methods. We assessed the activity of cetuximab in five gastric cancer cell lines (AGS, KATOIII, MKN1, MKN28 and MKN45). The viability of two cell lines, MKN1 and MKN28, was significantly reduced by cetuximab treatment. High EGFR expression and low levels of receptor activation were associated with cetuximab responsiveness. MET activation as well as mutations of KRAS and CDH1 (gene encoding E-cadherin) was associated with cetuximab resistance. These data indicate that our examinations may be clinically relevant, and the candidate markers should therefore be tested in clinical studies.

Paris Saponin I Sensitizes Gastric Cancer Cell Lines to Cisplatin via Cell Cycle Arrest and Apoptosis.

PubMed

Song, Shuichuan; Du, Leiwen; Jiang, Hao; Zhu, Xinhai; Li, Jinhui; Xu, Ji

2016-10-18

BACKGROUND Dose-related toxicity is the major restriction of cisplatin and cisplatin-combination chemotherapy, and is a challenge for advanced gastric cancer treatment. We explored the possibility of using Paris saponin I as an agent to sensitize gastric cancer cells to cisplatin, and examined the underlying mechanism. MATERIAL AND METHODS Growth inhibition was detected by MTT assay. The cell cycle and apoptosis were detected using flow cytometry and Annexin V/PI staining. The P21waf1/cip1, Bcl-2, Bax, and caspase-3 protein expression were detected using Western blot analysis. RESULTS The results revealed that PSI sensitized gastric cancer cells to cisplatin, with low toxicity. The IC50 value of cisplatin in SGC-7901 cell lines was decreased when combined with PSI. PSI promoted cisplatin-induced G2/M phase arrest and apoptosis in a cisplatin concentration-dependent manner. Bcl-2 protein expression decreased, but Bax, caspase-3, and P21waf1/cip1 protein expression increased with PSI treatment. CONCLUSIONS The underlying mechanism of Paris saponin I may be related to targeting the apoptosis pathway and cell cycle blocking, which suggests that PSI is a potential therapeutic sensitizer for cisplatin in treating gastric cancer.

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

PubMed

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

2014-12-01

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

Ferrocene-cinchona hybrids with triazolyl-chalcone linkers act as pro-oxidants and sensitize human cancer cell lines to paclitaxel.

PubMed

Podolski-Renić, Ana; Bősze, Szilvia; Dinić, Jelena; Kocsis, László; Hudecz, Ferenc; Csámpai, Antal; Pešić, Milica

2017-08-16

Recently, we demonstrated that ferrocene-containing compounds with a cinchona moiety displayed marked anticancer activity. Here we report on the effects of the most promising isomers encompassing quinine- (compounds 4 and 5) and quinidine-epimers (compounds 6 and 7) - synthesized using improved methods providing controlled diastereoselectivity - in three different human multidrug resistant (MDR) cancer cell lines and their sensitive counterparts (non-small cell lung carcinoma NCI-H460/R/NCI-H460, colorectal carcinoma DLD1-TxR/DLD1 and glioblastoma U87-TxR/U87). We observed that the presence of the MDR phenotype did not diminish the activity of the compounds suggesting that ferrocene quinine- and quinidine-epimers are not substrates for P-glycoprotein, which has been indicated as a major mechanism of MDR in the cell lines used. Considering that metal-based anticancer agents mainly act by increasing ROS production, we investigated the potential of ferrocene-quinidine epimers to generate ROS. We found that 6 and 7 more readily increased ROS production and induced mitochondrial damage in MDR cancer cells. According to cell death analysis, 6 and 7 were more active against MDR cancer cells showing collateral sensitivity. In addition, our data suggest that these compounds could act as inhibitors of autophagy. Importantly, simultaneous treatments of 6 and 7 with paclitaxel (PTX) increased the sensitivity of MDR cancer cells to PTX. In conclusion, the ferrocene-quinidine epimers, besides being selective towards MDR cancer cells, could also possess potential to overcome PTX resistance.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Chien-Yi; Hill, Richard J.; Solon, Mikhail P.

WIMP-nucleon scattering is analyzed at ordermore » $1/M$ in Heavy WIMP Effective Theory. The $1/M$ power corrections, where $$M\\gg m_W$$ is the WIMP mass, distinguish between different underlying UV models with the same universal limit and their impact on direct detection rates can be enhanced relative to naive expectations due to generic amplitude-level cancellations at leading order. The necessary one- and two-loop matching calculations onto the low-energy effective theory for WIMP interactions with Standard Model quarks and gluons are performed for the case of an electroweak SU(2) triplet WIMP, considering both the cases of elementary fermions and composite scalars. The low-velocity WIMP-nucleon scattering cross section is evaluated and compared with current experimental limits and projected future sensitivities. Our results provide the most robust prediction for electroweak triplet Majorana fermion dark matter direct detection rates; for this case, a cancellation between two sources of power corrections yields a small total $1/M$ correction, and a total cross section close to the universal limit for $$M \\gtrsim {\\rm few} \\times 100\\,{\\rm GeV}$$. For the SU(2) composite scalar, the $1/M$ corrections introduce dependence on underlying strong dynamics. Using a leading chiral logarithm evaluation, the total $1/M$ correction has a larger magnitude and uncertainty than in the fermionic case, with a sign that further suppresses the total cross section. These examples provide definite targets for future direct detection experiments and motivate large scale detectors capable of probing to the neutrino floor in the TeV mass regime.« less

Solar polarimetry through the K I lines at 770 nm

NASA Astrophysics Data System (ADS)

Quintero Noda, C.; Uitenbroek, H.; Katsukawa, Y.; Shimizu, T.; Oba, T.; Carlsson, M.; Orozco Suárez, D.; Ruiz Cobo, B.; Kubo, M.; Anan, T.; Ichimoto, K.; Suematsu, Y.

2017-09-01

We characterize the K I D1 & D2 lines in order to determine whether they could complement the 850 nm window, containing the Ca II infrared triplet lines and several Zeeman sensitive photospheric lines, that was studied previously. We investigate the effect of partial redistribution on the intensity profiles, their sensitivity to changes in different atmospheric parameters, and the spatial distribution of Zeeman polarization signals employing a realistic magnetohydrodynamic simulation. The results show that these lines form in the upper photosphere at around 500 km, and that they are sensitive to the line-of-sight velocity and magnetic field strength at heights where neither the photospheric lines nor the Ca II infrared lines are. However, at the same time, we found that their sensitivity to the temperature essentially comes from the photosphere. Then, we conclude that the K I lines provide a complement to the lines in the 850 nm window for the determination of atmospheric parameters in the upper photosphere, especially for the line-of-sight velocity and the magnetic field.

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

PubMed Central

2012-01-01

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

Neutrino physics with DARWIN

NASA Astrophysics Data System (ADS)

Benabderrahmane, M. L.

2017-09-01

DARWIN (DARk matter WImp search with liquid xenoN) will be a multi-ton dark matter detector with the primary goal of exploring the entire experimentally accessible parameter space for weakly interacting massive particles (WIMPs) over a wide mass-range. With its 40 tonne active liquid xenon target, low-energy threshold and ultra-low background level, DARWIN can also search for other rare interactions. Here we present its sensitivity to low-energy solar neutrinos and to neutrinoless double beta decay. In a low-energy window of 2-30 keV a rate of 105/year, from pp and 7Be neutrinos can be reached. Such a measurement, with 1% precision will allow testing neutrinos models. DARWIN could also reach a competitive half-life sensitivity of 8.5 · 1027 y to the neutrinoless double beta decay (0νββ) of 136Xe after an exposure of 140 t×y of natural xenon. Nuclear recoils from coherent scattering of solar neutrinos will limit the sensitivity to WIMP masses below 5 GeV/c2, and the event rate from 8B neutrinos would range from a few to a few tens of events per tonne and year, depending on the energy threshold of the detector. Deviations from the predicted but yet unmeasured neutrino flux would be an indication for physics beyond the Standard Model

Digital Model of Railway Electric Traction Lines

NASA Astrophysics Data System (ADS)

Garg, Rachana; Mahajan, Priya; Kumar, Parmod

2017-08-01

The characteristic impedance and propagation constant define the behavior of signal propagation over the transmission lines. The digital model for railway traction lines which includes railway tracks is developed, using curve fitting technique in MATLAB. The sensitivity of this model has been computed with respect to frequency. The digital sensitivity values are compared with the values of analog sensitivity. The developed model is useful for digital protection, integrated operation, control and planning of the system.

The LUX-Zeplin Dark Matter Detector

NASA Astrophysics Data System (ADS)

Mock, Jeremy; Lux-Zeplin (Lz) Collaboration

2016-03-01

The LUX-ZEPLIN (LZ) detector is a second generation dark matter experiment that will operate at the 4850 foot level of the Sanford Underground Research Experiment as a follow-up to the LUX detector, currently the world's most sensitive WIMP direct detection experiment. The LZ detector will contain 7 tonnes of active liquid xenon with a 5.6 tonne fiducial mass in the TPC. The TPC is surrounded by an active, instrumented, liquid-xenon ``skin'' region to veto gammas, then a layer of liquid scintillator to veto neutrons, all contained within a water shield. Modeling the detector is key to understanding the expected background, which in turn leads to a better understanding of the projected sensitivity, currently expected to be 2e-48 cm2 for a 50 GeV WIMP. I will discuss the current status of the LZ experiment as well as its projected sensitivity.

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

PubMed

Sobkowiak, Alicja; Jończyk, Maciej; Jarochowska, Emilia; Biecek, Przemysław; Trzcinska-Danielewicz, Joanna; Leipner, Jörg; Fronk, Jan; Sowiński, Paweł

2014-06-01

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.

Variation in cisplatinum sensitivity is not associated with Fanconi Anemia/BRCA pathway inactivation in head and neck squamous cell carcinoma cell lines.

PubMed

Snyder, Eric R; Ricker, Justin L; Chen, Zhong; Waes, Carter Van

2007-01-08

Fanconi Anemia has recently been associated with a high risk of head and neck squamous cell carcinoma (HNSCC). Inactivation of the Fanconi Anemia (FANC-BRCA) pathway via promoter methylation of the FANCF gene has been proposed to be responsible for variation in cisplatinum (CDDP) sensitivity seen in ovarian and HNSCCs. Promoter methylation of the FANCF gene has been observed in 15% of HNSCC specimens, but the relationship to FANC pathway activation and CDDP sensitivity has not been reported. In the present study, 10 HNSCC cell lines were examined for expression of nine genes involved in the FANC-BRCA pathway by RT-PCR: FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCL, BRCA1 and BRCA2. FANC pathway function was evaluated by western blotting for FANCD2 mono-ubiquitination. All of the cell lines were also analyzed for variation in CDDP cytotoxicity. While significant differences were found in CDDP cytotoxicity, Fanconi pathway defects are an infrequent cause, as no evidence of transcriptional down-regulation of FANCF or other FANC mRNAs, or functional FANC-BRCA pathway defects were observed. These findings suggest that the variation in CDDP sensitivity of many HNSCCs is most frequently due to factors other than FANC-BRCA pathway inactivation.

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

NASA Astrophysics Data System (ADS)

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

2010-02-01

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

Indirect detection of dark matter with γ rays.

PubMed

Funk, Stefan

2015-10-06

The details of what constitutes the majority of the mass that makes up dark matter in the Universe remains one of the prime puzzles of cosmology and particle physics today-80 y after the first observational indications. Today, it is widely accepted that dark matter exists and that it is very likely composed of elementary particles, which are weakly interacting and massive [weakly interacting massive particles (WIMPs)]. As important as dark matter is in our understanding of cosmology, the detection of these particles has thus far been elusive. Their primary properties such as mass and interaction cross sections are still unknown. Indirect detection searches for the products of WIMP annihilation or decay. This is generally done through observations of γ-ray photons or cosmic rays. Instruments such as the Fermi large-area telescope, high-energy stereoscopic system, major atmospheric gamma-ray imaging Cherenkov, and very energetic radiation imaging telescope array, combined with the future Cherenkov telescope array, will provide important complementarity to other search techniques. Given the expected sensitivities of all search techniques, we are at a stage where the WIMP scenario is facing stringent tests, and it can be expected that WIMPs will be either be detected or the scenario will be so severely constrained that it will have to be rethought. In this sense, we are on the threshold of discovery. In this article, I will give a general overview of the current status and future expectations for indirect searches of dark matter (WIMP) particles.

XENON100 Dark Matter Search: Scintillation Response of Liquid Xenon to Electronic Recoils

NASA Astrophysics Data System (ADS)

Lim, Kyungeun Elizabeth

Dark matter is one of the missing pieces necessary to complete the puzzle of the universe. Numerous astrophysical observations at all scales suggest that 23 % of the universe is made of nonluminous, cold, collisionless, nonbaryonic, yet undiscovered dark matter. Weakly Interacting Massive Particles (WIMPs) are the most well-motivated dark matter candidates and significant efforts have been made to search for WIMPs. The XENON100 dark matter experiment is currently the most sensitive experiment in the global race for the first direct detection of WIMP dark matter. XENON100 is a dual-phase (liquid-gas) time projection chamber containing a total of 161 kg of liquid xenon (LXe) with a 62kg WIMP target mass. It has been built with radiopure materials to achieve an ultra-low electromagnetic background and operated at the Laboratori Nazionali del Gran Sasso in Italy. WIMPs are expected to scatter off xenon nuclei in the target volume. Simultaneous measurement of ionization and scintillation produced by nuclear recoils allows for the detection of WIMPs in XENON100. Data from the XENON100 experiment have resulted in the most stringent limits on the spin-independent elastic WIMP-nucleon scattering cross sections for most of the significant WIMP masses. As the experimental precision increases, a better understanding of the scintillation and ionization response of LXe to low energy (< 10 keV) particles is crucial for the interpretation of data from LXe based WIMP searches. A setup has been built and operated at Columbia University to measure the scintillation response of LXe to both electronic and nuclear recoils down to energies of a few keV, in particular for the XENON100 experiment. In this thesis, I present the research carried out in the context of the XENON100 dark matter search experiment. For the theoretical foundation of the XENON100 experiment, the first two chapters are dedicated to the motivation for and detection medium choice of the XENON100 experiment

Olfactory discrimination and memory deficits in the Flinders Sensitive Line rodent model of depression.

PubMed

Cook, A; Pfeiffer, L-M; Thiele, S; Coenen, V A; Döbrössy, M D

2017-10-01

Major Depressive Disorder (MDD) is a heterogeneous psychiatric disorder with broad symptomatic manifestations. The current study examined, for the first time, olfactory memory and discrimination in the Flinders Sensitive Line (FSL) rodent model of depression. Male FSL rats and controls were trained on an Olfactory Discrimination (OD) and a Social Interaction (SI) test. On the OD test, the FSL and controls performed similarly at the shortest inter-trial interval (5min), however, with extended delay of 30min, the FSLs had a recall and odour discrimination deficit. At the longest delay (60min) both groups performed poorly. The FSL rats i.) had a deficit in olfactory discrimination suggesting impairment in olfactory memory and recall; ii.) were less likely to socialize with unfamiliar rats. The data suggests that FSL animals have an impaired olfactory information processing capacity. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of the skin sensitization potential of chemicals using expression of co-stimulatory molecules, CD54 and CD86, on the naive THP-1 cell line.

PubMed

Yoshida, Y; Sakaguchi, H; Ito, Y; Okuda, M; Suzuki, H

2003-04-01

It has been known that dendritic cells (DCs) including Langerhans cells (LCs) play a critical role in the skin sensitization process. Many attempts have been made to develop in vitro sensitization tests that employ DCs derived from peripheral blood mononuclear cells (PBMC-DC) or CD34+ hematopoietic progenitor cells (CD34+ HPC) purified from cord blood or bone marrow. However, the use of the DCs in in vitro methods has been difficult due to the nature of these cells such as low levels in the source and/or donor-to-donor variability. In our studies, we employed the human monocytic leukemia cell line, THP-1, in order to avoid some of these difficulties. At the start, we examined whether treatment of the cells with various cytokines could produce DCs from THP-1. Treatment of THP-1 cells with cytokines such as GM-CSF, IL-4, TNF-alpha, and/or PMA did induce some phenotypic changes in THP-1 cells that were characteristic of DCs. Subsequently, responses to a known sensitizer, dinitrochlorobenzene (DNCB), and a non-sensitizer, dimethyl sulfoxide (DMSO) or sodium lauryl sulfate (SLS), on the expression of co-stimulatory molecules, CD54 and CD86, were examined between the naive cells and the cytokine-treated cells. Interestingly, the naive THP-1 cells responded only to DNCB and the response to the sensitizer was more distinct than cytokine-treated THP-1 cells. Similar phenomena were also observed in the human myeloid leukemia cell line, KG-1. Furthermore, with treatment of DNCB, naive THP-1 cells showed augmented expression of HLA, CD80 and secretion of IL-1 beta. The response of THP-1 cells to a sensitizer was similar to that of LCs/DCs. Upon demonstrating the differentiation of monocyte cells in our system, we then evaluated a series of chemicals, including known sensitizers and non-sensitizers, for their potential to augment CD54 and CD86 expression on naive THP-1 cells. Indeed, known sensitizers such as PPD and 2-MBT significantly augmented CD54 and CD86 expression in a

First results from the DarkSide-50 dark matter experiment at Laboratori Nazionali del Gran Sasso

NASA Astrophysics Data System (ADS)

Agnes, P.; Alexander, T.; Alton, A.; Arisaka, K.; Back, H. O.; Baldin, B.; Biery, K.; Bonfini, G.; Bossa, M.; Brigatti, A.; Brodsky, J.; Budano, F.; Cadonati, L.; Calaprice, F.; Canci, N.; Candela, A.; Cao, H.; Cariello, M.; Cavalcante, P.; Chavarria, A.; Chepurnov, A.; Cocco, A. G.; Crippa, L.; D'Angelo, D.; D'Incecco, M.; Davini, S.; De Deo, M.; Derbin, A.; Devoto, A.; Di Eusanio, F.; Di Pietro, G.; Edkins, E.; Empl, A.; Fan, A.; Fiorillo, G.; Fomenko, K.; Forster, G.; Franco, D.; Gabriele, F.; Galbiati, C.; Goretti, A.; Grandi, L.; Gromov, M.; Guan, M. Y.; Guardincerri, Y.; Hackett, B.; Herner, K.; Hungerford, E. V.; Ianni, Al.; Ianni, An.; Jollet, C.; Keeter, K.; Kendziora, C.; Kidner, S.; Kobychev, V.; Koh, G.; Korablev, D.; Korga, G.; Kurlej, A.; Li, P. X.; Loer, B.; Lombardi, P.; Love, C.; Ludhova, L.; Luitz, S.; Ma, Y. Q.; Machulin, I.; Mandarano, A.; Mari, S.; Maricic, J.; Marini, L.; Martoff, C. J.; Meregaglia, A.; Meroni, E.; Meyers, P. D.; Milincic, R.; Montanari, D.; Monte, A.; Montuschi, M.; Monzani, M. E.; Mosteiro, P.; Mount, B.; Muratova, V.; Musico, P.; Nelson, A.; Odrowski, S.; Okounkova, M.; Orsini, M.; Ortica, F.; Pagani, L.; Pallavicini, M.; Pantic, E.; Papp, L.; Parmeggiano, S.; Parsells, R.; Pelczar, K.; Pelliccia, N.; Perasso, S.; Pocar, A.; Pordes, S.; Pugachev, D.; Qian, H.; Randle, K.; Ranucci, G.; Razeto, A.; Reinhold, B.; Renshaw, A.; Romani, A.; Rossi, B.; Rossi, N.; Rountree, S. D.; Sablone, D.; Saggese, P.; Saldanha, R.; Sands, W.; Sangiorgio, S.; Segreto, E.; Semenov, D.; Shields, E.; Skorokhvatov, M.; Smirnov, O.; Sotnikov, A.; Stanford, C.; Suvorov, Y.; Tartaglia, R.; Tatarowicz, J.; Testera, G.; Tonazzo, A.; Unzhakov, E.; Vogelaar, R. B.; Wada, M.; Walker, S.; Wang, H.; Wang, Y.; Watson, A.; Westerdale, S.; Wojcik, M.; Wright, A.; Xiang, X.; Xu, J.; Yang, C. G.; Yoo, J.; Zavatarelli, S.; Zec, A.; Zhu, C.; Zuzel, G.

2015-04-01

We report the first results of DarkSide-50, a direct search for dark matter operating in the underground Laboratori Nazionali del Gran Sasso (LNGS) and searching for the rare nuclear recoils possibly induced by weakly interacting massive particles (WIMPs). The dark matter detector is a Liquid Argon Time Projection Chamber with a (46.4 ± 0.7) kg active mass, operated inside a 30 t organic liquid scintillator neutron veto, which is in turn installed at the center of a 1 kt water Cherenkov veto for the residual flux of cosmic rays. We report here the null results of a dark matter search for a (1422 ± 67) kgd exposure with an atmospheric argon fill. This is the most sensitive dark matter search performed with an argon target, corresponding to a 90% CL upper limit on the WIMP-nucleon spin-independent cross section of 6.1 ×10-44 cm2 for a WIMP mass of 100 Gev /c2.

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

NASA Astrophysics Data System (ADS)

Rao, Gottipaty N.; Karpf, Andreas

2011-05-01

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

Dark Matter Searches in the Gamma-ray Extragalactic Background via Cross-correlations with Galaxy Catalogs

NASA Astrophysics Data System (ADS)

Cuoco, Alessandro; Xia, Jun-Qing; Regis, Marco; Branchini, Enzo; Fornengo, Nicolao; Viel, Matteo

2015-12-01

We compare the measured angular cross-correlation between the Fermi-Large Area Telescope γ-ray sky and catalogs of extragalactic objects with the expected signal induced by weakly interacting massive particle (WIMP) dark matter (DM). We include a detailed description of the contribution of astrophysical γ-ray emitters such as blazars, misaligned active galactic nucleus (AGN), and star-forming galaxies, and perform a global fit to the measured cross-correlation. Five catalogs are considered: Sloan Digital Sky Survey (SDSS)-DR6 quasars, Two Micron All Sky Survey galaxies, NRAO VLA Sky Survey radio galaxies, SDSS-DR8 Luminous Red Galaxies, and the SDSS-DR8 main galaxy sample. To model the cross-correlation signal, we use the halo occupation distribution formalism to estimate the number of galaxies of a given catalog in DM halos and their spatial correlation properties. We discuss uncertainties in the predicted cross-correlation signal arising from the DM clustering and WIMP microscopic properties, which set the DM γ-ray emission. The use of different catalogs probing objects at different redshifts significantly reduces, though not completely, the degeneracy among the different γ-ray components. We find that the presence of a significant WIMP DM signal is allowed by the data but not significantly preferred by the fit, although this is mainly due to a degeneracy with the misaligned AGN component. With modest substructure boost, the sensitivity of this method excludes thermal annihilation cross sections at 95% level for WIMP masses up to few tens of GeV. Constraining the low-redshift properties of astrophysical populations with future data will further improve the sensitivity to DM.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cuoco, Alessandro; Regis, Marco; Fornengo, Nicolao

We compare the measured angular cross-correlation between the Fermi-Large Area Telescope γ-ray sky and catalogs of extragalactic objects with the expected signal induced by weakly interacting massive particle (WIMP) dark matter (DM). We include a detailed description of the contribution of astrophysical γ-ray emitters such as blazars, misaligned active galactic nucleus (AGN), and star-forming galaxies, and perform a global fit to the measured cross-correlation. Five catalogs are considered: Sloan Digital Sky Survey (SDSS)-DR6 quasars, Two Micron All Sky Survey galaxies, NRAO VLA Sky Survey radio galaxies, SDSS-DR8 Luminous Red Galaxies, and the SDSS-DR8 main galaxy sample. To model the cross-correlation signal,more » we use the halo occupation distribution formalism to estimate the number of galaxies of a given catalog in DM halos and their spatial correlation properties. We discuss uncertainties in the predicted cross-correlation signal arising from the DM clustering and WIMP microscopic properties, which set the DM γ-ray emission. The use of different catalogs probing objects at different redshifts significantly reduces, though not completely, the degeneracy among the different γ-ray components. We find that the presence of a significant WIMP DM signal is allowed by the data but not significantly preferred by the fit, although this is mainly due to a degeneracy with the misaligned AGN component. With modest substructure boost, the sensitivity of this method excludes thermal annihilation cross sections at 95% level for WIMP masses up to few tens of GeV. Constraining the low-redshift properties of astrophysical populations with future data will further improve the sensitivity to DM.« less

Sensitivity to psychostimulants in mice bred for high and low stimulation to methamphetamine.

PubMed

Kamens, H M; Burkhart-Kasch, S; McKinnon, C S; Li, N; Reed, C; Phillips, T J

2005-03-01

Methamphetamine (MA) and cocaine induce behavioral effects primarily through modulation of dopamine neurotransmission. However, the genetic regulation of sensitivity to these two drugs may be similar or disparate. Using selective breeding, lines of mice were produced with extreme sensitivity (high MA activation; HMACT) and insensitivity (low MA activation; LMACT) to the locomotor stimulant effects of acute MA treatment. Studies were performed to determine whether there is pleiotropic genetic influence on sensitivity to the locomotor stimulant effect of MA and to other MA- and cocaine-related behaviors. The HMACT line exhibited more locomotor stimulation in response to several doses of MA and cocaine, compared to the LMACT line. Both lines exhibited locomotor sensitization to 2 mg/kg of MA and 10 mg/kg of cocaine; the magnitude of sensitization was similar in the two lines. However, the lines differed in the magnitude of sensitization to a 1 mg/kg dose of MA, a dose that did not produce a ceiling effect that may confound interpretation of studies using higher doses. The LMACT line consumed more MA and cocaine in a two-bottle choice drinking paradigm; the lines consumed similar amounts of saccharin and quinine, although the HMACT line exhibited slightly elevated preference for a low concentration of saccharin. These results suggest that some genes that influence sensitivity to the acute locomotor stimulant effect of MA have a pleiotropic influence on the magnitude of behavioral sensitization to MA and sensitivity to the stimulant effects of cocaine. Further, extreme sensitivity to MA may protect against MA and cocaine self-administration.

Indirect detection of dark matter with γ rays

PubMed Central

Funk, Stefan

2015-01-01

The details of what constitutes the majority of the mass that makes up dark matter in the Universe remains one of the prime puzzles of cosmology and particle physics today—80 y after the first observational indications. Today, it is widely accepted that dark matter exists and that it is very likely composed of elementary particles, which are weakly interacting and massive [weakly interacting massive particles (WIMPs)]. As important as dark matter is in our understanding of cosmology, the detection of these particles has thus far been elusive. Their primary properties such as mass and interaction cross sections are still unknown. Indirect detection searches for the products of WIMP annihilation or decay. This is generally done through observations of γ-ray photons or cosmic rays. Instruments such as the Fermi large-area telescope, high-energy stereoscopic system, major atmospheric gamma-ray imaging Cherenkov, and very energetic radiation imaging telescope array, combined with the future Cherenkov telescope array, will provide important complementarity to other search techniques. Given the expected sensitivities of all search techniques, we are at a stage where the WIMP scenario is facing stringent tests, and it can be expected that WIMPs will be either be detected or the scenario will be so severely constrained that it will have to be rethought. In this sense, we are on the threshold of discovery. In this article, I will give a general overview of the current status and future expectations for indirect searches of dark matter (WIMP) particles. PMID:24821791

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

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

2009-04-01

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.

[Establishment of Z-HL16C cell line.].

PubMed

Chen, J P; Li, J; Zhao, S L; Tian, J Y; Ye, F

2006-09-01

To establish and study the nature and the application of Z-HL16C cell line. The cell line was continuously passed, frozen stored and recovered. Its application was expanded and the cell type was identified. The cell line had an epithelial-cell-like shape, the size appeared uniform, the cell boundary was distinct. It has been continuously passed, frozen stored and recovered for ten years. Its recovery rate was about 90%. It has been proved to be sensitive to the tested viruses which were enteroviruses (Polio, Cox, Echo), influenza viruses, parainfluenzaviruses, adenoviruses, measles virus. This cell line has been identified as a cancerization cell. The cell line Z-HL16C has been stably established, it has a broad spectrum in sensitivity for culturing viruses.

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

PubMed Central

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

2014-01-01

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

Expression of surface markers on the human monocytic leukaemia cell line, THP-1, as indicators for the sensitizing potential of chemicals.

PubMed

An, Susun; Kim, Seoyoung; Huh, Yong; Lee, Tae Ryong; Kim, Han-Kon; Park, Kui-Lea; Eun, Hee Chul

2009-04-01

Evaluation of skin sensitization potential is an important part of the safety assessment of cosmetic ingredients and topical drugs. Recently, evaluation of changes in surface marker expression induced in dendritic cells (DC) or DC surrogate cell lines following exposure to chemicals represents one approach for in vitro test methods. The study aimed to test the change of expression patterns of surface markers on THP-1 cells by chemicals as a predictive in vitro method for contact sensitization. We investigated the expression of CD54, CD86, CD83, CD80, and CD40 after a 1-day exposure to sensitizers (1-chloro-2,4-dinitrobenzene; 2,4-dinitrofluorobenzene; benzocaine; 5-chloro-2-methyl-4-isothiazolin-3-one; hexyl cinnamic aldehyde; eugenol; nickel sulfate hexahydrate; potassium dichromate; cobalt sulfate; 2-mercaptobenzothiazole; and ammonium tetrachloroplatinate) and non-sensitizers (sodium lauryl sulfate, benzalkonium chloride, lactic acid, salicylic acid, isopropanol, and dimethyl sulphoxide). The test concentrations were 0.1x, 0.5x, and 1x of the 50% inhibitory concentration, and the relative fluorescence intensity was used as an expression indicator. By evaluating the expression patterns of CD54, CD86, and CD40, we could classify the chemicals as sensitizers or non-sensitizers, but CD80 and CD83 showed non-specific patterns of expression. These data suggest that the THP-1 cells are good model for screening contact sensitizers and CD40 could be a useful marker complementary to CD54 and CD86.

HER2/neu gene amplification determines the sensitivity of uterine serous carcinoma cell lines to AZD8055, a novel dual mTORC1/2 inhibitor.

PubMed

English, Diana P; Roque, Dana M; Carrara, Luisa; Lopez, Salvatore; Bellone, Stefania; Cocco, Emiliano; Bortolomai, Ileana; Schwartz, Peter E; Rutherford, Thomas; Santin, Alessandro D

2013-12-01

To evaluate c-erbB2 gene amplification in a series of primary uterine serous carcinoma (USC) cell lines. To assess the efficacy of AZD8055, a novel dual mTORC1/2 inhibitor against primary HER2/neu amplified vs HER2/neu not amplified USC cell lines. Twenty-two primary USC cell lines were evaluated for c-erbB2 oncogene amplification by FISH assays. In vitro sensitivity to AZD8055 was evaluated by flow-cytometry-based viability and proliferation assays. Cell cycle profile and downstream cellular responses to AZD8055 were assessed by measuring the DNA content of cells and by phosphorylation of the S6 protein by flow-cytometry. Nine of 22 (40.9%) USC cell lines demonstrated c-erbB2 gene amplification by FISH. AZD8055 caused a strong differential growth inhibition in USC cell lines, with high HER-2/neu-expressors demonstrating significantly higher sensitivity when compared to low HER-2/neu-expressors (AZD-8055 IC50 mean±SEM=0.27±0.05μM in c-erbB2 amplified versus 1.67±0.68μM in c-erbB2 not amplified tumors, P=0.03). AZD8055 growth-inhibition was associated with a significant and dose-dependent increase in the percentage of cells blocked in the G0/G1 cell cycle phase and a dose-dependent decline in pS6 levels in both c-erbB2 amplified vs c-erbB2 not amplified USC cell lines. AZD8055 may represent a novel targeted therapeutic agent in patients harboring advanced/recurrent/refractory USC. c-erbB2 gene amplification may represent a biomarker to identify USC patients who may benefit most from the use of AZD8055. © 2013.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, In-Gyu, E-mail: igkim@kaeri.re.kr; Department of Radiation Biotechnology and Applied Radioisotope, Korea University of Science and Technology; Lee, Jae-Ha

2014-11-21

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

LUX-ZEPLIN (LZ) Conceptual Design Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akerib, D. S.

2015-03-09

The design and performance of the LUX-ZEPLIN (LZ) detector is described as of March 2015 in this Conceptual Design Report. LZ is a second-generation dark-matter detector with the potential for unprecedented sensitivity to weakly interacting massive particles (WIMPs) of masses from a few GeV/c 2 to hundreds of TeV/c 2. With total liquid xenon mass of about 10 tonnes, LZ will be the most sensitive experiment for WIMPs in this mass region by the end of the decade. This report describes in detail the design of the LZ technical systems. Expected backgrounds are quantified and the performance of the experimentmore » is presented. The LZ detector will be located at the Sanford Underground Research Facility in South Dakota. The organization of the LZ Project and a summary of the expected cost and current schedule are given.« less

Pulse-shape discrimination between electron and nuclear recoils in a NaI(Tl) crystal

NASA Astrophysics Data System (ADS)

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

2015-08-01

We report on the response of a high light-output NaI(Tl) crystal to nuclear recoils induced by neutrons from an Am-Be source and compare the results with the response to electron recoils produced by Compton-scattered 662 keV γ-rays from a 137Cs source. The measured pulse-shape discrimination (PSD) power of the NaI(Tl) crystal is found to be significantly improved because of the high light output of the NaI(Tl) detector. We quantify the PSD power with a quality factor and estimate the sensitivity to the interaction rate for weakly interacting massive particles (WIMPs) with nucleons, and the result is compared with the annual modulation amplitude observed by the DAMA/LIBRA experiment. The sensitivity to spin-independent WIMP-nucleon interactions based on 100 kg·year of data from NaI detectors is estimated with simulated experiments, using the standard halo model.

SU-F-T-678: Clotrimazole Sensitizes MCF-7 Breast Cancer Cell Line to Radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garcia, L; Tambasco, M

2016-06-15

Purpose: To study the effects of Clotrimazole (CLT) on radiosensitivity of MCF-7 Cells in correlation to detachment of Hexokinase II from the Voltage Dependent Anion Channel on the outer membrane of the mitochondria. Apoptotic fractions were also analyzed in relation to the detachment of Hexokinase. Methods: This study focused on the mammary adenocarcinoma cell line, MCF-7. Colony forming assays were used to analyze radiosensitization by CLT. Flow cytometry methods were used to analyze apoptotic vs necrotic fractions after treatment with CLT. Spectrophotometery was used to analyze the mitochondrial bound and soluble fraction of Hexokinase by means of relative enzymatic activity.more » Results: Our preliminary data have shown that CLT sensitizes MCF-7 cells to radiation in a dose and incubation time dependent manner up. We have also demonstrated that there are two radiosensitizing periods in MCF-7 cells with the first corresponding to the cycle arrest after 24 hours observed in other cell lines. The second radiosensitizing period occurs with incubation in CLT after irradiation which reaches maximum effect around 24 hours of incubation time. Preliminary data from our Hexokinase detachment assay show a factor of two increase in the ratio of unbound to bound Hexokinase when comparing incubation for 24 hours in media containing 0 and 20 µM CLT. Conclusion: This study and others indicate CLT as a possible radiosensitizing agent in cancer therapies. While CLT itself shows toxicity to the liver in high doses, this study further demonstrates that disruption of the Warburg Effect and unbinding of mitochondrial bound Hexokinase as a possible pathway for cancer treatment.« less

Genetic Variation in Taste Sensitivity to Sugars in Drosophila melanogaster.

PubMed

Uchizono, Shun; Tanimura, Teiichi

2017-05-01

Taste sensitivity plays a major role in controlling feeding behavior, and alterations in feeding habit induced by changes in taste sensitivity can drive speciation. We investigated variability in taste preferences in wild-derived inbred lines from the Drosophila melanogaster Genetic Reference Panel. Preferences for different sugars, which are essential nutrients for fruit flies, were assessed using two-choice preference tests that paired glucose with fructose, sucrose, or trehalose. The two-choice tests revealed that individual lines have differential and widely variable sugar preferences, and that sugar taste sensitivity is polygenic in the inbred population tested. We focused on 2 strains that exhibited opposing preferences for glucose and fructose, and performed proboscis extension reflex tests and electrophysiological recordings on taste sensilla upon exposure to fructose and glucose. The results indicated that taste sensitivity to fructose is dimorphic between the 2 lines. Genetic analysis showed that high sensitivity to fructose is autosomal dominant over low sensitivity, and that multiple loci on chromosomes 2 and 3 influence sensitivity. Further genetic complementation tests for fructose sensitivity on putative gustatory receptor (Gr) genes for sugars suggested that the Gr64a-Gr64f locus, not the fructose receptor gene Gr43a, might contribute to the dimorphic sensitivity to fructose between the 2 lines. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Pharmacogenomic agreement between two cancer cell line data sets.

PubMed

2015-12-03

Large cancer cell line collections broadly capture the genomic diversity of human cancers and provide valuable insight into anti-cancer drug response. Here we show substantial agreement and biological consilience between drug sensitivity measurements and their associated genomic predictors from two publicly available large-scale pharmacogenomics resources: The Cancer Cell Line Encyclopedia and the Genomics of Drug Sensitivity in Cancer databases.

Reflectance measurements of PTFE, Kapton, and PEEK for xenon scintillation light for the LZ detector.

NASA Astrophysics Data System (ADS)

Arthurs, M.; Batista, E.; Haefner, J.; Lorenzon, W.; Morton, D.; Neff, A.; Okunawo, M.; Pushkin, K.; Sander, A.; Stephenson, S.; Wang, Y.; LZ Collaboration

2017-01-01

LZ (LUX-Zeplin) is an international collaboration that will look for dark matter candidates, WIMPs (Weakly Interacting Massive Particles), through direct detection by dual-phase time projection chamber (TPC) using liquid xenon. The LZ detector will be located nearly a mile underground at SURF, South Dakota, shielded from cosmic background radiation. Seven tons active mass of liquid xenon will be used for detecting the weak interaction of WIMPs with ordinary matter. Over three years of operation it is expected to reach the ultimate sensitivity of 2x10-48 cm2 for a WIMP mass of 50 GeV. As for many other rare event searches, high light collection efficiency is essential for LZ detector. Moreover, in order to achieve greater active volume for detection as well as reduce potential backgrounds, thinner detector walls without significant loss in reflectance are desired. Reflectance measurements of polytetrafluoroethylene (PTFE), Kapton, and PEEK for xenon scintillation light (178 nm), conducted at the University of Michigan using the Michigan Xenon Detector (MiX) will be presented. The University of Michigan, LZ Collaboration, The US Department of Energy.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agnes, P.

We report the first results of DarkSide-50, a direct search for dark matter operating in the underground Laboratori Nazionali del Gran Sasso (LNGS) and searching for the rare nuclear recoils possibly induced by weakly interacting massive particles (WIMPs). The dark matter detector is a Liquid Argon Time Projection Chamber with a (46.4 ± 0.7) kg active mass, operated inside a 30 t organic liquid scintillator neutron veto, which is in turn installed at the center of a 1 kt water Cherenkov veto for the residual flux of cosmic rays. We report here the null results of a dark matter searchmore » for a (1422 ± 67) kg d exposure with an atmospheric argon fill. As a result, this is the most sensitive dark matter search performed with an argon target, corresponding to a 90% CL upper limit on the WIMP-nucleon spin-independent cross section of 6.1×10 -44 cm 2 for a WIMP mass of 100 Gev/c 2.« less

Dark matter spin determination with directional direct detection experiments

NASA Astrophysics Data System (ADS)

Catena, Riccardo; Conrad, Jan; Döring, Christian; Ferella, Alfredo Davide; Krauss, Martin B.

2018-01-01

If dark matter has spin 0, only two WIMP-nucleon interaction operators can arise as leading operators from the nonrelativistic reduction of renormalizable single-mediator models for dark matter-quark interactions. Based on this crucial observation, we show that about 100 signal events at next generation directional detection experiments can be enough to enable a 2 σ rejection of the spin 0 dark matter hypothesis in favor of alternative hypotheses where the dark matter particle has spin 1 /2 or 1. In this context, directional sensitivity is crucial since anisotropy patterns in the sphere of nuclear recoil directions depend on the spin of the dark matter particle. For comparison, about 100 signal events are expected in a CF4 detector operating at a pressure of 30 torr with an exposure of approximately 26,000 cubic-meter-detector days for WIMPs of 100 GeV mass and a WIMP-fluorine scattering cross section of 0.25 pb. Comparable exposures require an array of cubic meter time projection chamber detectors.

First results from the DarkSide-50 dark matter experiment at Laboratori Nazionali del Gran Sasso

DOE PAGES

Agnes, P.

2015-03-11

We report the first results of DarkSide-50, a direct search for dark matter operating in the underground Laboratori Nazionali del Gran Sasso (LNGS) and searching for the rare nuclear recoils possibly induced by weakly interacting massive particles (WIMPs). The dark matter detector is a Liquid Argon Time Projection Chamber with a (46.4 ± 0.7) kg active mass, operated inside a 30 t organic liquid scintillator neutron veto, which is in turn installed at the center of a 1 kt water Cherenkov veto for the residual flux of cosmic rays. We report here the null results of a dark matter searchmore » for a (1422 ± 67) kg d exposure with an atmospheric argon fill. As a result, this is the most sensitive dark matter search performed with an argon target, corresponding to a 90% CL upper limit on the WIMP-nucleon spin-independent cross section of 6.1×10 -44 cm 2 for a WIMP mass of 100 Gev/c 2.« less

Technical results from the surface run of the LUX dark matter experiment

DOE PAGES

Akerib, D. S.; Bai, X.; Bernard, E.; ...

2013-03-07

We present the results of the three-month above-ground commissioning run of the Large Underground Xenon (LUX) experiment at the Sanford Underground Research Facility located in Lead, South Dakota, USA. LUX is a 370 kg liquid xenon detector that will search for cold dark matter in the form of Weakly Interacting Massive Particles (WIMPs). The commissioning run, conducted with the detector immersed in a water tank, validated the integration of the various sub-systems in preparation of the underground deployment. Using the data collected, we report excellent light collection properties, achieving 8.4 photoelectrons per keV for 662 keV electron recoils without anmore » applied electric field, measured in the center of the WIMP target. Here, we also find good energy and position resolution in relatively high-energy interactions from a variety of internal and external sources. Finally, we have used the commissioning data to tune the optical properties of our simulation and report updated sensitivity projections for spin-independent WIMP-nucleon scattering.« less

Sensitivity of bandpass filters using recirculating delay-line structures

NASA Astrophysics Data System (ADS)

Heyde, Eric C.

1996-12-01

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

Plasma stable, pH-sensitive fusogenic polymer-modified liposomes: A promising carrier for mitoxantrone.

PubMed

Ghanbarzadeh, Saeed; Arami, Sanam; Pourmoazzen, Zhaleh; Ghasemian-Yadegari, Javad; Khorrami, Arash

2014-07-01

pH-sensitive liposomes are designed to undergo acid-triggered destabilization. In the present study, we prepared polymer-modified, plasma stable, pH-sensitive fusogenic mitoxantrone liposomes to increase efficacy and selectivity on cancer cell lines. Conventional liposomes were prepared using cholesterol and dipalmitoyl-sn-glycero-3-phosphatidylethanolamine. Dioleoylphosphatidylethanolamine and a cholesteryl derivative, poly(monomethylitaconate)-co-poly(N,N-dimethylaminoethyl methacrylate) (PMMI-co-PDMAEMA), were used for the preparation of pH-sensitive fusogenic liposomes. Using polyethylene glycol (PEG)-poly(monomethylitaconate)-CholC6 (PEG-PMMI-CholC6) copolymers instead of cholesterol introduced pH-sensitive and plasma stability properties simultaneously in prepared liposomes. All formulations were prepared by thin film hydration method and subsequently, pH-sensitivity and stability in human serum were evaluated. The ability of pH-sensitive fusogenic liposomes to enhance the mitoxantrone cytotoxicity and selectivity in cancerous cell lines was assessed in vitro compared to normal cell line using human breast cancer cell line (MCF-7), human prostate cancer cell line (PC-3), and human umbilical vein endothelial cells line. Results revealed that both PMMI-co-PDMAEMA and PEG-PMMI-CholC6-based formulations showed pH-sensitive property and were found to rapidly release mitoxantrone under mildly acidic conditions. Nevertheless, only the PEG-PMMI-CholC6-based liposomes preserved pH-sensitivity after incubation in plasma. Mitoxantrone loaded-pH-sensitive fusogenic liposomes exhibited a higher cytotoxicity than the control conventional liposomes on MCF-7 and PC-3 cell lines. On the contrary, both pH-sensitive fusogenic liposomes showed lower cytotoxic effect on human umbilical vein endothelial cell line. Plasma stable, pH-sensitive fusogenic liposomes are promising carriers for enhancing the efficiency and selectivity, besides reduction of the side effects of anticancer

From direct detection to relic abundance: the case of proton-philic spin-dependent inelastic Dark Matter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scopel, Stefano; Yu, Hyeonhye, E-mail: scopel@sogang.ac.kr, E-mail: skyh2yu@gmail.com

We discuss strategies to make inferences on the thermal relic abundance of a Weakly Interacting Massive Particle (WIMP) when the same effective dimension-six operator that explains an experimental excess in direct detection is assumed to drive decoupling at freeze-out, and apply them to the explicit scenario of WIMP inelastic up-scattering with spin-dependent couplings to protons (proton-philic Spin-dependent Inelastic Dark Matter, pSIDM), a phenomenological set-up containing two Dark Matter (DM) particles χ{sub 1} and χ{sub 2} with masses m {sub χ}= m {sub χ{sub 1}} and m {sub χ{sub 2}}= m {sub χ}+δ that we have shown in a previous papermore » to explain the DAMA effect in compliance with the constraints from other detectors. We also update experimental constraints on pSIDM, extend the analysis to the most general spin-dependent momentum-dependent interactions allowed by non-relativistic Effective Field Theory (EFT), and consider for the WIMP velocity distribution in our Galaxy f ( v ) both a halo-independent approach and a standard Maxwellian. Under these conditions we find that the DAMA effect can be explained in terms of the particle χ{sub 1} in compliance with all the other constraints for all the analyzed EFT couplings and also for a Maxwellian f ( v ). As far as the relic abundance is concerned, we show that the problem of calculating it by using direct detection data to fix the model parameters is affected by a strong sensitivity on f ( v ) and by the degeneracy between the WIMP local density ρ{sub χ} and the WIMP-nucleon scattering cross section, since ρ{sub χ} must be rescaled with respect to the observed DM density in the neighborhood of the Sun when the calculated relic density Ω is smaller than the observed one Ω{sub 0}. As a consequence, a DM direct detection experiment is not directly sensitive to the physical cut-off scale of the EFT, but on some dimensional combination that does not depend on the actual value of Ω. However, such

Spin-dependent limits from the DRIFT-IId directional dark matter detector

NASA Astrophysics Data System (ADS)

Daw, E.; Fox, J. R.; Gauvreau, J.-L.; Ghag, C.; Harmon, L. J.; Gold, M.; Lee, E. R.; Loomba, D.; Miller, E. H.; Murphy, A. Stj.; Paling, S. M.; Landers, J. M.; Pipe, M.; Pushkin, K.; Robinson, M.; Snowden-Ifft, D. P.; Spooner, N. J. C.; Walker, D.

2012-02-01

Data are presented from the DRIFT-IId detector operated in the Boulby Underground Science Facility in England. A 0.8 m3 fiducial volume, containing partial pressures of 30 Torr CS2 and 10 Torr CF4, was exposed for a duration of 47.4 live-time days with sufficient passive shielding to provide a neutron free environment within the detector. The nuclear recoil events seen are consistent with a remaining low-level background from the decay of radon daughters attached to the central cathode of the detector. However, charge from such events must drift across the entire width of the detector, and thus display large diffusion upon reaching the readout planes of the device. Exploiting this feature, it is shown to be possible to reject energy depositions from these Radon Progeny Recoil events while still retaining sensitivity to fiducial-volume nuclear recoil events. The response of the detector is then interpreted, using the F nuclei content of the gas, in terms of sensitivity to proton spin-dependent WIMP-nucleon interactions, displaying a minimum in sensitivity cross section at 1.8 pb for a WIMP mass of 100 GeV/c2. This sensitivity was achieved without compromising the direction sensitivity of DRIFT.

Assessing alternatives for directional detection of a halo of weakly interacting massive particles

NASA Astrophysics Data System (ADS)

Copi, Craig J.; Krauss, Lawrence M.; Simmons-Duffin, David; Stroiney, Steven R.

2007-01-01

The future of direct terrestrial WIMP detection lies on two fronts: new, much larger low background detectors sensitive to energy deposition, and detectors with directional sensitivity. The former can explore a large range of WIMP parameter space using well-tested technology while the latter may be necessary if one is to disentangle particle physics parameters from astrophysical halo parameters. Because directional detectors will be quite difficult to construct it is worthwhile exploring in advance generally which experimental features will yield the greatest benefits at the lowest costs. We examine the sensitivity of directional detectors with varying angular tracking resolution with and without the ability to distinguish forward versus backward recoils, and compare these to the sensitivity of a detector where the track is projected onto a two-dimensional plane. The latter detector regardless of where it is placed on the Earth, can be oriented to produce a significantly better discrimination signal than a 3D detector without this capability, and with sensitivity within a factor of 2 of a full 3D tracking detector. Required event rates to distinguish signals from backgrounds for a simple isothermal halo range from the low teens in the best case to many thousands in the worst.

Assessing alternatives for directional detection of a halo of weakly interacting massive particles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Copi, Craig J.; Krauss, Lawrence M.; Department of Astronomy, Case Western Reserve University, 10900 Euclid Ave., Cleveland, Ohio 44106-7079

2007-01-15

The future of direct terrestrial WIMP detection lies on two fronts: new, much larger low background detectors sensitive to energy deposition, and detectors with directional sensitivity. The former can explore a large range of WIMP parameter space using well-tested technology while the latter may be necessary if one is to disentangle particle physics parameters from astrophysical halo parameters. Because directional detectors will be quite difficult to construct it is worthwhile exploring in advance generally which experimental features will yield the greatest benefits at the lowest costs. We examine the sensitivity of directional detectors with varying angular tracking resolution with andmore » without the ability to distinguish forward versus backward recoils, and compare these to the sensitivity of a detector where the track is projected onto a two-dimensional plane. The latter detector regardless of where it is placed on the Earth, can be oriented to produce a significantly better discrimination signal than a 3D detector without this capability, and with sensitivity within a factor of 2 of a full 3D tracking detector. Required event rates to distinguish signals from backgrounds for a simple isothermal halo range from the low teens in the best case to many thousands in the worst.« less

Efficacy of icotinib versus traditional chemotherapy as first-line treatment for preventing brain metastasis from advanced lung adenocarcinoma in patients with epidermal growth factor receptor-sensitive mutation.

PubMed

Zhao, Xiao; Zhu, Guangqin; Chen, Huoming; Yang, Ping; Li, Fang; Du, Nan

2016-01-01

This study aimed to investigate the potential use of icotinib as first-line treatment to prevent brain metastasis from advanced lung adenocarcinoma. This investigation was designed as a retrospective nonrandomized controlled study. Enrolled patients received either icotinib or traditional chemotherapy as their first-line treatment. The therapeutic efficacy was compared among patients with advanced. (stages IIIB and IV) lung adenocarcinoma with epidermal growth factor receptor (EGFR)-sensitive mutation. The primary endpoint was the cumulative incidence of brain metastasis, whereas, the secondary endpoint was overall survival(OS). Death without brain metastasis was considered a competitive risk to calculate the cumulative risk of brain metastasis. Survival analysis was conducted using the Kaplan-Meier method and statistical significance was determined using the log-rank test. The present study included 396 patients with 131 in the icotinib group and 265 in the chemotherapy group. Among those with EGFR-sensitive mutation, the cumulative risk of brain metastasis was lower in the icotinib group than in the chemotherapy group. However, no significant difference in OS was observed between the two groups. Icotinib can effectively reduce the incidence of brain metastasis and therefore improve prognosis in advanced lung adenocarcinoma patients with EGFR.sensitive mutation.

Efficacy of icotinib versus traditional chemotherapy as first-line treatment for preventing brain metastasis from advanced lung adenocarcinoma in patients with epidermal growth factor receptor-sensitive mutation.

PubMed

Zhao, Xiao; Zhu, Guangqin; Chen, Huoming; Yang, Ping; Li, Fang; Du, Nan

2014-11-01

This study aimed to investigate the potential use of icotinib as first-line treatment to prevent brain metastasis from advanced lung adenocarcinoma. This investigation was designed as a retrospective nonrandomized controlled study. Enrolled patients received either icotinib or traditional chemotherapy as their first-line treatment. The therapeutic efficacy was compared among patients with advanced (stages IIIB and IV) lung adenocarcinoma with epidermal growth factor receptor (EGFR)-sensitive mutation. The primary endpoint was the cumulative incidence of brain metastasis, whereas the secondary endpoint was overall survival (OS). Death without brain metastasis was considered a competitive risk to calculate the cumulative risk of brain metastasis. Survival analysis was conducted using the Kaplan-Meier method and statistical significance were determined using the log-rank test. The present study included 396 patients with 131 in the icotinib group and 265 in the chemotherapy group. Among those with EGFR-sensitive mutation, the cumulative risk of brain metastasis was lower in the icotinib group than in the chemotherapy group. However, no significant difference in OS was observed between the two groups. Icotinib can effectively reduce the incidence of brain metastasis and therefore improve prognosis in advanced lung adenocarcinoma patients with EGFR-sensitive mutation.

The Flinders Sensitive Line rat: a selectively bred putative animal model of depression.

PubMed

Overstreet, David H; Friedman, Elliot; Mathé, Aleksander A; Yadid, Gal

2005-01-01

The Flinders Sensitive Line (FSL) rats were originally selectively bred for increased responses to an anticholinesterase agent. The FSL rat partially resembles depressed individuals because it exhibits reduced appetite and psychomotor function but exhibits normal hedonic responses and cognitive function. The FSL rat also exhibits sleep and immune abnormalities that are observed in depressed individuals. Neurochemical and/or pharmacological evidence suggests that the FSL rat exhibits changes consistent with the cholinergic, serotonergic, dopaminergic, NPY, and circadian rhythm models but not the noradrenergic, HPA axis or GABAergic models of depression. However, evidence for the genetic basis of these changes is lacking and it remains to be determined which, if any, of the neurochemical changes are primary to the behavioral alterations. The FSL rat model has been very useful as a screen for antidepressants because known antidepressants reduced swim test immobility when given chronically and psychomotor stimulants did not. Furthermore, rolipram and a melatonin agonist were shown to have anti-immobility effects in the FSL rats and later to have antidepressant effects in humans. Thus, the FSL rat model of depression exhibits some behavioral, neurochemical, and pharmacological features that have been reported in depressed individuals and has been very effective in detecting antidepressants.

Dark Matter Limits From a 2L C3F8 Filled Bubble Chamber

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robinson, Alan Edward

2015-12-01

The PICO-2L C3F8 bubble chamber search forWeakly Interacting Massive Particle (WIMP) dark matter was operated in the SNOLAB underground laboratory at the same location as the previous CF3I lled COUPP-4kg detector. Neutron calibrations using photoneutron sources in C3F8 and CF3I lled calibration bubble chambers were performed to verify the sensitivity of these target uids to dark matter scattering. This data was combined with similar measurements using a low-energy neutron beam at the University of Montreal and in situ calibrations of the PICO-2L and COUPP-4kg detectors. C3F8 provides much greater sensitivity to WIMP-proton scattering than CF3I in bubble chamber detectors. PICO-2Lmore » searched for dark matter recoils with energy thresholds below 10 keV. Radiopurity assays of detector materials were performed and the expected neutron recoil background was evaluated to be 1.6+0:3« less

DEAP-3600 Dark Matter Search

NASA Astrophysics Data System (ADS)

Kuźniak, M.; Amaudruz, P.-A.; Batygov, M.; Beltran, B.; Bonatt, J.; Boulay, M. G.; Broerman, B.; Bueno, J. F.; Butcher, A.; Cai, B.; Chen, M.; Chouinard, R.; Cleveland, B. T.; Dering, K.; DiGioseffo, J.; Duncan, F.; Flower, T.; Ford, R.; Giampa, P.; Gorel, P.; Graham, K.; Grant, D. R.; Guliyev, E.; Hallin, A. L.; Hamstra, M.; Harvey, P.; Jillings, C. J.; Lawson, I.; Li, O.; Liimatainen, P.; Majewski, P.; McDonald, A. B.; McElroy, T.; McFarlane, K.; Monroe, J.; Muir, A.; Nantais, C.; Ng, C.; Noble, A. J.; Ouellet, C.; Palladino, K.; Pasuthip, P.; Peeters, S. J. M.; Pollmann, T.; Rau, W.; Retière, F.; Seeburn, N.; Singhrao, K.; Skensved, P.; Smith, B.; Sonley, T.; Tang, J.; Vázquez-Jáuregui, E.; Veloce, L.; Walding, J.; Ward, M.; DEAP Collaboration

2016-04-01

The DEAP-3600 experiment is located 2 km underground at SNOLAB, in Sudbury, Ontario. It is a single-phase detector that searches for dark matter particle interactions within a 1000-kg fiducial mass target of liquid argon. A first generation prototype detector (DEAP-1) with a 7-kg liquid argon target mass demonstrated a high level of pulse-shape discrimination (PSD) for reducing β / γ backgrounds and helped to develop low radioactivity techniques to mitigate surface-related α backgrounds. Construction of the DEAP-3600 detector is nearly complete and commissioning is starting in 2014. The target sensitivity to spin-independent scattering of Weakly Interacting Massive Particles (WIMPs) on nucleons of 10-46cm2 will allow one order of magnitude improvement in sensitivity over current searches at 100 GeV WIMP mass. This paper presents an overview and status of the DEAP-3600 project and discusses plans for a future multi-tonne experiment, DEAP-50T.

Radiation sensitivities of 31 human oesophageal squamous cell carcinoma cell lines

PubMed Central

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

2005-01-01

The purpose of this study was to determine the radiosensitivities of 31 human oesophageal squamous cell carcinoma cell lines with a colony-formation assay. A large variation in radiosensitivity existed among 31 cell lines. Such a large variation may partly explain the poor result of radiotherapy for this cancer. One cell line (KYSE190) demonstrated an unusual radiosensitivity. Ataxia-telangiectasia-mutated (ATM) gene in these cells had five missense mutations, and ATM protein was truncated or degraded. Inability to phosphorylate Chk2 in the irradiated KYSE190 cells suggests that the ATM protein in these cells had lost its function. The dysfunctional ATM protein may be a main cause of unusual radiosensitivity of KYSE190 cells. Because the donor of these cells was not diagnosed with ataxia telangiectasia, mutations in ATM gene might have occurred during the initiation and progression of cancer. Radiosensitive cancer developed in non-hereditary diseased patients must be a good target for radiotherapy. PMID:16045545

Selective breeding for magnitude of methamphetamine-induced sensitization alters methamphetamine consumption

PubMed Central

Scibelli, Angela C.; McKinnon, Carrie S.; Reed, Cheryl; Burkhart-Kasch, Sue; Li, Na; Baba, Harue; Wheeler, Jeanna M.

2012-01-01

Rationale Genetically determined differences in susceptibility to drug-induced sensitization could be related to risk for drug consumption. Objectives Studies were performed to determine whether selective breeding could be used to create lines of mice with different magnitudes of locomotor sensitization to methamphetamine (MA). MA sensitization (MASENS) lines were also examined for genetically correlated responses to MA. Methods Beginning with the F2 cross of C57BL/6J and DBA/2J strains, mice were tested for locomotor sensitization to repeated injections of 1 mg/kg MA and bred based on magnitude of sensitization. Five selected offspring generations were tested. All generations were also tested for MA consumption, and some were tested for dose-dependent locomotor-stimulant responses to MA, consumption of saccharin, quinine, and potassium chloride as a measure of taste sensitivity, and MA clearance after acute and repeated MA. Results Selective breeding resulted in creation of two lines [MA high sensitization (MAHSENS) and MA low sensitization (MALSENS)] that differed in magnitude of MA-induced sensitization. Initially, greater MA consumption in MAHSENS mice reversed over the course of selection so that MALSENS mice consumed more MA. MAHSENS mice exhibited greater sensitivity to the acute stimulant effects of MA, but there were no significant differences between the lines in MA clearance from blood. Conclusions Genetic factors influence magnitude of MA-induced locomotor sensitization and some of the genes involved in magnitude of this response also influence MA sensitivity and consumption. Genetic factors leading to greater MA-induced sensitization may serve a protective role against high levels of MA consumption. PMID:21088960

Recent approaches for enhancing sensitivity in enantioseparations by CE.

PubMed

Sánchez-Hernández, Laura; García-Ruiz, Carmen; Luisa Marina, María; Luis Crego, Antonio

2010-01-01

This article reviews the latest methodological and instrumental improvements for enhancing sensitivity in chiral analysis by CE. The review covers literature from March 2007 until May 2009, that is, the works published after the appearance of the latest review article on the same topic by Sánchez-Hernández et al. [Electrophoresis 2008, 29, 237-251]. Off-line and on-line sample treatment techniques, on-line sample preconcentration strategies based on electrophoretic and chromatographic principles, and alternative detection systems to the widely employed UV/Vis detection in CE are the most relevant approaches discussed for improving sensitivity. Microchip technologies are also included since they can open up great possibilities to achieve sensitive and fast enantiomeric separations.

Characterization of a hypoallergenic wheat line lacking ω-5 gliadin.

PubMed

Kohno, Kunie; Takahashi, Hitoshi; Endo, Takashi R; Matsuo, Hiroaki; Shiwaku, Kuninori; Morita, Eishin

2016-10-01

There is no curative treatment for wheat-dependent exercise-induced anaphylaxis (WDEIA). ω-5 Gliadin is one of the dominant allergens affecting WDEIA patients. The use of ω-5 gliadin-free wheat flour in the regular diet is considered one of the prophylactic approaches against the elicitation of allergic symptoms and sensitization to ω-5 gliadin. We sought to find hypoallergenic bread wheat (or common wheat) that lacked the genes encoding ω-5 gliadin and to evaluate its in vitro allergenicity. We also aimed to evaluate the sensitization ability of one of the selected hypoallergenic wheat lines by using a possible animal model of wheat allergy. We screened the deletion lines of bread wheat by western blotting to ascertain common wheat lines lacking the ω-5 gliadin locus. The deletion lines we used have partial deficiency of chromosome 1B (Endo and Gill, 1996). To assess sensitization ability of gluten from the selected deletion line, guinea pigs were fed with either the gluten from the selected deletion line or commercially available gluten, and allergic score was evaluated after challenging the same gluten preparations. We found that a deletion line 1BS-18 had the least deficiency of chromosome 1B among the deletion stocks lacking the ω-5 gliadin locus. The challenge test using the guinea pigs revealed that the symptoms induced by application of the 1BS-18 gluten were much less than that of commercially available gluten. The deletion line 1BS-18, which lacked the ω-5 gliadin locus, is likely to have a low sensitization capacity in the guinea pig. The use of the wheat products of the 1BS-18 line in daily life may provide a feasible solution for the onset of wheat allergy. Copyright © 2016 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

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.

PubMed

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

2010-09-01

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 expression on the surface of THP-1 cells, a human monocytic leukemia cell line, following 24h of chemical exposure. To examine protocol transferability, between-lab reproducibility, and predictive capacity, the h-CLAT has been evaluated by five independent laboratories in several ring trials (RTs) coordinated by the European Cosmetics Association (COLIPA). The results of the first and second RTs demonstrated that the protocol was transferable and basically had good between-lab reproducibility and predictivity, but there were some false negative data. To improve performance, protocol and prediction model were modified. Using the modified prediction model in the first and second RT, accuracy was improved. However, about 15% of the outcomes were not correctly identified, which exposes some of the limitations of the assay. For the chemicals evaluated, the limitation may due to chemical being a weak allergen or having low solubility (ex. alpha-hexylcinnamaldehyde). The third RT evaluated the modified prediction model and satisfactory results were obtained. From the RT data, the feasibility of utilizing cell lines as surrogate DC in development of in vitro skin sensitization methods shows promise. The data also support initiating formal pre-validation of the h-CLAT in order to fully understand the capabilities and limitations of the assay. Copyright 2010 Elsevier Ltd. All rights reserved.

Development of a Handheld Line Information Reader and Generator for Efficient Management of Optical Communication Lines

PubMed Central

Lee, Jaeyul; Kwon, Hyungwoo; Song, Jaewon; Jeon, Mansik; Kim, Jeehyun

2017-01-01

A handheld line information reader and a line information generator were developed for the efficient management of optical communication lines. The line information reader consists of a photo diode, trans-impedance amplifier, voltage amplifier, microcontroller unit, display panel, and communication modules. The line information generator consists of a laser diode, laser driving circuits, microcontroller unit, and communication modules. The line information reader can detect the optical radiation field of the test line by bending the optical fiber. To enhance the sensitivity of the line information reader, an additional lens was used with a focal length of 4.51 mm. Moreover, the simulation results obtained through BeamPROP® software from Synopsys, Inc. demonstrated a stronger optical radiation field of the fiber due to a longer transmission wavelength and larger bending angle of the fiber. Therefore, the developed devices can be considered as useful tools for the efficient management of optical communication lines. PMID:28837058

[Thermo-sensitive period and critical temperature of fertility transition of thermo-photo-sensitive genic male sterile wheat].

PubMed

Zhang, Jiankui; Feng, Li; He, Liren; Yu, Guodong

2003-01-01

The thermo-sensitive period and the critical temperature of fertility transition of C49S, a principal thermo-photosensitive genic male sterile line in two-line hybrid wheat, was studied in the growth chambers for controlling temperature and photoperiod. The seeds were sown on different time for some years. The results showed that the thermo-sensitive period in fertility expression of C49S was from PMC formation stage to mature pollen stage, and there were two most sensitive stages to temperature on fertility expression. One was the PMC meiosis stage, and the other was the middle microspore stage. The critical temperatures evoking a complete male sterility were the mean minimum temperature at PMC meiosis stage (Tmin1), the mean temperature at microspore stage (T2) and the mean minimum temperature at microspore stage (Tmin2) lower than 8.5 degrees C, 13.5 degrees C and 10.5 degrees C, respectively. The critical temperatures keeping a nearly normal male fertility Tmin1 and T2 and Tmin2 were higher than 11.5 degrees C, 15.0 degrees C and 12.5 degrees C, respectively. The value as well as the conditions and the risks of thermo-photo-sensitive genic male sterile line of wheat applied to hybrid wheat were evaluated in this paper.

Circumstellar radio molecular lines

NASA Technical Reports Server (NTRS)

NGUYEN-QUANG-RIEU

1987-01-01

Radio molecular lines appear to be useful probes into the stellar environment. Silicon oxide masers provide information on the physical conditions in the immediate vicinity of the stellar photosphere. Valuable information on the physics operating in the envelope of IRC + 10216 was recently obtained by high sensitivity observations and detailed theoretical analyses. Infrared speckle interferometry in the molecular lines and in the continuum is helpful in the investigation of the inner region of the envelope. These techniques are discussed in terms of late-type star mass loss.

Integrating heterogeneous drug sensitivity data from cancer pharmacogenomic studies.

PubMed

Pozdeyev, Nikita; Yoo, Minjae; Mackie, Ryan; Schweppe, Rebecca E; Tan, Aik Choon; Haugen, Bryan R

2016-08-09

The consistency of in vitro drug sensitivity data is of key importance for cancer pharmacogenomics. Previous attempts to correlate drug sensitivities from the large pharmacogenomics databases, such as the Cancer Cell Line Encyclopedia (CCLE) and the Genomics of Drug Sensitivity in Cancer (GDSC), have produced discordant results. We developed a new drug sensitivity metric, the area under the dose response curve adjusted for the range of tested drug concentrations, which allows integration of heterogeneous drug sensitivity data from the CCLE, the GDSC, and the Cancer Therapeutics Response Portal (CTRP). We show that there is moderate to good agreement of drug sensitivity data for many targeted therapies, particularly kinase inhibitors. The results of this largest cancer cell line drug sensitivity data analysis to date are accessible through the online portal, which serves as a platform for high power pharmacogenomics analysis.

Sensitivity Data File Formats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rearden, Bradley T.

2016-04-01

The format of the TSUNAMI-A sensitivity data file produced by SAMS for cases with deterministic transport solutions is given in Table 6.3.A.1. The occurrence of each entry in the data file is followed by an identification of the data contained on each line of the file and the FORTRAN edit descriptor denoting the format of each line. A brief description of each line is also presented. A sample of the TSUNAMI-A data file for the Flattop-25 sample problem is provided in Figure 6.3.A.1. Here, only two profiles out of the 130 computed are shown.

Report on Research in Experimental High Energy Physics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rusack, Roger W.; Cushman, Priscilla; Poling, Ronald

2016-01-06

In the past three years the groups supported by the DOE have all made significant progress and posted major successes. The Minnesota CMS group has played leading roles in five data analyses and has had major roles in detector operations, the data management and the detector upgrades that are planned for for the LHC and those that are planned for the high-luminosity LHC. The CDMS-II experiment held the lead in WIMP sensitivity over the last decade, and is still the most sensitive detector in the world in the low WIMP mass region, with a recent 3σ hint of 8 GeV/cmore » 2 WIMP candidates in the silicon data. SuperCDMS, with three orders of magnitude better electron recoil background rejection, has been collecting data since October 2011. Since all dark matter experiments require a better understanding of neutron backgrounds to make further advances in sensitivity, Cushman has expanded the Minnesota effort on backgrounds to the national level, where she is leading a coordinated effort in neutron simulations for underground physics. The work of Mandic on 100 mm detectors both for Super-CDMS and beyond has advanced rapidly. Also at the Intensity Frontier, the BESIII experiment has had a successful year of operation largely focused on searches for and studies of new "charmonium-like" states above DD threshold. At least one new state has been observed so far, with hints of others. An intensive effort to understand their nature and gain new insight into the strong interaction continues. BESIII has also produced a large number of other results in charmonium decay and light-hadronic physics.« less

Utility of human embryonic kidney cell line HEK-293 for rapid isolation of fixed and street rabies viruses: comparison with Neuro-2a and BHK-21 cell lines.

PubMed

Madhusudana, Shampur Narayan; Sundaramoorthy, Subha; Ullas, Padinjaremattatthil Thankappan

2010-12-01

A confirmatory rabies diagnosis can be achieved by rapid virus isolation in cell culture using brain tissue from the suspect animal. Several cell lines have been used for this purpose and the murine neuroblastoma cell line Neuro-2a has been found to be the most sensitive. The human embryonic kidney cell line HEK-293 is known to express several neuronal proteins and is believed to be of neuronal origin. We hypothesized that this cell line could be susceptible to rabies virus, which is highly neurotropic. First we tested the sensitivity of HEK-293 cells to the laboratory strain, challenge virus standard (CVS). We then tested 120 brain samples from different animals and humans suspected to have died of rabies by fluorescent antibody test (FAT). Both FAT-positive and FAT-negative brains were tested for virus isolation using Neuro-2a, BHK-21, and HEK-293 cell lines and also by mouse inoculation. There was 100% correlation between FAT, virus isolation in Neuro-2a and HEK-293 cells, and mouse inoculation. However, the rate of virus isolation in the BHK-21 cell line was only 28% when compared to the other cell lines. The sensitivity of HEK-293 to CVS strain of virus was similar to that of Neuro-2a. We conclude that the HEK-293 cell line is as sensitive as the Neuro-2a cell line for the rapid isolation of rabies virus and may serve as an alternative cell line for rabies diagnosis and future research. Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Enhanced expression of IL-8 in normal human keratinocytes and human keratinocyte cell line HaCaT in vitro after stimulation with contact sensitizers, tolerogens and irritants.

PubMed

Mohamadzadeh, M; Müller, M; Hultsch, T; Enk, A; Saloga, J; Knop, J

1994-12-01

To investigate the interleukin-8 production of keratinocytes after stimulation in vitro we have used various agents: (i) contact sensitizer (2,4-dinitrofluorobenzene, 3-n-pentadecylcatechol); (ii) tolerogen (5-methyl-3-n-pentadecylcatechol); (iii) irritant (sodium lauryl sulfate). Interleukin-8 gene expression was assessed by northern blot hybridization of the total cytoplasmic RNA extracted from subconfluent normal human keratinocyte cultures and the keratinocyte cell line HaCaT using a radiolabeled DNA probe specific for human interleukin-8. Interleukin-8 gene expression was markedly increased upon in vitro stimulation after 1-6 h with contact sensitizers, tolerogen and the irritant. In contrast, interleukin-8 production was not detectable in unstimulated normal human keratinocytes or the HaCaT keratinocyte cell line. These results suggest that the induction and production of interleukin-8 is a response to nonspecific stimuli and may play a critical role in the early response to immunogenic or inflammatory signals in man.

Material radioassay and selection for the XENON1T dark matter experiment

NASA Astrophysics Data System (ADS)

Aprile, E.; Aalbers, J.; Agostini, F.; Alfonsi, M.; Amaro, F. D.; Anthony, M.; Arneodo, F.; Barrow, P.; Baudis, L.; Bauermeister, B.; Benabderrahmane, M. L.; Berger, T.; Breur, P. A.; Brown, A.; Brown, E.; Bruenner, S.; Bruno, G.; Budnik, R.; Bütikofer, L.; Calvén, J.; Cardoso, J. M. R.; Cervantes, M.; Cichon, D.; Coderre, D.; Colijn, A. P.; Conrad, J.; Cussonneau, J. P.; Decowski, M. P.; de Perio, P.; Di Gangi, P.; Di Giovanni, A.; Diglio, S.; Eurin, G.; Fei, J.; Ferella, A. D.; Fieguth, A.; Franco, D.; Fulgione, W.; Gallo Rosso, A.; Galloway, M.; Gao, F.; Garbini, M.; Geis, C.; Goetzke, L. W.; Grandi, L.; Greene, Z.; Grignon, C.; Hasterok, C.; Hogenbirk, E.; Itay, R.; Kaminsky, B.; Kessler, G.; Kish, A.; Landsman, H.; Lang, R. F.; Lellouch, D.; Levinson, L.; Le Calloch, M.; Lin, Q.; Lindemann, S.; Lindner, M.; Lopes, J. A. M.; Manfredini, A.; Maris, I.; Marrodán Undagoitia, T.; Masbou, J.; Massoli, F. V.; Masson, D.; Mayani, D.; Messina, M.; Micheneau, K.; Miguez, B.; Molinario, A.; Murra, M.; Naganoma, J.; Ni, K.; Oberlack, U.; Pakarha, P.; Pelssers, B.; Persiani, R.; Piastra, F.; Pienaar, J.; Piro, M.-C.; Pizzella, V.; Plante, G.; Priel, N.; Rauch, L.; Reichard, S.; Reuter, C.; Rizzo, A.; Rosendahl, S.; Rupp, N.; Saldanha, R.; dos Santos, J. M. F.; Sartorelli, G.; Scheibelhut, M.; Schindler, S.; Schreiner, J.; Schumann, M.; Scotto Lavina, L.; Selvi, M.; Shagin, P.; Shockley, E.; Silva, M.; Simgen, H.; Sivers, M. v.; Stein, A.; Thers, D.; Tiseni, A.; Trinchero, G.; Tunnell, C.; Upole, N.; Wang, H.; Wei, Y.; Weinheimer, C.; Wulf, J.; Ye, J.; Zhang, Y.; Laubenstein, M.; Nisi, S.

2017-12-01

The XENON1T dark matter experiment aims to detect weakly interacting massive particles (WIMPs) through low-energy interactions with xenon atoms. To detect such a rare event necessitates the use of radiopure materials to minimize the number of background events within the expected WIMP signal region. In this paper we report the results of an extensive material radioassay campaign for the XENON1T experiment. Using gamma-ray spectroscopy and mass spectrometry techniques, systematic measurements of trace radioactive impurities in over one hundred samples within a wide range of materials were performed. The measured activities allowed for stringent selection and placement of materials during the detector construction phase and provided the input for XENON1T detection sensitivity estimates through Monte Carlo simulations.

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

PubMed

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

2013-01-01

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.

LUX-ZEPLIN (LZ) Technical Design Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mount, B. J.

In this Technical Design Report (TDR) we describe the LZ detector to be built at the Sanford Underground Research Facility (SURF). The LZ dark matter experiment is designed to achieve sensitivity to a WIMP-nucleon spin-independent cross section of three times ten to the negative forty-eighth square centimeters.

Line Intensity Mapping during the Epoch of Reionization

NASA Astrophysics Data System (ADS)

Silva, Marta B.; Zaroubi, Saleem

2018-05-01

Characterizing the properties and the evolution of the first stars and galaxies is a challenging task for traditional galaxy surveys since they are sensitivity limited and can only detect the brightest light sources. Three-dimensional intensity mapping (IM) of transition lines can be a valuable alternative to study the high redshift Universe given that this technique avoids sensitivity limitation problems by measuring the overall emission of a line, with a low resolution, without resolving its sources. While 21cm line IM surveys probe neutral hydrogen gas and can, therefore, be used to probe the state of the IGM and the evolution of the ionization field during the Epoch of Reionization (EoR). IM surveys of other lines, such as CO, CII, Ly-alpha or H-alpha, can be used to probe the galaxies which emitted most of the ionizing radiation responsible for the EoR. These lines will trace the different ISM gas phases, the excitation state of this gas, its metallicity, etc. This study addresses IM of multiple transition lines and how it can be used to probe the EoR and to constrain the redshift evolution of galaxy properties.

Advanced Learners' Comprehension of Discourse Connectives: The Role of L1 Transfer across On-Line and Off-Line Tasks

ERIC Educational Resources Information Center

Zufferey, Sandrine; Mak, Willem; Degand, Liesbeth; Sanders, Ted

2015-01-01

Discourse connectives are important indicators of textual coherence, and mastering them is an essential part of acquiring a language. In this article, we compare advanced learners' sensitivity to the meaning conveyed by connectives in an off-line grammaticality judgment task and an on-line reading experiment using eye-tracking. We also assess the…

Search for Dark Matter Interactions using Ionization Yield in Liquid Xenon

NASA Astrophysics Data System (ADS)

Uvarov, Sergey

Cosmological observations overwhelmingly support the existence of dark matter which constitutes 87% of the universe's total mass. Weakly Interacting Massive Particles (WIMPs) are a prime candidate for dark matter, and the Large Underground Xenon (LUX) experiment aims to a direct-detection of a WIMP-nucleon interaction. The LUX detector is a dual-phase xenon time-projection chamber housed 4,850 feet underground at Sanford Underground Research Facility in Lead, South Dakota. We present the ionization-only analysis of the LUX 2013 WIMP search data. In the 1.04 x 104 kg-days exposure, thirty events were observed out of the 24.8 expected from radioactive backgrounds. We employ a cut-and-count method to set a 1-sided 90% C.L. upper limit for spin-independent WIMP-nucleon cross-sections. A zero charge yield for nuclear-recoils below 0.7 keV is included upper limit calculation. This ionization-only analysis excludes an unexplored region of WIMP-nucleon cross-section for low-mass WIMPs achieving 1.56 x 10-43 cm2 WIMP-nucleon cross-section exclusion for a 5.1 GeV/ c2 WIMP.

Inhibition of PI3K-AKT-mTOR pathway sensitizes endometrial cancer cell lines to PARP inhibitors.

PubMed

Philip, Charles-André; Laskov, Ido; Beauchamp, Marie-Claude; Marques, Maud; Amin, Oreekha; Bitharas, Joanna; Kessous, Roy; Kogan, Liron; Baloch, Tahira; Gotlieb, Walter H; Yasmeen, Amber

2017-09-08

Phosphatase and Tensin homolog (PTEN) is a tumor suppressor gene. Loss of its function is the most frequent genetic alteration in endometrioid endometrial cancers (70-80%) and high grade tumors (90%). We assessed the sensitivity of endometrial cancer cell lines to PARP inhibitors (olaparib and BMN-673) and a PI3K inhibitor (BKM-120), alone or in combination, in the context of their PTEN mutation status. We also highlighted a direct pathway linking PTEN to DNA repair. Using endometrial cancer cellular models with known PTEN status, we evaluated their homologous recombination (HR) functionality by RAD51 foci formation assay. The 50% Inhibitory concentration (IC50) of PI3K and PARP inhibitors in these cells was assessed, and western blotting was performed to determine the expression of proteins involved in the PI3K/mTOR pathway. Moreover, we explored the interaction between RAD51 and PI3K/mTOR by immunofluorescence. Next, the combination effect of PI3K and PARP inhibitors on cell proliferation was evaluated by a clonogenic assay. Cells with mutated PTEN showed over-activation of the PI3K/mTOR pathway. These cells were more sensitive to PARP inhibition compared to PTEN wild-type cells. In addition, PI3K inhibitor treatment reduced RAD51 foci formation in PTEN mutated cells, and sensitized these cells to PARP inhibitor. Targeting both PARP and PI3K might lead to improved personalized therapeutic approaches in endometrial cancer patients with PTEN mutations. Understanding the complex interaction of PTEN mutations with DNA repair in endometrial cancer will help to better select patients that are likely to respond to some of the new and costly targeted therapies.

Impact of Weight Loss at Presentation on Survival in Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKI) Sensitive Mutant Advanced Non-small Cell Lung Cancer (NSCLC) Treated with First-line EGFR-TKI.

PubMed

Lin, Liping; Zhao, Juanjuan; Hu, Jiazhu; Huang, Fuxi; Han, Jianjun; He, Yan; Cao, Xiaolong

2018-01-01

Purpose The aim of this study is to evaluate the impact of weight loss at presentation on treatment outcomes of first-line EGFR-tyrosine kinase inhibitors (EGFR-TKI) in EGFR-TKI sensitive mutant NSCLC patients. Methods We retrospectively analyzed the clinical outcomes of 75 consecutive advanced NSCLC patients with EGFR-TKI sensitive mutations (exon 19 deletion or exon 21 L858R) received first-line gefitinib or erlotinib therapy according to weight loss status at presentation in our single center. Results Of 75 EGFR-TKI sensitive mutant NSCLC patients, 49 (65.3%) patients had no weight loss and 26 (34.7%) had weight loss at presentation, the objective response rate (ORR) to EGFR-TKI treatment were similar between the two groups (79.6% vs. 76.9%, p = 0.533). Patients without weight loss at presentation had significantly longer median progression free survival (PFS) (12.4 months vs. 7.6 months; hazard ratio [HR] 0.356, 95% confidence interval [CI] 0.212-0.596, p < 0.001) and overall survival (OS) (28.5 months vs. 20.7 months; HR 0.408, 95% CI 0.215-0.776, p = 0.006) than those with weight loss at presentation; moreover, the stratified analysis by EGFR-TKI sensitive mutation types also found similar trend between these two groups except for OS in EGFR exon 21 L858R mutation patients. Multivariate analysis identified weight loss at presentation and EGFR-TKI sensitive mutation types were independent predictive factors for PFS and OS. Conclusions Weight loss at presentation had a detrimental impact on PFS and OS in EGFR-TKI sensitive mutant advanced NSCLC patients treated with first-line EGFR-TKI. It should be considered as an important factor in the treatment decision or designing of EGFR-TKI clinical trials.

High speed parallel spectral-domain OCT using spectrally encoded line-field illumination

NASA Astrophysics Data System (ADS)

Lee, Kye-Sung; Hur, Hwan; Bae, Ji Yong; Kim, I. Jong; Kim, Dong Uk; Nam, Ki-Hwan; Kim, Geon-Hee; Chang, Ki Soo

2018-01-01

We report parallel spectral-domain optical coherence tomography (OCT) at 500 000 A-scan/s. This is the highest-speed spectral-domain (SD) OCT system using a single line camera. Spectrally encoded line-field scanning is proposed to increase the imaging speed in SD-OCT effectively, and the tradeoff between speed, depth range, and sensitivity is demonstrated. We show that three imaging modes of 125k, 250k, and 500k A-scan/s can be simply switched according to the sample to be imaged considering the depth range and sensitivity. To demonstrate the biological imaging performance of the high-speed imaging modes of the spectrally encoded line-field OCT system, human skin and a whole leaf were imaged at the speed of 250k and 500k A-scan/s, respectively. In addition, there is no sensitivity dependence in the B-scan direction, which is implicit in line-field parallel OCT using line focusing of a Gaussian beam with a cylindrical lens.

Status of the Large Underground Xenon (LUX) Detector

NASA Astrophysics Data System (ADS)

Larsen, Nicole

2012-03-01

The LUX (Large Underground Xenon) experiment is a 350-kg xenon-based direct dark matter detection experiment consisting of a two-phase (liquid/gas) xenon time projection chamber with a 100-kg fiducial mass. This technology has many advantages, including scalability, self-shielding, the absence of any long-lived isotopes, high gamma ray stopping power, and the ability to precisely measure the charge-to-light ratio of interactions within the detector, which provides an accurate method for discriminating between electron recoils (gamma rays, beta decays) and nuclear recoils (neutrons, WIMPS) within the detector. LUX's projected sensitivity for 300 days of acquisition is a cross-section of 7 x10-46 cm^2 for a WIMP mass of 100 GeV, representing an increase of nearly an order of magnitude over previous WIMP cross-section limits. From November 2011 through February 2012, LUX was deployed in a surface laboratory at the Homestake Mine in South Dakota for its second surface run. This talk will provide an overview of the LUX design and a report on the status of the experiment after the surface run and before underground deployment.

An in vitro test to screen skin sensitizers using a stable THP-1-derived IL-8 reporter cell line, THP-G8.

PubMed

Takahashi, Toshiya; Kimura, Yutaka; Saito, Rumiko; Nakajima, Yoshihiro; Ohmiya, Yoshihiro; Yamasaki, Kenshi; Aiba, Setsuya

2011-12-01

Several studies have suggested that interleukin (IL)-8 can serve as a biomarker for discrimination of skin sensitizers from nonsensitizers. We established a stable THP-1-derived IL-8 reporter cell line, THP-G8, which harbors SLO and SLR luciferase genes under the control of IL-8 and glyceraldehyde 3-phosphate dehydrogenase promoters, respectively. After 6 h treatment with chemicals, normalized SLO luciferase activity (nSLO-LA) was calculated by dividing SLO-LA by SLR-LA, and the fold induction of nSLO-LA (FInSLO-LA) was calculated by dividing nSLO-LA of chemically treated cells by that of nontreated cells. The nSLO-LA of THP-G8 cells increased in response to lipopolysaccharide (LPS) and several sensitizers. The FInSLO-LA in THP-G8 cells induced by LPS or sensitizers positively correlated with their induction of IL-8 messenger RNA in THP-1 cells. The nSLO-LA value of THP-G8 cells was significantly increased (FInSLO-LA ≥ 1.4) by 13 of the 15 sensitizers as well as by 5 of the 7 nonsensitizers. Interestingly, pretreatment with N-acetylcysteine suppressed the increase in FInSLO-LA induced by all sensitizers (inhibition index (II) ≤ 0.8) but did not suppress that induced by most of the nonsensitizers. We then evaluated the performance of this assay using values of FInSLO-LA ≥ 1.4 and II ≤ 0.8 in at least two of three independent experiments as the criteria of a sensitizer, which resulted in test accuracies of 82% for the 22 chemicals used and of 88% for the chemicals proposed by European Center for the Validation of Alternative Methods. This newly developed assay is a candidate replacement for animal tests of skin sensitization because of its accuracy, convenience, and high throughput performance.

Electron density diagnositc line ratios from the n = 3 lines of O v

DOE Office of Scientific and Technical Information (OSTI.GOV)

Widing, K.G.; Doyle, J.G.; Dufton, P.L.

New atomic physic calculations are presented for electron excitation rates for transitions between the n = 2 and n = 3 levels of O v. These are used to calculate theoretical line intensity ratios for the 192 A, 215 A, 220 A and 248 A lines of O v. These line intensity ratios are electron density sensitive and provide valuable diagnostics at T/sub e/approx.2 x 10/sup 5/ K for samll impulsive flare events in which the transition zone ions are enhanced relative to the coronal ions. Two flares observed by NRL spectroheliograph on Skylab, on 1973 December 22 and 1974more » January 21, are studied, with electron densities of approximately 3 x 10/sup 11/ cm/sup -3/ being deduced.« less

Unveiling the nature of dark matter with high redshift 21 cm line experiments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Evoli, C.; Mesinger, A.; Ferrara, A., E-mail: carmelo.evoli@desy.de, E-mail: andrei.mesinger@sns.it, E-mail: andrea.ferrara@sns.it

2014-11-01

Observations of the redshifted 21 cm line from neutral hydrogen will open a new window on the early Universe. By influencing the thermal and ionization history of the intergalactic medium (IGM), annihilating dark matter (DM) can leave a detectable imprint in the 21 cm signal. Building on the publicly available 21cmFAST code, we compute the 21 cm signal for a 10 GeV WIMP DM candidate. The most pronounced role of DM annihilations is in heating the IGM earlier and more uniformly than astrophysical sources of X-rays. This leaves several unambiguous, qualitative signatures in the redshift evolution of the large-scale (k ≅ 0.1more » Mpc{sup -1}) 21 cm power amplitude: (i) the local maximum (peak) associated with IGM heating can be lower than the other maxima; (ii) the heating peak can occur while the IGM is in emission against the cosmic microwave background (CMB); (iii) there can be a dramatic drop in power (a global minimum) corresponding to the epoch when the IGM temperature is comparable to the CMB temperature. These signatures are robust to astrophysical uncertainties, and will be easily detectable with second generation interferometers. We also briefly show that decaying warm dark matter has a negligible role in heating the IGM.« less

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

PubMed

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

2015-07-07

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

Kalanchoe blossfeldiana plants expressing the Arabidopsis etr1-1 allele show reduced ethylene sensitivity.

PubMed

Sanikhani, Mohsen; Mibus, Heiko; Stummann, Bjarne M; Serek, Margrethe

2008-04-01

Transgenic Kalanchoe blossfeldiana Poelln. with reduced ethylene sensitivity in flowers was obtained by Agrobacterium tumefaciens-mediated transformation using the plasmid pBEO210 containing the mutant ethylene receptor gene etr1-1 from Arabidopsis thaliana under the control of the flower-specific fbp1-promoter from Petunia. Three ethylene-resistent T0 lines, 300, 324 and 331, were selected and analyzed for postharvest-performance and morphological characteristics. Line 324 was found to be infertile and only slightly less ethylene-sensitive than control-plants, but lines 300 and 331 had significantly increased ethylene-resistance and were fertile. These two lines were analyzed for copy-number of the etr1-1 gene by Southern blotting and were crossed with the ethylene-sensitive cultivar 'Celine' to create T1 progeny. Line 300 contains two T-DNA copies per nucleus, one of which is rearranged, and these are unlinked according to segregation data from the crossing to 'Celine' and PCR-analysis of progeny plants. For control plants all flowers were closed after 2 days at 2 microl l(-1 )ethylene, but for line 300 only 33% were closed after 10 days. Line 331 contains three T-DNA copies per nucleus and is more sensitive to ethylene than line 300. In the line 300 the etr1-1 gene was found by RT-PCR to be expressed in petals and stamens but not in carpels and sepals. Both lines 300 and 331, and their progeny, appear morphologically and physiologically identical to control plants except for the higher ethylene resistance. Line 300 and its progeny with only one T-DNA copy have very low ethylene sensitivity and may be useful in future breeding.

Search for Neutrinos from Annihilation of Captured Low-Mass Dark Matter Particles in the Sun by Super-Kamiokande

NASA Astrophysics Data System (ADS)

Choi, K.; Abe, K.; Haga, Y.; Hayato, Y.; Iyogi, K.; Kameda, J.; Kishimoto, Y.; Miura, M.; Moriyama, S.; Nakahata, M.; Nakano, Y.; Nakayama, S.; Sekiya, H.; Shiozawa, M.; Suzuki, Y.; Takeda, A.; Tomura, T.; Wendell, R. A.; Irvine, T.; Kajita, T.; Kametani, I.; Kaneyuki, K.; Lee, K. P.; Nishimura, Y.; Okumura, K.; McLachlan, T.; Labarga, L.; Kearns, E.; Raaf, J. L.; Stone, J. L.; Sulak, L. R.; Berkman, S.; Tanaka, H. A.; Tobayama, S.; Goldhaber, M.; Carminati, G.; Kropp, W. R.; Mine, S.; Renshaw, A.; Smy, M. B.; Sobel, H. W.; Ganezer, K. S.; Hill, J.; Hong, N.; Kim, J. Y.; Lim, I. T.; Akiri, T.; Himmel, A.; Scholberg, K.; Walter, C. W.; Wongjirad, T.; Ishizuka, T.; Tasaka, S.; Jang, J. S.; Learned, J. G.; Matsuno, S.; Smith, S. N.; Hasegawa, T.; Ishida, T.; Ishii, T.; Kobayashi, T.; Nakadaira, T.; Nakamura, K.; Oyama, Y.; Sakashita, K.; Sekiguchi, T.; Tsukamoto, T.; Suzuki, A. T.; Takeuchi, Y.; Bronner, C.; Hirota, S.; Huang, K.; Ieki, K.; Ikeda, M.; Kikawa, T.; Minamino, A.; Nakaya, T.; Suzuki, K.; Takahashi, S.; Fukuda, Y.; Itow, Y.; Mitsuka, G.; Mijakowski, P.; Hignight, J.; Imber, J.; Jung, C. K.; Yanagisawa, C.; Ishino, H.; Kibayashi, A.; Koshio, Y.; Mori, T.; Sakuda, M.; Yano, T.; Kuno, Y.; Tacik, R.; Kim, S. B.; Okazawa, H.; Choi, Y.; Nishijima, K.; Koshiba, M.; Totsuka, Y.; Yokoyama, M.; Martens, K.; Marti, Ll.; Vagins, M. R.; Martin, J. F.; de Perio, P.; Konaka, A.; Wilking, M. J.; Chen, S.; Zhang, Y.; Wilkes, R. J.; Super-Kamiokande Collaboration

2015-04-01

Super-Kamiokande (SK) can search for weakly interacting massive particles (WIMPs) by detecting neutrinos produced from WIMP annihilations occurring inside the Sun. In this analysis, we include neutrino events with interaction vertices in the detector in addition to upward-going muons produced in the surrounding rock. Compared to the previous result, which used the upward-going muons only, the signal acceptances for light (few-GeV /c2-200 -GeV /c2 ) WIMPs are significantly increased. We fit 3903 days of SK data to search for the contribution of neutrinos from WIMP annihilation in the Sun. We found no significant excess over expected atmospheric-neutrino background and the result is interpreted in terms of upper limits on WIMP-nucleon elastic scattering cross sections under different assumptions about the annihilation channel. We set the current best limits on the spin-dependent WIMP-proton cross section for WIMP masses below 200 GeV /c2 (at 10 GeV /c2 , 1.49 ×10-39 cm2 for χ χ →b b ¯ and 1.31 ×10-40 cm2 for χ χ →τ+τ- annihilation channels), also ruling out some fraction of WIMP candidates with spin-independent coupling in the few-GeV /c2 mass range.

The Case for Space-Borne Far-Infrared Line Surveys

NASA Technical Reports Server (NTRS)

Bock, J. J.; Bradford, C. M.; Dragovan, M.; Earle, L.; Glenn, J.; Naylor, B.; Nguyen, H. T.; Zmuidzinas, J.

2004-01-01

The combination of sensitive direct detectors and a cooled aperture promises orders of magnitude improvement in the sensitivity and survey time for far-infrared and submillimeter spectroscopy compared to existing or planned capabilities. Continuing advances in direct detector technology enable spectroscopy that approaches the background limit available only from space at these wavelengths. Because the spectral confusion limit is significantly lower than the more familiar spatial confusion limit encountered in imaging applications, spectroscopy can be carried out to comparable depth with a significantly smaller aperture. We are developing a novel waveguide-coupled grating spectrometer that disperses radiation into a wide instantaneous bandwidth with moderate resolution (R 1000) in a compact 2-dimensional format. A line survey instrument coupled to a modest cooled single aperture provides an attractive scientific application for spectroscopy with direct detectors. Using a suite of waveguide spectrometers, we can obtain complete coverage over the entire far-infrared and sub-millimeter. This concept requires no moving parts to modulate the optical signal. Such an instrument would be able to conduct a far-infrared line survey 10 6 times faster than planned capabilities, assuming existing detector technology. However, if historical improvements in bolometer sensitivity continue, so that photon-limited sensitivity is obtained, the integration time can be further reduced by 2 to 4 orders of magnitude, depending on wavelength. The line flux sensitivity would be comparable to ALMA, but at shorter wavelengths and with the continuous coverage needed to extract line fluxes for sources at unknown redshifts. For example, this capability would break the current spectroscopic bottleneck in the study of far-infrared galaxies, the recently discovered, rapidly evolving objects abundant at cosmological distances.

Expected background in the LZ experiment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kudryavtsev, Vitaly A.

2015-08-17

The LZ experiment, featuring a 7-tonne active liquid xenon target, is aimed at achieving unprecedented sensitivity to WIMPs with the background expected to be dominated by astrophysical neutrinos. To reach this goal, extensive simulations are carried out to accurately calculate the electron recoil and nuclear recoil rates in the detector. Both internal (from target material) and external (from detector components and surrounding environment) backgrounds are considered. A very efficient suppression of background rate is achieved with an outer liquid scintillator veto, liquid xenon skin and fiducialisation. Based on the current measurements of radioactivity of different materials, it is shown thatmore » LZ can achieve the reduction of a total background for a WIMP search down to about 2 events in 1000 live days for 5.6 tonne fiducial mass.« less

Expected background in the LZ experiment

NASA Astrophysics Data System (ADS)

Kudryavtsev, Vitaly A.

2015-08-01

The LZ experiment, featuring a 7-tonne active liquid xenon target, is aimed at achieving unprecedented sensitivity to WIMPs with the background expected to be dominated by astrophysical neutrinos. To reach this goal, extensive simulations are carried out to accurately calculate the electron recoil and nuclear recoil rates in the detector. Both internal (from target material) and external (from detector components and surrounding environment) backgrounds are considered. A very efficient suppression of background rate is achieved with an outer liquid scintillator veto, liquid xenon skin and fiducialisation. Based on the current measurements of radioactivity of different materials, it is shown that LZ can achieve the reduction of a total background for a WIMP search down to about 2 events in 1000 live days for 5.6 tonne fiducial mass.

Dark matter in the Reticulum II dSph: a radio search

NASA Astrophysics Data System (ADS)

Regis, Marco; Richter, Laura; Colafrancesco, Sergio

2017-07-01

We present a deep radio search in the Reticulum II dwarf spheroidal (dSph) galaxy performed with the Australia Telescope Compact Array. Observations were conducted at 16 cm wavelength, with an rms sensitivity of 0.01 mJy/beam, and with the goal of searching for synchrotron emission induced by annihilation or decay of weakly interacting massive particles (WIMPs). Data were complemented with observations on large angular scales taken with the KAT-7 telescope. We find no evidence for a diffuse emission from the dSph and we derive competitive bounds on the WIMP properties. In addition, we detect more than 200 new background radio sources. Among them, we show there are two compelling candidates for being the radio counterpart of the possible γ-ray emission reported by other groups using Fermi-LAT data.

Margin and sensitivity methods for security analysis of electric power systems

NASA Astrophysics Data System (ADS)

Greene, Scott L.

Reliable operation of large scale electric power networks requires that system voltages and currents stay within design limits. Operation beyond those limits can lead to equipment failures and blackouts. Security margins measure the amount by which system loads or power transfers can change before a security violation, such as an overloaded transmission line, is encountered. This thesis shows how to efficiently compute security margins defined by limiting events and instabilities, and the sensitivity of those margins with respect to assumptions, system parameters, operating policy, and transactions. Security margins to voltage collapse blackouts, oscillatory instability, generator limits, voltage constraints and line overloads are considered. The usefulness of computing the sensitivities of these margins with respect to interarea transfers, loading parameters, generator dispatch, transmission line parameters, and VAR support is established for networks as large as 1500 buses. The sensitivity formulas presented apply to a range of power system models. Conventional sensitivity formulas such as line distribution factors, outage distribution factors, participation factors and penalty factors are shown to be special cases of the general sensitivity formulas derived in this thesis. The sensitivity formulas readily accommodate sparse matrix techniques. Margin sensitivity methods are shown to work effectively for avoiding voltage collapse blackouts caused by either saddle node bifurcation of equilibria or immediate instability due to generator reactive power limits. Extremely fast contingency analysis for voltage collapse can be implemented with margin sensitivity based rankings. Interarea transfer can be limited by voltage limits, line limits, or voltage stability. The sensitivity formulas presented in this thesis apply to security margins defined by any limit criteria. A method to compute transfer margins by directly locating intermediate events reduces the total number

Solar atmospheric neutrinos: A new neutrino floor for dark matter searches

NASA Astrophysics Data System (ADS)

Ng, Kenny C. Y.; Beacom, John F.; Peter, Annika H. G.; Rott, Carsten

2017-11-01

As is well known, dark matter direct detection experiments will ultimately be limited by a "neutrino floor," due to the scattering of nuclei by MeV neutrinos from, e.g., nuclear fusion in the Sun. Here we point out the existence of a new neutrino floor that will similarly limit indirect detection with the Sun, due to high-energy neutrinos from cosmic-ray interactions with the solar atmosphere. We have two key findings. First, solar atmospheric neutrinos ≲1 TeV cause a sensitivity floor for standard weakly interacting massive particles (WIMP) scenarios, for which higher-energy neutrinos are absorbed in the Sun. This floor will be reached once the present sensitivity is improved by just 1 order of magnitude. Second, for neutrinos ≳1 TeV , which can be isolated by muon energy loss rate, solar atmospheric neutrinos should soon be detectable in IceCube. Discovery will help probe the complicated effects of solar magnetic fields on cosmic rays. These events will be backgrounds to WIMP scenarios with long-lived mediators, for which higher-energy neutrinos can escape from the Sun.

Highly sensitive and selective determination of Hg(II) based on microfluidic chip with on-line fluorescent derivatization.

PubMed

Peng, Guilong; Chen, Yi; Deng, Ruoyu; He, Qiang; Liu, Dun; Lu, Ying; Lin, Jin-Ming

2018-06-07

In this study, a convenient, sensitive, rapid and simple method was developed on microfluidic chip which was integrated with on-line complexing and laser-induced fluorescence detection. A rhodamine derivative (RD) was developed as a fluorescent chemosensor for Hg(II). It exhibited high selective recognition toward Hg(II) over other examined metal ions in water samples. Under the optimized conditions, the response was linearly proportional to the concentration of Hg(II) in the range of 0-70 μM with a detection limit of 0.031 μM. Satisfactory repeatability and reproducibility were achieved, with a relative standard deviation (RSD) of 6.62%. The established method was successfully applied for the determination of Hg(II) in environmental water samples (surface water, tap water, and waste water). Recoveries obtained for the determination of Hg(II) in spiking samples ranged from 85% to 103%. Copyright © 2018. Published by Elsevier B.V.

Genetic Variation and Combining Ability Analysis of Bruising Sensitivity in Agaricus bisporus

PubMed Central

Gao, Wei; Baars, Johan J. P.; Dolstra, Oene; Visser, Richard G. F.; Sonnenberg, Anton S. M.

2013-01-01

Advanced button mushroom cultivars that are less sensitive to mechanical bruising are required by the mushroom industry, where automated harvesting still cannot be used for the fresh mushroom market. The genetic variation in bruising sensitivity (BS) of Agaricus bisporus was studied through an incomplete set of diallel crosses to get insight in the heritability of BS and the combining ability of the parental lines used and, in this way, to estimate their breeding value. To this end nineteen homokaryotic lines recovered from wild strains and cultivars were inter-crossed in a diallel scheme. Fifty-one successful hybrids were grown under controlled conditions, and the BS of these hybrids was assessed. BS was shown to be a trait with a very high heritability. The results also showed that brown hybrids were generally less sensitive to bruising than white hybrids. The diallel scheme allowed to estimate the general combining ability (GCA) for each homokaryotic parental line and to estimate the specific combining ability (SCA) of each hybrid. The line with the lowest GCA is seen as the most attractive donor for improving resistance to bruising. The line gave rise to hybrids sensitive to bruising having the highest GCA value. The highest negative SCA possibly indicates heterosis effects for resistance to bruising. This study provides a foundation for estimating breeding value of parental lines to further study the genetic factors underlying bruising sensitivity and other quality-related traits, and to select potential parental lines for further heterosis breeding. The approach of studying combining ability in a diallel scheme was used for the first time in button mushroom breeding. PMID:24116171

Transition between bulk and surface refractive index sensitivity of micro-cavity in-line Mach-Zehnder interferometer induced by thin film deposition.

PubMed

Śmietana, Mateusz; Janik, Monika; Koba, Marcin; Bock, Wojtek J

2017-10-16

In this work we discuss the refractive index (RI) sensitivity of a micro-cavity in-line Mach-Zehnder interferometer in the form of a cylindrical hole (40-50 μm in diameter) fabricated in a standard single-mode optical fiber using a femtosecond laser. The surface of the micro-cavity was coated with up to 400 nm aluminum oxide thin film using the atomic layer deposition method. Next, the film was progressively chemically etched and the influence on changes in the RI of liquid in the micro-cavity was determined at different stages of the experiment, i.e., at different thicknesses of the film. An effect of transition between sensitivity to the film thickness (surface) and the RI of liquid in the cavity (bulk) is demonstrated for the first time. We have found that depending on the interferometer working conditions determined by thin film properties, the device can be used for investigation of phenomena taking place at the surface, such as in case of specific label-free biosensing applications, or for small-volume RI analysis as required in analytical chemistry.

Development of the PEFP's beam line BPM

NASA Astrophysics Data System (ADS)

Ryu, Jin-Yeong; Kwon, Hyeok-Jung; Jang, Ji-Ho; Kim, Han-Sung; Seol, Kyung-Tae; Cho, Yong-Sub

2013-01-01

The Proton Engineering Frontier Project (PEFP) has 20-MeV and 100-MeV beam lines to supply proton beams to users. A stripline-type Beam Position Monitor (BPM) was designed and fabricated in order to measure the beam's position in the beam line. The RF properties of the BPM were measured and compared with the simulation. After the sensitivity of the BPM at a test stand had been obtained, we performed a beam test in a test beam line of the PEFP 20-MeV proton linac.

Sensitivity analysis of hydrodynamic stability operators

NASA Technical Reports Server (NTRS)

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

1992-01-01

The eigenvalue sensitivity for hydrodynamic stability operators is investigated. Classical matrix perturbation techniques as well as the concept of epsilon-pseudoeigenvalues are applied to show that parts of the spectrum are highly sensitive to small perturbations. Applications are drawn from incompressible plane Couette, trailing line vortex flow and compressible Blasius boundary layer flow. Parametric studies indicate a monotonically increasing effect of the Reynolds number on the sensitivity. The phenomenon of eigenvalue sensitivity is due to the non-normality of the operators and their discrete matrix analogs and may be associated with large transient growth of the corresponding initial value problem.

Neuropeptide S alters anxiety, but not depression-like behaviour in Flinders Sensitive Line rats: a genetic animal model of depression.

PubMed

Wegener, Gregers; Finger, Beate C; Elfving, Betina; Keller, Kirsten; Liebenberg, Nico; Fischer, Christina W; Singewald, Nicolas; Slattery, David A; Neumann, Inga D; Mathé, Aleksander A

2012-04-01

Neuropeptide S (NPS) and its receptor (NPSR) have been implicated in the mediation of anxiolytic-like behaviour in rodents. However, little knowledge is available regarding the NPS system in depression-related behaviours, and whether NPS also exerts anxiolytic effects in an animal model of psychopathology. Therefore, the aim of this work was to characterize the effects of NPS on depression- and anxiety-related parameters, using male and female rats in a well-validated animal model of depression: the Flinders Sensitive Line (FSL), their controls, the Flinders Resistant Line (FRL), and Sprague-Dawley (SD) rats. We found that FSL showed greater immobility in the forced swim test (FST) than FRL, confirming their phenotype. However, NPS did not affect depression-related behaviour in any rat line. No significant differences in baseline anxiety levels between the FSL and FRL strains were observed, but FSL and FRL rats displayed less anxiety-like behaviour compared to SD rats. NPS decreased anxiety-like behaviour on the elevated plus-maze in all strains. The expression of the NPSR in the amygdala, periventricular hypothalamic nucleus, and hippocampus was equal in all male strains, although a trend towards reduced expression within the amygdala was observed in FSL rats compared to SD rats. In conclusion, NPS had a marked anxiolytic effect in FSL, FRL and SD rats, but did not modify the depression-related behaviour in any strain, in spite of the significant differences in innate level between the strains. These findings suggest that NPS specifically modifies anxiety behaviour but cannot overcome/reverse a genetically mediated depression phenotype.

HMOX1 and NQO1 genes are upregulated in response to contact sensitizers in dendritic cells and THP-1 cell line: role of the Keap1/Nrf2 pathway.

PubMed

Ade, Nadège; Leon, Fanny; Pallardy, Marc; Peiffer, Jean-Luc; Kerdine-Romer, Saadia; Tissier, Marie-Hélène; Bonnet, Pierre-Antoine; Fabre, Isabelle; Ourlin, Jean-Claude

2009-02-01

Electrophilicity is one of the most common features of skin contact sensitizers and is necessary for protein haptenation. The Keap1 (Kelch-like ECH-associated protein 1)/Nrf2 -signaling pathway is dedicated to the detection of electrophilic stress in cells leading to the upregulation of genes involved in protection or neutralization of chemical reactive species. Signals provided by chemical stress could play an important role in dendritic cell activation and the aim of this work was to test whether contact sensitizers were specific activators of the Keap1/Nrf2 pathway. CD34-derived dendritic cells (CD34-DC) and the THP-1 myeloid cell line were treated by a panel of sensitizers (Ni, 1-chloro 2,4-dinitrobenzene, cinnamaldehyde, 7-hydroxycitronellal, 1,4-dihydroquinone, alpha-methyl-trans-cinnamaldehyde, 2-4-tert-(butylbenzyl)propionaldehyde or Lilial, and 1,4-phenylenediamine), irritants (sodium dodecyl sulfate, benzalkonium chloride), and a nonsensitizer molecule (chlorobenzene). Three well-known Nrf2 activators (tert-butylhydroquinone, lipoic acid, sulforaphane) were also tested. Expression of hmox1 and nqo1 was measured using real-time PCR and cellular accumulation of Nrf2 was assessed by Western blot. Our results showed an increased expression at early time points of hmox1 and nqo1 mRNAs in response to sensitizers but not to irritants. Accumulation of the Nrf2 protein was also observed only with chemical sensitizers. A significant inhibition of the expression of hmox1 and nqo1 mRNAs and CD86 expression was found in 1-chloro 2,4-dinitrobenzene-treated THP-1 cells preincubated with N-acetyl cysteine, a glutathione precursor. Altogether, these data suggested that the Keap1/Nrf2-signaling pathway was activated by electrophilic molecules including sensitizers in dendritic cells and in the THP-1 cell line. Monitoring of this pathway may provide new biomarkers (e.g., Nrf2, hmox1) for the detection of the sensitization potential of chemicals.

Research Progress on Dark Matter Model Based on Weakly Interacting Massive Particles

NASA Astrophysics Data System (ADS)

He, Yu; Lin, Wen-bin

2017-04-01

The cosmological model of cold dark matter (CDM) with the dark energy and a scale-invariant adiabatic primordial power spectrum has been considered as the standard cosmological model, i.e. the ΛCDM model. Weakly interacting massive particles (WIMPs) become a prominent candidate for the CDM. Many models extended from the standard model can provide the WIMPs naturally. The standard calculations of relic abundance of dark matter show that the WIMPs are well in agreement with the astronomical observation of ΩDM h2 ≈0.11. The WIMPs have a relatively large mass, and a relatively slow velocity, so they are easy to aggregate into clusters, and the results of numerical simulations based on the WIMPs agree well with the observational results of cosmic large-scale structures. In the aspect of experiments, the present accelerator or non-accelerator direct/indirect detections are mostly designed for the WIMPs. Thus, a wide attention has been paid to the CDM model based on the WIMPs. However, the ΛCDM model has a serious problem for explaining the small-scale structures under one Mpc. Different dark matter models have been proposed to alleviate the small-scale problem. However, so far there is no strong evidence enough to exclude the CDM model. We plan to introduce the research progress of the dark matter model based on the WIMPs, such as the WIMPs miracle, numerical simulation, small-scale problem, and the direct/indirect detection, to analyze the criterion for discriminating the ;cold;, ;hot;, and ;warm; dark matter, and present the future prospects for the study in this field.

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

PubMed

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

1999-01-01

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

Spent Pot Lining Characterization Framework

NASA Astrophysics Data System (ADS)

Ospina, Gustavo; Hassan, Mohamed I.

2017-09-01

Spent pot lining (SPL) management represents a major concern for aluminum smelters. There are two key elements for spent pot lining management: recycling and safe storage. Spent pot lining waste can potentially have beneficial uses in co-firing in cement plants. Also, safe storage of SPL is of utmost importance. Gas generation of SPL reaction with water and ignition sensitivity must be studied. However, determining the feasibility of SPL co-firing and developing the required procedures for safe storage rely on determining experimentally all the necessary SPL properties along with the appropriate test methods, recognized by emissions standards and fire safety design codes. The applicable regulations and relevant SPL properties for this purpose are presented along with the corresponding test methods.

Genetic and molecular characterization of photoperiod and thermo-sensitive male sterility in rice.

PubMed

Fan, Yourong; Zhang, Qifa

2018-03-01

A review on photoperiod and temperature-sensitive genic male sterility in rice. Male sterility in plants, facilitating the development of hybrid crops, has made great contribution to crop productivity worldwide. Environment-sensitive genic male sterility (EGMS), including photoperiod-sensitive genic male sterility (PGMS) and temperature-sensitive genic male sterility (TGMS), has provided a special class of germplasms for the breeding of "two-line" hybrids in several crops. In rice, the finding of the PGMS NK58S mutant in 1973 started the journey of research and breeding of two-line hybrids. Genetic and molecular characterization of these germplasms demonstrated diverse genes and molecular mechanisms of male sterility regulation. Two loci identified from NK58S, PMS1 and PMS3, both encode long noncoding RNAs. A major TGMS locus, TMS5, found in the TGMS line Annong S-1, encodes an RNase Z. A reverse PGMS mutant carbon starved anther encodes an R2R3 MYB transcription factor. Breeding efforts in the last three decades have resulted in hundreds of EGMS lines and two-line hybrids released to rice production, which have greatly elevated the yield potential and grain quality of rice varieties. The enhanced molecular understanding will offer new strategies for the development of EGMS lines thus further improving two-line hybrid breeding of rice as well as other crops.

Radiation Response in Two HPV-Infected Head-and-Neck Cancer Cell Lines in Comparison to a Non-HPV-Infected Cell Line and Relationship to Signaling Through AKT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gupta, Anjali K.; Lee, John H.; Wilke, Werner W.

2009-07-01

Purpose: Human papilloma virus (HPV)-associated cancers of the head and neck (H and N) are increasing in frequency and are often treated with radiation. There are conflicting data in the literature regarding the radiation response in the presence of HPV infection, with some data suggesting they may be more sensitive to radiation. There are few studies looking at in vitro effects of HPV and further sensitization by inhibitors of specific signaling pathways. We are in the process of starting a clinical trial in H and N cancer patients using nelfinavir (NFV) (which inhibits Akt) and it would be important tomore » know the effect of HPV on radiation response {+-} NFV. Methods and Materials: Two naturally infected HPV-16 cell lines (UPCI-SCC90 and UMSCC47) and the HPV-negative SQ20B H and N squamous carcinoma cells were used. Western blots with or without 10 uM NFV were done to evaluate signaling from the PI3K-Akt pathway. Clonogenic assays were done in the three cell lines with or without NFV. Results: Both UPCI-SCC90 and UMSCC47 cells were sensitive to radiation as compared with SQ20B and the degree corresponded to Akt activation. The SQ20B cell line has an activating mutation in EGFR resulting in phosphorylation (P) of Akt; UMSCC47 has decreased P-phosphatase and TENsin (PTEN), resulting in increased P-Akt; UPCI-SCC90 had overexpression of P-PTEN and decreased P-Akt. NFV resulted in downregulation of Akt in all three cell lines, resulting in sensitization to radiation. Conclusions: HPV-infected H and N cancers are sensitive to radiation. The degree of sensitivity correlates to Akt activation and they can be further sensitized by NFV00.« less

Phenotypic and transcriptional response to selection for alcohol sensitivity in Drosophila melanogaster

PubMed Central

Morozova, Tatiana V; Anholt, Robert RH; Mackay, Trudy FC

2007-01-01

Background Alcoholism is a complex disorder determined by interactions between genetic and environmental risk factors. Drosophila represents a powerful model system to dissect the genetic architecture of alcohol sensitivity, as large numbers of flies can readily be reared in defined genetic backgrounds and under controlled environmental conditions. Furthermore, flies exposed to ethanol undergo physiological and behavioral changes that resemble human alcohol intoxication, including loss of postural control, sedation, and development of tolerance. Results We performed artificial selection for alcohol sensitivity for 35 generations and created duplicate selection lines that are either highly sensitive or resistant to ethanol exposure along with unselected control lines. We used whole genome expression analysis to identify 1,678 probe sets with different expression levels between the divergent lines, pooled across replicates, at a false discovery rate of q < 0.001. We assessed to what extent genes with altered transcriptional regulation might be causally associated with ethanol sensitivity by measuring alcohol sensitivity of 37 co-isogenic P-element insertional mutations in 35 candidate genes, and found that 32 of these mutants differed in sensitivity to ethanol exposure from their co-isogenic controls. Furthermore, 23 of these novel genes have human orthologues. Conclusion Combining whole genome expression profiling with selection for genetically divergent lines is an effective approach for identifying candidate genes that affect complex traits, such as alcohol sensitivity. Because of evolutionary conservation of function, it is likely that human orthologues of genes affecting alcohol sensitivity in Drosophila may contribute to alcohol-associated phenotypes in humans. PMID:17973985

Temperature sensitivity of differential absorption lidar measurements of water vapor in the 720-nm region

NASA Technical Reports Server (NTRS)

Browell, Edward V.; Ismail, Syed; Grossmann, Benoist E.

1991-01-01

Recently measured properties of water vapor (H2O) absorption lines have been used in calculations to evalute the temperature sensitivity of differential absorption lidar (Dial) H2O measurements. This paper estimates the temperature sensitivity of H2O lines in the 717-733-nm region for both H2O mixing ratio and number density measurements, and discusses the influence of the H2O line ground state energies E-double-prime, the H2O absorption linewidths, the linewidth temperature dependence parameter, and the atmospheric temperature and pressure variations with altitude and location on the temperature sensitivity calculations. Line parameters and temperature sensitivity calculations for 67 H2O lines in the 720-nm band are given which can be directly used in field experiments. Water vapor lines with E-double-prime values in the 100-300/cm range were found to be optimum for Dial measurements of H2O number densities, while E-double-prime values in the 250-500/cm range were found to be optimum for H2O mixing ratio measurements.

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

PubMed Central

2012-01-01

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

Linear Polarization Measurements of Chromospheric Emission Lines

NASA Technical Reports Server (NTRS)

Sheeley, N. R., Jr.; Keller, C. U.

2003-01-01

We have used the Zurich Imaging Stokes Polarimeter (ZIMPOL I) with the McMath-Pierce 1.5 m main telescope on Kitt Peak to obtain linear polarization measurements of the off-limb chromosphere with a sensitivity better than 1 x 10(exp -5). We found that the off-disk observations require a combination of good seeing (to show the emission lines) and a clean heliostat (to avoid contamination by scattered light from the Sun's disk). When these conditions were met, we obtained the following principal results: 1. Sometimes self-reversed emission lines of neutral and singly ionized metals showed linear polarization caused by the transverse Zeeman effect or by instrumental cross talk from the longitudinal Zeeman effect in chromospheric magnetic fields. Otherwise, these lines tended to depolarize the scattered continuum radiation by amounts that ranged up to 0.2%. 2. Lines previously known to show scattering polarization just inside the limb (such as the Na I lambda5889 D2 and the He I lambda5876 D3 lines) showed even more polarization above the Sun's limb, with values approaching 0.7%. 3. The O I triplet at lambda7772, lambda7774, and lambda7775 showed a range of polarizations. The lambda7775 line, whose maximum intrinsic polarizability, P(sub max), is less than 1%, revealed mainly Zeeman contributions from chromospheric magnetic fields. However, the more sensitive lambda7772 (P(sub max) = 19%) and lambda7774 (P(sub max) = 29%) lines had relatively strong scattering polarizations of approximately 0.3% in addition to their Zeeman polarizations. At times of good seeing, the polarization spectra resolve into fine structures that seem to be chromospheric spicules.

Transposon-mediated generation of BCR-ABL1-expressing transgenic cell lines for unbiased sensitivity testing of tyrosine kinase inhibitors.

PubMed

Byrgazov, Konstantin; Lucini, Chantal Blanche; Berkowitsch, Bettina; Koenig, Margit; Haas, Oskar A; Hoermann, Gregor; Valent, Peter; Lion, Thomas

2016-11-22

Point mutations in the ABL1 kinase domain are an important mechanism of resistance to tyrosine kinase inhibitors (TKI) in BCR-ABL1-positive and, as recently shown, BCR-ABL1-like leukemias. The cell line Ba/F3 lentivirally transduced with mutant BCR-ABL1 constructs is widely used for in vitro sensitivity testing and response prediction to tyrosine kinase inhibitors. The transposon-based Sleeping Beauty system presented offers several advantages over lentiviral transduction including the absence of biosafety issues, faster generation of transgenic cell lines, and greater efficacy in introducing large gene constructs. Nevertheless, both methods can mediate multiple insertions in the genome. Here we show that multiple BCR-ABL1 insertions result in elevated IC50 levels for individual TKIs, thus overestimating the actual resistance of mutant subclones. We have therefore established flow-sorting-based fractionation of BCR-ABL1-transformed Ba/F3 cells facilitating efficient enrichment of cells carrying single-site insertions, as demonstrated by FISH-analysis. Fractions of unselected Ba/F3 cells not only showed a greater number of BCR-ABL1 hybridization signals, but also revealed higher IC50 values for the TKIs tested. The data presented highlight the need to carefully select transfected cells by flow-sorting, and to control the insertion numbers by FISH and real-time PCR to permit unbiased in vitro testing of drug resistance.

Transposon-mediated generation of BCR-ABL1-expressing transgenic cell lines for unbiased sensitivity testing of tyrosine kinase inhibitors

PubMed Central

Berkowitsch, Bettina; Koenig, Margit; Haas, Oskar A.; Hoermann, Gregor; Valent, Peter; Lion, Thomas

2016-01-01

Point mutations in the ABL1 kinase domain are an important mechanism of resistance to tyrosine kinase inhibitors (TKI) in BCR-ABL1-positive and, as recently shown, BCR-ABL1-like leukemias. The cell line Ba/F3 lentivirally transduced with mutant BCR-ABL1 constructs is widely used for in vitro sensitivity testing and response prediction to tyrosine kinase inhibitors. The transposon-based Sleeping Beauty system presented offers several advantages over lentiviral transduction including the absence of biosafety issues, faster generation of transgenic cell lines, and greater efficacy in introducing large gene constructs. Nevertheless, both methods can mediate multiple insertions in the genome. Here we show that multiple BCR-ABL1 insertions result in elevated IC50 levels for individual TKIs, thus overestimating the actual resistance of mutant subclones. We have therefore established flow-sorting-based fractionation of BCR-ABL1-transformed Ba/F3 cells facilitating efficient enrichment of cells carrying single-site insertions, as demonstrated by FISH-analysis. Fractions of unselected Ba/F3 cells not only showed a greater number of BCR-ABL1 hybridization signals, but also revealed higher IC50 values for the TKIs tested. The data presented highlight the need to carefully select transfected cells by flow-sorting, and to control the insertion numbers by FISH and real-time PCR to permit unbiased in vitro testing of drug resistance. PMID:27801667

Inelastic dark matter in light of DAMA/LIBRA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, Spencer; Weiner, Neal; Kribs, Graham D.

2009-02-15

Inelastic dark matter, in which weakly interacting massive particle (WIMP)-nucleus scatterings occur through a transition to an excited WIMP state {approx}100 keV above the ground state, provides a compelling explanation of the DAMA annual modulation signal. We demonstrate that the relative sensitivities of various dark matter direct detection experiments are modified such that the DAMA annual modulation signal can be reconciled with the absence of a reported signal at CDMS-Soudan, XENON10, ZEPLIN, CRESST, and KIMS for inelastic WIMPs with masses O(100 GeV). We review the status of these experiments, and make predictions for upcoming ones. In particular, we note thatmore » inelastic dark matter leads to highly suppressed signals at low energy, with most events typically occurring between 20 and 45 keV (unquenched) at xenon and iodine experiments, and generally no events at low ({approx}10 keV) energies. Suppressing the background in this high-energy region is essential to testing this scenario. The recent CRESST data suggest seven observed tungsten events, which is consistent with expectations from this model. If the tungsten signal persists at future CRESST runs, it would provide compelling evidence for inelastic dark matter, while its absence should exclude it.« less

Physiological joint line total knee arthroplasty designs are especially sensitive to rotational placement - A finite element analysis.

PubMed

Moewis, Philippe; Checa, Sara; Kutzner, Ines; Hommel, Hagen; Duda, Georg N

2018-01-01

Mechanical and kinematical aligning techniques are the usual positioning methods during total knee arthroplasty. However, alteration of the physiological joint line and unbalanced medio-lateral load distribution are considered disadvantages in the mechanical and kinematical techniques, respectively. The aim of this study was to analyse the influence of the joint line on the strain and stress distributions in an implanted knee and their sensitivity to rotational mal-alignment. Finite element calculations were conducted to analyse the stresses in the PE-Inlay and the mechanical strains at the bone side of the tibia component-tibia bone interface during normal positioning of the components and internal and external mal-rotation of the tibial component. Two designs were included, a horizontal and a physiological implant. The loading conditions are based on internal knee joint loads during walking. A medialization of the stresses on the PE-Inlay was observed in the physiological implant in a normal position, accompanied by higher stresses in the mal-rotated positions. Within the tibia component-tibia bone interface, similar strain distributions were observed in both implant geometries in the normal position. However, a medialization of the strains was observed in the physiological implant in both mal-rotated conditions with greater bone volume affected by higher strains. Although evident changes due to mal-rotation were observed, the stresses do not suggest a local plastic deformation of the PE-Inlay. The strains values within most of the tibia component-tibia bone interface were in the physiological strain zone and no significant bone changes would be expected. The physiological cut on the articular aspect showed no detrimental effect compared to the horizontal implant.

Direct Search for Dark Matter with DarkSide

NASA Astrophysics Data System (ADS)

Agnes, P.; Alexander, T.; Alton, A.; Arisaka, K.; Back, H. O.; Baldin, B.; Biery, K.; Bonfini, G.; Bossa, M.; Brigatti, A.; Brodsky, J.; Budano, F.; Cadonati, L.; Calaprice, F.; Canci, N.; Candela, A.; Cao, H.; Cariello, M.; Cavalcante, P.; Chavarria, A.; Chepurnov, A.; Cocco, A. G.; Crippa, L.; D'Angelo, D.; D'Incecco, M.; Davini, S.; De Deo, M.; Derbin, A.; Devoto, A.; Di Eusanio, F.; Di Pietro, G.; Edkins, E.; Empl, A.; Fan, A.; Fiorillo, G.; Fomenko, K.; Forster, G.; Franco, D.; Gabriele, F.; Galbiati, C.; Goretti, A.; Grandi, L.; Gromov, M.; Guan, M. Y.; Guardincerri, Y.; Hackett, B.; Herner, K.; Hungerford, E. V.; Ianni, Al; Ianni, An; Jollet, C.; Keeter, K.; Kendziora, C.; Kidner, S.; Kobychev, V.; Koh, G.; Korablev, D.; Korga, G.; Kurlej, A.; Li, P. X.; Loer, B.; Lombardi, P.; Love, C.; Ludhova, L.; Luitz, S.; Ma, Y. Q.; Machulin, I.; Mandarano, A.; Mari, S.; Maricic, J.; Marini, L.; Martoff, C. J.; Meregaglia, A.; Meroni, E.; Meyers, P. D.; Milincic, R.; Montanari, D.; Montuschi, M.; Monzani, M. E.; Mosteiro, P.; Mount, B.; Muratova, V.; Musico, P.; Nelson, A.; Odrowski, S.; Okounkova, M.; Orsini, M.; Ortica, F.; Pagani, L.; Pallavicini, M.; Pantic, E.; Papp, L.; Parmeggiano, S.; Parsells, R.; Pelczar, K.; Pelliccia, N.; Perasso, S.; Pocar, A.; Pordes, S.; Pugachev, D.; Qian, H.; Randle, K.; Ranucci, G.; Razeto, A.; Reinhold, B.; Renshaw, A.; Romani, A.; Rossi, B.; Rossi, N.; Rountree, S. D.; Sablone, D.; Saggese, P.; Saldanha, R.; Sands, W.; Sangiorgio, S.; Segreto, E.; Semenov, D.; Shields, E.; Skorokhvatov, M.; Smirnov, O.; Sotnikov, A.; Stanford, C.; Suvorov, Y.; Tartaglia, R.; Tatarowicz, J.; Testera, G.; Tonazzo, A.; Unzhakov, E.; Vogelaar, R. B.; Wada, M.; Walker, S.; Wang, H.; Wang, Y.; Watson, A.; Westerdale, S.; Wojcik, M.; Wright, A.; Xiang, X.; Xu, J.; Yang, C. G.; Yoo, J.; Zavatarelli, S.; Zec, A.; Zhu, C.; Zuzel, G.

2015-11-01

The DarkSide experiment is designed for the direct detection of Dark Matter with a double phase liquid Argon TPC operating underground at Laboratori Nazionali del Gran Sasso. The TPC is placed inside a 30 tons liquid organic scintillator sphere, acting as a neutron veto, which is in turn installed inside a 1 kt water Cherenkov detector. The current detector is running since November 2013 with a 50 kg atmospheric Argon fill and we report here the first null results of a Dark Matter search for a (1422 ± 67) kg.d exposure. This result correspond to a 90% CL upper limit on the WIMP-nucleon cross section of 6.1 × 10-44 cm2 (for a WIMP mass of 100 GeV/c2) and it's currently the most sensitive limit obtained with an Argon target.

Dark matter in the Reticulum II dSph: a radio search

DOE Office of Scientific and Technical Information (OSTI.GOV)

Regis, Marco; Richter, Laura; Colafrancesco, Sergio, E-mail: regis@to.infn.it, E-mail: llrichter@gmail.com, E-mail: sergio.colafrancesco@wits.ac.za

2017-07-01

We present a deep radio search in the Reticulum II dwarf spheroidal (dSph) galaxy performed with the Australia Telescope Compact Array. Observations were conducted at 16 cm wavelength, with an rms sensitivity of 0.01 mJy/beam, and with the goal of searching for synchrotron emission induced by annihilation or decay of weakly interacting massive particles (WIMPs). Data were complemented with observations on large angular scales taken with the KAT-7 telescope. We find no evidence for a diffuse emission from the dSph and we derive competitive bounds on the WIMP properties. In addition, we detect more than 200 new background radio sources.more » Among them, we show there are two compelling candidates for being the radio counterpart of the possible γ-ray emission reported by other groups using Fermi-LAT data.« less

Model-independent analyses of dark-matter particle interactions

DOE PAGES

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

2015-03-24

A model-independent treatment of dark-matter particle elastic scattering has been developed, yielding the most general interaction for WIMP-nucleon low-energy scattering, and the resulting amplitude has been embedded into the nucleus, taking into account the selection rules imposed by parity and time-reversal. One finds that, in contrast to the usual spin-independent/spin-dependent (SI/SD) formulation, the resulting cross section contains six independent nuclear response functions, three of which are associated with possible velocity-dependent interactions. We find that current experiments are four orders of magnitude more sensitive to derivative couplings than is apparent in the standard SI/SD treatment, which necessarily associated such interactions withmore » cross sections proportional to v 2 T ~ 10⁻⁶, where v T is the WIMP velocity relative to the center of mass of the nuclear target.« less

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

Code of Federal Regulations, 2010 CFR

2010-10-01

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

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

Code of Federal Regulations, 2011 CFR

2011-10-01

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

The phenomenology of maverick dark matter

NASA Astrophysics Data System (ADS)

Krusberg, Zosia Anna Celina

Astrophysical observations from galactic to cosmological scales point to a substantial non-baryonic component to the universe's total matter density. Although very little is presently known about the physical properties of dark matter, its existence offers some of the most compelling evidence for physics beyond the standard model (BSM). In the weakly interacting massive particle (WIMP) scenario, the dark matter consists of particles that possess weak-scale interactions with the particles of the standard model, offering a compelling theoretical framework that allows us to understand the relic abundance of dark matter as a natural consequence of the thermal history of the early universe. From the perspective of particle physics phenomenology, the WIMP scenario is appealing for two additional reasons. First, many theories of BSM physics contain attractive WIMP candidates. Second, the weak-scale interactions between WIMPs and standard model particles imply the possibility of detecting scatterings between relic WIMPs and detector nuclei in direct detection experiments, products of WIMP annihilations at locations throughout the galaxy in indirect detection programs, and WIMP production signals at high-energy particle colliders. In this work, we use an effective field theory approach to study model-independent dark matter phenomenology in direct detection and collider experiments. The maverick dark matter scenario is defined by an effective field theory in which the WIMP is the only new particle within the energy range accessible to the Large Hadron Collider (LHC). Although certain assumptions are necessary to keep the problem tractable, we describe our WIMP candidate generically by specifying only its spin and dominant interaction form with standard model particles. Constraints are placed on the masses and coupling constants of the maverick WIMPs using the Wilkinson Microwave Anisotropy Probe (WMAP) relic density measurement and direct detection exclusion data from both

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

PubMed

Olschläger, Veronika; Schrader, Andreas; Hockertz, Stefan

2009-01-01

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

In vitro cytotoxicity of Indonesian stingless bee products against human cancer cell lines

PubMed Central

Kustiawan, Paula M.; Puthong, Songchan; Arung, Enos T.; Chanchao, Chanpen

2014-01-01

Objective To screen crude extracts of propolis, bee pollen and honey from four stingless bee species [Trigona incisa (T. incisa)], Timia apicalis, Trigona fusco-balteata and Trigona fuscibasis) native to East Kalimantan, Indonesia for cytotoxic activity against five human cancer cell lines (HepG2, SW620, ChaGo-I, KATO-III and BT474). Methods All samples were extracted with methanol, and then subpartitioned with n-hexane and ethyl acetate. Each crude extract was screened at 20 µg/mL for in vitro cytotoxicity against the cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. In addition, four previously shown bioactive components from propolis (apigenin, caffeic acid phenyl ester, kaempferol and naringenin) and two chemotherapeutic drugs (doxorubicin and 5-fluorouracil) were used to evaluate the sensitivity of the cell lines. Results Overall, crude extracts from propolis and honey had higher cytotoxic activities than bee pollen, but the activity was dependent upon the extraction solvent, bee species and cell line. Propolis extracts from T. incisa and Timia apicalis showed the highest and lowest cytotoxic activity, respectively. Only the HepG2 cell line was broadly sensitive to the honey extracts. For pure compounds, doxorubicin was the most cytotoxic, the four propolis compounds the least, but the ChaGo-I cell line was sensitive to kaempferol at 10 µg/mL and KATO-III was sensitive to kaempferol and apigenin at 10 µg/mL. All pure compounds were effective against the BT474 cell line. Conclusions Propolis from T. incisa and Trigona fusco-balteata contain an in vitro cytotoxic activity against human cancer cell lines. Further study is required, including the isolation and characterization of the active antiproliferative agent(s). PMID:25183275

In vitro cytotoxicity of Indonesian stingless bee products against human cancer cell lines.

PubMed

Kustiawan, Paula M; Puthong, Songchan; Arung, Enos T; Chanchao, Chanpen

2014-07-01

To screen crude extracts of propolis, bee pollen and honey from four stingless bee species [Trigona incisa (T. incisa)], Timia apicalis, Trigona fusco-balteata and Trigona fuscibasis) native to East Kalimantan, Indonesia for cytotoxic activity against five human cancer cell lines (HepG2, SW620, ChaGo-I, KATO-III and BT474). All samples were extracted with methanol, and then subpartitioned with n-hexane and ethyl acetate. Each crude extract was screened at 20 µg/mL for in vitro cytotoxicity against the cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. In addition, four previously shown bioactive components from propolis (apigenin, caffeic acid phenyl ester, kaempferol and naringenin) and two chemotherapeutic drugs (doxorubicin and 5-fluorouracil) were used to evaluate the sensitivity of the cell lines. Overall, crude extracts from propolis and honey had higher cytotoxic activities than bee pollen, but the activity was dependent upon the extraction solvent, bee species and cell line. Propolis extracts from T. incisa and Timia apicalis showed the highest and lowest cytotoxic activity, respectively. Only the HepG2 cell line was broadly sensitive to the honey extracts. For pure compounds, doxorubicin was the most cytotoxic, the four propolis compounds the least, but the ChaGo-I cell line was sensitive to kaempferol at 10 µg/mL and KATO-III was sensitive to kaempferol and apigenin at 10 µg/mL. All pure compounds were effective against the BT474 cell line. Propolis from T. incisa and Trigona fusco-balteata contain an in vitro cytotoxic activity against human cancer cell lines. Further study is required, including the isolation and characterization of the active antiproliferative agent(s).

Lower limit on dark matter production at the CERN Large Hadron Collider.

PubMed

Feng, Jonathan L; Su, Shufang; Takayama, Fumihiro

2006-04-21

We evaluate the prospects for finding evidence of dark matter production at the CERN Large Hadron Collider. We consider weakly interacting massive particles (WIMPs) and superWIMPs and characterize their properties through model-independent parametrizations. The observed relic density then implies lower bounds on dark matter production rates as functions of a few parameters. For WIMPs, the resulting signal is indistinguishable from background. For superWIMPs, however, this analysis implies significant production of metastable charged particles. For natural parameters, these rates may far exceed Drell-Yan cross sections and yield spectacular signals.

Contribution functions for Zeeman-split lines, and line formation in photospheric faculae

NASA Technical Reports Server (NTRS)

Vanballegooijen, A. A.

1985-01-01

The transfer of polarized light in an inhomogeneous stellar atmosphere, and the formation of magnetically sensitive spectral lines, are discussed. A new method for the solution of the transfer equations is proposed. The method gives a natural definition of the contribution functions for Stokes' parameters, i.e., functions describing the contributions from different parts along the line-of-sight (LOS). The formalism includes all magneto-optical effects, and allows for an arbitrary variation of magnetic field, velocity field, temperature, density, etc., along the LOS. The formation of FeI lambda 5250.2 in photospheric faculae is described. A potential-field model of a facular element is presented, and spectra profiles and contribution functions are computed for the Stokes parameters I, Q, and V.

Dependence of NMR noise line shapes on tuning, matching, and transmission line properties

PubMed Central

Bendet-Taicher, Eli; Müller, Norbert; Jerschow, Alexej

2014-01-01

The tuning and matching conditions of rf circuits, as well as the properties of the transmission lines connecting these to the preamplifier, have direct consequences for NMR probe sensitivity and as for the optimum delivery of rf power to the sample. In addition, tuning/matching conditions influence radiation damping effects, which manifest themselves as fast signal flip-back and line broadening effects, and can lead to concentration-dependent frequency shifts. Previous studies have also shown that the appearance of spin-noise and absorbed circuit noise signals heavily depended on tuning settings. Consequently, all these phenomena are linked together. The mutual connections and interdependences of these effects are highlighted and reviewed here. PMID:25505374

Local Group dSph radio survey with ATCA (III): constraints on particle dark matter

NASA Astrophysics Data System (ADS)

Regis, Marco; Colafrancesco, Sergio; Profumo, Stefano; de Blok, W. J. G.; Massardi, Marcella; Richter, Laura

2014-10-01

We performed a deep search for radio synchrotron emissions induced by weakly interacting massive particles (WIMPs) annihilation or decay in six dwarf spheroidal (dSph) galaxies of the Local Group. Observations were conducted with the Australia Telescope Compact Array (ATCA) at 16 cm wavelength, with an rms sensitivity better than 0.05 mJy/beam in each field. In this work, we first discuss the uncertainties associated with the modeling of the expected signal, such as the shape of the dark matter (DM) profile and the dSph magnetic properties. We then investigate the possibility that point-sources detected in the proximity of the dSph optical center might be due to the emission from a DM cuspy profile. No evidence for an extended emission over a size of few arcmin (which is the DM halo size) has been detected. We present the associated bounds on the WIMP parameter space for different annihilation/decay final states and for different astrophysical assumptions. If the confinement of electrons and positrons in the dSph is such that the majority of their power is radiated within the dSph region, we obtain constraints on the WIMP annihilation rate which are well below the thermal value for masses up to few TeV. On the other hand, for conservative assumptions on the dSph magnetic properties, the bounds can be dramatically relaxed. We show however that, within the next 10 years and regardless of the astrophysical assumptions, it will be possible to progressively close in on the full parameter space of WIMPs by searching for radio signals in dSphs with SKA and its precursors.

Exact theory of freeze-out

NASA Astrophysics Data System (ADS)

Cannoni, Mirco

2015-03-01

We show that the standard theory of thermal production and chemical decoupling of WIMPs is incomplete. The hypothesis that WIMPs are produced and decouple from a thermal bath implies that the rate equation the bath particles interacting with the WIMPs is an algebraic equation that constraints the actual WIMPs abundance to have a precise analytical form down to the temperature . The point , which coincides with the stationary point of the equation for the quantity , is where the maximum departure of the WIMPs abundance from the thermal value is reached. For each mass and total annihilation cross section , the temperature and the actual WIMPs abundance are exactly known. This value provides the true initial condition for the usual differential equation that have to be integrated in the interval . The matching of the two abundances at is continuous and differentiable. The dependence of the present relic abundance on the abundance at an intermediate temperature is an exact result. The exact theory suggests a new analytical approximation that furnishes the relic abundance accurate at the level of 1-2 % in the case of -wave and -wave scattering cross sections. We conclude the paper studying the evolution of the WIMPs chemical potential and the entropy production using methods of non-equilibrium thermodynamics.

Identifying Determinants of PARP Inhibitor Sensitivity in Ovarian Cancer

DTIC Science & Technology

2016-10-01

inhibitors. Ovarian cancer patients that harbored germ- line BRCA1 mutations treated with PARP inhibitors exhibited meaningful responses in early phase...hypothesized that a range of common ovarian cancer predisposing germ- line BRCA1 gene mutations produce semi-functional proteins that are capable of...we have started our work examining exome sequences and gene expression in PARPi sensitive and resistance cancer cell lines . I attended and presented

A sensitive WST-8-based bioassay for PEGylated granulocyte colony stimulating factor using the NFS-60 cell line.

PubMed

Tiwari, Krishna; Wavdhane, Madan; Haque, Shafiul; Govender, Thavendran; Kruger, Hendrik G; Mishra, Maheshwari K; Chandra, Ramesh; Tiwari, Dileep

2015-06-01

Granulocyte colony stimulating factor (G-CSF) has been commonly used to treat neutropenia caused by chemotherapy, radiotherapy, and organ transplants. Improved in vitro efficacy of G-CSF has already been observed by conjugating it to polyethylene glycol (PEG). The in vivo bioassay using tetrazolium dye with the NFS-60 cell line has been recommended for G-CSF but no such monographs are available for PEGylated G-CSF in pharmacopeias. In the present study, the assay recommended for G-CSF was evaluated for its suitability to PEGylated G-CSF. The generally used MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium]-based assay was compared with a bioassay employing a water-soluble tetrazolium dye, WST-8 [2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium], using NFS-60 cells at a concentration of 7 × 10(5) cells/ml against 800 IU/ml of PEGylated G-CSF at 24, 48, 72, and 72 h time points to determine the efficacy of PEGylated G-CSF. Further, the optimized WST-8 dye-based assay was used to test the potency of various commercially available PEGylated G-CSF preparations. The results demonstrated enhanced sensitivity of the WST-8-based assay over the conventional MTS-based assay for determining the potency of PEGylated G-CSF using the NFS-60 cell line. Our study demonstrates the potential application of WST-8-based bioassays for other biotherapeutic proteins of human and veterinary interest.

Characterization of ibrutinib-sensitive and -resistant mantle lymphoma cells.

PubMed

Ma, Jiao; Lu, Pin; Guo, Ailin; Cheng, Shuhua; Zong, Hongliang; Martin, Peter; Coleman, Morton; Wang, Y Lynn

2014-09-01

Ibrutinib inhibits Bruton tyrosine kinase (BTK), a key component of early B-cell receptor (BCR) signalling pathways. A multicentre phase 2 trial of ibrutinib in patients with relapsed/refractory mantle cell lymphoma (MCL) demonstrated a remarkable response rate. However, approximately one-third of patients have primary resistance to the drug while other patients appear to lose response and develop secondary resistance. Understanding the molecular mechanisms underlying ibrutinib sensitivity is of paramount importance. In this study, we investigated cell lines and primary MCL cells that display differential sensitivity to ibrutinib. We found that the primary cells display a higher BTK activity than normal B cells and MCL cells show differential sensitivity to BTK inhibition. Genetic knockdown of BTK inhibits the growth, survival and proliferation of ibrutinib-sensitive but not resistant MCL cell lines, suggesting that ibrutinib acts through BTK to produce its anti-tumour activities. Interestingly, inhibition of ERK1/2 and AKT, but not BTK phosphorylation per se, correlates well with cellular response to BTK inhibition in cell lines as well as in primary tumours. Our study suggests that, to prevent primary resistance or to overcome secondary resistance to BTK inhibition, a combinatory strategy that targets multiple components or multiple pathways may represent the most effective approach. © 2014 John Wiley & Sons Ltd.

absorption sensor for sensitive temperature and species measurements in high-temperature gases

NASA Astrophysics Data System (ADS)

Spearrin, R. M.; Ren, W.; Jeffries, J. B.; Hanson, R. K.

2014-09-01

A continuous-wave laser absorption diagnostic, based on the infrared CO2 bands near 4.2 and 2.7 μm, was developed for sensitive temperature and concentration measurements in high-temperature gas systems using fixed-wavelength methods. Transitions in the respective R-branches of both the fundamental υ 3 band (~2,350 cm-1) and combination υ 1 + υ 3 band (~3,610 cm-1) were chosen based on absorption line-strength, spectral isolation, and temperature sensitivity. The R(76) line near 2,390.52 cm-1 was selected for sensitive CO2 concentration measurements, and a detection limit of <5 ppm was achieved in shock tube kinetics experiments (~1,300 K). A cross-band, two-line thermometry technique was also established utilizing the R(96) line near 2,395.14 cm-1, paired with the R(28) line near 3,633.08 cm-1. This combination yields high temperature sensitivity (ΔE" = 3,305 cm-1) and expanded range compared with previous intra-band CO2 sensors. Thermometry performance was validated in a shock tube over a range of temperatures (600-1,800 K) important for combustion. Measured temperature accuracy was demonstrated to be better than 1 % over the entire range of conditions, with a standard error of ~0.5 % and µs temporal resolution.

Cancer stem cell-like cells from a single cell of oral squamous carcinoma cell lines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Felthaus, O.; Department of Oral and Maxillofacial Surgery, University of Regensburg; Ettl, T.

2011-04-01

Research highlights: {yields} Four oral squamous cancer cell lines (OSCCL) were analyzed for cancer stem cells (CSCs). {yields} Single cell derived colonies of OSCCL express CSC-marker CD133 differentially. {yields} Monoclonal cell lines showed reduced sensitivity for Paclitaxel. {yields} In situ CD133{sup +} cells are slow cycling (Ki67-) indicating a reduced drug sensitivity. {yields} CD133{sup +} and CSC-like cells can be obtained from single colony forming cells of OSCCL. -- Abstract: Resistance of oral squamous cell carcinomas (OSCC) to conventional chemotherapy or radiation therapy might be due to cancer stem cells (CSCs). The development of novel anticancer drugs requires a simplemore » method for the enrichment of CSCs. CSCs can be enriched from OSCC cell lines, for example, after cultivation in serum-free cell culture medium (SFM). In our study, we analyzed four OSCC cell lines for the presence of CSCs. CSC-like cells could not be enriched with SFM. However, cell lines obtained from holoclone colonies showed CSC-like properties such as a reduced rate of cell proliferation and a reduced sensitivity to Paclitaxel in comparison to cells from the parental lineage. Moreover, these cell lines differentially expressed the CSC-marker CD133, which is also upregulated in OSCC tissues. Interestingly, CD133{sup +} cells in OSCC tissues expressed little to no Ki67, the cell proliferation marker that also indicates reduced drug sensitivity. Our study shows a method for the isolation of CSC-like cell lines from OSCC cell lines. These CSC-like cell lines could be new targets for the development of anticancer drugs under in vitro conditions.« less

Genome characterization of the selected long- and short-sleep mouse lines.

PubMed

Dowell, Robin; Odell, Aaron; Richmond, Phillip; Malmer, Daniel; Halper-Stromberg, Eitan; Bennett, Beth; Larson, Colin; Leach, Sonia; Radcliffe, Richard A

2016-12-01

The Inbred Long- and Short-Sleep (ILS, ISS) mouse lines were selected for differences in acute ethanol sensitivity using the loss of righting response (LORR) as the selection trait. The lines show an over tenfold difference in LORR and, along with a recombinant inbred panel derived from them (the LXS), have been widely used to dissect the genetic underpinnings of acute ethanol sensitivity. Here we have sequenced the genomes of the ILS and ISS to investigate the DNA variants that contribute to their sensitivity difference. We identified ~2.7 million high-confidence SNPs and small indels and ~7000 structural variants between the lines; variants were found to occur in 6382 annotated genes. Using a hidden Markov model, we were able to reconstruct the genome-wide ancestry patterns of the eight inbred progenitor strains from which the ILS and ISS were derived, and found that quantitative trait loci that have been mapped for LORR were slightly enriched for DNA variants. Finally, by mapping and quantifying RNA-seq reads from the ILS and ISS to their strain-specific genomes rather than to the reference genome, we found a substantial improvement in a differential expression analysis between the lines. This work will help in identifying and characterizing the DNA sequence variants that contribute to the difference in ethanol sensitivity between the ILS and ISS and will also aid in accurate quantification of RNA-seq data generated from the LXS RIs.

Neutral line chaos and phase space structure

NASA Technical Reports Server (NTRS)

Burkhart, Grant R.; Speiser, Theodore W.; Martin, Richard F., Jr.; Dusenbery, Paul B.

1991-01-01

Phase space structure and chaos near a neutral line are studied with numerical surface-of-section (SOS) techniques and analytic methods. Results are presented for a linear neutral line model with zero crosstail electric field. It was found that particle motion can be divided into three regimes dependening on the value of the conserved canonical momentum, Py, and the conserved Hamiltonian, h. The phase space structure, using Poincare SOS plots, is highly sensitive to bn = Bn/B0 variations, but not to h variations. It is verified that the slow motion preserves the action, Jz, as evaluated by Sonnerup (1971), when the period of the fast motion is smaller than the time scale of the slow motion. Results show that the phase space structure and particle chaos depend sensitively upon Py and bn, but are independent of h.

Drug/Cell-line Browser: interactive canvas visualization of cancer drug/cell-line viability assay datasets.

PubMed

Duan, Qiaonan; Wang, Zichen; Fernandez, Nicolas F; Rouillard, Andrew D; Tan, Christopher M; Benes, Cyril H; Ma'ayan, Avi

2014-11-15

Recently, several high profile studies collected cell viability data from panels of cancer cell lines treated with many drugs applied at different concentrations. Such drug sensitivity data for cancer cell lines provide suggestive treatments for different types and subtypes of cancer. Visualization of these datasets can reveal patterns that may not be obvious by examining the data without such efforts. Here we introduce Drug/Cell-line Browser (DCB), an online interactive HTML5 data visualization tool for interacting with three of the recently published datasets of cancer cell lines/drug-viability studies. DCB uses clustering and canvas visualization of the drugs and the cell lines, as well as a bar graph that summarizes drug effectiveness for the tissue of origin or the cancer subtypes for single or multiple drugs. DCB can help in understanding drug response patterns and prioritizing drug/cancer cell line interactions by tissue of origin or cancer subtype. DCB is an open source Web-based tool that is freely available at: http://www.maayanlab.net/LINCS/DCB CONTACT: avi.maayan@mssm.edu Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Detecting Weak Spectral Lines in Interferometric Data through Matched Filtering

NASA Astrophysics Data System (ADS)

Loomis, Ryan A.; Öberg, Karin I.; Andrews, Sean M.; Walsh, Catherine; Czekala, Ian; Huang, Jane; Rosenfeld, Katherine A.

2018-04-01

Modern radio interferometers enable observations of spectral lines with unprecedented spatial resolution and sensitivity. In spite of these technical advances, many lines of interest are still at best weakly detected and therefore necessitate detection and analysis techniques specialized for the low signal-to-noise ratio (S/N) regime. Matched filters can leverage knowledge of the source structure and kinematics to increase sensitivity of spectral line observations. Application of the filter in the native Fourier domain improves S/N while simultaneously avoiding the computational cost and ambiguities associated with imaging, making matched filtering a fast and robust method for weak spectral line detection. We demonstrate how an approximate matched filter can be constructed from a previously observed line or from a model of the source, and we show how this filter can be used to robustly infer a detection significance for weak spectral lines. When applied to ALMA Cycle 2 observations of CH3OH in the protoplanetary disk around TW Hya, the technique yields a ≈53% S/N boost over aperture-based spectral extraction methods, and we show that an even higher boost will be achieved for observations at higher spatial resolution. A Python-based open-source implementation of this technique is available under the MIT license at http://github.com/AstroChem/VISIBLE.

Multiple-Line Inference of Selection on Quantitative Traits

PubMed Central

Riedel, Nico; Khatri, Bhavin S.; Lässig, Michael; Berg, Johannes

2015-01-01

Trait differences between species may be attributable to natural selection. However, quantifying the strength of evidence for selection acting on a particular trait is a difficult task. Here we develop a population genetics test for selection acting on a quantitative trait that is based on multiple-line crosses. We show that using multiple lines increases both the power and the scope of selection inferences. First, a test based on three or more lines detects selection with strongly increased statistical significance, and we show explicitly how the sensitivity of the test depends on the number of lines. Second, a multiple-line test can distinguish between different lineage-specific selection scenarios. Our analytical results are complemented by extensive numerical simulations. We then apply the multiple-line test to QTL data on floral character traits in plant species of the Mimulus genus and on photoperiodic traits in different maize strains, where we find a signature of lineage-specific selection not seen in two-line tests. PMID:26139839

Plectin deficiency in liver cancer cells promotes cell migration and sensitivity to sorafenib treatment.

PubMed

Cheng, Chiung-Chi; Chao, Wei-Ting; Liao, Chen-Chun; Tseng, Yu-Hui; Lai, Yen-Chang Clark; Lai, Yih-Shyong; Hsu, Yung-Hsiang; Liu, Yi-Hsiang

2018-01-02

Plectin involved in activation of kinases in cell signaling pathway and plays important role in cell morphology and migration. Plectin knockdown promotes cell migration by activating focal adhesion kinase and Rac1-GTPase activity in liver cells. Sorafenib is a multi-targeting tyrosine kinase inhibitor that improves patient survival on hepatocellular carcinoma. The aim of this study is to investigate the correlation between the expression of plectin and cell migration as well as the sensitivity of hepatoma cell lines exposing to sorafenib. Hepatoma cell lines PLC/PRF/5 and HepG2 were used to examine the level of plectin expression and cell migration in comparison with Chang liver cell line. In addition, sensitivity of the 3 cell lines to sorafenib treatment was also measured. Expression of plectin was lower in PLC/PRF/5 and HepG2 hepatoma cells than that of Chang liver cells whereas HepG2 and PLC/PRF/5 cells exhibit higher rate of cell migration in trans-well migration assay. Immunohistofluorecent staining on E-cadherin revealed the highest rate of collective cell migration in HepG2 cells and the lowest was found in Chang liver cells. Likewise, HepG2 cell line was most sensitive to sorafenib treatment and Chang liver cells exhibited the least sensitivity. The drug sensitivity to sorafenib treatment showed inverse correlation with the expression of plectin. We suggest that plectin deficiency and increased E-cadherin in hepatoma cells were associated with higher rates of cell motility, collective cell migration as well as higher drug sensitivity to sorafenib treatment.

Nitric oxide sensitizes prostate carcinoma cell lines to TRAIL-mediated apoptosis via inactivation of NF-kappa B and inhibition of Bcl-xl expression.

PubMed

Huerta-Yepez, Sara; Vega, Mario; Jazirehi, Ali; Garban, Hermes; Hongo, Fumiya; Cheng, Genhong; Bonavida, Benjamin

2004-06-24

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to be selective in the induction of apoptosis in cancer cells with minimal toxicity to normal tissues and this prompted its potential therapeutic application in cancer. However, not all cancers are sensitive to TRAIL-mediated apoptosis and, therefore, TRAIL-resistant cancer cells must be sensitized first to become sensitive to TRAIL. Treatment of prostate cancer (CaP) cell lines (DU145, PC-3, CL-1, and LNCaP) with nitric oxide donors (e.g. (Z)-1-[2-(2-aminoethyl)-N-(2-ammonio-ethyl)amino]diazen-1-ium-1, 2-diolate (DETANONOate)) sensitized CaP cells to TRAIL-induced apoptosis and synergy was achieved. The mechanism by which DETANONOate mediated the sensitization was examined. DETANONOate inhibited the constitutive NF-kappa B activity as assessed by EMSA. Also, p50 was S-nitrosylated by DETANONOate resulting in inhibition of NF-kappa B. Inhibition of NF-kappa B activity by the chemical inhibitor Bay 11-7085, like DETANONOate, sensitized CaP to TRAIL apoptosis. In addition, DETANONOate downregulated the expression of Bcl-2 related gene (Bcl-(xL)) which is under the transcriptional regulation of NF-kappa B. The regulation of NF-kappa B and Bcl-(xL) by DETANONOate was corroborated by the use of Bcl-(xL) and Bcl-x kappa B reporter systems. DETANONOate inhibited luciferase activity in the wild type and had no effect on the mutant cells. Inhibition of NF-kappa B resulted in downregulation of Bcl-(xL) expression and sensitized CaP to TRAIL-induced apoptosis. The role of Bcl-(xL) in the regulation of TRAIL apoptosis was corroborated by inhibiting Bcl-(xL) function by the chemical inhibitor 2-methoxyantimycin A(3) and this resulted in sensitization of the cells to TRAIL apoptosis. Signaling by DETANONOate and TRAIL for apoptosis was examined. DETANONOate altered the mitochondria by inducing membrane depolarization and releasing modest amounts of cytochrome c and Smac/DIABLO in the absence of

Line Narrowing Parameter Measurement by Modulation Spectroscopy

NASA Technical Reports Server (NTRS)

Dharamsi, Amin N.

1998-01-01

Accurate Characterization of Oxygen A-Band Line Parameters by Wavelength Modulation Spectroscopy with tunable diode lasers is an ongoing research at Old Dominion University, under sponsorship from NASA Langley research Center. The work proposed here will be undertaken under the guidance of Dr. William Chu and Dr. Lamont Poole of the Aerosol Research Branch at NASA Langley-Research Center in Hampton, Virginia. The research was started about two years ago and utilizes wavelength modulation absorption spectroscopy with higher harmonic detection, a technique that we developed at Old Dominion University, to obtain the absorption line characteristics of the Oxygen A-band rovibronic lines. Accurate characterization of this absorption band is needed for processing of data that will be obtained in experiments such as the NASA Stratospheric Aerosol and Gas Experiment III (SAGE III) as part of the US Mission to Planet Earth. The research work for Summer Fellowship undertook a measurement of the Dicke line-narrowing parameters of the Oxygen A-Band lines by using wavelength modulation spectroscopy. Our previous theoretical results had indicated that such a measurement could be done sensitively and in a convenient fashion by using this type of spectroscopy. In particular, theoretical results had indicated that the signal magnitude would depend on pressure in a manner that was very sensitive to the narrowing parameter. One of the major tasks undertaken during the summer of 1998 was to establish experimentally that these theoretical predictions were correct. This was done successfully and the results of the work are being prepared for publication. Experimental Results were obtained in which the magnitude of the signal was measured as a function of pressure, for various harmonic detection orders (N = 1, 2, 3, 4, 5). A comparison with theoretical results was made, and it was shown that the agreement between theory and experiment was very good. More importantly, however, it was shown

Comprehensive analysis of line-edge and line-width roughness for EUV lithography

NASA Astrophysics Data System (ADS)

Bonam, Ravi; Liu, Chi-Chun; Breton, Mary; Sieg, Stuart; Seshadri, Indira; Saulnier, Nicole; Shearer, Jeffrey; Muthinti, Raja; Patlolla, Raghuveer; Huang, Huai

2017-03-01

Pattern transfer fidelity is always a major challenge for any lithography process and needs continuous improvement. Lithographic processes in semiconductor industry are primarily driven by optical imaging on photosensitive polymeric material (resists). Quality of pattern transfer can be assessed by quantifying multiple parameters such as, feature size uniformity (CD), placement, roughness, sidewall angles etc. Roughness in features primarily corresponds to variation of line edge or line width and has gained considerable significance, particularly due to shrinking feature sizes and variations of features in the same order. This has caused downstream processes (Etch (RIE), Chemical Mechanical Polish (CMP) etc.) to reconsider respective tolerance levels. A very important aspect of this work is relevance of roughness metrology from pattern formation at resist to subsequent processes, particularly electrical validity. A major drawback of current LER/LWR metric (sigma) is its lack of relevance across multiple downstream processes which effects material selection at various unit processes. In this work we present a comprehensive assessment of Line Edge and Line Width Roughness at multiple lithographic transfer processes. To simulate effect of roughness a pattern was designed with periodic jogs on the edges of lines with varying amplitudes and frequencies. There are numerous methodologies proposed to analyze roughness and in this work we apply them to programmed roughness structures to assess each technique's sensitivity. This work also aims to identify a relevant methodology to quantify roughness with relevance across downstream processes.

A simple and highly sensitive on-line column extraction liquid chromatography-tandem mass spectrometry method for the determination of protein-unbound tacrolimus in human plasma samples.

PubMed

Bittersohl, Heike; Schniedewind, Björn; Christians, Uwe; Luppa, Peter B

2018-04-27

Therapeutic drug monitoring (TDM) of the immunosuppressive drug tacrolimus is essential to avoid side effects and rejection of the allograft after transplantation. In the blood circulation, tacrolimus is largely located inside erythrocytes or bound to plasma proteins and less than 0.1% is protein-unbound (free). One basic principle of clinical pharmacology is that only free drug is pharmacologically active and monitoring this portion has the potential to better reflect the drug effect than conventional measurements of total tacrolimus in whole blood. To address this, a highly sensitive and straightforward on-line liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed, validated and applied to patient plasma samples. The sample preparation included ultracentrifugation and addition of the stable isotope labeled drug analogue D2,13C-tacrolimus, followed by on-line sample extraction and measurement using a Sciex QTRAP ® 6500 in the multiple reaction monitoring mode. Due to very low concentrations of protein-unbound tacrolimus, it was important to develop a highly sensitive, precise and accurate assay. Here, we first report the efficient formation of tacrolimus lithium adduct ions, which greatly increased assay sensitivity. A lower limit of quantification (LLOQ) of 1 pg/mL (10 fg on column) was achieved and the assay was linear between 1 and 200 pg/mL. There was no carry-over detected. The inaccuracy ranged from -9.8 to 7.4% and the greatest imprecision was 7.5%. The matrix factor was found to be smaller than 1.1%. In summary, this method represents a suitable tool to investigate the potential clinical value of free tacrolimus monitoring in organ transplant recipients. Copyright © 2018 Elsevier B.V. All rights reserved.

Direct search for dark matter with DarkSide

DOE PAGES

Agnes, P.

2015-11-16

Here, the DarkSide experiment is designed for the direct detection of Dark Matter with a double phase liquid Argon TPC operating underground at Laboratori Nazionali del Gran Sasso. The TPC is placed inside a 30 tons liquid organic scintillator sphere, acting as a neutron veto, which is in turn installed inside a 1 kt water Cherenkov detector. The current detector is running since November 2013 with a 50 kg atmospheric Argon fill and we report here the first null results of a Dark Matter search for a (1422 ± 67) kg.d exposure. This result correspond to a 90% CL uppermore » limit on the WIMP-nucleon cross section of 6.1 × 10 -44 cm 2 (for a WIMP mass of 100 GeV/c 2) and it's currently the most sensitive limit obtained with an Argon target.« less

Development of an artificial neural network model for risk assessment of skin sensitization using human cell line activation test, direct peptide reactivity assay, KeratinoSens™ and in silico structure alert parameter.

PubMed

Hirota, Morihiko; Ashikaga, Takao; Kouzuki, Hirokazu

2018-04-01

It is important to predict the potential of cosmetic ingredients to cause skin sensitization, and in accordance with the European Union cosmetic directive for the replacement of animal tests, several in vitro tests based on the adverse outcome pathway have been developed for hazard identification, such as the direct peptide reactivity assay, KeratinoSens™ and the human cell line activation test. Here, we describe the development of an artificial neural network (ANN) prediction model for skin sensitization risk assessment based on the integrated testing strategy concept, using direct peptide reactivity assay, KeratinoSens™, human cell line activation test and an in silico or structure alert parameter. We first investigated the relationship between published murine local lymph node assay EC3 values, which represent skin sensitization potency, and in vitro test results using a panel of about 134 chemicals for which all the required data were available. Predictions based on ANN analysis using combinations of parameters from all three in vitro tests showed a good correlation with local lymph node assay EC3 values. However, when the ANN model was applied to a testing set of 28 chemicals that had not been included in the training set, predicted EC3s were overestimated for some chemicals. Incorporation of an additional in silico or structure alert descriptor (obtained with TIMES-M or Toxtree software) in the ANN model improved the results. Our findings suggest that the ANN model based on the integrated testing strategy concept could be useful for evaluating the skin sensitization potential. Copyright © 2017 John Wiley & Sons, Ltd.

Theoretical study on sensitivity enhancement in energy-deficit region of chemically amplified resists used for extreme ultraviolet lithography

NASA Astrophysics Data System (ADS)

Kozawa, Takahiro; Santillan, Julius Joseph; Itani, Toshiro

2017-10-01

The role of photons in lithography is to transfer the energy and information required for resist pattern formation. In the information-deficit region, a trade-off relationship is observed between line edge roughness (LER) and sensitivity. However, the sensitivity can be increased without increasing LER in the energy-deficit region. In this study, the sensitivity enhancement limit was investigated, assuming line-and-space patterns with a half-pitch of 11 nm. LER was calculated by a Monte Carlo method. It was unrealistic to increase the sensitivity twofold while keeping the line width roughness (LWR) within 10% critical dimension (CD), whereas the twofold sensitivity enhancement with 20% CD LWR was feasible. The requirements are roughly that the sensitization distance should be less than 2 nm and that the total sensitizer concentration should be higher than 0.3 nm-3.

De-optical-line-terminal hybrid access-aggregation optical network for time-sensitive services based on software-defined networking orchestration

NASA Astrophysics Data System (ADS)

Bai, Wei; Yang, Hui; Xiao, Hongyun; Yu, Ao; He, Linkuan; Zhang, Jie; Li, Zhen; Du, Yi

2017-11-01

With the increase in varieties of services in network, time-sensitive services (TSSs) appear and bring forward an impending need for delay performance. Ultralow-latency communication has become one of the important development goals for many scenarios in the coming 5G era (e.g., robotics and driverless cars). However, the conventional methods, which decrease delay by promoting the available resources and the network transmission speed, have limited effect; a new breakthrough for ultralow-latency communication is necessary. We propose a de-optical-line-terminal (De-OLT) hybrid access-aggregation optical network (DAON) for TSS based on software-defined networking (SDN) orchestration. In this network, low-latency all-optical communication based on optical burst switching can be achieved by removing OLT. For supporting this network and guaranteeing the quality of service for TSSs, we design SDN-driven control method and service provision method. Numerical results demonstrate the proposed DAON promotes network service efficiency and avoids traffic congestion.

Absolute sensitivity calibration of an extreme ultraviolet spectrometer for tokamak measurements

NASA Astrophysics Data System (ADS)

Guirlet, R.; Schwob, J. L.; Meyer, O.; Vartanian, S.

2017-01-01

An extreme ultraviolet spectrometer installed on the Tore Supra tokamak has been calibrated in absolute units of brightness in the range 10-340 Å. This has been performed by means of a combination of techniques. The range 10-113 Å was absolutely calibrated by using an ultrasoft-X ray source emitting six spectral lines in this range. The calibration transfer to the range 113-182 Å was performed using the spectral line intensity branching ratio method. The range 182-340 Å was calibrated thanks to radiative-collisional modelling of spectral line intensity ratios. The maximum sensitivity of the spectrometer was found to lie around 100 Å. Around this wavelength, the sensitivity is fairly flat in a 80 Å wide interval. The spatial variations of sensitivity along the detector assembly were also measured. The observed trend is related to the quantum efficiency decrease as the angle of the incoming photon trajectories becomes more grazing.

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

PubMed

Hindmarsh, Richard C A

2006-07-15

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

High sensitive FBG load cell for icing of overhead transmission lines

NASA Astrophysics Data System (ADS)

Mao, Naiqiang; Ma, Guoming; Li, Chengrong; Li, Yabo; Shi, Cheng; Du, Yue

2017-04-01

Heavy ice coating of overhead transmission lines created the serious threat on the safe operation of power grid. The measurement of conductor icing had been an effective and reliable methods to prevent potential risks, such as conductor breakage, insulator flashover and tower collapse. Because of the advantages of immunity to electromagnetic interference and no demand for power supply in site, the optical load cell has been widely applied in monitoring the ice coating of overhead transmission lines. In this paper, we have adopted the shearing structure with additional grooves as elastic element of load cell to detect the eccentric load. Then, two welding package fiber Bragg gratings (FBGs) were mounted onto the grooves of elastic element with a direction deviation of 90° to eliminate temperature effects on strain measurement without extra FBG. After that, to avoid the occurrence of load cell breakage in heavy load measurement, the protection part has been proposed and added to the elastic element. The results of tension experiments indicate that the resolution of the load cell is 7.78 N in the conventional measuring range (0-10 kN). And in addition, the load cell proposed in this paper also has a good performance in actual experiment in which the load and temperature change simultaneously.

Can tonne-scale direct detection experiments discover nuclear dark matter?

NASA Astrophysics Data System (ADS)

Butcher, Alistair; Kirk, Russell; Monroe, Jocelyn; West, Stephen M.

2017-10-01

Models of nuclear dark matter propose that the dark sector contains large composite states consisting of dark nucleons in analogy to Standard Model nuclei. We examine the direct detection phenomenology of a particular class of nuclear dark matter model at the current generation of tonne-scale liquid noble experiments, in particular DEAP-3600 and XENON1T. In our chosen nuclear dark matter scenario distinctive features arise in the recoil energy spectra due to the non-point-like nature of the composite dark matter state. We calculate the number of events required to distinguish these spectra from those of a standard point-like WIMP state with a decaying exponential recoil spectrum. In the most favourable regions of nuclear dark matter parameter space, we find that a few tens of events are needed to distinguish nuclear dark matter from WIMPs at the 3 σ level in a single experiment. Given the total exposure time of DEAP-3600 and XENON1T we find that at best a 2 σ distinction is possible by these experiments individually, while 3 σ sensitivity is reached for a range of parameters by the combination of the two experiments. We show that future upgrades of these experiments have potential to distinguish a large range of nuclear dark matter models from that of a WIMP at greater than 3 σ.

Can tonne-scale direct detection experiments discover nuclear dark matter?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Butcher, Alistair; Kirk, Russell; Monroe, Jocelyn

Models of nuclear dark matter propose that the dark sector contains large composite states consisting of dark nucleons in analogy to Standard Model nuclei. We examine the direct detection phenomenology of a particular class of nuclear dark matter model at the current generation of tonne-scale liquid noble experiments, in particular DEAP-3600 and XENON1T. In our chosen nuclear dark matter scenario distinctive features arise in the recoil energy spectra due to the non-point-like nature of the composite dark matter state. We calculate the number of events required to distinguish these spectra from those of a standard point-like WIMP state with amore » decaying exponential recoil spectrum. In the most favourable regions of nuclear dark matter parameter space, we find that a few tens of events are needed to distinguish nuclear dark matter from WIMPs at the 3 σ level in a single experiment. Given the total exposure time of DEAP-3600 and XENON1T we find that at best a 2 σ distinction is possible by these experiments individually, while 3 σ sensitivity is reached for a range of parameters by the combination of the two experiments. We show that future upgrades of these experiments have potential to distinguish a large range of nuclear dark matter models from that of a WIMP at greater than 3 σ .« less

DarkSide-20k: A 20 tonne two-phase LAr TPC for direct dark matter detection at LNGS

NASA Astrophysics Data System (ADS)

Aalseth, C. E.; Acerbi, F.; Agnes, P.; Albuquerque, I. F. M.; Alexander, T.; Alici, A.; Alton, A. K.; Antonioli, P.; Arcelli, S.; Ardito, R.; Arnquist, I. J.; Asner, D. M.; Ave, M.; Back, H. O.; Barrado Olmedo, A. I.; Batignani, G.; Bertoldo, E.; Bettarini, S.; Bisogni, M. G.; Bocci, V.; Bondar, A.; Bonfini, G.; Bonivento, W.; Bossa, M.; Bottino, B.; Boulay, M.; Bunker, R.; Bussino, S.; Buzulutskov, A.; Cadeddu, M.; Cadoni, M.; Caminata, A.; Canci, N.; Candela, A.; Cantini, C.; Caravati, M.; Cariello, M.; Carlini, M.; Carpinelli, M.; Castellani, A.; Catalanotti, S.; Cataudella, V.; Cavalcante, P.; Cavuoti, S.; Cereseto, R.; Chepurnov, A.; Cicalò, C.; Cifarelli, L.; Citterio, M.; Cocco, A. G.; Colocci, M.; Corgiolu, S.; Covone, G.; Crivelli, P.; D'Antone, I.; D'Incecco, M.; D'Urso, D.; Da Rocha Rolo, M. D.; Daniel, M.; Davini, S.; de Candia, A.; De Cecco, S.; De Deo, M.; De Filippis, G.; De Guido, G.; De Rosa, G.; Dellacasa, G.; Della Valle, M.; Demontis, P.; Derbin, A.; Devoto, A.; Di Eusanio, F.; Di Pietro, G.; Dionisi, C.; Dolgov, A.; Dormia, I.; Dussoni, S.; Empl, A.; Fernandez Diaz, M.; Ferri, A.; Filip, C.; Fiorillo, G.; Fomenko, K.; Franco, D.; Froudakis, G. E.; Gabriele, F.; Gabrieli, A.; Galbiati, C.; Garcia Abia, P.; Gendotti, A.; Ghisi, A.; Giagu, S.; Giampa, P.; Gibertoni, G.; Giganti, C.; Giorgi, M. A.; Giovanetti, G. K.; Gligan, M. L.; Gola, A.; Gorchakov, O.; Goretti, A. M.; Granato, F.; Grassi, M.; Grate, J. W.; Grigoriev, G. Y.; Gromov, M.; Guan, M.; Guerra, M. B. B.; Guerzoni, M.; Gulino, M.; Haaland, R. K.; Hallin, A.; Harrop, B.; Hoppe, E. W.; Horikawa, S.; Hosseini, B.; Hughes, D.; Humble, P.; Hungerford, E. V.; Ianni, An.; Jillings, C.; Johnson, T. N.; Keeter, K.; Kendziora, C. L.; Kim, S.; Koh, G.; Korablev, D.; Korga, G.; Kubankin, A.; Kuss, M.; Kuźniak, M.; La Commara, M.; Lehnert, B.; Li, X.; Lissia, M.; Lodi, G. U.; Loer, B.; Longo, G.; Loverre, P.; Lussana, R.; Luzzi, L.; Ma, Y.; Machado, A. A.; Machulin, I. N.; Mandarano, A.; Mapelli, L.; Marcante, M.; Margotti, A.; Mari, S. M.; Mariani, M.; Maricic, J.; Martoff, C. J.; Mascia, M.; Mayer, M.; McDonald, A. B.; Messina, A.; Meyers, P. D.; Milincic, R.; Moggi, A.; Moioli, S.; Monroe, J.; Monte, A.; Morrocchi, M.; Mount, B. J.; Mu, W.; Muratova, V. N.; Murphy, S.; Musico, P.; Nania, R.; Navrer Agasson, A.; Nikulin, I.; Nosov, V.; Nozdrina, A. O.; Nurakhov, N. N.; Oleinik, A.; Oleynikov, V.; Orsini, M.; Ortica, F.; Pagani, L.; Pallavicini, M.; Palmas, S.; Pandola, L.; Pantic, E.; Paoloni, E.; Paternoster, G.; Pavletcov, V.; Pazzona, F.; Peeters, S.; Pelczar, K.; Pellegrini, L. A.; Pelliccia, N.; Perotti, F.; Perruzza, R.; Pesudo, V.; Piemonte, C.; Pilo, F.; Pocar, A.; Pollmann, T.; Portaluppi, D.; Pugachev, D. A.; Qian, H.; Radics, B.; Raffaelli, F.; Ragusa, F.; Razeti, M.; Razeto, A.; Regazzoni, V.; Regenfus, C.; Reinhold, B.; Renshaw, A. L.; Rescigno, M.; Retière, F.; Riffard, Q.; Rivetti, A.; Rizzardini, S.; Romani, A.; Romero, L.; Rossi, B.; Rossi, N.; Rubbia, A.; Sablone, D.; Salatino, P.; Samoylov, O.; Sánchez García, E.; Sands, W.; Sanfilippo, S.; Sant, M.; Santorelli, R.; Savarese, C.; Scapparone, E.; Schlitzer, B.; Scioli, G.; Segreto, E.; Seifert, A.; Semenov, D. A.; Shchagin, A.; Shekhtman, L.; Shemyakina, E.; Sheshukov, A.; Simeone, M.; Singh, P. N.; Skensved, P.; Skorokhvatov, M. D.; Smirnov, O.; Sobrero, G.; Sokolov, A.; Sotnikov, A.; Speziale, F.; Stainforth, R.; Stanford, C.; Suffritti, G. B.; Suvorov, Y.; Tartaglia, R.; Testera, G.; Tonazzo, A.; Tosi, A.; Trinchese, P.; Unzhakov, E. V.; Vacca, A.; Vázquez-Jáuregui, E.; Verducci, M.; Viant, T.; Villa, F.; Vishneva, A.; Vogelaar, B.; Wada, M.; Wahl, J.; Walding, J.; Wang, H.; Wang, Y.; Watson, A. W.; Westerdale, S.; Williams, R.; Wojcik, M. M.; Wu, S.; Xiang, X.; Xiao, X.; Yang, C.; Ye, Z.; Yllera de Llano, A.; Zappa, F.; Zappalà, G.; Zhu, C.; Zichichi, A.; Zullo, M.; Zullo, A.; Zuzel, G.

2018-03-01

Building on the successful experience in operating the DarkSide-50 detector, the DarkSide Collaboration is going to construct DarkSide-20k, a direct WIMP search detector using a two-phase Liquid Argon Time Projection Chamber (LAr TPC) with an active (fiducial) mass of 23 t (20 t). This paper describes a preliminary design for the experiment, in which the DarkSide-20k LAr TPC is deployed within a shield/veto with a spherical Liquid Scintillator Veto (LSV) inside a cylindrical Water Cherenkov Veto (WCV). This preliminary design provides a baseline for the experiment to achieve its physics goals, while further development work will lead to the final optimization of the detector parameters and an eventual technical design. Operation of DarkSide-50 demonstrated a major reduction in the dominant 39Ar background when using argon extracted from an underground source, before applying pulse shape analysis. Data from DarkSide-50, in combination with MC simulation and analytical modeling, shows that a rejection factor for discrimination between electron and nuclear recoils of >3 × 109 is achievable. This, along with the use of the veto system and utilizing silicon photomultipliers in the LAr TPC, are the keys to unlocking the path to large LAr TPC detector masses, while maintaining an experiment in which less than < 0.1 events (other than ν-induced nuclear recoils) is expected to occur within the WIMP search region during the planned exposure. DarkSide-20k will have ultra-low backgrounds than can be measured in situ, giving sensitivity to WIMP-nucleon cross sections of 1.2 × 10^{-47} cm2 (1.1 × 10^{-46} cm2) for WIMPs of 1 TeV/c 2 (10 TeV/c 2) mass, to be achieved during a 5 yr run producing an exposure of 100 t yr free from any instrumental background.

Isolation of Temperature-Sensitive Mutants of Arabidopsis thaliana That Are Defective in the Redifferentiation of Shoots.

PubMed Central

Yasutani, I.; Ozawa, S.; Nishida, T.; Sugiyama, M.; Komamine, A.

1994-01-01

Three temperature-sensitive mutants of Arabidopsis thaliana that were defective in the redifferentiation of shoots were isolated as tools for the study of organogenesis. M3 lines were constructed by harvesting M3 seeds separately from each M2 plant. Comparative examination of shoot redifferentiation in root explants of 2700 M3 lines at 22[deg]C (permissive temperature) and at 27[deg]C (restrictive temperature) led to the identification of seven temperature-sensitive mutant lines. Genetic tests of three of the seven mutant lines indicated that temperature-sensitive redifferentiation of shoots in these three lines resulted from single, nuclear, recessive mutations in three different genes, designated SRD1, SRD2, and SRD3. The morphology of root explants of srd mutants cultured at the restrictive temperature suggests that the products of these SRD genes function at different stages of the redifferentiation of shoots. PMID:12232244

[Establishment and characterization of a cell line derived from human ovarian mucinous cystadenocarcinoma].

PubMed

Wan, Q; Xu, D; Li, Z

2001-07-01

To establish a cell line of human ovarian cancer, and study its characterization. The cell line was established by the cultivation of subsides walls, and kept by freezing. The morphology was observed by microscope and electromicroscope. The authors studied its growth and propagation, the agglutination test of phytohemagglutinin (PHA), the chromosome analysis, heterotransplanting, immuno-histochemistry staining, the analysis of hormone, the pollution examination and the test of sensitivity to virus etc. A new human ovarian carcinoma cell line, designated ovarian mucinous cystadenocarcinoma 685 (OMC685), was established from mucinous cystadenocarcinoma. This cell line had subcultured to 91 generations, and some had been frozen for 8 years and revived, still grew well. This cell line possessed the feature of glandular epithelium cancer cell. The cells grew exuberantly, and the agglutinating test of PHA was positive. Karyotype was subtriploid with distortion. Heterotransplantations, alcian blue periobic acid-schiff (AbPAS), mucicarmine, alcian blue stainings, estradiol (E2) and progesterone were all positive. Without being polluted, it was sensitive to polivirus-I, adenovirus 7 and measles virus. OMC685 is a distinct human ovarian tumous cell line.

Calcium influences sensitivity to growth inhibition induced by a cell surface sialoglycopeptide

NASA Technical Reports Server (NTRS)

Betz, N. A.; Fattaey, H. K.; Johnson, T. C.; Spooner, B. S. (Principal Investigator)

1994-01-01

While studies concerning mitogenic factors have been an important area of research for many years, much less is understood about the mechanisms of action of cell surface growth inhibitors. We have purified an 18 kDa cell surface sialoglycopeptide growth inhibitor (CeReS-18) which can reversibly inhibit the proliferation of diverse cell types. The studies discussed in this article show that three mouse keratinocyte cell lines exhibit sixty-fold greater sensitivity than other fibroblasts and epithelial-like cells to CeReS-18-induced growth inhibition. Growth inhibition induced by CeReS-18 treatment is a reversible process, and the three mouse keratinocyte cell lines exhibited either single or multiple cell cycle arrest points, although a predominantly G0/G1 cell cycle arrest point was exhibited in Swiss 3T3 fibroblasts. The sensitivity of the mouse keratinocyte cell lines to CeReS-18-induced growth inhibition was not affected by the degree of tumorigenic progression in the cell lines and was not due to differences in CeReS-18 binding affinity or number of cell surface receptors per cell. However, the sensitivity of both murine fibroblasts and keratinocytes could be altered by changing the extracellular calcium concentration, such that increased extracellular calcium concentrations resulted in decreased sensitivity to CeReS-18-induced proliferation inhibition. Thus the increased sensitivity of the murine keratinocyte cell lines to CeReS-18 could be ascribed to the low calcium concentration used in their propagation. Studies are currently under way investigating the role of calcium in CeReS-18-induced growth arrest. The CeReS-18 may serve as a very useful tool to study negative growth control and the signal transduction events associated with cell cycling.

Shrinking of Binaries in a WIMPY Background at the Galactic Center

NASA Astrophysics Data System (ADS)

Hills, J. G.

2001-12-01

The nature of the dark matter in the Galactic Halo is still not clear. Constraints can be placed on it; e.g., it cannot be in baryons less massive than about 1022 grams (Hills, 1986, Astron. J. 92, 595). It may be in elementary weakly interacting massive particles, WIMPS. Apart from providing most of the mass of the Galaxy, the only known significant dynamical effect of WIMPS is to cause a gradual shrinking of tightly bound binaries (Hills 1983, Astron. J. 88, 1269) as they interact with the background soup of WIMPS. This effect may be observable in binaries close to the Galactic Center if a significant fraction of the mass density near the central black hole is from WIMPS. The requisite binaries would have to have orbital velocities greater than the local velocity dispersion of the WIMPS relative to the binary. The velocity dispersion increases near the black hole. The binary cannot be too close to the black hole or its tidal field will breakup the binary. If the local WIMP density is 107 g/cm3, the fractional rate of reduction in the binary orbital period is about 5 x 10-10/yr for a binary having a semimajor axis equal to 3 solar radii in a soup of WIMPS having a velocity dispersion of 200 km/s relative to the binary. This gradual erosion of the binary period may be detectable, particularly, if one of the binary components is a pulsar.

High-intensity xenon plasma discharge lamp for bulk-sensitive high-resolution photoemission spectroscopy.

PubMed

Souma, S; Sato, T; Takahashi, T; Baltzer, P

2007-12-01

We have developed a highly brilliant xenon (Xe) discharge lamp operated by microwave-induced electron cyclotron resonance (ECR) for ultrahigh-resolution bulk-sensitive photoemission spectroscopy (PES). We observed at least eight strong radiation lines from neutral or singly ionized Xe atoms in the energy region of 8.4-10.7 eV. The photon flux of the strongest Xe I resonance line at 8.437 eV is comparable to that of the He Ialpha line (21.218 eV) from the He-ECR discharge lamp. Stable operation for more than 300 h is achieved by efficient air-cooling of a ceramic tube in the resonance cavity. The high bulk sensitivity and high-energy resolution of PES using the Xe lines are demonstrated for some typical materials.

ON SPECTROPOLARIMETRIC MEASUREMENTS WITH VISIBLE LINES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Del Toro Iniesta, J. C.; Bellot Rubio, L. R.; Orozco Suarez, D., E-mail: jti@iaa.e, E-mail: lbellot@iaa.e, E-mail: d.orozco@nao.ac.j

The ability of new instruments for providing accurate inferences of vector magnetic fields and line-of-sight velocities of the solar plasma depends a great deal on the sensitivity to these physical quantities of the spectral lines chosen to be measured. Recently, doubts have been raised about visible Stokes profiles to provide a clear distinction between weak fields and strong ones filling a small fraction of the observed area. The goal of this paper is to give qualitative and quantitative arguments that help in settling the debate since several instruments that employ visible lines are either operating or planned for the nearmore » future. The sensitivity of the Stokes profiles is calculated through the response functions (RFs), for e.g., by Ruiz Cobo and Del Toro Iniesta. Both theoretical and empirical evidences are gathered in favor of the reliability of visible Stokes profiles. The RFs are also used for estimating the uncertainties in the physical quantities due to noise in observations. A useful formula has been derived that takes into account the measurement technique (number of polarization measurements, polarimetric efficiencies, and number of wavelength samples), the model assumptions (number of free parameters and the filling factor), and the radiative transfer (RFs). We conclude that a scenario with a weak magnetic field can reasonably be distinguished with visible lines from another with a strong field but a similar Stokes V amplitude, provided that the Milne-Eddington approximation is good enough to describe the solar atmosphere and the polarization signal is at least 3 or 4 times larger than the typical rms noise of 10{sup -3} I{sub c} reached in the observations.« less

ATM inhibitor KU-55933 increases the TMZ responsiveness of only inherently TMZ sensitive GBM cells.

PubMed

Nadkarni, Aditi; Shrivastav, Meena; Mladek, Ann C; Schwingler, Paul M; Grogan, Patrick T; Chen, Junjie; Sarkaria, Jann N

2012-12-01

Ataxia telangiectasia mutated (ATM) kinase is critical in sensing and repairing DNA double-stranded breaks (DSBs) such as those induced by temozolomide (TMZ). ATM deficiency increases TMZ sensitivity, which suggests that ATM inhibitors may be effective TMZ sensitizing agents. In this study, the TMZ sensitizing effects of 2 ATM specific inhibitors were studied in established and xenograft-derived glioblastoma (GBM) lines that are inherently sensitive to TMZ and derivative TMZ-resistant lines. In parental U251 and U87 glioma lines, the addition of KU-55933 to TMZ significantly increased cell killing compared to TMZ alone [U251 survival: 0.004 ± 0.0015 vs. 0.08 ± 0.01 (p < 0.001), respectively, and U87 survival: 0.02 ± 0.005 vs. 0.04 ± 0.002 (p < 0.001), respectively] and also elevated the fraction of cells arrested in G2/M [U251 G2/M fraction: 61.8 ± 1.1 % vs. 35 ± 0.8 % (p < 0.001), respectively, and U87 G2/M fraction 25 ± 0.2 % vs.18.6 ± 0.4 % (p < 0.001), respectively]. In contrast, KU-55933 did not sensitize the resistant lines to TMZ, and neither TMZ alone or combined with KU-55933 induced a G2/M arrest. While KU-55933 did not enhance TMZ induced Chk1/Chk2 activation, it increased TMZ-induced residual γ-H2AX foci in the parental cells but not in the TMZ resistant cells. Similar sensitization was observed with either KU-55933 or CP-466722 combined with TMZ in GBM12 xenograft line but not in GBM12TMZ, which is resistant to TMZ due to MGMT overexpression. These findings are consistent with a model where ATM inhibition suppresses the repair of TMZ-induced DSBs in inherently TMZ-sensitive tumor lines, which suggests an ATM inhibitor potentially could be deployed with an improvement in the therapeutic window when combined with TMZ.

First results from the Cryogenic Dark Matter Search in the Soudan Underground Laboratory.

PubMed

Akerib, D S; Alvaro-Dean, J; Armel-Funkhouser, M S; Attisha, M J; Baudis, L; Bauer, D A; Beaty, J; Brink, P L; Bunker, R; Burke, S P; Cabrera, B; Caldwell, D O; Callahan, D; Castle, J P; Chang, C L; Choate, R; Crisler, M B; Cushman, P; Dixon, R; Dragowsky, M R; Driscoll, D D; Duong, L; Emes, J; Ferril, R; Filippini, J; Gaitskell, R J; Haldeman, M; Hale, D; Holmgren, D; Huber, M E; Johnson, B; Johnson, W; Kamat, S; Kozlovsky, M; Kula, L; Kyre, S; Lambin, B; Lu, A; Mahapatra, R; Manalaysay, A G; Mandic, V; May, J; McDonald, R; Merkel, B; Meunier, P; Mirabolfathi, N; Morrison, S; Nelson, H; Nelson, R; Novak, L; Ogburn, R W; Orr, S; Perera, T A; Perillo Isaac, M C; Ramberg, E; Rau, W; Reisetter, A; Ross, R R; Saab, T; Sadoulet, B; Sander, J; Savage, C; Schmitt, R L; Schnee, R W; Seitz, D N; Serfass, B; Smith, A; Smith, G; Spadafora, A L; Sundqvist, K; Thompson, J-P F; Tomada, A; Wang, G; Williams, J; Yellin, S; Young, B A

2004-11-19

We report the first results from a search for weakly interacting massive particles (WIMPs) in the Cryogenic Dark Matter Search experiment at the Soudan Underground Laboratory. Four Ge and two Si detectors were operated for 52.6 live days, providing 19.4 kg d of Ge net exposure after cuts for recoil energies between 10 and 100 keV. A blind analysis was performed using only calibration data to define the energy threshold and selection criteria for nuclear-recoil candidates. Using the standard dark-matter halo and nuclear-physics WIMP model, these data set the world's lowest exclusion limits on the coherent WIMP-nucleon scalar cross section for all WIMP masses above 15 GeV/c2, ruling out a significant range of neutralino supersymmetric models. The minimum of this limit curve at the 90% C.L. is 4 x 10(-43) cm2 at a WIMP mass of 60 GeV/c2.

The role of line junctions in object recognition: The case of reading musical notation.

PubMed

Wong, Yetta Kwailing; Wong, Alan C-N

2018-04-30

Previous work has shown that line junctions are informative features for visual perception of objects, letters, and words. However, the sources of such sensitivity and their generalizability to other object categories are largely unclear. We addressed these questions by studying perceptual expertise in reading musical notation, a domain in which individuals with different levels of expertise are readily available. We observed that removing line junctions created by the contact between musical notes and staff lines selectively impaired recognition performance in experts and intermediate readers, but not in novices. The degree of performance impairment was predicted by individual fluency in reading musical notation. Our findings suggest that line junctions provide diagnostic information about object identity across various categories, including musical notation. However, human sensitivity to line junctions does not readily transfer from familiar to unfamiliar object categories, and has to be acquired through perceptual experience with the specific objects.

The EVE Doppler Sensitivity and Flare Observations

NASA Technical Reports Server (NTRS)

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

2011-01-01

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

Metabolic Response to NAD Depletion across Cell Lines Is Highly Variable.

PubMed

Xiao, Yang; Kwong, Mandy; Daemen, Anneleen; Belvin, Marcia; Liang, Xiaorong; Hatzivassiliou, Georgia; O'Brien, Thomas

2016-01-01

Nicotinamide adenine dinucleotide (NAD) is a cofactor involved in a wide range of cellular metabolic processes and is a key metabolite required for tumor growth. NAMPT, nicotinamide phosphoribosyltransferase, which converts nicotinamide (NAM) to nicotinamide mononucleotide (NMN), the immediate precursor of NAD, is an attractive therapeutic target as inhibition of NAMPT reduces cellular NAD levels and inhibits tumor growth in vivo. However, there is limited understanding of the metabolic response to NAD depletion across cancer cell lines and whether all cell lines respond in a uniform manner. To explore this we selected two non-small cell lung carcinoma cell lines that are sensitive to the NAMPT inhibitor GNE-617 (A549, NCI-H1334), one that shows intermediate sensitivity (NCI-H441), and one that is insensitive (LC-KJ). Even though NAD was reduced in all cell lines there was surprising heterogeneity in their metabolic response. Both sensitive cell lines reduced glycolysis and levels of di- and tri-nucleotides and modestly increased oxidative phosphorylation, but they differed in their ability to combat oxidative stress. H1334 cells activated the stress kinase AMPK, whereas A549 cells were unable to activate AMPK as they contain a mutation in LKB1, which prevents activation of AMPK. However, A549 cells increased utilization of the Pentose Phosphate pathway (PPP) and had lower reactive oxygen species (ROS) levels than H1334 cells, indicating that A549 cells are better able to modulate an increase in oxidative stress. Inherent resistance of LC-KJ cells is associated with higher baseline levels of NADPH and a delayed reduction of NAD upon NAMPT inhibition. Our data reveals that cell lines show heterogeneous response to NAD depletion and that the underlying molecular and genetic framework in cells can influence the metabolic response to NAMPT inhibition.

Effective field theory search for high-energy nuclear recoils using the XENON100 dark matter detector

NASA Astrophysics Data System (ADS)

Aprile, E.; Aalbers, J.; Agostini, F.; Alfonsi, M.; Amaro, F. D.; Anthony, M.; Arneodo, F.; Barrow, P.; Baudis, L.; Bauermeister, B.; Benabderrahmane, M. L.; Berger, T.; Breur, P. A.; Brown, A.; Brown, E.; Bruenner, S.; Bruno, G.; Budnik, R.; Bütikofer, L.; Calvén, J.; Cardoso, J. M. R.; Cervantes, M.; Cichon, D.; Coderre, D.; Colijn, A. P.; Conrad, J.; Cussonneau, J. P.; Decowski, M. P.; de Perio, P.; di Gangi, P.; di Giovanni, A.; Diglio, S.; Eurin, G.; Fei, J.; Ferella, A. D.; Fieguth, A.; Fulgione, W.; Gallo Rosso, A.; Galloway, M.; Gao, F.; Garbini, M.; Geis, C.; Goetzke, L. W.; Greene, Z.; Grignon, C.; Hasterok, C.; Hogenbirk, E.; Itay, R.; Kaminsky, B.; Kazama, S.; Kessler, G.; Kish, A.; Landsman, H.; Lang, R. F.; Lellouch, D.; Levinson, L.; Lin, Q.; Lindemann, S.; Lindner, M.; Lombardi, F.; Lopes, J. A. M.; Manfredini, A.; Maris, I.; Marrodán Undagoitia, T.; Masbou, J.; Massoli, F. V.; Masson, D.; Mayani, D.; Messina, M.; Micheneau, K.; Molinario, A.; Morâ, K.; Murra, M.; Naganoma, J.; Ni, K.; Oberlack, U.; Pakarha, P.; Pelssers, B.; Persiani, R.; Piastra, F.; Pienaar, J.; Pizzella, V.; Piro, M.-C.; Plante, G.; Priel, N.; Rauch, L.; Reichard, S.; Reuter, C.; Rizzo, A.; Rosendahl, S.; Rupp, N.; Dos Santos, J. M. F.; Sartorelli, G.; Scheibelhut, M.; Schindler, S.; Schreiner, J.; Schumann, M.; Scotto Lavina, L.; Selvi, M.; Shagin, P.; Silva, M.; Simgen, H.; Sivers, M. V.; Stein, A.; Thers, D.; Tiseni, A.; Trinchero, G.; Tunnell, C.; Vargas, M.; Wang, H.; Wang, Z.; Wei, Y.; Weinheimer, C.; Wulf, J.; Ye, J.; Zhang., Y.; Farmer, B.; Xenon Collaboration

2017-08-01

We report on weakly interacting massive particles (WIMPs) search results in the XENON100 detector using a nonrelativistic effective field theory approach. The data from science run II (34 kg ×224.6 live days) were reanalyzed, with an increased recoil energy interval compared to previous analyses, ranging from (6.6 -240 ) keVnr . The data are found to be compatible with the background-only hypothesis. We present 90% confidence level exclusion limits on the coupling constants of WIMP-nucleon effective operators using a binned profile likelihood method. We also consider the case of inelastic WIMP scattering, where incident WIMPs may up-scatter to a higher mass state, and set exclusion limits on this model as well.

Measurements of charge and light in pure high pressure Xe towards the study of Xe+TMA mixtures with dark matter directionality sensitivity and supra-intrinsic energy resolution for 0νββ decay searches

DOE PAGES

Oliveira, C. A.B.; Gehman, V.; Goldschmidt, A.; ...

2015-03-24

Trimethylamine (TMA) may improve the energy resolution of gaseous xenon based detectors for 0νββ decay searches through the reduction of the Fano factor by the Penning effect. This molecule may also be the key for sensing directionality of nuclear recoils induced by Weakly Interacting Massive Particles (WIMPs) in monolithic massive (ton-scale) detectors, without the need of track imaging, by making use of columnar recombination. Nuclear recoil directionality may be the path for a definite discovery of the WIMP nature of Dark Matter. An ionization chamber has been constructed and operated to explore the properties of high pressure gaseous Xe +more » TMA mixtures for particle detection in rare-event experiments. The ionization, scintillation and electroluminescence (EL) signals are measured as function of pressure and electric field. We present results for pure xenon at pressures up to 8 bar. This work has been carried out within the context of the NEXT collaboration.« less

Proposed low-energy absolute calibration of nuclear recoils in a dual-phase noble element TPC using D-D neutron scattering kinematics

NASA Astrophysics Data System (ADS)

Verbus, J. R.; Rhyne, C. A.; Malling, D. C.; Genecov, M.; Ghosh, S.; Moskowitz, A. G.; Chan, S.; Chapman, J. J.; de Viveiros, L.; Faham, C. H.; Fiorucci, S.; Huang, D. Q.; Pangilinan, M.; Taylor, W. C.; Gaitskell, R. J.

2017-04-01

We propose a new technique for the calibration of nuclear recoils in large noble element dual-phase time projection chambers used to search for WIMP dark matter in the local galactic halo. This technique provides an in situ measurement of the low-energy nuclear recoil response of the target media using the measured scattering angle between multiple neutron interactions within the detector volume. The low-energy reach and reduced systematics of this calibration have particular significance for the low-mass WIMP sensitivity of several leading dark matter experiments. Multiple strategies for improving this calibration technique are discussed, including the creation of a new type of quasi-monoenergetic neutron source with a minimum possible peak energy of 272 keV. We report results from a time-of-flight-based measurement of the neutron energy spectrum produced by an Adelphi Technology, Inc. DD108 neutron generator, confirming its suitability for the proposed nuclear recoil calibration.

Comprehensive Evaluation of the Contribution of X Chromosome Genes to Platinum Sensitivity

PubMed Central

Gamazon, Eric R.; Im, Hae Kyung; O’Donnell, Peter H.; Ziliak, Dana; Stark, Amy L.; Cox, Nancy J.; Dolan, M. Eileen; Huang, Rong Stephanie

2011-01-01

Utilizing a genome-wide gene expression dataset generated from Affymetrix GeneChip® Human Exon 1.0ST array, we comprehensively surveyed the role of 322 X chromosome gene expression traits on cellular sensitivity to cisplatin and carboplatin. We identified 31 and 17 X chromosome genes whose expression levels are significantly correlated (after multiple testing correction) with sensitivity to carboplatin and cisplatin, respectively, in the combined HapMap CEU and YRI populations (false discovery rate, FDR<0.05). Of those, 14 overlap for both cisplatin and carboplatin. Employing an independent gene expression quantification method, the Illumina Sentrix Human-6 Expression BeadChip, measured on the same HapMap cell lines, we found that 4 and 2 of these genes are significantly associated with carboplatin and cisplatin sensitivity respectively in both analyses. Two genes, CTPS2 and DLG3, were identified by both genome-wide gene expression analyses as correlated with cellular sensitivity to both platinating agents. The expression of DLG3 gene was also found to correlate with cellular sensitivity to platinating agents in NCI60 cancer cell lines. In addition, we evaluated the role of X chromosome gene expression to the observed differences in sensitivity to the platinums between CEU and YRI derived cell lines. Of the 34 distinct genes significantly correlated with either carboplatin or cisplatin sensitivity, 14 are differentially expressed (defined as p<0.05) between CEU and YRI. Thus, sex chromosome genes play a role in cellular sensitivity to platinating agents and differences in the expression level of these genes are an important source of variation that should be included in comprehensive pharmacogenomic studies. PMID:21252287

Glutamine drives glutathione synthesis and contributes to radiation sensitivity of A549 and H460 lung cancer cell lines

PubMed Central

Sappington, Daniel R.; Siegel, Eric R.; Hiatt, Gloria; Desai, Abhishek; Penney, Rosalind B.; Jamshidi-Parsian, Azemat; Griffin, Robert J.; Boysen, Gunnar

2016-01-01

Background Increased glutamine uptake is known to drive cancer cell proliferation, making tumor cells glutamine-dependent. Glutamine provides additional carbon and nitrogen sources for cell growth. The first step in glutamine utilization is its conversion to glutamate by glutaminase (GLS). Glutamate is a precursor for glutathione synthesis, and we investigated the hypothesis that glutamine drives glutathione synthesis and thereby contributes to cellular defense systems. Methods The importance of glutamine for glutathione synthesis was studied in H460 and A549 lung cancer cell lines using glutamine-free medium and Bis-2-(5-phenyl-acetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) a GLS inhibitor. Metabolic activities were determined by targeted mass spectrometry. Results A significant correlation between glutamine consumption and glutathione excretion was demonstrated in H460 and A549 tumor cells. Culturing in the presence of [13C5]glutamine demonstrated that by 12 hrs >50% of excreted glutathione is derived from glutamine. Culturing in glutamine-free medium or treatment with BPTES, a glutaminase (GLS)-specific inhibitor, reduced cell proliferation and viability, and abolished glutathione excretion. Treatment with glutathione-ester prevented BPTES induced cytotoxicity. Inhibition of GLS markedly radiosensitized the lung tumor cell lines, suggesting an important role of glutamine-derived glutathione in determining radiation sensitivity. Conclusions We demonstrate here for the first time that a significant amount of extracellular glutathione is directly derived from glutamine. This finding adds yet another important function to the already known glutamine dependence of tumor cells and probably tumors as well. General significance Glutamine is essential for synthesis and excretion of glutathione to promote cell growth and viability. PMID:26825773

The mutation studies of mutagen-sensitive and DNA repair mutants of Chinese hamster fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schultz, R.A.; Chang, C.C.; Trosko, J.E.

1981-01-01

We have previously reported the isolation and partial characterization of DNA repair and/or mutagen-sensitive mutant Chinese hamster cell strains. Here we present the results of a detailed study of the ultraviolet light (UV)-induced mutability of one of these strains, UVs-7, and provide preliminary mutability data on two additional lines, UVr-23 and UVs-40. UVs-7 in extremely deficient in unscheduled DNA synthesis (UDS) but only slightly more sensitive to UV than the parental line. When examined for the UV-inducibility of mutants resistant to ouabain, 6-thioguanine, or diphtheria toxin, UVs-7 was found to be hypermutable at all three loci as compared to themore » parental line. The degree of hypermutability was not the same for any two loci. UVs-40, a highly UV-sensitive strain, was also found to be hypermutable at the ouabain-resistant (ouar) locus. UVr-23, which is UV-resistant and more proficient at UDS than the parental line, appeared to exhibit a tendency toward hypomutability at both the ouabain(ouar) and 6-thioguanine--resistant (6TGr) loci. Further characterization of all these lines should aid in delineating mammalian mechanisms of DNA repair and mutagenesis.« less

Avian behavior and mortality at power lines in coastal South Carolina

USGS Publications Warehouse

Savereno, A.J.; Savereno, L.A.; Boettcher, R.; Haig, S.M.

1996-01-01

We compared avian behavior and mortality associated with two 115-kV transmission lines on the central South Carolina coast during 3,392 hours of observation from May 1991 through May 1994. One line was marked with 30-cm-diameter yellow aviation markers. The second line was unmarked, but was similar in most other aspects. We conducted ground searches (n = 445) beneath each line year-round to document avian mortality due to power-line collisions. At marked lines, birds that approached at line height changed behavior more at unmarked lines (P< 0.001), and fewer crossed between static and conductor wires. Collision rate was 53% lower at marked than unmarked lines. Among collisions at both sites, 82% of birds collided with static wires. Based on observed collisions and carcass recoveries, wading birds particularly appeared to be at risk. We concluded that aviation markers were effective at increasing line visibility and reducing collisions and recommend marking static wires of power lines in potentially sensitive areas.

The BCL2 antagonist of cell death pathway influences endometrial cancer cell sensitivity to cisplatin.

PubMed

Chon, Hye Sook; Marchion, Douglas C; Xiong, Yin; Chen, Ning; Bicaku, Elona; Stickles, Xiaomang Ba; Bou Zgheib, Nadim; Judson, Patricia L; Hakam, Ardeshir; Gonzalez-Bosquet, Jesus; Wenham, Robert M; Apte, Sachin M; Lancaster, Johnathan M

2012-01-01

To identify pathways that influence endometrial cancer (EC) cell sensitivity to cisplatin and to characterize the BCL2 antagonist of cell death (BAD) pathway as a therapeutic target to increase cisplatin sensitivity. Eight EC cell lines (Ishikawa, MFE296, RL 95-2, AN3CA, KLE, MFE280, MFE319, HEC-1-A) were subjected to Affymetrix Human U133A GeneChip expression analysis of approximately 22,000 probe sets. In parallel, endometrial cell line sensitivity to cisplatin was quantified by MTS assay, and IC(50) values were calculated. Pearson's correlation test was used to identify genes associated with response to cisplatin. Genes associated with cisplatin responsiveness were subjected to pathway analysis. The BAD pathway was identified and subjected to targeted modulation, and the effect on cisplatin sensitivity was evaluated. Pearson's correlation analysis identified 1443 genes associated with cisplatin resistance (P<0.05), which included representation of the BAD-apoptosis pathway. Small interfering RNA (siRNA) knockdown of BAD pathway protein phosphatase PP2C expression was associated with increased phosphorylated BAD (serine-155) levels and a parallel increase in cisplatin resistance in Ishikawa (P=0.004) and HEC-1-A (P=0.02) cell lines. In contrast, siRNA knockdown of protein kinase A expression increased cisplatin sensitivity in the Ishikawa (P=0.02) cell line. The BAD pathway influences EC cell sensitivity to cisplatin, likely via modulation of the phosphorylation status of the BAD protein. The BAD pathway represents an appealing therapeutic target to increase EC cell sensitivity to cisplatin. Copyright © 2011 Elsevier Inc. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sebastian, Katrin, E-mail: ksebastian@ukaachen.de; Ott, Hagen; Zwadlo-Klarwasser, Gabriele

Since the 7th amendment to the EU cosmetics directive foresees a complete ban on animal testing, alternative in vitro methods have been established to evaluate the sensitizing potential of small molecular weight compounds. To find out whether these novel in vitro assays are also capable to predict the sensitizing potential of small molecular weight drugs, model compounds such as beta-lactams and sulfonamides – which are the most frequent cause of adverse drug reactions – were co-incubated with THP-1, MUTZ-LC, or primary monocyte‐derived dendritic cells for 48 h and subsequent expression of selected marker genes (IL-8, IL-1β, CES1, NQO1, GCLM, PIRmore » 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.« less

Flow Line, Durafill VS, and Dycal toxicity to dental pulp cells: effects of growth factors

PubMed Central

Furey, Alyssa; Hjelmhaug, Julie; Lobner, Doug

2010-01-01

Introduction The objective was to determine the effects of growth factor treatment on dental pulp cell sensitivity to toxicity of two composite restoration materials, Flow Line and Durafill VS, and a calcium hydroxide pulp capping material, Dycal. Methods Toxicity of the dental materials to cultures of primary dental pulp cells was determined by the MTT metabolism assay. The ability of six different growth factors to influence the toxicity was tested. Results A 24 hour exposure to either Flow Line or Durafill VS caused approximately 40% cell death, while Dycal exposure caused approximately 80% cell death. The toxicity of Flow Line and Durafill VS was mediated by oxidative stress. Four of the growth factors tested (BMP-2, BMP-7, EGF, and TGF-β) decreased the basal MTT values while making the cells resistant to Flow Line and Durafill VS toxicity, except BMP-2 which made the cells more sensitive to Flow Line. Treatment with FGF-2 caused no change in basal MTT metabolism, prevented the toxicity of Durafill VS, but increased the toxicity of Flow Line. Treatment with IGF-I increased basal MTT metabolism and made the cells resistant to Flow Line and Durafill VS toxicity. None of the growth factors made the cells resistant to Dycal toxicity. Conclusions The results indicate that growth factors can be used to alter the sensitivity of dental pulp cells to commonly used restoration materials. The growth factors BMP-7, EGF, TGF-β, and IGF-I provided the best profile of effects, making the cells resistant to both Flow Line and Durafill VS toxicity. PMID:20630288

Easy Observation of Infrared Spectral Lines

ERIC Educational Resources Information Center

Cortel, Adolf

2012-01-01

The spectra of some chemical elements display intense infrared (IR) lines that can be used more effectively than the ones in the visible region for identification purposes. A simple setup, based on the IR sensitivity of a handycam in nightshot mode, is described to record the visible as well as the IR spectra from decorative bulbs or salts on the…

A novel on-line spatial-temporal k-anonymity method for location privacy protection from sequence rules-based inference attacks.

PubMed

Zhang, Haitao; Wu, Chenxue; Chen, Zewei; Liu, Zhao; Zhu, Yunhong

2017-01-01

Analyzing large-scale spatial-temporal k-anonymity datasets recorded in location-based service (LBS) application servers can benefit some LBS applications. However, such analyses can allow adversaries to make inference attacks that cannot be handled by spatial-temporal k-anonymity methods or other methods for protecting sensitive knowledge. In response to this challenge, first we defined a destination location prediction attack model based on privacy-sensitive sequence rules mined from large scale anonymity datasets. Then we proposed a novel on-line spatial-temporal k-anonymity method that can resist such inference attacks. Our anti-attack technique generates new anonymity datasets with awareness of privacy-sensitive sequence rules. The new datasets extend the original sequence database of anonymity datasets to hide the privacy-sensitive rules progressively. The process includes two phases: off-line analysis and on-line application. In the off-line phase, sequence rules are mined from an original sequence database of anonymity datasets, and privacy-sensitive sequence rules are developed by correlating privacy-sensitive spatial regions with spatial grid cells among the sequence rules. In the on-line phase, new anonymity datasets are generated upon LBS requests by adopting specific generalization and avoidance principles to hide the privacy-sensitive sequence rules progressively from the extended sequence anonymity datasets database. We conducted extensive experiments to test the performance of the proposed method, and to explore the influence of the parameter K value. The results demonstrated that our proposed approach is faster and more effective for hiding privacy-sensitive sequence rules in terms of hiding sensitive rules ratios to eliminate inference attacks. Our method also had fewer side effects in terms of generating new sensitive rules ratios than the traditional spatial-temporal k-anonymity method, and had basically the same side effects in terms of non-sensitive

A novel on-line spatial-temporal k-anonymity method for location privacy protection from sequence rules-based inference attacks

PubMed Central

Wu, Chenxue; Liu, Zhao; Zhu, Yunhong

2017-01-01

Analyzing large-scale spatial-temporal k-anonymity datasets recorded in location-based service (LBS) application servers can benefit some LBS applications. However, such analyses can allow adversaries to make inference attacks that cannot be handled by spatial-temporal k-anonymity methods or other methods for protecting sensitive knowledge. In response to this challenge, first we defined a destination location prediction attack model based on privacy-sensitive sequence rules mined from large scale anonymity datasets. Then we proposed a novel on-line spatial-temporal k-anonymity method that can resist such inference attacks. Our anti-attack technique generates new anonymity datasets with awareness of privacy-sensitive sequence rules. The new datasets extend the original sequence database of anonymity datasets to hide the privacy-sensitive rules progressively. The process includes two phases: off-line analysis and on-line application. In the off-line phase, sequence rules are mined from an original sequence database of anonymity datasets, and privacy-sensitive sequence rules are developed by correlating privacy-sensitive spatial regions with spatial grid cells among the sequence rules. In the on-line phase, new anonymity datasets are generated upon LBS requests by adopting specific generalization and avoidance principles to hide the privacy-sensitive sequence rules progressively from the extended sequence anonymity datasets database. We conducted extensive experiments to test the performance of the proposed method, and to explore the influence of the parameter K value. The results demonstrated that our proposed approach is faster and more effective for hiding privacy-sensitive sequence rules in terms of hiding sensitive rules ratios to eliminate inference attacks. Our method also had fewer side effects in terms of generating new sensitive rules ratios than the traditional spatial-temporal k-anonymity method, and had basically the same side effects in terms of non-sensitive

Metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides

NASA Astrophysics Data System (ADS)

Birsoy, Kıvanç; Possemato, Richard; Lorbeer, Franziska K.; Bayraktar, Erol C.; Thiru, Prathapan; Yucel, Burcu; Wang, Tim; Chen, Walter W.; Clish, Clary B.; Sabatini, David M.

2014-04-01

As the concentrations of highly consumed nutrients, particularly glucose, are generally lower in tumours than in normal tissues, cancer cells must adapt their metabolism to the tumour microenvironment. A better understanding of these adaptations might reveal cancer cell liabilities that can be exploited for therapeutic benefit. Here we developed a continuous-flow culture apparatus (Nutrostat) for maintaining proliferating cells in low-nutrient media for long periods of time, and used it to undertake competitive proliferation assays on a pooled collection of barcoded cancer cell lines cultured in low-glucose conditions. Sensitivity to low glucose varies amongst cell lines, and an RNA interference (RNAi) screen pinpointed mitochondrial oxidative phosphorylation (OXPHOS) as the major pathway required for optimal proliferation in low glucose. We found that cell lines most sensitive to low glucose are defective in the OXPHOS upregulation that is normally caused by glucose limitation as a result of either mitochondrial DNA (mtDNA) mutations in complex I genes or impaired glucose utilization. These defects predict sensitivity to biguanides, antidiabetic drugs that inhibit OXPHOS, when cancer cells are grown in low glucose or as tumour xenografts. Notably, the biguanide sensitivity of cancer cells with mtDNA mutations was reversed by ectopic expression of yeast NDI1, a ubiquinone oxidoreductase that allows bypass of complex I function. Thus, we conclude that mtDNA mutations and impaired glucose utilization are potential biomarkers for identifying tumours with increased sensitivity to OXPHOS inhibitors.

SENSITIVE TO FREEZING2 Aids in Resilience to Salt and Drought in Freezing-Sensitive Tomato

DOE PAGES

Wang, Kun; Hersh, Hope Lynn; Benning, Christoph

2016-09-06

SENSITIVE TO FREEZING2 (SFR2) is crucial for protecting chloroplast membranes following freezing in Arabidopsis (Arabidopsis thaliana). It has been shown that SFR2 homologs are present in all land plants, including freezing-sensitive species, raising the question of SFR2 function beyond freezing tolerance. Similar to freezing, salt and drought can cause dehydration. Thus, it is hypothesized that in freezing-sensitive plants SFR2 may play roles in their resilience to salt or drought. To test this hypothesis, SlSFR2 RNAi lines were generated in the cold/freezing-sensitive species tomato (Solanum lycopersicum [M82 cv]). Hypersensitivity to salt and drought of SlSFR2-RNAi lines was observed. Higher tolerance ofmore » wild-type tomatoes was correlated with the production of trigalactosyldiacylglycerol, a product of SFR2 activity. Tomato SFR2 in vitro activity is Mg 2+-dependent and its optimal pH is 7.5, similar to that of Arabidopsis SFR2, but the specific activity of tomato SFR2 in vitro is almost double that of Arabidopsis SFR2. When salt and drought stress were applied to Arabidopsis, no conditions could be identified at which SFR2 was induced prior to irreversibly impacting plant growth, suggesting that SFR2 protects Arabidopsis primarily against freezing. Discovery of tomato SFR2 function in drought and salt resilience provides further insights into general membrane lipid remodeling-based stress tolerance mechanisms and together with protection against freezing in freezing-resistant plants such as Arabidopsis, it adds lipid remodeling as a possible target for the engineering of abiotic stress-resilient crops.« less

SENSITIVE TO FREEZING2 Aids in Resilience to Salt and Drought in Freezing-Sensitive Tomato

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Kun; Hersh, Hope Lynn; Benning, Christoph

SENSITIVE TO FREEZING2 (SFR2) is crucial for protecting chloroplast membranes following freezing in Arabidopsis (Arabidopsis thaliana). It has been shown that SFR2 homologs are present in all land plants, including freezing-sensitive species, raising the question of SFR2 function beyond freezing tolerance. Similar to freezing, salt and drought can cause dehydration. Thus, it is hypothesized that in freezing-sensitive plants SFR2 may play roles in their resilience to salt or drought. To test this hypothesis, SlSFR2 RNAi lines were generated in the cold/freezing-sensitive species tomato (Solanum lycopersicum [M82 cv]). Hypersensitivity to salt and drought of SlSFR2-RNAi lines was observed. Higher tolerance ofmore » wild-type tomatoes was correlated with the production of trigalactosyldiacylglycerol, a product of SFR2 activity. Tomato SFR2 in vitro activity is Mg 2+-dependent and its optimal pH is 7.5, similar to that of Arabidopsis SFR2, but the specific activity of tomato SFR2 in vitro is almost double that of Arabidopsis SFR2. When salt and drought stress were applied to Arabidopsis, no conditions could be identified at which SFR2 was induced prior to irreversibly impacting plant growth, suggesting that SFR2 protects Arabidopsis primarily against freezing. Discovery of tomato SFR2 function in drought and salt resilience provides further insights into general membrane lipid remodeling-based stress tolerance mechanisms and together with protection against freezing in freezing-resistant plants such as Arabidopsis, it adds lipid remodeling as a possible target for the engineering of abiotic stress-resilient crops.« less

Increased sensitivity to thiopurines in methylthioadenosine phosphorylase-deleted cancers

PubMed Central

Coulthard, Sally A.; Redfern, Christopher P.F.; Vikingsson, Svante; Appell, Malin Lindqvist; Skoglund, Karin; Falk, Ingrid Jakobsen; Hall, Andrew G.; Taylor, Gordon A.; Hogarth, Linda A.

2011-01-01

The thiopurines, 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) are used in the treatment of leukaemia. Incorporation of deoxythioguanosine nucleotides (dGs) into the DNA of thiopurine-treated cells causes cell death but there is also evidence that thiopurine metabolites, particularly the 6-MP metabolite methylthioinosine monophosphate (MeTIMP), inhibit de novo purine synthesis (DNPS). The toxicity of DNPS inhibitors is influenced by methylthioadenosine phosphorylase (MTAP), a gene frequently deleted in cancers. Since the growth of MTAP-deleted tumour cells is dependent on DNPS or hypoxanthine salvage, we would predict such cells to show differential sensitivity to 6-MP and 6-TG. To test this hypothesis, sensitivity to 6-MP and 6-TG was compared in relation to MTAP status using cytotoxicity assays in two MTAP-deficient cell lines transfected to express MTAP: the T-cell acute lymphoblastic leukaemic cell line, Jurkat, transfected with MTAP cDNA under the control of a tetracycline-inducible promoter, and a lung cancer cell line (A549-MTAP−ve) transfected to express MTAP constitutively (A549-MTAP+ve). Sensitivity to 6-MP or methyl mercaptopurine riboside, which is converted intra-cellularly to MeTIMP, was markedly higher in both cell lines under MTAP−ve conditions. Measurement of thiopurine metabolites support the hypothesis that DNPS inhibition is a major cause of cell death with 6-MP, whereas dGs incorporation is the main cause of cytotoxicity with 6-TG. These data suggest that thiopurines, particularly 6-MP, may be more effective in patients with deleted MTAP. PMID:21282358

Real-time polarization-sensitive optical coherence tomography data processing with parallel computing

PubMed Central

Liu, Gangjun; Zhang, Jun; Yu, Lingfeng; Xie, Tuqiang; Chen, Zhongping

2010-01-01

With the increase of the A-line speed of optical coherence tomography (OCT) systems, real-time processing of acquired data has become a bottleneck. The shared-memory parallel computing technique is used to process OCT data in real time. The real-time processing power of a quad-core personal computer (PC) is analyzed. It is shown that the quad-core PC could provide real-time OCT data processing ability of more than 80K A-lines per second. A real-time, fiber-based, swept source polarization-sensitive OCT system with 20K A-line speed is demonstrated with this technique. The real-time 2D and 3D polarization-sensitive imaging of chicken muscle and pig tendon is also demonstrated. PMID:19904337

Systemic analysis of different colorectal cancer cell lines and TCGA datasets identified IGF-1R/EGFR-PPAR-CASPASE axis as important indicator for radiotherapy sensitivity.

PubMed

Chen, Lin; Zhu, Zhe; Gao, Wei; Jiang, Qixin; Yu, Jiangming; Fu, Chuangang

2017-09-05

Insulin-like growth factor 1 receptor (IGF-1R) is proved to contribute the development of many types of cancers. But, little is known about its roles in radio-resistance of colorectal cancer (CRC). Here, we demonstrated that low IGF-1R expression value was associated with the better radiotherapy sensitivity of CRC. Besides, through Quantitative Real-time PCR (qRT-PCR), the elevated expression value of epidermal growth factor receptor (EGFR) was observed in CRC cell lines (HT29, RKO) with high radio-sensitivity compared with those with low sensitivity (SW480, LOVO). The irradiation induced apoptosis rates of wild type and EGFR agonist (EGF) or IGF-1R inhibitor (NVP-ADW742) treated HT29 and SW480 cells were quantified by flow cytometry. As a result, the apoptosis rate of EGF and NVP-ADW742 treated HT29 cells was significantly higher than that of those wild type ones, which indicated that high EGFR and low IGF-1R expression level in CRC was associated with the high sensitivity to radiotherapy. We next conducted systemic bioinformatics analysis of genome-wide expression profiles of CRC samples from the Cancer Genome Atlas (TCGA). Differential expression analysis between IGF-1R and EGFR abnormal CRC samples, i.e. CRC samples with higher IGF-1R and lower EGFR expression levels based on their median expression values, and the rest of CRC samples identified potential genes contribute to radiotherapy sensitivity. Functional enrichment of analysis of those differential expression genes (DEGs) in the Database for Annotation, Visualization and Integrated Discovery (DAVID) indicated PPAR signaling pathway as an important pathway for the radio-resistance of CRC. Our study identified the potential biomarkers for the rational selection of radiotherapy for CRC patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Flash Mob Project Creates Awareness of Environmental Sensitivities: Making "Multiple Chemical Sensitivity" a Household Name

ERIC Educational Resources Information Center

Smith, Melva Gail

2011-01-01

Having severe Asthma and trying to maintain a social life isn't easy, but when one adds the disability of Multiple Chemical Sensitivity (MCS) to the combination, the challenges become even tougher. As a dancer with both Asthma and MCS, the author was forced to give up the sport for 15 years before finding a group of line dancers that were…

Low energy analysis techniques for CUORE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alduino, C.; Alfonso, K.; Artusa, D. R.

CUORE is a tonne-scale cryogenic detector operating at the Laboratori Nazionali del Gran Sasso (LNGS) that uses tellurium dioxide bolometers to search for neutrinoless double-beta decay of 130Te. CUORE is also suitable to search for low energy rare events such as solar axions or WIMP scattering, thanks to its ultra-low background and large target mass. However, to conduct such sensitive searches requires improving the energy threshold to 10 keV. Here in this article, we describe the analysis techniques developed for the low energy analysis of CUORE-like detectors, using the data acquired from November 2013 to March 2015 by CUORE-0, amore » single-tower prototype designed to validate the assembly procedure and new cleaning techniques of CUORE. We explain the energy threshold optimization, continuous monitoring of the trigger efficiency, data and event selection, and energy calibration at low energies in detail. We also present the low energy background spectrum of CUORE-0 below 60keV. Finally, we report the sensitivity of CUORE to WIMP annual modulation using the CUORE-0 energy threshold and background, as well as an estimate of the uncertainty on the nuclear quenching factor from nuclear recoils inCUORE-0.« less

Measurement of the scintillation time spectra and pulse-shape discrimination of low-energy β and nuclear recoils in liquid argon with DEAP-1

DOE PAGES

Amaudruz, P. -A.; Batygov, M.; Beltran, B.; ...

2016-09-17

The DEAP-1 low-background liquid argon detector has been used to measure scintillation pulse shapes of beta decays and nuclear recoil events and to demonstrate the feasibility of pulse-shape discrimination down to an electron-equivalent energy of 20 keV ee. The relative intensities of singlet/triplet states in liquid argon have been measured as a function of energy between 15 and 500 keVee for both beta and nuclear recoils. Using a triple-coincidence tag we find the fraction of beta events that are misidentified as nuclear recoils to be less than 6 x 10 -8 between 43-86 keV ee and that the discrimination parametermore » agrees with a simple analytic model. The discrimination measurement is currently limited by nuclear recoils induced by cosmic-ray generated neutrons, and is expected to improve by operating the detector underground at SNOLAB. The analytic model predicts a beta misidentification fraction of 10 -10 for an electron-equivalent energy threshold of 20 keV ee. This reduction allows for a sensitive search for spin-independent scattering of WIMPs from 1000 kg of liquid argon with a WIMP-nucleon cross-section sensitivity of 10 -46 cm 2.« less

Measurement of the scintillation time spectra and pulse-shape discrimination of low-energy β and nuclear recoils in liquid argon with DEAP-1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amaudruz, P. -A.; Batygov, M.; Beltran, B.

The DEAP-1 low-background liquid argon detector has been used to measure scintillation pulse shapes of beta decays and nuclear recoil events and to demonstrate the feasibility of pulse-shape discrimination down to an electron-equivalent energy of 20 keV ee. The relative intensities of singlet/triplet states in liquid argon have been measured as a function of energy between 15 and 500 keVee for both beta and nuclear recoils. Using a triple-coincidence tag we find the fraction of beta events that are misidentified as nuclear recoils to be less than 6 x 10 -8 between 43-86 keV ee and that the discrimination parametermore » agrees with a simple analytic model. The discrimination measurement is currently limited by nuclear recoils induced by cosmic-ray generated neutrons, and is expected to improve by operating the detector underground at SNOLAB. The analytic model predicts a beta misidentification fraction of 10 -10 for an electron-equivalent energy threshold of 20 keV ee. This reduction allows for a sensitive search for spin-independent scattering of WIMPs from 1000 kg of liquid argon with a WIMP-nucleon cross-section sensitivity of 10 -46 cm 2.« less

Low energy analysis techniques for CUORE

DOE PAGES

Alduino, C.; Alfonso, K.; Artusa, D. R.; ...

2017-12-12

CUORE is a tonne-scale cryogenic detector operating at the Laboratori Nazionali del Gran Sasso (LNGS) that uses tellurium dioxide bolometers to search for neutrinoless double-beta decay of 130Te. CUORE is also suitable to search for low energy rare events such as solar axions or WIMP scattering, thanks to its ultra-low background and large target mass. However, to conduct such sensitive searches requires improving the energy threshold to 10 keV. Here in this article, we describe the analysis techniques developed for the low energy analysis of CUORE-like detectors, using the data acquired from November 2013 to March 2015 by CUORE-0, amore » single-tower prototype designed to validate the assembly procedure and new cleaning techniques of CUORE. We explain the energy threshold optimization, continuous monitoring of the trigger efficiency, data and event selection, and energy calibration at low energies in detail. We also present the low energy background spectrum of CUORE-0 below 60keV. Finally, we report the sensitivity of CUORE to WIMP annual modulation using the CUORE-0 energy threshold and background, as well as an estimate of the uncertainty on the nuclear quenching factor from nuclear recoils inCUORE-0.« less

Mechanisms of cellular uptake, intracellular transportation, and degradation of CIGB-300, a Tat-conjugated peptide, in tumor cell lines.

PubMed

Benavent Acero, Fernando R; Perera Negrin, Yasser; Alonso, Daniel F; Perea, Silvio E; Gomez, Daniel E; Farina, Hernán G

2014-06-02

CIGB-300 is a cyclic synthetic peptide that induces apoptosis in malignant cells, elicits antitumor activity in cancer animal models, and shows tumor reduction signs when assayed in first-in-human phase I trial in patients with cervical tumors. CIGB-300 impairs phosphorylation by casein kinase 2 through targeting the substrate's phosphoacceptor domain. CIGB-300 was linked to the cell penetrating peptide Tat to facilitate the delivery into cells. Previously, we showed that CIGB-300 had a differential antiproliferative behavior in different tumor cell lines. In this work, we studied differential antiproliferative behavior in terms of cellular uptake, intracellular transportation, and degradation in tumor cell lines with dissimilar sensitivity to CIGB-300. The internalization of CIGB-300 was studied in different malignant cell lines. We found that the cell membrane heparan sulfate proteoglycans act as main receptors for extracellular CIGB-300 uptake. The most sensitive tumor cell lines showed higher intracellular incorporation of CIGB-300 in comparison to less sensitive cell lines. Furthermore, CIGB-300 uptake is time- and concentration-dependent in all studied cell lines. It was shown that CIGB-300 has the ability to penetrate cells mainly by direct membrane translocation. However, a minor proportion of the peptide uses an energy-dependent endocytic pathway mechanism to gain access into cells. CIGB-300 is internalized and transported into cells preferentially by caveolae-mediated endocytosis. Lysosomes are involved in CIGB-300 degradation; highly sensitive cell lines showed degradation at earlier times compared to low sensitive cells. Altogether, our data suggests a mechanism of internalization, vesicular transportation, and degradation for CIGB-300 in tumor cells.

Identification of flubendazole as potential anti-neuroblastoma compound in a large cell line screen.

PubMed

Michaelis, Martin; Agha, Bishr; Rothweiler, Florian; Löschmann, Nadine; Voges, Yvonne; Mittelbronn, Michel; Starzetz, Tatjana; Harter, Patrick N; Abhari, Behnaz A; Fulda, Simone; Westermann, Frank; Riecken, Kristoffer; Spek, Silvia; Langer, Klaus; Wiese, Michael; Dirks, Wilhelm G; Zehner, Richard; Cinatl, Jaroslav; Wass, Mark N; Cinatl, Jindrich

2015-02-03

Flubendazole was shown to exert anti-leukaemia and anti-myeloma activity through inhibition of microtubule function. Here, flubendazole was tested for its effects on the viability of in total 461 cancer cell lines. Neuroblastoma was identified as highly flubendazole-sensitive cancer entity in a screen of 321 cell lines from 26 cancer entities. Flubendazole also reduced the viability of five primary neuroblastoma samples in nanomolar concentrations thought to be achievable in humans and inhibited vessel formation and neuroblastoma tumour growth in the chick chorioallantoic membrane assay. Resistance acquisition is a major problem in high-risk neuroblastoma. 119 cell lines from a panel of 140 neuroblastoma cell lines with acquired resistance to various anti-cancer drugs were sensitive to flubendazole in nanomolar concentrations. Tubulin-binding agent-resistant cell lines displayed the highest flubendazole IC50 and IC90 values but differences between drug classes did not reach statistical significance. Flubendazole induced p53-mediated apoptosis. The siRNA-mediated depletion of the p53 targets p21, BAX, or PUMA reduced the neuroblastoma cell sensitivity to flubendazole with PUMA depletion resulting in the most pronounced effects. The MDM2 inhibitor and p53 activator nutlin-3 increased flubendazole efficacy while RNAi-mediated p53-depletion reduced its activity. In conclusion, flubendazole represents a potential treatment option for neuroblastoma including therapy-refractory cells.

Identification of flubendazole as potential anti-neuroblastoma compound in a large cell line screen

PubMed Central

Michaelis, Martin; Agha, Bishr; Rothweiler, Florian; Löschmann, Nadine; Voges, Yvonne; Mittelbronn, Michel; Starzetz, Tatjana; Harter, Patrick N.; Abhari, Behnaz A.; Fulda, Simone; Westermann, Frank; Riecken, Kristoffer; Spek, Silvia; Langer, Klaus; Wiese, Michael; Dirks, Wilhelm G.; Zehner, Richard; Cinatl, Jaroslav; Wass, Mark N.; Cinatl, Jindrich

2015-01-01

Flubendazole was shown to exert anti-leukaemia and anti-myeloma activity through inhibition of microtubule function. Here, flubendazole was tested for its effects on the viability of in total 461 cancer cell lines. Neuroblastoma was identified as highly flubendazole-sensitive cancer entity in a screen of 321 cell lines from 26 cancer entities. Flubendazole also reduced the viability of five primary neuroblastoma samples in nanomolar concentrations thought to be achievable in humans and inhibited vessel formation and neuroblastoma tumour growth in the chick chorioallantoic membrane assay. Resistance acquisition is a major problem in high-risk neuroblastoma. 119 cell lines from a panel of 140 neuroblastoma cell lines with acquired resistance to various anti-cancer drugs were sensitive to flubendazole in nanomolar concentrations. Tubulin-binding agent-resistant cell lines displayed the highest flubendazole IC50 and IC90 values but differences between drug classes did not reach statistical significance. Flubendazole induced p53-mediated apoptosis. The siRNA-mediated depletion of the p53 targets p21, BAX, or PUMA reduced the neuroblastoma cell sensitivity to flubendazole with PUMA depletion resulting in the most pronounced effects. The MDM2 inhibitor and p53 activator nutlin-3 increased flubendazole efficacy while RNAi-mediated p53-depletion reduced its activity. In conclusion, flubendazole represents a potential treatment option for neuroblastoma including therapy-refractory cells. PMID:25644037

Measurement of Nuclear Recoils in the CDMS II Dark Matter Search

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fallows, Scott Mathew

The Cryogenic Dark Matter Search (CDMS) experiment is designed to directly detect elastic scatters of weakly-interacting massive dark matter particles (WIMPs), on target nuclei in semiconductor crystals composed of Si and Ge. These scatters would occur very rarely, in an overwhelming background composed primarily of electron recoils from photons and electrons, as well as a smaller but non-negligible background of WIMP-like nuclear recoils from neutrons. The CDMS II generation of detectors simultaneously measure ionization and athermal phonon signals from each scatter, allowing discrimination against virtually all electron recoils in the detector bulk. Pulse-shape timing analysis allows discrimination against nearly allmore » remaining electron recoils taking place near detector surfaces. Along with carefully limited neutron backgrounds, this experimental program allowed for \\background- free" operation of CDMS II at Soudan, with less than one background event expected in each WIMP-search analysis. As a result, exclusionary upper-limits on WIMP-nucleon interaction cross section were placed over a wide range of candidate WIMP masses, ruling out large new regions of parameter space.« less

The effects of 6-mercaptopurine nucleotide derivatives on the growth and survival of 6-mercaptopurine-sensitive and -resistant cell culture lines.

PubMed

Johnston, H P; Hawley, P; White, S E; Gibson, I; Tidd, D M

1985-04-01

6-Mercaptopurine (MP)-sensitive and -resistant cell culture lines were used to further characterize the apparent ability of MP nucleotide derivatives to overcome resistance to the parent drug. 6-Mercaptopurine-9-beta-D-ribofuranoside 5'-monophosphate [MPRP], bis(6-mercaptopurine-9-beta-D-ribofuranoside)-5', 5"'-monophosphate [bis(MPR)P], bis(O2',O3'-dibutyryl-6-mercaptopurine-9-beta-D-ribofuranoside)-5', 5"'-monophosphate [bis(dibut.MPR)P], and O2',O3'-dibutyryl-6-mercaptopurine-9-beta-D-ribofuranoside 5'-monophosphate [dibut.MPRP] were tested for cytotoxic and/or growth inhibitory effects against MP-resistant sublines of V79 Chinese hamster lung fibroblasts (CH/TG) and L1210 mouse leukaemia cells (L1210/MPR) in which deficiencies of hypoxanthine-guanine phosphoribosyltransferase, and hence drug nucleotide forming capacity were the basis of resistance. L1210/MPR cells were totally resistant to 1 mM 6-mercaptopurine-9-beta-D-ribofuranoside [MPR] and 2 mM MPRP, but were inhibited by high concentrations (greater than 0.25 mM) of bis(MPR)P. These results suggested that bis(MPR)P was taken up by cells as the intact molecule since MPR and MPRP were its extracellular breakdown products. L1210/MPR cells were much more sensitive to the lipophilic bis(dibut.MPR)P derivative which had a predominantly cytotoxic action as judged by trypan blue staining and the ability of treated cells to produce macroscopic colonies in soft agar medium. However, cells killed by bis(dibut.MPR)P did not disintegrate appreciably over periods of up to 10 days. The effects of bis(dibut.MPR)P were probably the result of cellular uptake of the intact molecule. Dibut.MPRP showed minimal ability to inhibit L1210/MPR cells although this compound was a possible breakdown product of bis(dibut.MPR)P and a source of the same extracellular degradation products. The median cell size decreased in L1210/MPR cultures during exposure to both bis(MPR)P and bis(dibut.MPR)P. This effect was elicited more rapidly and

The effects of 6-mercaptopurine nucleotide derivatives on the growth and survival of 6-mercaptopurine-sensitive and -resistant cell culture lines.

PubMed Central

Johnston, H. P.; Hawley, P.; White, S. E.; Gibson, I.; Tidd, D. M.

1985-01-01

6-Mercaptopurine (MP)-sensitive and -resistant cell culture lines were used to further characterize the apparent ability of MP nucleotide derivatives to overcome resistance to the parent drug. 6-Mercaptopurine-9-beta-D-ribofuranoside 5'-monophosphate [MPRP], bis(6-mercaptopurine-9-beta-D-ribofuranoside)-5', 5"'-monophosphate [bis(MPR)P], bis(O2',O3'-dibutyryl-6-mercaptopurine-9-beta-D-ribofuranoside)-5', 5"'-monophosphate [bis(dibut.MPR)P], and O2',O3'-dibutyryl-6-mercaptopurine-9-beta-D-ribofuranoside 5'-monophosphate [dibut.MPRP] were tested for cytotoxic and/or growth inhibitory effects against MP-resistant sublines of V79 Chinese hamster lung fibroblasts (CH/TG) and L1210 mouse leukaemia cells (L1210/MPR) in which deficiencies of hypoxanthine-guanine phosphoribosyltransferase, and hence drug nucleotide forming capacity were the basis of resistance. L1210/MPR cells were totally resistant to 1 mM 6-mercaptopurine-9-beta-D-ribofuranoside [MPR] and 2 mM MPRP, but were inhibited by high concentrations (greater than 0.25 mM) of bis(MPR)P. These results suggested that bis(MPR)P was taken up by cells as the intact molecule since MPR and MPRP were its extracellular breakdown products. L1210/MPR cells were much more sensitive to the lipophilic bis(dibut.MPR)P derivative which had a predominantly cytotoxic action as judged by trypan blue staining and the ability of treated cells to produce macroscopic colonies in soft agar medium. However, cells killed by bis(dibut.MPR)P did not disintegrate appreciably over periods of up to 10 days. The effects of bis(dibut.MPR)P were probably the result of cellular uptake of the intact molecule. Dibut.MPRP showed minimal ability to inhibit L1210/MPR cells although this compound was a possible breakdown product of bis(dibut.MPR)P and a source of the same extracellular degradation products. The median cell size decreased in L1210/MPR cultures during exposure to both bis(MPR)P and bis(dibut.MPR)P. This effect was elicited more rapidly and

Selenium Nanoparticles Induce the Chemo-Sensitivity of Fluorouracil Nanoparticles in Breast and Colon Cancer Cells.

PubMed

Abd-Rabou, Ahmed A; Shalby, Aziza B; Ahmed, Hanaa H

2018-05-11

Drug resistance is a major challenge of breast and colon cancer therapies leading to treatment failure. The main objective of the current study is to investigate whether selenium nanoparticles (nano-Se) can induce the chemo-sensitivity of 5-fluorouracil (FU)-encapsulated poly (D, L-lactide-co-glycolide) nanoparticles (nano-FU) in breast and colon cancer cell lines. Nano-Se and nano-FU were synthesized and characterized, then applied individually or in combination upon MCF7, MDA-MB-231, HCT 116, and Caco-2 cancerous cell lines. Cytotoxicity, cellular glucose uptake, and apoptosis, as well as malondialdehyde (MDA), nitric oxide (NO), and zinc (Zn) levels, were investigated upon the different treatments. We have resulted that nano-FU induced cell death in MCF7 and Caco-2 more effectively than MDA-MB-231 and HCT 116 cell lines. Moreover, nano-FU plus nano-Se potentiate MCF7 and Caco-2 chemo-sensitivity were higher than MDA-MB-231 and HCT 116 cancerous cell lines. It is relevant to note that Se and FU nano-formulations inhibited cancer cell bioenergetics via glucose uptake slight blockage. Furthermore, nano-FU increased the levels of NO and MDA in media over cancer cells, while their combinations with nano-Se rebalance the redox status with Zn increment. We noticed that MCF7 cell line is sensitive, while MDA-MB-231 cell line is resistant to Se and nano-Se. This novel approach could be of great potential to enhance the chemo-sensitivity in breast and colon cancer cells.

Collagen gel droplet-embedded culture drug sensitivity testing in squamous cell carcinoma cell lines derived from human oral cancers: Optimal contact concentrations of cisplatin and fluorouracil.

PubMed

Sakuma, Kaname; Tanaka, Akira; Mataga, Izumi

2016-12-01

The collagen gel droplet-embedded culture drug sensitivity test (CD-DST) is an anticancer drug sensitivity test that uses a method of three-dimensional culture of extremely small samples, and it is suited to primary cultures of human cancer cells. It is a useful method for oral squamous cell carcinoma (OSCC), in which the cancer tissues available for testing are limited. However, since the optimal contact concentrations of anticancer drugs have yet to be established in OSCC, CD-DST for detecting drug sensitivities of OSCC is currently performed by applying the optimal contact concentrations for stomach cancer. In the present study, squamous carcinoma cell lines from human oral cancer were used to investigate the optimal contact concentrations of cisplatin (CDDP) and fluorouracil (5-FU) during CD-DST for OSCC. CD-DST was performed in 7 squamous cell carcinoma cell lines derived from human oral cancers (Ca9-22, HSC-3, HSC-4, HO-1-N-1, KON, OSC-19 and SAS) using CDDP (0.15, 0.3, 1.25, 2.5, 5.0 and 10.0 µg/ml) and 5-FU (0.4, 0.9, 1.8, 3.8, 7.5, 15.0 and 30.0 µg/ml), and the optimal contact concentrations were calculated from the clinical response rate of OSCC to single-drug treatment and the in vitro efficacy rate curve. The optimal concentrations were 0.5 µg/ml for CDDP and 0.7 µg/ml for 5-FU. The antitumor efficacy of CDDP at this optimal contact concentration in CD-DST was compared to the antitumor efficacy in the nude mouse method. The T/C values, which were calculated as the ratio of the colony volume of the treatment group and the colony volume of the control group, at the optimal contact concentration of CDDP and of the nude mouse method were almost in agreement (P<0.05) and predicted clinical efficacy, indicating that the calculated optimal contact concentration is valid. Therefore, chemotherapy for OSCC based on anticancer drug sensitivity tests offers patients a greater freedom of choice and is likely to assume a greater importance in the selection of

SENSITIVE TO FREEZING2 Aids in Resilience to Salt and Drought in Freezing-Sensitive Tomato1[OPEN

PubMed Central

Hersh, Hope Lynn

2016-01-01

SENSITIVE TO FREEZING2 (SFR2) is crucial for protecting chloroplast membranes following freezing in Arabidopsis (Arabidopsis thaliana). It has been shown that SFR2 homologs are present in all land plants, including freezing-sensitive species, raising the question of SFR2 function beyond freezing tolerance. Similar to freezing, salt and drought can cause dehydration. Thus, it is hypothesized that in freezing-sensitive plants SFR2 may play roles in their resilience to salt or drought. To test this hypothesis, SlSFR2 RNAi lines were generated in the cold/freezing-sensitive species tomato (Solanum lycopersicum [M82 cv]). Hypersensitivity to salt and drought of SlSFR2-RNAi lines was observed. Higher tolerance of wild-type tomatoes was correlated with the production of trigalactosyldiacylglycerol, a product of SFR2 activity. Tomato SFR2 in vitro activity is Mg2+-dependent and its optimal pH is 7.5, similar to that of Arabidopsis SFR2, but the specific activity of tomato SFR2 in vitro is almost double that of Arabidopsis SFR2. When salt and drought stress were applied to Arabidopsis, no conditions could be identified at which SFR2 was induced prior to irreversibly impacting plant growth, suggesting that SFR2 protects Arabidopsis primarily against freezing. Discovery of tomato SFR2 function in drought and salt resilience provides further insights into general membrane lipid remodeling-based stress tolerance mechanisms and together with protection against freezing in freezing-resistant plants such as Arabidopsis, it adds lipid remodeling as a possible target for the engineering of abiotic stress-resilient crops. PMID:27600812

Radiosensitivity profiles from a panel of ovarian cancer cell lines exhibiting genetic alterations in p53 and disparate DNA-dependent protein kinase activities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Langland, Gregory T.; Yannone, Steven M.; Langland, Rachel A.

2009-09-07

The variability of radiation responses in ovarian tumors and tumor-derived cell lines is poorly understood. Since both DNA repair capacity and p53 status can significantly alter radiation sensitivity, we evaluated these factors along with radiation sensitivity in a panel of sporadic human ovarian carcinoma cell lines. We observed a gradation of radiation sensitivity among these sixteen lines, with a five-fold difference in the LD50 between the most radiosensitive and the most radioresistant cells. The DNA-dependent protein kinase (DNA-PK) is essential for the repair of radiation induced DNA double-strand breaks in human somatic cells. Therefore, we measured gene copy number, expressionmore » levels, protein abundance, genomic copy and kinase activity for DNA-PK in all of our cell lines. While there were detectable differences in DNA-PK between the cell lines, there was no clear correlation with any of these differences and radiation sensitivity. In contrast, p53 function as determined by two independent methods, correlated well with radiation sensitivity, indicating p53 mutant ovarian cancer cells are typically radioresistant relative to p53 wild-type lines. These data suggest that the activity of regulatory molecules such as p53 may be better indicators of radiation sensitivity than DNA repair enzymes such as DNAPK in ovarian cancer.« less

BAD phosphorylation determines ovarian cancer chemo-sensitivity and patient survival

PubMed Central

Marchion, Douglas C.; Cottrill, Hope M.; Xiong, Yin; Chen, Ning; Bicaku, Elona; Fulp, William J.; Bansal, Nisha; Chon, Hye Sook; Stickles, Xiaomang B.; Kamath, Siddharth G.; Hakam, Ardeshir; Li, Lihua; Su, Dan; Moreno, Carolina; Judson, Patricia L.; Berchuck, Andrew; Wenham, Robert M.; Apte, Sachin M.; Gonzalez-Bosquet, Jesus; Bloom, Gregory C.; Eschrich, Steven A.; Sebti, Said; Chen, Dung-Tsa; Lancaster, Johnathan M.

2011-01-01

Purpose Despite initial sensitivity to chemotherapy, ovarian cancers (OVCA) often develop drug-resistance, which limits patient survival. Using specimens and/or genomic data from 289 patients and a panel of cancer cell lines, we explored genome-wide expression changes that underlie the evolution of OVCA chemo-resistance and characterized the BCL2 antagonist of cell death (BAD) apoptosis pathway as a determinant of chemo-sensitivity and patient survival. Experimental Design Serial OVCA cell cisplatin treatments were performed in parallel with measurements of genome-wide expression changes. Pathway analysis was performed on genes associated with increasing cisplatin-resistance (EC50). BAD-pathway expression and BAD-protein phosphorylation were evaluated in patient samples and cell lines as determinants of chemo-sensitivity and/or clinical outcome and as therapeutic targets. Results Induced in vitro OVCA cisplatin-resistance was associated with BAD-pathway expression (P < 0.001). In OVCA cell lines and primary specimens, BAD-protein phosphorylation was associated with platinum-resistance (n = 147, P < 0.0001) and also with overall patient survival (n = 134, P = 0.0007). Targeted modulation of BAD-phosphorylation levels influenced cisplatin sensitivity. A 47-gene BAD-pathway score was associated with in vitro phosphorylated-BAD levels and with survival in 142 patients with advanced-stage (III/IV) serous OVCA. Integration of BAD-phosphorylation or BAD-pathway score with OVCA surgical cytoreductive status was significantly associated with overall survival by log-rank test (P = 0.004 and <0.0001, respectively). Conclusion The BAD apoptosis pathway influences OVCA chemo-sensitivity and overall survival, likely via modulation of BAD-phosphorylation. The pathway has clinical relevance as a biomarker of therapeutic response, patient survival, and as a promising therapeutic target. PMID:21849418

Compendium of Instrumentation Whitepapers on Frontier Physics Needs for Snowmass 2013

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lipton, R.

2013-01-01

Contents of collection of whitepapers include: Operation of Collider Experiments at High Luminosity; Level 1 Track Triggers at HL-LHC; Tracking and Vertex Detectors for a Muon Collider; Triggers for hadron colliders at the energy frontier; ATLAS Upgrade Instrumentation; Instrumentation for the Energy Frontier; Particle Flow Calorimetry for CMS; Noble Liquid Calorimeters; Hadronic dual-readout calorimetry for high energy colliders; Another Detector for the International Linear Collider; e+e- Linear Colliders Detector Requirements and Limitations; Electromagnetic Calorimetry in Project X Experiments The Project X Physics Study; Intensity Frontier Instrumentation; Project X Physics Study Calorimetry Report; Project X Physics Study Tracking Report; The LHCbmore » Upgrade; Neutrino Detectors Working Group Summary; Advanced Water Cherenkov R&D for WATCHMAN; Liquid Argon Time Projection Chamber (LArTPC); Liquid Scintillator Instrumentation for Physics Frontiers; A readout architecture for 100,000 pixel Microwave Kinetic In- ductance Detector array; Instrumentation for New Measurements of the Cosmic Microwave Background polarization; Future Atmospheric and Water Cherenkov ?-ray Detectors; Dark Energy; Can Columnar Recombination Provide Directional Sensitivity in WIMP Search?; Instrumentation Needs for Detection of Ultra-high Energy Neu- trinos; Low Background Materials for Direct Detection of Dark Matter; Physics Motivation for WIMP Dark Matter Directional Detection; Solid Xenon R&D at Fermilab; Ultra High Energy Neutrinos; Instrumentation Frontier: Direct Detection of WIMPs; nEXO detector R&D; Large Arrays of Air Cherenkov Detectors; and Applications of Laser Interferometry in Fundamental Physics Experiments.« less

Exploring the particle nature of dark matter with the All-sky Medium Energy Gamma-ray Observatory (AMEGO)

NASA Astrophysics Data System (ADS)

Caputo, Regina; Meyer, Manuel; Sánchez-Conde, Miguel; AMEGO

2018-01-01

The era of precision cosmology has revealed that ~80% of the matter in the universe is dark matter. Two leading candidates, motivated by both particle and astrophysics, are Weakly Interacting Massive Particles (WIMPs) and Weakly Interacting Sub-eV Particles (WISPs) like axions and axionlike particles. Both WIMPs and WISPs have distinct gamma-ray signatures. Data from the Fermi Large Area Telescope (Fermi-LAT) continues to be an integral part of the search for these dark matter signatures spanning the 50 MeV to >300 GeV energy range in a variety of astrophysical targets. Thus far, there are no conclusive detections; however, there is an intriguing excess of gamma rays associated with Galactic center (GCE) that could be explained with WIMP annihilation. The angular resolution of the LAT at lower energies makes source selection challenging and the true nature of the detected signal remains unknown. WISP searches using, e.g. supernova explosions, spectra of blazars, or strongly magnetized environments, would also greatly benefit from increased angular and energy resolution, as well as from polarization measurements. To address these, we are developing AMEGO, the All-sky Medium Energy Gamma-ray Observatory. This instrument has a projected energy and angular resolution that will increase sensitivity by a factor of 20-50 over previous instruments. This will allow us to explore new areas of dark matter parameter space and provide unprecedented access to its particle nature.

High-sensitivity interference-free diagnostic for measurement of methane in shock tubes

NASA Astrophysics Data System (ADS)

Sur, Ritobrata; Wang, Shengkai; Sun, Kai; Davidson, David F.; Jeffries, Jay B.; Hanson, Ronald K.

2015-05-01

A sensitive CW laser absorption diagnostic for in-situ measurement of methane mole fraction at high temperatures is developed. The selected transitions for the diagnostic are a cluster of lines near 3148.8 cm-1 from the R-branch of the ν3 band of the CH4 absorption spectrum. The selected transitions have 2-3 times more sensitivity to CH4 concentration than the P-branch in the 3.3 μm region, lower interference from major interfering intermediate species in most hydrocarbon reactions, and applicability over a wide range of pressures and temperatures. Absorption cross-sections for a broad collection of hydrocarbons were simulated to evaluate interference absorption, and were generally found to be negligible near 3148.8 cm-1. However, minor interference from hot bands of C2H2 and C2H4 was observed and was characterized experimentally, revealing a weak dependence on wavelength. To eliminate such interferences, a two-color on-line and off-line measurement scheme is proposed to determine CH4 concentration. The colors selected, i.e., for on-line (3148.81 cm-1) and off-line (3148.66 cm-1), are characterized between 0.2-4 atm and 500 K-2100 K by absorption coefficient measurements in a shock tube. Minimum detectable levels of CH4 in shock tube experiments are reported for this range of temperatures and pressures. An example measurement is shown for sensitive detection of CH4 in a shock tube chemical kinetics experiment.

A flexible tactile sensitive sheet using a hetero-core fiber optic sensor

NASA Astrophysics Data System (ADS)

Fujino, S.; Yamazaki, H.; Hosoki, A.; Watanabe, K.

2014-05-01

In this report, we have designed a tactile sensitive sheet based on a hetero-core fiber-optic sensor, which realize an areal sensing by using single sensor potion in one optical fiber line. Recently, flexible and wide-area tactile sensing technology is expected to applied to acquired biological information in living space and robot achieve long-term care services such as welfare and nursing-care and humanoid technology. A hetero-core fiber-optic sensor has several advantages such as thin and flexible transmission line, immunity to EMI. Additionally this sensor is sensitive to moderate bending actions with optical loss changes and is independent of temperature fluctuation. Thus, the hetero-core fiber-optic sensor can be suitable for areal tactile sensing. We measure pressure characteristic of the proposed sensitive sheet by changing the pressure position and pinching characteristic on the surface. The proposed tactile sensitive sheet shows monotonic responses on the whole sensitive sheet surface although different sensitivity by the position is observed at the sensitive sheet surface. Moreover, the tactile sensitive sheet could sufficiently detect the pinching motion. In addition, in order to realize the discrimination between pressure and pinch, we fabricated a doubled-over sensor using a set of tactile sensitive sheets, which has different kinds of silicon robbers as a sensitive sheet surface. In conclusion, the flexible material could be given to the tactile sensation which is attached under proposed sensitive sheet.

Effects of curcumin on stem-like cells in human esophageal squamous carcinoma cell lines.

PubMed

Almanaa, Taghreed N; Geusz, Michael E; Jamasbi, Roudabeh J

2012-10-24

Many cancers contain cell subpopulations that display characteristics of stem cells. Because these cancer stem cells (CSCs) appear to provide resistance to chemo-radiation therapy, development of therapeutic agents that target CSCs is essential. Curcumin is a phytochemical agent that is currently used in clinical trials to test its effectiveness against cancer. However, the effect of curcumin on CSCs is not well established. The current study evaluated curcumin-induced cell death in six cancer cell lines derived from human esophageal squamous cell carcinomas. Moreover, these cell lines and the ones established from cells that survived curcumin treatments were characterized. Cell loss was assayed after TE-1, TE-8, KY-5, KY-10, YES-1, and YES-2 cells were exposed to 20-80 μM curcumin for 30 hrs. Cell lines surviving 40 or 60 μM curcumin were established from these six original lines. The stem cell markers aldehyde dehydrogenase-1A1 (ALDH1A1) and CD44 as well as NF-κB were used to compare CSC-like subpopulations within and among the original lines as well as the curcumin-surviving lines. YES-2 was tested for tumorsphere-forming capabilities. Finally, the surviving lines were treated with 40 and 60 μM curcumin to determine whether their sensitivity was different from the original lines. The cell loss after curcumin treatment increased in a dose-dependent manner in all cell lines. The percentage of cells remaining after 60 μM curcumin treatment varied from 10.9% to 36.3% across the six lines. The cell lines were heterogeneous with respect to ALDH1A1, NF-κB and CD44 expression. KY-5 and YES-1 were the least sensitive and had the highest number of stem-like cells whereas TE-1 had the lowest. The curcumin-surviving lines showed a significant loss in the high staining ALDH1A1 and CD44 cell populations. Tumorspheres formed from YES-2 but were small and rare in the YES-2 surviving line. The curcumin-surviving lines showed a small but significant decrease in sensitivity

Characterization of a cultured human T-cell line with genetically altered ribonucleotide reductase activity. Model for immunodeficiency.

PubMed

Waddell, D; Ullman, B

1983-04-10

From human CCRF-CEM T-cells growing in continuous culture, we have selected, isolated, and characterized a clonal cell line, APHID-D2, with altered ribonucleotide reductase activity. In comparative growth rate experiments, the APHID-D2 cell line is less sensitive than the parental cell line to growth inhibition by deoxyadenosine in the presence of 10 microM erythro-9-(2-hydroxy-3-nonyl)adenine, an inhibitor of adenosine deaminase. The APHID-D2 cell line has elevated levels of all four dNTPs. The resistance of the APHID-D2 cell line to growth inhibition by deoxyadenosine and the abnormal dNTP levels can be explained by the fact that the APHID-D2 ribonucleotide reductase, unlike the parental ribonucleotide reductase, is not normally sensitive to inhibition by dATP. These results suggest that the allosteric site of ribonucleotide reductase which binds both dATP and ATP is altered in the APHID-D2 line. The isolation of a mutant clone of human T-cells which contains a ribonucleotide reductase that has lost its normal sensitivity to dATP and which is resistant to deoxyadenosine-mediated growth inhibition suggests that a primary pathogenic target of accumulated dATP in lymphocytes from patients with adenosine deaminase deficiency may be the cellular ribonucleotide reductase.

Bcl-2/Bax protein ratio predicts 5-fluorouracil sensitivity independently of p53 status

PubMed Central

Mirjolet, J-F; Barberi-Heyob, M; Didelot, C; Peyrat, J-P; Abecassis, J; Millon, R; Merlin, J-L

2000-01-01

p53 tumour-suppressor gene is involved in cell growth control, arrest and apoptosis. Nevertheless cell cycle arrest and apoptosis induction can be observed in p53-defective cells after exposure to DNA-damaging agents such as 5-fluorouracil (5-FU) suggesting the importance of alternative pathways via p53-independent mechanisms. In order to establish relationship between p53 status, cell cycle arrest, Bcl-2/Bax regulation and 5-FU sensitivity, we examined p53 mRNA and protein expression and p53 protein functionality in wild-type (wt) and mutant (mt) p53 cell lines. p53 mRNA and p53 protein expression were determined before and after exposure to equitoxic 5-FU concentration in six human carcinoma cell lines differing in p53 status and displaying marked differences in 5-FU sensitivity, with IC 50 values ranging from 0.2–22.6 mM. 5-FU induced a rise in p53 mRNA expression in mt p53 cell lines and in human papilloma virus positive wt p53 cell line, whereas significant decrease in p53 mRNA expression was found in wt p53 cell line. Whatever p53 status, 5-FU altered p53 transcriptional and translational regulation leading to up-regulation of p53 protein. In relation with p53 functionality, but independently of p53 mutational status, after exposure to 5-FU equitoxic concentration, all cell lines were able to arrest in G1. No relationship was evidenced between G1 accumulation ability and 5-FU sensitivity. Moreover, after 5-FU exposure, Bax and Bcl-2 proteins regulation was under p53 protein control and a statistically significant relationship (r= 0.880,P= 0.0097) was observed between Bcl-2/Bax ratio and 5-FU sensitivity. In conclusion, whatever p53 status, Bcl-2 or Bax induction and Bcl-2/Bax protein ratio were correlated to 5-FU sensitivity. © 2000 Cancer Research Campaign PMID:11044365

High sensitive volumetric imaging of renal microcirculation in vivo using ultrahigh sensitive optical microangiography

NASA Astrophysics Data System (ADS)

Zhi, Zhongwei; Jung, Yeongri; Jia, Yali; An, Lin; Wang, Ruikang K.

2011-03-01

We present a non-invasive, label-free imaging technique called Ultrahigh Sensitive Optical Microangiography (UHSOMAG) for high sensitive volumetric imaging of renal microcirculation. The UHS-OMAG imaging system is based on spectral domain optical coherence tomography (SD-OCT), which uses a 47000 A-line scan rate CCD camera to perform an imaging speed of 150 frames per second that takes only ~7 seconds to acquire a 3D image. The technique, capable of measuring slow blood flow down to 4 um/s, is sensitive enough to image capillary networks, such as peritubular capillaries and glomerulus within renal cortex. We show superior performance of UHS-OMAG in providing depthresolved volumetric images of rich renal microcirculation. We monitored the dynamics of renal microvasculature during renal ischemia and reperfusion. Obvious reduction of renal microvascular density due to renal ischemia was visualized and quantitatively analyzed. This technique can be helpful for the assessment of chronic kidney disease (CKD) which relates to abnormal microvasculature.

In vivo and ex vivo cetuximab sensitivity assay using three-dimensional primary culture system to stratify KRAS mutant colorectal cancer

PubMed Central

Tashiro, Takahiro; Okuyama, Hiroaki; Endo, Hiroko; Kawada, Kenji; Ashida, Yasuko; Ohue, Masayuki; Sakai, Yoshiharu; Inoue, Masahiro

2017-01-01

In clinic, cetuximab, an anti-EGFR antibody, improves treatment outcomes in colorectal cancer (CRC). KRAS-mutant CRC is generally resistant to cetuximab, although difference of the sensitivity among KRAS-mutants has not been studied in detail. We previously developed the cancer tissue-originated spheroid (CTOS) method, a primary culture method for cancer cells. We applied CTOS method to investigate whether ex vivo cetuximab sensitivity assays reflect the difference in sensitivity in the xenografts. Firstly, in vivo cetuximab treatment was performed with xenografts derived from 10 CTOS lines (3 KRAS-wildtype and 7 KRAS mutants). All two CTOS lines which exhibited tumor regression were KRAS-wildtype, meanwhile all KRAS-mutant CTOS lines grew more than the initial size: were resistant to cetuximab according to the clinical evaluation criteria, although the sensitivity was quite diverse. We divided KRAS-mutants into two groups; partially responsive group in which cetuximab had a substantial growth inhibitory effect, and resistant group which exhibited no effect. The ex vivo signaling assay with EGF stimulation revealed that the partially responsive group, but not the resistant group, exhibited suppressed ERK phosphorylation ex vivo. Furthermore, two lines from the partially responsive group, but none of the lines in the resistant group, exhibited a combinatory effect of cetuximab and trametinib, a MEK inhibitor, ex vivo and in vivo. Taken together, the results indicate that ex vivo signaling assay reflects the difference in sensitivity in vivo and stratifies KRAS mutant CTOS lines by sensitivity. Therefore, coupling the in vivo and ex vivo assays with CTOS can be a useful platform for understanding the mechanism of diversity in drug sensitivity. PMID:28301591

Sensitivity of magnetic field-line pitch angle measurements to sawtooth events in tokamaks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ko, J., E-mail: jinseok@nfri.re.kr

2016-11-15

The sensitivity of the pitch angle profiles measured by the motional Stark effect (MSE) diagnostic to the evolution of the safety factor, q, profiles during the tokamak sawtooth events has been investigated for Korea Superconducting Tokamak Advanced Research (KSTAR). An analytic relation between the tokamak pitch angle, γ, and q estimates that Δγ ∼ 0.1° is required for detecting Δq ∼ 0.05 near the magnetic axis (not at the magnetic axis, though). The pitch angle becomes less sensitive to the same Δq for the middle and outer regions of the plasma (Δγ ∼ 0.5°). At the magnetic axis, it ismore » not straightforward to directly relate the γ sensitivity to Δq since the gradient of γ(R), where R is the major radius of the tokamak, is involved. Many of the MSE data obtained from the 2015 KSTAR campaign, when calibrated carefully, can meet these requirements with the time integration down to 10 ms. The analysis with the measured data shows that the pitch angle profiles and their gradients near the magnetic axis can resolve the change of the q profiles including the central safety factor, q{sub 0}, during the sawtooth events.« less

Integrated analysis of breast cancer cell lines reveals unique signaling pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heiser, Laura M.; Wang, Nicholas J.; Talcott, Carolyn L.

Cancer is a heterogeneous disease resulting from the accumulation of genetic defects that negatively impact control of cell division, motility, adhesion and apoptosis. Deregulation in signaling along the EGFR-MAPK pathway is common in breast cancer, though the manner in which deregulation occurs varies between both individuals and cancer subtypes. We were interested in identifying subnetworks within the EGFR-MAPK pathway that are similarly deregulated across subsets of breast cancers. To that end, we mapped genomic, transcriptional and proteomic profiles for 30 breast cancer cell lines onto a curated Pathway Logic symbolic systems model of EGFR-MEK signaling. This model was comprised ofmore » 539 molecular states and 396 rules governing signaling between active states. We analyzed these models and identified several subtype specific subnetworks, including one that suggested PAK1 is particularly important in regulating the MAPK cascade when it is over-expressed. We hypothesized that PAK1 overexpressing cell lines would have increased sensitivity to MEK inhibitors. We tested this experimentally by measuring quantitative responses of 20 breast cancer cell lines to three MEK inhibitors. We found that PAK1 over-expressing luminal breast cancer cell lines are significantly more sensitive to MEK inhibition as compared to those that express PAK1 at low levels. This indicates that PAK1 over-expression may be a useful clinical marker to identify patient populations that may be sensitive to MEK inhibitors. All together, our results support the utility of symbolic system biology models for identification of therapeutic approaches that will be effective against breast cancer subsets.« less

Integrated analysis of breast cancer cell lines reveals unique signaling pathways.

PubMed

Heiser, Laura M; Wang, Nicholas J; Talcott, Carolyn L; Laderoute, Keith R; Knapp, Merrill; Guan, Yinghui; Hu, Zhi; Ziyad, Safiyyah; Weber, Barbara L; Laquerre, Sylvie; Jackson, Jeffrey R; Wooster, Richard F; Kuo, Wen Lin; Gray, Joe W; Spellman, Paul T

2009-01-01

Cancer is a heterogeneous disease resulting from the accumulation of genetic defects that negatively impact control of cell division, motility, adhesion and apoptosis. Deregulation in signaling along the EgfR-MAPK pathway is common in breast cancer, though the manner in which deregulation occurs varies between both individuals and cancer subtypes. We were interested in identifying subnetworks within the EgfR-MAPK pathway that are similarly deregulated across subsets of breast cancers. To that end, we mapped genomic, transcriptional and proteomic profiles for 30 breast cancer cell lines onto a curated Pathway Logic symbolic systems model of EgfR-MAPK signaling. This model was composed of 539 molecular states and 396 rules governing signaling between active states. We analyzed these models and identified several subtype-specific subnetworks, including one that suggested Pak1 is particularly important in regulating the MAPK cascade when it is over-expressed. We hypothesized that Pak1 over-expressing cell lines would have increased sensitivity to Mek inhibitors. We tested this experimentally by measuring quantitative responses of 20 breast cancer cell lines to three Mek inhibitors. We found that Pak1 over-expressing luminal breast cancer cell lines are significantly more sensitive to Mek inhibition compared to those that express Pak1 at low levels. This indicates that Pak1 over-expression may be a useful clinical marker to identify patient populations that may be sensitive to Mek inhibitors. All together, our results support the utility of symbolic system biology models for identification of therapeutic approaches that will be effective against breast cancer subsets.

Identification of heat-sensitive QTL derived from common wild rice (Oryza rufipogon Griff.).

PubMed

Lei, Dongyang; Tan, Lubin; Liu, Fengxia; Chen, Liyun; Sun, Chuanqing

2013-03-01

Understanding the responses of rice plants to heat-stress is a challenging, yet crucial, endeavor. A set of introgression lines was previously developed using an advanced backcrossing strategy that involved the elite indica cultivar Teqing as the recipient and an accession of common wild rice (Oryza rufipongon Griff.) as the donor. In this study, we evaluated the responses of 90 of these previously developed introgression lines to heat stress. Five quantitative trait loci (QTLs) related to heat response were detected. The phenotypic variances explained by these QTLs ranged from 6.83% to 14.63%, and O. rufipogon-derived alleles at one locus reduced sensitivity to heat. A heat-sensitive introgression line, YIL106, was identified and characterized. Genotypic analysis demonstrated that YIL106 contained four introgressed segments derived from O. rufipongon and two QTLs (qHTS1-1 and qHTS3) related to heat response. Physiological tests, including measurements of chlorophyll content, electrolyte leakage, malondialdehyde content, and soluble sugar content, were consistent with the heat sensitivity observed in YIL106. Ultrastructural analysis of YIL106 mesophyll cells showed that they were severely damaged following heat stress. This suggests that modification of the cell membrane system is a primary response to heat stress in plants. Identification and characterization of the heat-sensitive line YIL106 may facilitate the isolation of genes associated with the response of rice plants to heat stress. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Real-time line-width measurements: a new feature for reticle inspection systems

NASA Astrophysics Data System (ADS)

Eran, Yair; Greenberg, Gad; Joseph, Amnon; Lustig, Cornel; Mizrahi, Eyal

1997-07-01

The significance of line width control in mask production has become greater with the lessening of defect size. There are two conventional methods used for controlling line widths dimensions which employed in the manufacturing of masks for sub micron devices. These two methods are the critical dimensions (CD) measurement and the detection of edge defects. Achieving reliable and accurate control of line width errors is one of the most challenging tasks in mask production. Neither of the two methods cited above (namely CD measurement and the detection of edge defects) guarantees the detection of line width errors with good sensitivity over the whole mask area. This stems from the fact that CD measurement provides only statistical data on the mask features whereas applying edge defect detection method checks defects on each edge by itself, and does not supply information on the combined result of error detection on two adjacent edges. For example, a combination of a small edge defect together with a CD non- uniformity which are both within the allowed tolerance, may yield a significant line width error, which will not be detected using the conventional methods (see figure 1). A new approach for the detection of line width errors which overcomes this difficulty is presented. Based on this approach, a new sensitive line width error detector was developed and added to Orbot's RT-8000 die-to-database reticle inspection system. This innovative detector operates continuously during the mask inspection process and scans (inspects) the entire area of the reticle for line width errors. The detection is based on a comparison of measured line width that are taken on both the design database and the scanned image of the reticle. In section 2, the motivation for developing this new detector is presented. The section covers an analysis of various defect types, which are difficult to detect using conventional edge detection methods or, alternatively, CD measurements. In section 3

NK sensitivity of neuroblastoma cells determined by a highly sensitive coupled luminescent method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ogbomo, Henry; Hahn, Anke; Geiler, Janina

2006-01-06

The measurement of natural killer (NK) cells toxicity against tumor or virus-infected cells especially in cases with small blood samples requires highly sensitive methods. Here, a coupled luminescent method (CLM) based on glyceraldehyde-3-phosphate dehydrogenase release from injured target cells was used to evaluate the cytotoxicity of interleukin-2 activated NK cells against neuroblastoma cell lines. In contrast to most other methods, CLM does not require the pretreatment of target cells with labeling substances which could be toxic or radioactive. The effective killing of tumor cells was achieved by low effector/target ratios ranging from 0.5:1 to 4:1. CLM provides highly sensitive, safe,more » and fast procedure for measurement of NK cell activity with small blood samples such as those obtained from pediatric patients.« less

Methotrexate induces high level of apoptosis in canine lymphoma/leukemia cell lines.

PubMed

Pawlak, Aleksandra; Kutkowska, Justyna; Obmińska-Mrukowicz, Bożena; Rapak, Andrzej

2017-10-01

Methotrexate is an antimetabolite used in the treatment of cancer and non-malignant diseases including rheumatoid arthritis, psoriasis and graft vs. host disease. Combination therapy with methotrexate was successful in the treatment of canine lymphoma, mammary tumor and invasive urinary bladder cancer. Lymphoma, the most common hematopoietic cancer in dogs, and leukemia are sensitive to chemotherapy, which is why methotrexate may be an important treatment option for these diseases. Although methotrexate is already used in veterinary oncology its effects on canine cancer cells has not been tested. The aim of the study was to evaluate for the first time methotrexate concentration-dependent cytotoxicity and its capability of inducing apoptosis in selected canine lymphoma/leukemia cell lines: CLBL-1, GL-1 and CL-1 as a first step before the in vitro development of new therapeutic options with the use of methotrexate. Methotrexate exhibited concentration-dependent inhibitory effect on proliferation of all the examined cell lines with different degree of apoptosis induction. The most methotrexate sensitive cells belonged to CL-1 cell line derived from T cell neoplasia and previously characterized by high resistance to the majority of anticancer drugs used in the therapy of lymphoma/leukemia in dogs. Canine lymphoma and leukemia cell lines are sensitive to methotrexate, and this drug may be useful in effective treatment of canine neoplasms and especially of T-type leukemia/lymphoma. Copyright © 2017 Elsevier Ltd. All rights reserved.

Genetic heterogeneity after first-line chemotherapy in high-grade serous ovarian cancer.

PubMed

Lambrechts, Sandrina; Smeets, Dominiek; Moisse, Matthieu; Braicu, Elena Ioana; Vanderstichele, Adriaan; Zhao, Hui; Van Nieuwenhuysen, Els; Berns, Els; Sehouli, Jalid; Zeillinger, Robert; Darb-Esfahani, Silvia; Cacsire Castillo-Tong, Dan; Lambrechts, Diether; Vergote, Ignace

2016-01-01

Most high-grade serous ovarian carcinoma (HGSOC) patients benefit from first-line platinum-based chemotherapy, but progressively develop resistance during subsequent lines. Re-activating BRCA1 or MDR1 mutations can underlie platinum resistance in end-stage patients. However, little is known about resistance mechanisms occurring after a single line of platinum, when patients still qualify for other treatments. In 31 patients with primary platinum-sensitive HGSOC, we profiled tumours collected during debulking surgery before and after first-line chemotherapy using whole-exome sequencing and single nucleotide polymorphism profiling. Besides germline BRCA1/2 mutations, we observed frequent loss-of-heterozygosity in homologous recombination (HR) genes and mutation spectra characteristic of HR-deficiency in all tumours. At relapse, tumours differed considerably from their primary counterparts. There was, however, no evidence of events reactivating the HR pathway, also not in tumours resistant to second-line platinum. Instead, a platinum score of 13 copy number regions, among other genes including MECOM, CCNE1 and ERBB2, correlated with platinum-free interval (PFI) after first-line therapy, whereas an increase of this score in recurrent tumours predicted the change in PFI during subsequent therapy. Already after a single line of platinum, there is huge variability between primary and recurrent tumours, advocating that in HGSOC biopsies need to be collected at relapse to tailor treatment options to the underlying genetic profile. Nevertheless, all primary platinum-sensitive HGSOCs remained HR-deficient, irrespective of whether they became resistant to second-line platinum, further suggesting these tumours qualify for second-line Poly APD ribose polymerase (PARP) inhibitor treatment. Finally, chromosomal instability contributes to acquired resistance after a single line of platinum therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Differential pathway dependency discovery associated with drug response across cancer cell lines* | Office of Cancer Genomics

Cancer.gov

The effort to personalize treatment plans for cancer patients involves the identification of drug treatments that can effectively target the disease while minimizing the likelihood of adverse reactions. In this study, the gene-expression profile of 810 cancer cell lines and their response data to 368 small molecules from the Cancer Therapeutics Research Portal (CTRP) are analyzed to identify pathways with significant rewiring between genes, or differential gene dependency, between sensitive and non-sensitive cell lines.

Method for rapid isolation of sensitive mutants

DOEpatents

Freyer, J.P.

1997-07-29

Sensitive mammalian cell mutants are rapidly isolated using flow cytometry. A first population of clonal spheroids is established to contain both normal and mutant cells. The population may be naturally occurring or may arise from mutagenized cells. The first population is then flow sorted by size to obtain a second population of clonal spheroids of a first uniform size. The second population is then exposed to a DNA-damaging agent that is being investigated. The exposed second population is placed in a growth medium to form a third population of clonal spheroids comprising spheroids of increased size from the mammalian cells that are resistant to the DNA-damaging agent and spheroids of substantially the first uniform size formed from the mammalian cells that are sensitive to the DNA-damaging agent. The third population is not flow sorted to differentiate the spheroids formed from resistant mammalian cells from spheroids formed from sensitive mammalian cells. The spheroids formed from sensitive mammalian cells are now treated to recover viable sensitive cells from which a sensitive cell line can be cloned. 15 figs.

Method for rapid isolation of sensitive mutants

DOEpatents

Freyer, James P.

1997-01-01

Sensitive mammalian cell mutants are rapidly isolated using flow cytometry. A first population of clonal spheroids is established to contain both normal and mutant cells. The population may be naturally occurring or may arise from mutagenized cells. The first population is then flow sorted by size to obtain a second population of clonal spheroids of a first uniform size. The second population is then exposed to a DNA-damaging agent that is being investigated. The exposed second population is placed in a growth medium to form a third population of clonal spheroids comprising spheroids of increased size from the mammalian cells that are resistant to the DNA-damaging agent and spheroids of substantially the first uniform size formed from the mammalian cells that are sensitive to the DNA-damaging agent. The third population is not flow sorted to differentiate the spheroids formed from resistant mammalian cells from spheroids formed from sensitive mammalian cells. The spheroids formed from sensitive mammalian cells are now treated to recover viable sensitive cells from which a sensitive cell line can be cloned.

Constraining dark matter annihilation with the isotropic γ-ray background: Updated limits and future potential

NASA Astrophysics Data System (ADS)

Bringmann, Torsten; Calore, Francesca; Di Mauro, Mattia; Donato, Fiorenza

2014-01-01

The nature of the isotropic γ-ray background (IGRB) measured by the Large Area Telescope (LAT) on the Fermi γ-ray space telescope (Fermi) remains partially unexplained. Non-negligible contributions may originate from extragalactic populations of unresolved sources such as blazars, star-forming galaxies or galactic millisecond pulsars. A recent prediction of the diffuse γ-ray emission from active galactic nuclei (AGN) with a large viewing angle with respect to the line of sight has demonstrated that this faint but numerous population is also expected to contribute significantly to the total IGRB intensity. A more exotic contribution to the IGRB invokes the pair annihilation of dark matter (DM) weakly interacting massive particles (WIMPs) into γ rays. In this work, we evaluate the room left for galactic DM at high latitudes (>10∘) by including photons from both prompt emission and inverse Compton scattering, emphasizing the impact of the newly discovered contribution from misaligned AGN (MAGN) for such an analysis. Summing up all significant galactic and extragalactic components of the IGRB, we find that an improved understanding of the associated astrophysical uncertainties is still mandatory to put stringent bounds on thermally produced DM. On the other hand, we also demonstrate that the IGRB has the potential to be one of the most competitive future ways to test the DM WIMP hypothesis, once the present uncertainties are even slightly reduced. In fact, if MAGN contribute even at 90% of the maximal level consistent with our current understanding, thermally produced WIMPs would be severely constrained as DM candidates for masses up to several TeV.

A study of ecological red-line area partitioning in the Chishui River Basin in Guizhou

NASA Astrophysics Data System (ADS)

Yang, S. F.; An, Y. L.

2016-08-01

Maintaining ecosystem balance and realizing the strategic goal of sustainable development are key objectives in the field of environmental sciences. Accordingly, drawing ecological red lines in sensitive and vulnerable environmental areas and important ecological function areas, determining the distribution range of ecological red-line areas, providing scientific guidance for developmental activities, and effectively managing the ecological environment are significant work tasks supported by policy guidance from the State Council and from knowledge gained in educational circles. Taking the Chishui River Basin in Guizhou as the study object, this research selected water and soil loss sensitivity, as well as assessments of karst rocky desertification sensitivity as background assessments of the eco-environment. Furthermore, the functions of soil conservation, water conservation, and biodiversity protection were integrated with exploitation-prohibited areas, and an organic combination of ecological needs and social service functions was created. Spatial comprehensive overlay analysis and processing revealed that the combination marked nine major ecological red-line areas in a total area of 5,030.58 km2, which occupied 44.16% of the total basin area. By combining the current eco-environmental situation of the Chishui River Basin with the marked out red-line areas, this research proposed corresponding ecological red-line area management suggestions. These suggestions are expected to provide a scientific foundation for eco-environmental protection and subsequent scientific research in Chishui River Basin.

Influence of Mesenchymal Stem Cells Conditioned Media on Proliferation of Urinary Tract Cancer Cell Lines and Their Sensitivity to Ciprofloxacin.

PubMed

Maj, Malgorzata; Bajek, Anna; Nalejska, Ewelina; Porowinska, Dorota; Kloskowski, Tomasz; Gackowska, Lidia; Drewa, Tomasz

2017-06-01

Mesenchymal stem cells (MSCs) are known to interact with cancer cells through direct cell-to-cell contact and secretion of paracrine factors, although their exact influence on tumor progression in vivo remains unclear. To better understand how fetal and adult stem cells affect tumors, we analyzed viability of human renal (786-0) and bladder (T24) carcinoma cell lines cultured in conditioned media harvested from amniotic fluid-derived stem cells (AFSCs) and adipose-derived stem cells (ASCs). Both media reduced metabolic activity of 786-0 cells, however, decreased viability of T24 cells was noted only after incubation with conditioned medium from ASCs. To test the hypothesis that MSCs-secreted factors might be involved in chemoresistance acquisition, we further analyzed influence of mesenchymal stem cell conditioned media (MSC-CM) on cancer cells sensitivity to ciprofloxacin, that is considered as potential candidate agent for urinary tract cancers treatment. Significantly increased resistance to tested drug indicates that MSCs may protect cancer cells from chemotherapy. J. Cell. Biochem. 118: 1361-1368, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Distance determination to Broad Line Absorbers in AGN

NASA Astrophysics Data System (ADS)

Bautista, Manuel; Arav, N.; Dunn, J.; Edmonds, D.; Korista, K. T.; Moe, M.; Benn, C.; Ignacio, G.

2009-01-01

We present various techniques for the determination of the physical conditions (density, temperature, total hydrogen column density, and ionization structure), chemical composition, and distances of Broad Line Absorbers (BAL) to the central engine in AGN. We start by discussing various density diagnostics from absorption lines from species such as C II, Si II, and Fe III. On the other hand, lines from metastable levels Fe II are often affected by Bowen fluorescence by scattered C IV photons. Lines from metastable levels of Ni II are usually excited by continuum fluorescence and mostly sensitive to the strength of the radiation field shortward of the Lyman continuum and as such they cam be used as direct distance indicators. Further, we show how the total hydrogen density of the absorber, its ionization parameter and distance can be determined through photoionization modeling of the absorber. Finally, we present our results for outflows of three different quasars: QSO 2359-1241 and SDSS J0318-0600.

Protein disulfide isomerases: Impact of thapsigargin treatment on their expression in melanoma cell lines.

PubMed

Silva, Zélia; Veríssimo, Teresa; Videira, Paula A; Novo, Carlos

2015-08-01

Anti-cancer treatments usually elevate the content of unfolded or misfolded proteins in the endoplasmic reticulum (ER). Here we aimed to get insights into the relation between sensitivity of melanoma cell lines to the ER stress inducer thapsigargin (THG) and the genetic expression of protein disulfide isomerase family members (PDIs). The expression of PDIs was analysed by flow cytometry and real-time PCR. The results showed that SK-MEL-30, the less THG sensitive cell line, displays higher basal PDIs' expression levels and the sensitivity is increased by the PDIs inhibitor bacitracin. While SK-MEL-30 PDIs' expression is not THG dose-dependent, an increase in glucose related protein 78 (GRP78), PDIA5, PDIA6, and thioredoxin-related-transmembrane proteins' (TMX3 and TMX4) expression, in response to higher drug concentrations, was observed in MNT-1. The differences in PDIs' gene expression in MNT-1 suggest a different response to ER stress compared to the other cell lines and highlight the importance of understanding the diversity among cancer cells. Copyright © 2015 Elsevier B.V. All rights reserved.

Discrimination of skin sensitizers from non-sensitizers by interleukin-1α and interleukin-6 production on cultured human keratinocytes.

PubMed

Jung, Daun; Che, Jeong-Hwan; Lim, Kyung-Min; Chun, Young-Jin; Heo, Yong; Seok, Seung Hyeok

2016-09-01

In vitro testing methods for classifying sensitizers could be valuable alternatives to in vivo sensitization testing using animal models, such as the murine local lymph node assay (LLNA) and the guinea pig maximization test (GMT), but there remains a need for in vitro methods that are more accurate and simpler to distinguish skin sensitizers from non-sensitizers. Thus, the aim of our study was to establish an in vitro assay as a screening tool for detecting skin sensitizers using the human keratinocyte cell line, HaCaT. HaCaT cells were exposed to 16 relevant skin sensitizers and 6 skin non-sensitizers. The highest dose used was the dose causing 75% cell viability (CV75) that we determined by an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The levels of extracellular production of interleukin-1α (IL-1α) and IL-6 were measured. The sensitivity of IL-1α was 63%, specificity was 83% and accuracy was 68%. In the case of IL-6, sensitivity: 69%, specificity: 83% and accuracy: 73%. Thus, this study suggests that measuring extracellular production of pro-inflammatory cytokines IL-1α and IL-6 by human HaCaT cells may potentially classify skin sensitizers from non-sensitizers. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Does gravity influence the visual line bisection task?

PubMed

Drakul, A; Bockisch, C J; Tarnutzer, A A

2016-08-01

The visual line bisection task (LBT) is sensitive to perceptual biases of visuospatial attention, showing slight leftward (for horizontal lines) and upward (for vertical lines) errors in healthy subjects. It may be solved in an egocentric or allocentric reference frame, and there is no obvious need for graviceptive input. However, for other visual line adjustments, such as the subjective visual vertical, otolith input is integrated. We hypothesized that graviceptive input is incorporated when performing the LBT and predicted reduced accuracy and precision when roll-tilted. Twenty healthy right-handed subjects repetitively bisected Earth-horizontal and body-horizontal lines in darkness. Recordings were obtained before, during, and after roll-tilt (±45°, ±90°) for 5 min each. Additionally, bisections of Earth-vertical and oblique lines were obtained in 17 subjects. When roll-tilted ±90° ear-down, bisections of Earth-horizontal (i.e., body-vertical) lines were shifted toward the direction of the head (P < 0.001). However, after correction for vertical line-bisection errors when upright, shifts disappeared. Bisecting body-horizontal lines while roll-tilted did not cause any shifts. The precision of Earth-horizontal line bisections decreased (P ≤ 0.006) when roll-tilted, while no such changes were observed for body-horizontal lines. Regardless of the trial condition and paradigm, the scanning direction of the bisecting cursor (leftward vs. rightward) significantly (P ≤ 0.021) affected line bisections. Our findings reject our hypothesis and suggest that gravity does not modulate the LBT. Roll-tilt-dependent shifts are instead explained by the headward bias when bisecting lines oriented along a body-vertical axis. Increased variability when roll-tilted likely reflects larger variability when bisecting body-vertical than body-horizontal lines. Copyright © 2016 the American Physiological Society.

Silicon X-ray line emission from solar flares and active regions

NASA Technical Reports Server (NTRS)

Parkinson, J. H.; Wolff, R. S.; Kestenbaum, H. L.; Ku, W. H.-M.; Lemen, J. R.; Long, K. S.; Novick, R.; Suozzo, R. J.; Weisskopf, M. C.

1978-01-01

New observations of solar flare and active region X-ray spectra obtained with the Columbia University instrument on OSO-8 are presented and discussed. The high sensitivity of the graphite crystal panel has allowed both line and continuum spectra to be served with moderate spectral resolution. Observations with higher spectral resolution have been made with a panel of pentaerythritol crystals. Twenty-nine lines between 1.5 and 7.0 A have been resolved and identified, including several dielectronic recombination satellite lines to Si XIV and Si XIII lines which have been observed for the first time. It has been found that thermal continuum models specified by single values of temperature and emission measure have fitted the data adequately, there being good agreement with the values of these parameters derived from line intensity ratios.

Modeling Auditory-Haptic Interface Cues from an Analog Multi-line Telephone

NASA Technical Reports Server (NTRS)

Begault, Durand R.; Anderson, Mark R.; Bittner, Rachael M.

2012-01-01

The Western Electric Company produced a multi-line telephone during the 1940s-1970s using a six-button interface design that provided robust tactile, haptic and auditory cues regarding the "state" of the communication system. This multi-line telephone was used as a model for a trade study comparison of two interfaces: a touchscreen interface (iPad)) versus a pressure-sensitive strain gauge button interface (Phidget USB interface controllers). The experiment and its results are detailed in the authors' AES 133rd convention paper " Multimodal Information Management: Evaluation of Auditory and Haptic Cues for NextGen Communication Dispays". This Engineering Brief describes how the interface logic, visual indications, and auditory cues of the original telephone were synthesized using MAX/MSP, including the logic for line selection, line hold, and priority line activation.

An Emission Measure Analysis of Stars Near the Transition Region Dividing Line

NASA Astrophysics Data System (ADS)

Linsky, Jeffery L.

We request high dispersion, short wavelength IUE spectra for three of the stars beta Gem (K0III), alpha Tau (K5III), epsilon Gem (G81b) and beta Cam (G0Ib) with exposure times of 16 hours or greater. These data will allow the measurement of line profiles, widths and Doppler shifts as well as density sensitive and opacity sensitive line ratios. Models of chromospheric and transition region structure will be calculated by emission measure techniques and model atmosphere computations for optically thick resonance lines such as MgII h and k, including partial redistribution radiation transfer. The chromospheric models will be used to investigate the energy balance of the atmosphere and the nature of the energy deposition processes. These results will be considered in relation to the evolutionary status of the stars, and will be compared with the atmospheric model properties of other stars previously studied by the authors and their collaborators.

Center-to-limb variation of solar line profiles as a test of NLTE line formation calculations

NASA Astrophysics Data System (ADS)

Allende Prieto, C.; Asplund, M.; Fabiani Bendicho, P.

2004-09-01

We present new observations of the center-to-limb variation of spectral lines in the quiet Sun. Our long-slit spectra are corrected for scattered light, which amounts to 4-8% of the continuum intensity, by comparison with a Fourier transform spectrum of the disk center. Different spectral lines exhibit different behaviors, depending on their sensitivity to the physical conditions in the photosphere and the range of depths they probe as a function of the observing angle, providing a rich database to test models of the solar photosphere and line formation. We examine the effect of inelastic collisions with neutral hydrogen in NLTE line formation calculations of the oxygen infrared triplet, and the Na I λ6160.8 line. Adopting a classical one-dimensional theoretical model atmosphere, we find that the sodium transition, formed in higher layers, is more effectively thermalized by hydrogen collisions than the high-excitation oxygen lines. This result appears as a simple consequence of the decrease of the ratio NH/Ne with depth in the solar photosphere. The center-to-limb variation of the selected lines is studied both under LTE and NLTE conditions. In the NLTE analysis, inelastic collisions with hydrogen atoms are considered with a simple approximation or neglected, in an attempt to test the validity of such approximation. For the sodium line studied, the best agreement between theory and observation happens when NLTE is considered and inelastic collisions with hydrogen are neglected in the rate equations. The analysis of the oxygen triplet benefits from a very detailed calculation using an LTE three-dimensional model atmosphere and NLTE line formation. The χ2 statistics favors including hydrogen collisions with the approximation adopted, but the oxygen abundance derived in that case is significantly higher than the value derived from OH infrared transitions. GCT spectra are only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130

Characterization of LHY-821, a novel moderately differentiated endometrial carcinoma cell line.

PubMed

Hu, Qian; Yu, Li; Chen, Rui; Zhang, Yan; Xie, Ya; Liao, Qinping

2012-08-01

Endometrial cancer is a major problem for women but only a small number of comprehensively characterized cell models are available for studies. Here, we established a new cell line derived from a Stage IIIc(1) Grade 2 endometrial adenocarcinoma. The cell line, designated LHY-821, was characterized using growth curve, karyotyping, immunohistochemical staining, immunoblotting, drug sensitivity assay, invasion assay, and xenografting in nude mice. LHY-821 has a doubling time of about 46 h and a colony-forming efficiency of approximately 71 %. These cells expresse high levels of progesterone receptor but not estrogen receptor and are sensitive to medroxyprogesterone acetate (MPA). LHY-821 also expresses pan-cytokeratin, PTEN, p53, β-catenin, IGF-1, and IGF-2. In addition, karyotype analysis revealed that LHY-821 possessed a near diploid karyotype including 6q-, 10p-, Xq-, 13q+, 17p+, and Triplo-12. LHY-821 showed highly tumorigenicity in nude mice (100 %) and weak invasiveness. Chemosensitivity tests showed that LHY-821 was sensitive to both carboplatin and paclitaxel. LHY-821 is an immortalized cell line which had survived more than 80 serial passages; it may provide a novel tool to study the molecular mechanism and potential treatment for endometrial cancer.

Observability of atomic line features in strong magnetic fields

NASA Technical Reports Server (NTRS)

Wunner, G.; Ruder, H.; Herold, H.; Truemper, J.

1981-01-01

The physical properties of atoms in superstrong magnetic fields, characteristic of neutron stars, and the possibility of detecting magnetically strongly shifted atomic lines in the spectra of magnetized X-ray pulsars are discussed. It is suggested that it is recommendable to look for magnetically strongly shifted Fe 26 Lyman lines in rotating neutron stars of not too high luminosity using spectrometers working in the energy range 10 - 20 keV, with sensitivities to minus 4 power photons per sq cm and second, and resolution E/delta E approx. 10-100.

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

PubMed

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

2007-02-01

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

The semi-Hooperon: Gamma-ray and anti-proton excesses in the Galactic Center

NASA Astrophysics Data System (ADS)

Arcadi, Giorgio; Queiroz, Farinaldo S.; Siqueira, Clarissa

2017-12-01

A puzzling excess in gamma-rays at GeV energies has been observed in the center of our galaxy using Fermi-LAT data. Its origin is still unknown, but it is well fitted by Weakly Interacting Massive Particles (WIMPs) annihilations into quarks with a cross section around 10-26 cm3s-1 with masses of 20-50 GeV, scenario which is promptly revisited. An excess favoring similar WIMP properties has also been seen in anti-protons with AMS-02 data potentially coming from the Galactic Center as well. In this work, we explore the possibility of fitting these excesses in terms of semi-annihilating dark matter, dubbed as semi-Hooperon, with the process WIMP WIMP → WIMP X being responsible for the gamma-ray excess, where X = h , Z. An interesting feature of semi-annihilations is the change in the relic density prediction compared to the standard case, and the possibility to alleviate stringent limits stemming from direct detection searches. Moreover, we discuss which models might give rise to a successful semi-Hooperon setup in the context of Z3,Z4 and extra "dark" gauge symmetries.

EVIDENCE FOR PHOTOIONIZATION-DRIVEN BROAD ABSORPTION LINE VARIABILITY

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Tinggui; Yang, Chenwei; Wang, Huiyuan

2015-12-01

We present a qualitative analysis of the variability of quasar broad absorption lines using the large multi-epoch spectroscopic data set of the Sloan Digital Sky Survey Data Release 10. We confirm that variations of absorption lines are highly coordinated among different components of the same ion or the same absorption component of different ions for C iv, Si iv, and N v. Furthermore, we show that the equivalent widths (EWs) of the lines decrease or increase statistically when the continuum brightens or dims. This is further supported by the synchronized variations of emission and absorption-line EWs when the well-established intrinsicmore » Baldwin effect for emission lines is taken into account. We find that the emergence of an absorption component is usually accompanied by the dimming of the continuum while the disappearance of an absorption-line component is accompanied by the brightening of the continuum. This suggests that the emergence or disappearance of a C iv absorption component is only the extreme case, when the ionic column density is very sensitive to continuum variations or the continuum variability the amplitude is larger. These results support the idea that absorption-line variability is driven mainly by changes in the gas ionization in response to continuum variations, that the line-absorbing gas is highly ionized, and in some extreme cases, too highly ionized to be detected in UV absorption lines. Due to uncertainties in the spectroscopic flux calibration, we cannot quantify the fraction of quasars with asynchronized continuum and absorption-line variations.« less

The DarkSide-50 Experiment: Electron Recoil Calibrations and A Global Energy Variable

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hackett, Brianne Rae

2017-01-01

Over the course of decades, there has been mounting astronomical evidence for non-baryonic dark matter, yet its precise nature remains elusive. A favored candidate for dark matter is the Weakly Interacting Massive Particle (WIMP) which arises naturally out of extensions to the Standard Model. WIMPs are expected to occasionally interact with particles of normal matter through nuclear recoils. DarkSide-50 aims to detect this type of particle through the use of a two-phase liquid argon time projection chamber. To make a claim of discovery, an accurate understanding of the background and WIMP search region is imperative. Knowledge of the backgrounds ismore » done through extensive studies of DarkSide-50's response to electron and nuclear recoils. The CALibration Insertion System (CALIS) was designed and built for the purpose of introduc- ing radioactive sources into or near the detector in a joint eort between Fermi National Laboratory (FNAL) and the University of Hawai'i at Manoa. This work describes the testing, installation, and commissioning of CALIS at the Laboratori Nazionali del Gran Sasso. CALIS has been used in mul- tiple calibration campaigns with both neutron and sources. In this work, DarkSide-50's response to electron recoils, which are important for background estimations, was studied through the use of calibration sources by constructing a global energy variable which takes into account the anti- correlation between scintillation and ionization signals produced by interactions in the liquid argon. Accurately reconstructing the event energy correlates directly with quantitatively understanding the WIMP sensitivity in DarkSide-50. This work also validates the theoretically predicted decay spectrum of 39Ar against 39Ar decay data collected in the early days of DarkSide-50 while it was lled with atmospheric argon; a validation of this type is not readily found in the literature. Finally, we show how well the constructed energy variable can predict energy

The Darkside-50 Experiment: Electron Recoil Calibrations and a Global Energy Variable

NASA Astrophysics Data System (ADS)

Hackett, Brianne R.

Over the course of decades, there has been mounting astronomical evidence for non-baryonic dark matter, yet its precise nature remains elusive. A favored candidate for dark matter is the Weakly Interacting Massive Particle (WIMP) which arises naturally out of extensions to the Standard Model. WIMPs are expected to occasionally interact with particles of normal matter through nuclear recoils. DarkSide-50 aims to detect this type of particle through the use of a two-phase liquid argon time projection chamber. To make a claim of discovery, an accurate understanding of the background and WIMP search region is imperative. Knowledge of the backgrounds is done through extensive studies of DarkSide-50's response to electron and nuclear recoils. The CALibration Insertion System (CALIS) was designed and built for the purpose of introducing radioactive sources into or near the detector in a joint effort between Fermi National Laboratory (FNAL) and the University of Hawai'i at Manoa. This work describes the testing, installation, and commissioning of CALIS at the Laboratori Nazionali del Gran Sasso. CALIS has been used in multiple calibration campaigns with both neutron and gamma sources. In this work, DarkSide-50's response to electron recoils, which are important for background estimations, was studied through the use of gamma calibration sources by constructing a global energy variable which takes into account the anti-correlation between scintillation and ionization signals produced by interactions in the liquid argon. Accurately reconstructing the event energy correlates directly with quantitatively understanding the WIMP sensitivity in DarkSide-50. This work also validates the theoretically predicted beta decay spectrum of 39Ar against 39Ar beta decay data collected in the early days of DarkSide-50 while it was filled with atmospheric argon; a validation of this type is not readily found in the literature. Finally, we show how well the constructed energy variable can

Grounding line migration of Petermann Gletscher, north Greenland, detected using satellite radar interferometry

NASA Technical Reports Server (NTRS)

Rignot, Eric

1997-01-01

Ice Sheet grounding lines are sensitive indicator of changes in ice thickness, sea level or elevation of the sea bed. Here, we use the synthetic-aperture radar interferometry technique to detect the migration of thel imit of tidal flexing, or hinge line, of Petermann Gletscher, a major outlet glacier of north Greenland which develops an extensive floating tongue.

Quality Assurance in the Polio Laboratory. Cell Sensitivity and Cell Authentication Assays.

PubMed

Dunn, Glynis

2016-01-01

The accuracy of poliovirus surveillance is largely dependent on the quality of the cell lines used for virus isolation, which is the foundation of poliovirus diagnostic work. Many cell lines are available for the isolation of enteroviruses, whilst genetically modified L20B cells can be used as a diagnostic tool for the identification of polioviruses. To be confident that cells can consistently isolate the virus of interest, it is necessary to have a quality assurance system in place, which will ensure that the cells in use are not contaminated with other cell lines or microorganisms and that they remain sensitive to the viruses being studied.The sensitivity of cell lines can be assessed by the regular testing of a virus standard of known titer in the cell lines used for virus isolation. The titers obtained are compared to previously obtained titers in the same assay, so that any loss of sensitivity can be detected.However, the detection of cell line cross contamination is more difficult. DNA bar coding is a technique that uses a short DNA sequence from a standardized position in the genome as a molecular diagnostic assay for species-level identification. For almost all groups of higher animals, the cytochrome c oxidase subunit 1 of mitochondrial DNA (CO1) is emerging as the standard barcode region. This region is 648 nucleotide base pairs long in most phylogenetic groups and is flanked by regions of conserved sequences, making it relatively easy to isolate and analyze. DNA barcodes vary among individuals of the same species to a very minor degree (generally less than 1-2 %), and a growing number of studies have shown that the COI sequences of even closely related species differ by several per cent, making it possible to identify different species with high confidence.

Diatomic predissociation line widths

NASA Technical Reports Server (NTRS)

Child, M. S.

1973-01-01

Predissociation by rotation and curve crossing in diatomic molecules is discussed. The pattern of predissociation line widths is seen as providing a highly sensitive yardstick for the determination of unknown potential curves. In addition, the computation of such a pattern for given potential curves is considered a matter of routine, unless the predissociation happens to occur from an adiabatic potential curve. Analytic formulas are used to provide physical insight into the details of the predissociation pattern, to the extent that a direct inversion procedure is developed for determination of the repulsive potential curves for Type 1 predissociations.

Results from the Super Cryogenic Dark Matter Search Experiment at Soudan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agnese, R.; Aramaki, T.; Arnquist, I. J.

We report the result of a blinded search for Weakly Interacting Massive Particles (WIMPs) using the full SuperCDMS Soudan dataset. With an exposure of 1690 kg days, a single event was observed after unblinding, consistent with expected backgrounds. This analysis (combined with previous Ge results) sets an upper limit on the spin-independent WIMP-nucleon cross section of 1.4x10^-44 (1.0x10^-44) cm^2 at 46 GeV/c^2 . These results set the strongest limits for WIMP-germanium-nucleus interactions for masses >12 GeV/c^2.

More on molecular excitations: Dark matter detection in ice

DOE PAGES

Va'vra, J.

2016-08-10

In this paper we investigate di-atomic molecules embedded in ice crystals under strain. In this environment coherent vibrations of many OH-bonds may be generated by one WIMP collision. The detection of such multiple-photon signals may provide a signature of a 100 GeV/c 2 WIMP. To do a proper lab test of “WIMP-induced” multi-photon emission is very difficult. As a result, we suggest that Ice Cube make a search for multi-photon events, and investigate whether the rate of such events exhibits yearly modulation.

Comparison of on-line and off-line methods to quantify reactive oxygen species (ROS) in atmospheric aerosols

NASA Astrophysics Data System (ADS)

Fuller, S. J.; Wragg, F. P. H.; Nutter, J.; Kalberer, M.

2014-08-01

Atmospheric aerosol particle concentrations have been linked with a wide range of pulmonary and cardio-vascular diseases but the particle properties responsible for these negative health effects are largely unknown. It is often speculated that reactive oxygen species (ROS) present in atmospheric particles lead to oxidative stress in, and ultimately disease of, the human lung. The quantification of ROS is highly challenging because some ROS components such as radicals are highly reactive and therefore short-lived. Thus, fast analysis methods are likely advantageous over methods with a long delay between aerosol sampling and ROS analysis. We present for the first time a detailed comparison of conventional off-line and fast on-line methods to quantify ROS in organic aerosols. For this comparison a new and fast on-line instrument was built and characterized to quantify ROS in aerosol particles with high sensitivity and a limit of detection of 4 nmol H2O2 equivalents per m3 air. ROS concentrations are measured with a time resolution of approximately 15 min, which allows the tracking of fast changing atmospheric conditions. The comparison of the off-line and on-line method shows that, in oxidized organic model aerosol particles, the majority of ROS have a very short lifetime of a few minutes whereas a small fraction is stable for a day or longer. This indicates that off-line techniques, where there is often a delay of hours to days between particle collection and ROS analysis, may severely underestimate true ROS concentrations and that fast on-line techniques are necessary for a reliable ROS quantification in atmospheric aerosol particles and a meaningful correlation with health outcomes.

Human Adenocarcinoma Cell Line Sensitivity to Essential Oil Phytocomplexes from Pistacia Species: a Multivariate Approach.

PubMed

Buriani, Alessandro; Fortinguerra, Stefano; Sorrenti, Vincenzo; Dall'Acqua, Stefano; Innocenti, Gabbriella; Montopoli, Monica; Gabbia, Daniela; Carrara, Maria

2017-08-11

Principal component analysis (PCA) multivariate analysis was applied to study the cytotoxic activity of essential oils from various species of the Pistacia genus on human tumor cell lines. In particular, the cytotoxic activity of essential oils obtained from P. lentiscus , P. lentiscus var. chia (mastic gum), P. terebinthus , P. vera , and P. integerrima , was screened on three human adenocarcinoma cell lines: MCF-7 (breast), 2008 (ovarian), and LoVo (colon). The results indicate that all the Pistacia phytocomplexes, with the exception of mastic gum oil, induce cytotoxic effects on one or more of the three cell lines. PCA highlighted the presence of different cooperating clusters of bioactive molecules. Cluster variability among species, and even within the same species, could explain some of the differences seen among samples suggesting the presence of both common and species-specific mechanisms. Single molecules from one of the most significant clusters were tested, but only bornyl-acetate presented cytotoxic activity, although at much higher concentrations (IC 50 = 138.5 µg/mL) than those present in the essential oils, indicating that understanding of the full biological effect requires a holistic vision of the phytocomplexes with all its constituents.

Estradiol impairs the antiproliferative and proapoptotic effect of Zoledronic acid in hormone sensitive breast cancer cells in vitro.

PubMed

Gschwantler-Kaulich, Daphne; Weingartshofer, Sigrid; Grunt, Thomas W; Mairhofer, Mario; Tan, Yen; Gamper, Jutta; Singer, Christian F

2017-01-01

Zoledronic acid (ZA) has antiresorptive effects and protects from bone metastasis in women with early breast cancer. In addition, in postmenopausal women with endocrine responsive breast cancer ZA prolongs DFS. The exact mechanism is still unclear. We have therefore investigated the effect of increasing concentrations of ZA in breast cancer cell lines in the absence or presence of estradiol to mimic the hormonal environment in vitro. Using assays for cell proliferation (EZ4U, BrdU) and cell death (Annexin/PI), we have analyzed the dose-dependent antiproliferative and pro-apoptotic effects of ZA in two hormone sensitive cell lines (MCF-7 and T47D) and a hormone insensitive, triple negative cell line (MDA-MB-231) in the presence of 0, 1 and 10 nM estradiol. In the absence of estradiol, ZA exerts dose-dependent antiproliferative and pro-apoptotic antitumor effects in both, hormone sensitive (MCF-7, T47D) and -insensitive (MDA-MB-231) breast cancer cell lines (p<0.0001). In the presence of estradiol, the antitumoral effect of ZA was significantly decreased only in the hormone sensitive MCF-7 and T47D cell lines (p = 0.0008 and p = 0.0008, respectively). We have demonstrated that estradiol impairs the antiproliferative and proapoptotic effect of ZA in hormone sensitive, but not in hormone insensitive breast cancer cell lines. Our findings provide a possible explanation for the differential effect of ZA on DFS in pre- and postmenopausal patients with hormone sensitive early breast cancer, which has been demonstrated clinically. We further hypothesize that endocrine insensitive tumors such as triple negative breast cancer (TNBC) should benefit from ZA irrespective of their menopausal status.

l-Type Amino Acid Transporter-1 Overexpression and Melphalan Sensitivity in Barrett's Adenocarcinoma1

PubMed Central

Lin, Jules; Raoof, Duna A; Thomas, Dafydd G; Greenson, Joel K; Giordano, Thomas J; Robinson, Gregory S; Bourner, Maureen J; Bauer, Christopher T; Orringer, Mark B; Beer, David G

2004-01-01

Abstract The L-type amino acid transporter-1 (LAT-1) has been associated with tumor growth. Using cDNA microarrays, overexpression of LAT-1 was found in 87.5% (7/8) of esophageal adenocarcinomas relative to 12 Barrett's samples (33% metaplasia and 66% dysplasia) and was confirmed in 100% (28/28) of Barrett's adenocarcinomas by quantitative reverse transcription polymerase chain reaction. Immunohistochemistry revealed LAT-1 staining in 37.5% (24/64) of esophageal adenocarcinomas on tissue microarray. LAT-1 also transports the amino acid-related chemotherapeutic agent, melphalan. Two esophageal adenocarcinoma and one esophageal squamous cell line, expressing LAT-1 on Western blot analysis, were sensitive to therapeutic doses of melphalan (P < .001). Simultaneous treatment with the competitive inhibitor, BCH [2-aminobicyclo-(2,1,1)-heptane-2-carboxylic acid], decreased sensitivity to melphalan (P < .05). In addition, confluent esophageal squamous cultures were less sensitive to melphalan (P < .001) and had a decrease in LAT-1 protein expression. Tumors from two esophageal adenocarcinoma cell lines grown in nude mice retained LAT-1 mRNA expression. These results demonstrate that LAT-1 is highly expressed in a subset of esophageal adenocarcinomas and that Barrett's adenocarcinoma cell lines expressing LAT-1 are sensitive to melphalan. LAT-1 expression is also retained in cell lines grown in nude mice providing a model to evaluate melphalan as a chemotherapeutic agent against esophageal adenocarcinomas expressing LAT-1. PMID:15068672

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

PubMed Central

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

2016-01-01

The objective of this study was to investigate the optimization of a high energy in-line phase sensitive x-ray imaging prototype under different geometric and operating conditions for mammography application. A phase retrieval algorithm based on phase attenuation duality (PAD) was applied to the phase contrast images acquired by the prototype. Imaging performance was investigated at four magnification values of 1.67, 2, 2.5 and 3 using an acrylic edge, an American College of Radiology (ACR) mammography phantom and contrast detail (CD) phantom with tube potentials of 100, 120 and 140 kVp. The ACR and CD images were acquired at the same mean glandular dose (MGD) of 1.29 mGy with a computed radiography (CR) detector of 43.75 µm pixel pitch at a fixed source to image distance (SID) of 170 cm. The x-ray tube focal spot size was kept constant as 7 µm while a 2.5 mm thick aluminum (Al) filter was used for beam hardening. The performance of phase contrast and phase retrieved images were compared with computer simulations based on the relative phase contrast factor (RPF) at high x-ray energies. The imaging results showed that the x-ray tube operated at 100 kVp under the magnification of 2.5 exhibits superior imaging performance which is in accordance to the computer simulations. As compared to the phase contrast images, the phase retrieved images of the ACR and CD phantoms demonstrated improved imaging contrast and target discrimination. We compared the CD phantom images acquired in conventional contact mode with and without the anti-scatter grid using the same prototype at 1.295 mGy and 2.59 mGy using 40 kVp, a 25 µm rhodium (Rh) filter. At the same radiation dose, the phase sensitive images provided improved detection capabilities for both the large and small discs, while compared to the double dose image acquired in conventional mode, the observer study also indicated that the phase sensitive images provided improved detection capabilities for the large discs. This

Fabrics Protect Sensitive Skin from UV Rays

NASA Technical Reports Server (NTRS)

2009-01-01

Late Johnson Space Center engineer Dr. Robert Dotts headed a team to develop cool suits for children suffering from life-threatening sun sensitivities. Dotts hoped to develop ultraviolet-blocking technology in a fabric that -- unlike in a bulky space suit -- could remain comfortable, light, and breathable in the sun and heat. The team worked with SPF 4 US LLC (SPF) of Madison, Wisconsin to design ultraviolet-blocking cool suits, which protect sun-sensitive patients and enable them to experience life outdoors safely. Using knowledge gained during the NASA collaboration, SPF created an entire line of ultraviolet-blocking apparel.

Bioanalytical Applications of Fluorescence Line-Narrowing and Non-Line-Narrowing Spectroscopy Interfaced with Capillary Electrophoresis and High-Performance Liquid Chromatography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roberts, Kenneth Paul

Capillary electrophoresis (CE) and high-performance liquid chromatography (HPLC) are widely used analytical separation techniques with many applications in chemical, biochemical, and biomedical sciences. Conventional analyte identification in these techniques is based on retention/migration times of standards; requiring a high degree of reproducibility, availability of reliable standards, and absence of coelution. From this, several new information-rich detection methods (also known as hyphenated techniques) are being explored that would be capable of providing unambiguous on-line identification of separating analytes in CE and HPLC. As further discussed, a number of such on-line detection methods have shown considerable success, including Raman, nuclear magnetic resonancemore » (NMR), mass spectrometry (MS), and fluorescence line-narrowing spectroscopy (FLNS). In this thesis, the feasibility and potential of combining the highly sensitive and selective laser-based detection method of FLNS with analytical separation techniques are discussed and presented. A summary of previously demonstrated FLNS detection interfaced with chromatography and electrophoresis is given, and recent results from on-line FLNS detection in CE (CE-FLNS), and the new combination of HPLC-FLNS, are shown.« less

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

NASA Astrophysics Data System (ADS)

Linnarsson, M. K.; Hallén, A.; Åström, J.; Primetzhofer, D.; Legendre, S.; Possnert, G.

2012-09-01

A new beam line for medium energy ion mass scattering (MEIS) has been designed and set up at the Ångström 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, 1H+, 4He+, and 11B+. 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.

Research and analysis on response characteristics of bracket-line coupling system under wind load

NASA Astrophysics Data System (ADS)

Jiayu, Zhao; Qing, Sun

2018-01-01

In this paper, a three-dimensional finite element model of bracket-line coupling system is established based on ANSYS software. Using the wind velocity time series which is generated by MATLAB as a power input, by comparing and analyzing the influence of different wind speeds and different wind attack angles, it is found that when 0 degree wind acts on the structure, wires have a certain damping effect in the bracket-line coupling system and at the same wind speed, the 90 degree direction is the most unfavorable wind direction for the whole structure according to the three kinds of angle wind calculated at present. In the bracket-line coupling system, the bracket structure is more sensitive to the increase of wind speed while the conductors are more sensitive to the change of wind attack angle.

Rabeprazole, Minocycline, Amoxicillin, and Bismuth as First-Line and Second-Line Regimens for Helicobacter pylori Eradication.

PubMed

Song, Zhiqiang; Suo, Baojun; Zhang, Lingyun; Zhou, Liya

2016-12-01

Because of general unavailability of tetracycline, common adverse effects, and complicated administration, the clinical application of bismuth quadruple therapy often faces difficulties. Whether the combination of minocycline and amoxicillin can replace tetracycline and metronidazole for Helicobacter pylori eradication remains unclear. This study was to determine the efficacy, compliance, and safety of rabeprazole, minocycline, amoxicillin, and bismuth (RMAB) therapy as first-line and second-line regimens. Between July 2013 and December 2015, a total of 160 patients in first-line and 70 patients in second-line therapies received rabeprazole 10 mg, minocycline 100 mg, amoxicillin 1000 mg, and bismuth potassium citrate 220 mg twice daily for 14 days. Eradication status was assessed 6-12 weeks after treatment. RMAB therapy achieved the eradication rates of 87.5% (95% confidence interval, 81.9-92.5%, intention-to-treat analysis), 90.9% (85.7-95.5%, modified intention-to-treat analysis), and 92.6% (88.5-96.6%, per-protocol analysis) in first-line therapy in a setting with high antibiotic resistance rates (amoxicillin 3.4%, clarithromycin 39.7%, metronidazole 60.3%, levofloxacin 36.2%, tetracycline 3.4%, and minocycline 6.9%). As for second-line therapy, the eradication rates were 82.9% (74.3-91.4%, intention-to-treat analysis), 86.6% (77.6-94.0%, modified intention-to-treat analysis), and 89.1% (81.3-95.3%, per-protocol analysis). Totally, 24.0% patients had adverse effects, 2.2% discontinued medications, and good compliance was achieved in 94.7%. Poor compliance and minocycline resistance were identified as the risk factors for treatment failure. Significant differences in efficacy existed among the groups of both sensitive (48/51 and 18/20), isolated amoxicillin resistance (1/1 and 0/0), isolated minocycline resistance (2/3 and 1/1), and dual resistance (0/1 and 0/1) in both first-line (p = .004) and second-line (p = .035) therapies. The eradication efficacies of RMAB

Pressurized capillary electrochromatographic analysis of water-soluble vitamins by combining with on-line concentration technique.

PubMed

Jia, Li; Liu, Yaling; Du, Yanyan; Xing, Da

2007-06-22

A pressurized capillary electrochromatography (pCEC) system was developed for the separation of water-soluble vitamins, in which UV absorbance was used as the detection method and a monolithic silica-ODS column as the separation column. The parameters (type and content of organic solvent in the mobile phase, type and concentration of electrolyte, pH of the electrolyte buffer, applied voltage and flow rate) affecting the separation resolution were evaluated. The combination of two on-line concentration techniques, namely, solvent gradient zone sharpening effect and field-enhanced sample stacking, was utilized to improve detection sensitivity, which proved to be beneficial to enhance the detection sensitivity by enabling the injection of large volumes of samples. Coupling electrokinetic injection with the on-line concentration techniques was much more beneficial for the concentration of positively charged vitamins. Comparing with the conventional injection mode, the enhancement in the detection sensitivities of water-soluble vitamins using the on-line concentration technique is in the range of 3 to 35-fold. The developed pCEC method was applied to evaluate water-soluble vitamins in corns.

Update on the MiniCLEAN dark matter experiment

DOE PAGES

Rielage, K.; Akashi-Ronquest, M.; Bodmer, M.; ...

2015-03-24

The direct search for dark matter is entering a period of increased sensitivity to the hypothetical Weakly Interacting Massive Particle (WIMP). One such technology that is being examined is a scintillation only noble liquid experiment, MiniCLEAN. MiniCLEAN utilizes over 500 kg of liquid cryogen to detect nuclear recoils from WIMP dark matter and serves as a demonstration for a future detector of order 50 to 100 tonnes. The liquid cryogen is interchangeable between argon and neon to study the A² dependence of the potential signal and examine backgrounds. MiniCLEAN utilizes a unique modular design with spherical geometry to maximize themore » light yield using cold photomultiplier tubes in a single-phase detector. Pulse shape discrimination techniques are used to separate nuclear recoil signals from electron recoil backgrounds. MiniCLEAN will be spiked with additional ³⁹Ar to demonstrate the effective reach of the pulse shape discrimination capability. Assembly of the experiment is underway at SNOLAB and an update on the project is given.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rielage, K.; Akashi-Ronquest, M.; Bodmer, M.

The direct search for dark matter is entering a period of increased sensitivity to the hypothetical Weakly Interacting Massive Particle (WIMP). One such technology that is being examined is a scintillation only noble liquid experiment, MiniCLEAN. MiniCLEAN utilizes over 500 kg of liquid cryogen to detect nuclear recoils from WIMP dark matter and serves as a demonstration for a future detector of order 50 to 100 tonnes. The liquid cryogen is interchangeable between argon and neon to study the A² dependence of the potential signal and examine backgrounds. MiniCLEAN utilizes a unique modular design with spherical geometry to maximize themore » light yield using cold photomultiplier tubes in a single-phase detector. Pulse shape discrimination techniques are used to separate nuclear recoil signals from electron recoil backgrounds. MiniCLEAN will be spiked with additional ³⁹Ar to demonstrate the effective reach of the pulse shape discrimination capability. Assembly of the experiment is underway at SNOLAB and an update on the project is given.« less

Balancing data sharing requirements for analyses with data sensitivity

USGS Publications Warehouse

Jarnevich, C.S.; Graham, J.J.; Newman, G.J.; Crall, A.W.; Stohlgren, T.J.

2007-01-01

Data sensitivity can pose a formidable barrier to data sharing. Knowledge of species current distributions from data sharing is critical for the creation of watch lists and an early warning/rapid response system and for model generation for the spread of invasive species. We have created an on-line system to synthesize disparate datasets of non-native species locations that includes a mechanism to account for data sensitivity. Data contributors are able to mark their data as sensitive. This data is then 'fuzzed' in mapping applications and downloaded files to quarter-quadrangle grid cells, but the actual locations are available for analyses. We propose that this system overcomes the hurdles to data sharing posed by sensitive data. ?? 2006 Springer Science+Business Media B.V.

Combination of suberoylanilide hydroxamic acid with heavy ion therapy shows promising effects in infantile sarcoma cell lines

PubMed Central

2011-01-01

Introduction The pan-HDAC inhibitor (HDACI) suberoylanilide hydroxamic acid (SAHA) has previously shown to be a radio-sensitizer to conventional photon radiotherapy (XRT) in pediatric sarcoma cell lines. Here, we investigate its effect on the response of two sarcoma cell lines and a normal tissue cell line to heavy ion irradiation (HIT). Materials and methods Clonogenic assays after different doses of heavy ions were performed. DNA damage and repair were evaluated by measuring γH2AX via flow-cytometry. Apoptosis and cell cycle analysis were also measured via flow cytometry. Protein expression of repair proteins, p53 and p21 were measured using immunoblot analysis. Changes of nuclear architecture after treatment with SAHA and HIT were observed in one of the sarcoma cell lines via light microscopy after staining towards chromatin and γH2AX. Results Corresponding with previously reported photon data, SAHA lead to an increase of sensitivity to heavy ions along with an increase of DSB and apoptosis in the two sarcoma cell lines. In contrast, in the osteoblast cell line (hFOB 1.19), the combination of SAHA and HIT showed a significant radio-protective effect. Laser scanning microscopy revealed no significant morphologic changes after HIT compared to the combined treatment with SAHA. Immunoblot analysis revealed no significant up or down regulation of p53. However, p21 was significantly increased by SAHA and combination treatment as compared to HIT only in the two sarcoma cell lines - again in contrast to the osteoblast cell line. Changes in the repair kinetics of DSB p53-independent apoptosis with p21 involvement may be part of the underlying mechanisms for radio-sensitization by SAHA. Conclusion Our in vitro data suggest an increase of the therapeutic ratio by the combination of SAHA with HIT in infantile sarcoma cell lines. PMID:21933400

Stellar rotation periods determined from simultaneously measured Ca II H&K and Ca II IRT lines

NASA Astrophysics Data System (ADS)

Mittag, M.; Hempelmann, A.; Schmitt, J. H. M. M.; Fuhrmeister, B.; González-Pérez, J. N.; Schröder, K.-P.

2017-11-01

Aims: Previous studies have shown that, for late-type stars, activity indicators derived from the Ca II infrared-triplet (IRT) lines are correlated with the indicators derived from the Ca II H&K lines. Therefore, the Ca II IRT lines are in principle usable for activity studies, but they may be less sensitive when measuring the rotation period. Our goal is to determine whether the Ca II IRT lines are sufficiently sensitive to measure rotation periods and how any Ca II IRT derived rotation periods compare with periods derived from the "classical" Mount Wilson S-index. Methods: To analyse the Ca II IRT lines' sensitivity and to measure rotation periods, we define an activity index for each of the Ca II IRT lines similar to the Mount Wilson S-index and perform a period analysis for the lines separately and jointly. Results: For eleven late-type stars we can measure the rotation periods using the Ca II IRT indices similar to those found in the Mount Wilson S-index time series and find that a period derived from all four indices gives the most probable rotation period; we find good agreement for stars with already existing literature values. In a few cases the computed periodograms show a complicated structure with multiple peaks, meaning that formally different periods are derived in different indices. We show that in one case, this is due to data sampling effects and argue that denser cadence sampling is necessary to provide credible evidence for differential rotation. However, our TIGRE data for HD 101501 shows good evidence for the presence of differential rotation.

PI3K pathway dependencies in endometrioid endometrial cancer cell lines

PubMed Central

Weigelt, Britta; Warne, Patricia H; Lambros, Maryou B; Reis-Filho, Jorge S; Downward, Julian

2013-01-01

Purpose Endometrioid endometrial cancers (EECs) frequently harbor coexisting mutations in PI3K pathway genes, including PTEN, PIK3CA, PIK3R1, and KRAS. We sought to define the genetic determinants of PI3K pathway inhibitor response in EEC cells, and whether PTEN-mutant EEC cell lines rely on p110β signaling for survival. Experimental Design Twenty-four human EEC cell lines were characterized for their mutation profile and activation state of PI3K and MAPK signaling pathway proteins. Cells were treated with pan-class I PI3K, p110α and p110β isoform-specific, allosteric mTOR, mTOR kinase, dual PI3K/mTOR, MEK and RAF inhibitors. RNA interference (RNAi) was employed to assess effects of KRAS silencing in EEC cells. Results EEC cell lines harboring PIK3CA and PTEN mutations were selectively sensitive to the pan-class I PI3K inhibitor GDC-0941 and allosteric mTOR inhibitor Temsirolimus, respectively. Subsets of EEC cells with concurrent PIK3CA and/or PTEN and KRAS mutations were sensitive to PI3K pathway inhibition, and only 2/6 KRAS-mutant cell lines showed response to MEK inhibition. KRAS RNAi silencing did not induce apoptosis in KRAS-mutant EEC cells. PTEN-mutant EEC cell lines were resistant to the p110β inhibitors GSK2636771 and AZD6482, and only in combination with the p110α selective inhibitor A66, a decrease in cell viability was observed. Conclusions Targeted pan-PI3K and mTOR inhibition in EEC cells may be most effective in PIK3CA-mutant and PTEN-mutant tumors, respectively, even in a subset of EECs concurrently harboring KRAS mutations. Inhibition of p110β alone may not be sufficient to sensitize PTEN-mutant EEC cells and combination with other targeted agents may be required. PMID:23674493

PI3K pathway dependencies in endometrioid endometrial cancer cell lines.

PubMed

Weigelt, Britta; Warne, Patricia H; Lambros, Maryou B; Reis-Filho, Jorge S; Downward, Julian

2013-07-01

Endometrioid endometrial cancers (EEC) frequently harbor coexisting mutations in phosphoinositide 3-kinase (PI3K) pathway genes, including PTEN, PIK3CA, PIK3R1, and KRAS. We sought to define the genetic determinants of PI3K pathway inhibitor response in EEC cells, and whether PTEN-mutant EEC cell lines rely on p110β signaling for survival. Twenty-four human EEC cell lines were characterized for their mutation profile and activation state of PI3K and mitogen-activated protein kinase (MAPK) signaling pathway proteins. Cells were treated with pan-class I PI3K, p110α, and p110β isoform-specific, allosteric mTOR, mTOR kinase, dual PI3K/mTOR, mitogen-activated protein/extracellular signal-regulated kinase (MEK), and RAF inhibitors. RNA interference (RNAi) was used to assess effects of KRAS silencing in EEC cells. EEC cell lines harboring PIK3CA and PTEN mutations were selectively sensitive to the pan-class I PI3K inhibitor GDC-0941 and allosteric mTOR inhibitor temsirolimus, respectively. Subsets of EEC cells with concurrent PIK3CA and/or PTEN and KRAS mutations were sensitive to PI3K pathway inhibition, and only 2 of 6 KRAS-mutant cell lines showed response to MEK inhibition. KRAS RNAi silencing did not induce apoptosis in KRAS-mutant EEC cells. PTEN-mutant EEC cell lines were resistant to the p110β inhibitors GSK2636771 and AZD6482, and only in combination with the p110α selective inhibitor A66 was a decrease in cell viability observed. Targeted pan-PI3K and mTOR inhibition in EEC cells may be most effective in PIK3CA- and PTEN-mutant tumors, respectively, even in a subset of EECs concurrently harboring KRAS mutations. Inhibition of p110β alone may not be sufficient to sensitize PTEN-mutant EEC cells and combination with other targeted agents may be required. ©2013 AACR.

Critical comparison of the on-line and off-line molecularly imprinted solid-phase extraction of patulin coupled with liquid chromatography.