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Search Results: 1 - 10 of 117851 matches for " T. Akiri "
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Solution of Transportation Problem with South-East Corner Method, North-East Corner Method and Comparison with Existing Method  [PDF]
Sasikala Sasikala, Sridhar Akiri, Pavankumar Subbara
Open Access Library Journal (OALib Journal) , 2019, DOI: 10.4236/oalib.1105377
Abstract:
Finding an initial basic feasible solution is the prime requirement to obtain an optimal solution for the transportation problems. In this paper, two methods are proposed to find an initial basic feasible solution for the transportation problems. The South-East Corner Method (SECM) and the North-East Corner Method (NECM) are adopted to compute the Initial Basic Feasible Solution (IBFS) of the transportation problem. A comparative study is carried out with existing methods like Vogel’s approximation method (VAM) which is to find an initial basic feasible solution and Modified Distribution (MODI) Method which is to find the optimal solution and the methods are also illustrated with numerical examples.
The Waveform Digitiser of the Double Chooz Experiment: Performance and Quantisation Effects on PhotoMultiplier Tube Signals
Y. Abe,T. Akiri,A. Cabrera,B. Courty,J. V. Dawson,L. F. G. Gonzalez,A. Hourlier,M. Ishitsuka,H. de Kerret,D. Kryn,P. Novella,M. Obolensky,S. Perasso,A. Remoto,R. Roncin
Physics , 2013, DOI: 10.1088/1748-0221/8/08/P08015
Abstract: We present the waveform digitiser used in the Double Chooz experiment. We describe the hardware and the custom-built firmware specifically developed for the experiment. The performance of the device is tested with regards to digitising low light level signals from photomultiplier tubes and measuring pulse charge. This highlights the role of quantisation effects and leads to some general recommendations on the design and use of waveform digitisers.
The antioxidant and antiproliferative activities of methanolic extracts from Njavara rice bran
Akiri SVC Rao, Sareddy G Reddy, Phanithi P Babu, Attipalli R Reddy
BMC Complementary and Alternative Medicine , 2010, DOI: 10.1186/1472-6882-10-4
Abstract: Methanolic extracts of rice bran from four varieties; Vasumathi, Yamini, Jyothi and Njavara were used to study their total phenolic and flavonoid contents, in vitro antioxidant activities including total antioxidant activity, scavenging of nitric oxide and 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical, reducing power and cytotoxic activity in C6 glioma cells. Correlation coefficient and regression analysis were done by using Sigmastat version 3.1 and Stata statistical package respectively.Rice bran methanolic extract from Njavara showed the highest antioxidant and cell cytotoxic properties compared to the other three rice varieties. IC50 values for scavenging DPPH and nitric oxide were in the range of 30.85-87.72 μg/ml and 52.25-107.18 μg/ml respectively. Total antioxidant activity and reducing power were increased with increasing amounts of the extract. Total phenolic and flavonoid contents were in the range of 3.2-12.4 mg gallic acid-equivalent (GAE)/g bran and 1.68-8.5 mg quercetin-equivalent (QEE)/g bran respectively. IC50 values of cytotoxic assay (MTT assay) were 17.53-57.78 μg/ml. Correlation coefficient and regression analysis of phenolic content with DPPH and NO scavenging, MTT (-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay, total antioxidant assay and reducing power showed a highly significant correlation coefficient values (96-99%) and regression values (91-98%).The results of the present study show that the crude methanolic extract from Njavara rice bran contains significantly high polyphenolic compounds with superior antioxidant activity as evidenced by scavenging of free radicals including DPPH and NO. Njavara extracts also showed highest reducing power activity, anti-proliferative property in C6 glioma cells. In conclusion, it is conceivable that the Njavara rice variety could be exploited as one of the potential sources for plant - based pharmaceutical products.Rice bran is a rich source of natural antioxidants which can be used
First Indication of Terrestrial Matter Effects on Solar Neutrino Oscillation
A. Renshaw,K. Abe,Y. Hayato,K. Iyogi,J. Kameda,Y. Kishimoto,M. Miura,S. Moriyama,M. Nakahata,Y. Nakano,S. Nakayama,H. Sekiya,M. Shiozawa,Y. Suzuki,A. Takeda,Y. Takenaga,T. Tomura,K. Ueno,T. Yokozawa,R. A. Wendell,T. Irvine,T. Kajita,K. Kaneyuki,K. P. Lee,Y. Nishimura,K. Okumura,T. McLachlan,L. Labarga,S. Berkman,H. A. Tanaka,S. Tobayama,E. Kearns,J. L. Raaf,J. L. Stone,L. R. Sulak,M. Goldhabar,K. Bays,G. Carminati,W. R. Kropp,S. Mine,M. B. Smy,H. W. Sobel,K. S. Ganezer,J. Hill,W. E. Keig,N. Hong,J. Y. Kim,I. T. Lim,T. Akiri,A. Himmel,K. Scholberg,C. W. Walter,T. Wongjirad,T. Ishizuka,S. Tasaka,J. S. Jang,J. G. Learned,S. Matsuno,S. N. Smith,T. Hasegawa,T. Ishida,T. Ishii,T. Kobayashi,T. Nakadaira,K. Nakamura,Y. Oyama,K. Sakashita,T. Sekiguchi,T. Tsukamoto,A. T. Suzuki,Y. Takeuchi,C. Bronner,S. Hirota,K. Huang,K. Ieki,M. Ikeda,T. Kikawa,A. Minamino,T. Nakaya,K. Suzuki,S. Takahashi,Y. Fukuda,K. Choi,Y. Itow,G. Mitsuka,P. Mijakowski,J. Hignight,J. Imber,C. K. Jung,C. Yanagisawa,H. Ishino,A. Kibayashi,Y. Koshio,T. Mori,M. Sakuda,T. Yano,Y. Kuno,R. Tacik,S. B. Kim,H. Okazawa,Y. Choi,K. Nishijima,M. Koshiba,Y. Totsuka,M. Yokoyama,K. Martens,Ll. Marti,M. R. Vagins,J. F. Martin,P. de Perio,A. Konaka,M. J. Wilking,S. Chen,Y. Zhang,R. J. Wilkes
Physics , 2013, DOI: 10.1103/PhysRevLett.112.091805
Abstract: We report an indication that the elastic scattering rate of solar $^8$B neutrinos with electrons in the Super-Kamiokande detector is larger when the neutrinos pass through the Earth during nighttime. We determine the day/night asymmetry, defined as the difference of the average day rate and average night rate divided by the average of those two rates, to be $(-3.2\pm1.1(\text{stat})\pm0.5(\text{syst}))\%$, which deviates from zero by 2.7 $\sigma$. Since the elastic scattering process is mostly sensitive to electron-flavored solar neutrinos, a non-zero day/night asymmetry implies that the flavor oscillations of solar neutrinos are affected by the presence of matter within the neutrinos' flight path. Super-Kamiokande's day/night asymmetry is consistent with neutrino oscillations for $4\times10^{-5}$eV$^2\leq\Delta m^2_{21}\leq7\times10^{-5}$eV$^2$ and large mixing values of $\theta_{12}$, at the $68\%$ C.L.
Search for dinucleon decay into pions at Super-Kamiokande
J. Gustafson,K. Abe,Y. Haga,Y. Hayato,M. Ikeda,K. Iyogi,J. Kameda,Y. Kishimoto,M. Miura,S. Moriyama,M. Nakahata,T. Nakajima,Y. Nakano,S. Nakayama,A. Orii,H. Sekiya,M. Shiozawa,A. Takeda,H. Tanaka,T. Tomura,R. A. Wendell,T. Irvine,T. Kajita,I. Kametani,K. Kaneyuki,Y. Nishimura,E. Richard,K. Okumura,L. Labarga,P. Fernandez,S. Berkman,H. A. Tanaka,S. Tobayama,E. Kearns,J. L. Raaf,J. L. Stone,L. R. Sulak,M. Goldhaber,G. Carminati,W. R. Kropp,S. Mine,P. Weatherly,A. Renshaw,M. B. Smy,H. W. Sobel,V. Takhistov,K. S. Ganezer,B. L. Hartfiel,J. Hill,N. Hong,J. Y. Kim,I. T. Lim,T. Akiri,A. Himmel,K. Scholberg,C. W. Walter,T. Wongjirad,T. Ishizuka,S. Tasaka,J. S. Jang,J. G. Learned,S. Matsuno,S. N. Smith,T. Hasegawa,T. Ishida,T. Ishii,T. Kobayashi,T. Nakadaira,K. Nakamura,Y. Oyama,K. Sakashita,T. Sekiguchi,T. TsukamotoA. T. Suzuki,Y. Takeuchi,T. Yano,S. Hirota,K. Huang,K. Ieki,T. Kikawa,A. Minamino,T. Nakaya,K. Suzuki,S. Takahashi,Y. Fukuda,K. Choi,Y. Itow,G. Mitsuka,T. Suzuki,P. Mijakowski,J. Hignight,J. Imber,C. K. Jung,J. L. Palomino,C. Yanagisawa,H. Ishino,T. Kayano,A. Kibayashi,Y. Koshio,T. Mori,M. Sakuda,Y. Kuno,R. Tacik,S. B. Kim,H. Okazawa,Y. Choi,K. Nishijima,M. Koshiba,Y. Suda,Y. Totsuka,M. Yokoyama,C. Bronner,K. Martens,Ll. Marti,Y. Suzuki,M. R. Vagins,J. F. Martin,P. de Perio,A. Konaka,M. J. Wilking,S. Chen,Y. Zhang,R. J. Wilkes
Physics , 2015, DOI: 10.1103/PhysRevD.91.072009
Abstract: A search for dinucleon decay into pions with the Super-Kamiokande detector has been performed with an exposure of 282.1 kiloton-years. Dinucleon decay is a process that violates baryon number by two units. We present the first search for dinucleon decay to pions in a large water Cherenkov detector. The modes $^{16}$O$(pp) \rightarrow$ $^{14}$C$\pi^{+}\pi^{+}$, $^{16}$O$(pn) \rightarrow$ $^{14}$N$\pi^{+}\pi^{0}$, and $^{16}$O$(nn) \rightarrow$ $^{14}$O$\pi^{0}\pi^{0}$ are investigated. No significant excess in the Super-Kamiokande data has been found, so a lower limit on the lifetime of the process per oxygen nucleus is determined. These limits are: $\tau_{pp\rightarrow\pi^{+}\pi^{+}} > 7.22 \times 10^{31}$ years, $\tau_{pn\rightarrow\pi^{+}\pi^{0}} > 1.70 \times 10^{32}$ years, and $\tau_{nn\rightarrow\pi^{0}\pi^{0}} > 4.04 \times 10^{32}$ years. The lower limits on each mode are about two orders of magnitude better than previous limits from searches for dinucleon decay in iron.
Calibration of the Super-Kamiokande Detector
K. Abe,Y. Hayato,T. Iida,K. Iyogi,J. Kameda,Y. Kishimoto,Y. Koshio,Ll. Marti,M. Miura,S. Moriyama,M. Nakahata,Y. Nakano,S. Nakayama,Y. Obayashi,H. Sekiya,M. Shiozawa,Y. Suzuki,A. Takeda,Y. Takenaga,H. Tanaka,T. Tomura,K. Ueno,R. A. Wendell,T. Yokozawa,T. J. Irvine,H. Kaji,T. Kajita,K. Kaneyuki,K. P. Lee,Y. Nishimura,K. Okumura,T. McLachlan,L. Labarga,E. Kearns,J. L. Raaf,J. L. Stone,L. R. Sulak,S. Berkman,H. A. Tanaka,S. Tobayama,M. Goldhaber,K. Bays,G. Carminati,W. R. Kropp,S. Mine,A. Renshaw,M. B. Smy,H. W. Sobel,K. S. Ganezer,J. Hill,W. E. Keig,J. S. Jang,J. Y. Kim,I. T. Lim,N. Hong,T. Akiri,J. B. Albert,A. Himmel,K. Scholberg,C. W. Walter,T. Wongjirad,T. Ishizuka,S. Tasaka,J. G. Learned,S. Matsuno,S. N. Smith,T. Hasegawa,T. Ishida,T. Ishii,T. Kobayashi,T. Nakadaira,K. Nakamura,K. Nishikawa,Y. Oyama,K. Sakashita,T. Sekiguchi,T. Tsukamoto,A. T. Suzuki,Y. Takeuchi,K. Huang,K. Ieki,M. Ikeda,T. Kikawa,H. Kubo,A. Minamino,A. Murakami,T. Nakaya,M. Otani,K. Suzuki,S. Takahashi,Y. Fukuda,K. Choi,Y. Itow,G. Mitsuka,M. Miyake,P. Mijakowski,R. Tacik,J. Hignight,J. Imber,C. K. Jung,I. Taylor,C. Yanagisawa,Y. Idehara,H. Ishino,A. Kibayashi,T. Mori,M. Sakuda,R. Yamaguchi,T. Yano,Y. Kuno,S. B. Kim,B. S. Yang,H. Okazawa,Y. Choi,K. Nishijima,M. Koshiba,Y. Totsuka,M. Yokoyama,K. Martens,M. R. Vagins,J. F. Martin,P. de Perio,A. Konaka,M. J. Wilking,S. Chen,Y. Heng,H. Sui,Z. Yang,H. Zhang,Y. Zhenwei,K. Connolly,M. Dziomba,R. J. Wilkes
Physics , 2013, DOI: 10.1016/j.nima.2013.11.081
Abstract: Procedures and results on hardware level detector calibration in Super-Kamiokande (SK) are presented in this paper. In particular, we report improvements made in our calibration methods for the experimental phase IV in which new readout electronics have been operating since 2008. The topics are separated into two parts. The first part describes the determination of constants needed to interpret the digitized output of our electronics so that we can obtain physical numbers such as photon counts and their arrival times for each photomultiplier tube (PMT). In this context, we developed an in-situ procedure to determine high-voltage settings for PMTs in large detectors like SK, as well as a new method for measuring PMT quantum efficiency and gain in such a detector. The second part describes the modeling of the detector in our Monte Carlo simulation, including in particular the optical properties of its water target and their variability over time. Detailed studies on the water quality are also presented. As a result of this work, we achieved a precision sufficient for physics analysis over a wide energy range (from a few MeV to above a TeV). For example, the charge determination was understood at the 1% level, and the timing resolution was 2.1 nsec at the one-photoelectron charge level and 0.5 nsec at the 100-photoelectron charge level.
Limits on sterile neutrino mixing using atmospheric neutrinos in Super-Kamiokande
The Super-Kamiokande Collaboration,:,K. Abe,Y. Haga,Y. Hayato,M. Ikeda,K. Iyogi,J. Kameda,Y. Kishimoto,M. Miura,S. Moriyama,M. Nakahata,Y. Nakano,S. Nakayama,H. Sekiya,M. Shiozawa,Y. Suzuki,A. Takeda,H. Tanaka,T. Tomura,K. Ueno,R. A. Wendell,T. Yokozawa,T. Irvine,T. Kajita,I. Kametani,K. Kaneyuki,K. P. Lee,T. McLachlan,Y. Nishimura,E. Richard,K. Okumura,L. Labarga,P. Fernandez,S. Berkman,H. A. Tanaka,S. Tobayama,J. Gustafson,E. Kearns,J. L. Raaf,J. L. Stone,L. R. Sulak,M. Goldhaber,G. Carminati,W. R. Kropp,S. Mine,P. Weatherly,A. Renshaw,M. B. Smy,H. W. Sobel,V. Takhistov,K. S. Ganezer,B. L. Hartfiel,J. Hill,W. E. Keig,N. Hong,J. Y. Kim,I. T. Lim,T. Akiri,A. Himmel,K. Scholberg,C. W. Walter,T. Wongjirad,T. Ishizuka,S. Tasaka,J. S. Jang,J. G. Learned,S. Matsuno,S. N. Smith,T. Hasegawa,T. Ishida,T. Ishii,T. Kobayashi,T. Nakadaira,K. Nakamura,Y. Oyama,K. Sakashita,T. Sekiguchi,T. Tsukamoto,A. T. Suzuki,Y. Takeuchi,C. Bronner,S. Hirota,K. Huang,K. Ieki,T. Kikawa,A. Minamino,A. Murakami,T. Nakaya,K. Suzuki,S. Takahashi,K. Tateishi,Y. Fukuda,K. Choi,Y. Itow,G. Mitsuka,P. Mijakowski,J. Hignight,J. Imber,C. K. Jung,C. Yanagisawa,H. Ishino,A. Kibayashi,Y. Koshio,T. Mori,M. Sakuda,R. Yamaguchi,T. Yano,Y. Kuno,R. Tacik,S. B. Kim,H. Okazawa,Y. Choi,K. Nishijima,M. Koshiba,Y. Suda,Y. Totsuka,M. Yokoyama,K. Martens,Ll. Marti,M. R. Vagins,J. F. Martin,P. de Perio,A. Konaka,M. J. Wilking,S. Chen,Y. Zhang,K. Connolly,R. J. Wilkes
Physics , 2014, DOI: 10.1103/PhysRevD.91.052019
Abstract: We present limits on sterile neutrino mixing using 4,438 live-days of atmospheric neutrino data from the Super-Kamiokande experiment. We search for fast oscillations driven by an eV$^2$-scale mass splitting and for oscillations into sterile neutrinos instead of tau neutrinos at the atmospheric mass splitting. When performing both these searches we assume that the sterile mass splitting is large, allowing $\sin^2(\Delta m^2 L/4E)$ to be approximated as $0.5$, and we assume that there is no mixing between electron neutrinos and sterile neutrinos ($|U_{e4}|^2 = 0$). No evidence of sterile oscillations is seen and we limit $|U_{\mu4}|^2$ to less than 0.041 and $|U_{\tau4}|^2$ to less than 0.18 for $\Delta m^2 > 0.8$ eV$^2$ at the 90% C.L. in a 3+1 framework. The approximations that can be made with atmospheric neutrinos allow these limits to be easily applied to 3+N models, and we provide our results in a generic format to allow comparisons with other sterile neutrino models.
Test of Lorentz invariance with atmospheric neutrinos
The Super-Kamiokande Collaboration,:,K. Abe,Y. Haga,Y. Hayato,M. Ikeda,K. Iyogi,J. Kameda,Y. Kishimoto,M. Miura,S. Moriyama,M. Nakahata,Y. Nakano,S. Nakayama,H. Sekiya,M. Shiozawa,Y. Suzuki,A. Takeda,H. Tanaka,T. Tomura,K. Ueno,R. A. Wendell,T. Yokozawa,T. Irvine,T. Kajita,I. Kametani,K. Kaneyuki,K. P. Lee,T. McLachlan,Y. Nishimura,E. Richard,K. Okumura,L. Labarga,P. Fernandez,J. Gustafson,E. Kearns,J. L. Raaf,S. Berkman,H. A. Tanaka,S. Tobayama,J. L. Stone,L. R. Sulak,M. Goldhaber,G. Carminati,W. R. Kropp,S. Mine,P. Weatherly,A. Renshaw,M. B. Smy,H. W. Sobel,V. Takhistov,K. S. Ganezer,B. L. Hartfiel,J. Hill,W. E. Keig,N. Hong,J. Y. Kim,I. T. Lim,T. Akiri,A. Himmel,K. Scholberg,C. W. Walter,T. Wongjirad,T. Ishizuka,S. Tasaka,J. S. Jang,J. G. Learned,S. Matsuno,S. N. Smith,T. Hasegawa,T. Ishida,T. Ishii,T. Kobayashi,T. Nakadaira,K. Nakamura,Y. Oyama,K. Sakashita,T. Sekiguchi,T. Tsukamoto,A. T. Suzuki,Y. Takeuchi,C. Bronner,S. Hirota,K. Huang,K. Ieki,T. Kikawa,A. Minamino,A. Murakami,T. Nakaya,K. Suzuki,S. Takahashi,K. Tateishi,Y. Fukuda,K. Choi,Y. Itow,G. Mitsuka,P. Mijakowski,J. Hignight,J. Imber,C. K. Jung,C. Yanagisawa,H. Ishino,A. Kibayashi,Y. Koshio,T. Mori,M. Sakuda,R. Yamaguchi,T. Yano,Y. Kuno,R. Tacik,S. B. Kim,H. Okazawa,Y. Choi,K. Nishijima,M. Koshiba,Y. Suda,Y. Totsuka,M. Yokoyama,K. Martens,Ll. Marti,M. R. Vagins,J. F. Martin,P. de Perio,A. Konaka,M. J. Wilking,S. Chen,Y. Zhang,K. Connolly,R. J. Wilkes
Physics , 2014, DOI: 10.1103/PhysRevD.91.052003
Abstract: A search for neutrino oscillations induced by Lorentz violation has been performed using 4,438 live-days of Super-Kamiokande atmospheric neutrino data. The Lorentz violation is included in addition to standard three-flavor oscillations using the non-perturbative Standard Model Extension (SME), allowing the use of the full range of neutrino path lengths, ranging from 15 to 12,800 km, and energies ranging from 100 MeV to more than 100 TeV in the search. No evidence of Lorentz violation was observed, so limits are set on the renormalizable isotropic SME coefficients in the $e\mu$, $\mu\tau$, and $e\tau$ sectors, improving the existing limits by up to seven orders of magnitude and setting limits for the first time in the neutrino $\mu\tau$ sector of the SME.
Search for Trilepton Nucleon Decay via $p \rightarrow e^+ νν$ and $p \rightarrow μ^+ νν$ in the Super-Kamiokande Experiment
V. Takhistov,K. Abe,Y. Haga,Y. Hayato,M. Ikeda,K. Iyogi,J. Kameda,Y. Kishimoto,M. Miura,S. Moriyama,M. Nakahata,Y. Nakano,S. Nakayama,H. Sekiya,M. Shiozawa,Y. Suzuki,A. Takeda,H. Tanaka,T. Tomura,K. Ueno,R. A. Wendell,T. Yokozawa,T. Irvine,T. Kajita,I. Kametani,K. Kaneyuki,K. P. Lee,T. McLachlan,Y. Nishimura,E. Richard,K. Okumura,L. Labarga,P. Fernandez,S. Berkman,H. A. Tanaka,S. Tobayama,J. Gustafson,E. Kearns,J. L. Raaf,J. L. Stone,L. R. Sulak,M. Goldhaber,G. Carminati,W. R. Kropp,S. Mine,P. Weatherly,A. Renshaw,M. B. Smy,H. W. Sobel,K. S. Ganezer,B. L. Hartfiel,J. Hill,W. E. Keig,N. Hong,J. Y. Kim,I. T. Lim,T. Akiri,A. Himmel,K. Scholberg,C. W. Walter,T. Wongjirad,T. Ishizuka,S. Tasaka,J. S. Jang,J. G. Learned,S. Matsuno,S. N. Smith,T. Hasegawa,T. Ishida,T. Ishii,T. Kobayashi,T. Nakadaira,K. Nakamura,Y. Oyama,K. Sakashita,T. Sekiguchi,T. Tsukamoto,A. T. Suzuki,Y. Takeuchi,C. Bronner,S. Hirota,K. Huang,K. Ieki,T. Kikawa,A. Minamino,A. Murakami,T. Nakaya,K. Suzuki,S. Takahashi,K. Tateishi,Y. Fukuda,K. Choi,Y. Itow,G. Mitsuka,P. Mijakowski,J. Hignight,J. Imber,C. K. Jung,C. Yanagisawa,H. Ishino,A. Kibayashi,Y. Koshio,T. Mori,M. Sakuda,R. Yamaguchi,T. Yano,Y. Kuno,R. Tacik,S. B. Kim,H. Okazawa,Y. Choi,K. Nishijima,M. Koshiba,Y. Suda,Y. Totsuka,M. Yokoyama,K. Martens,Ll. Marti,M. R. Vagins,J. F. Martin,P. de Perio,A. Konaka,M. J. Wilking,S. Chen,Y. Zhang,K. Connolly,R. J. Wilkes
Physics , 2014, DOI: 10.1103/PhysRevLett.113.101801
Abstract: The trilepton nucleon decay modes $p \rightarrow e^+ \nu \nu$ and $p \rightarrow \mu^+ \nu \nu$ violate $|\Delta (B - L)|$ by two units. Using data from a 273.4 kiloton year exposure of Super-Kamiokande a search for these decays yields a fit consistent with no signal. Accordingly, lower limits on the partial lifetimes of $\tau_{p \rightarrow e^+ \nu \nu} > 1.7 \times 10^{32}$ years and $\tau_{p \rightarrow \mu^+ \nu \nu} > 2.2 \times 10^{32}$ years at a $90 \% $ confidence level are obtained. These limits can constrain Grand Unified Theories which allow for such processes.
β-Catenin-Independent Activation of TCF1/LEF1 in Human Hematopoietic Tumor Cells through Interaction with ATF2 Transcription Factors
Luca Grumolato,Guizhong Liu,Tomomi Haremaki,Sathish Kumar Mungamuri,Phyllus Mong,Gal Akiri,Pablo Lopez-Bergami,Adriana Arita,Youssef Anouar,Marek Mlodzik,Ze'ev A. Ronai,Joshua Brody,Daniel C. Weinstein,Stuart A. Aaronson
PLOS Genetics , 2013, DOI: 10.1371/journal.pgen.1003603
Abstract: The role of Wnt signaling in embryonic development and stem cell maintenance is well established and aberrations leading to the constitutive up-regulation of this pathway are frequent in several types of human cancers. Upon ligand-mediated activation, Wnt receptors promote the stabilization of β-catenin, which translocates to the nucleus and binds to the T-cell factor/lymphoid enhancer factor (TCF/LEF) family of transcription factors to regulate the expression of Wnt target genes. When not bound to β-catenin, the TCF/LEF proteins are believed to act as transcriptional repressors. Using a specific lentiviral reporter, we identified hematopoietic tumor cells displaying constitutive TCF/LEF transcriptional activation in the absence of β-catenin stabilization. Suppression of TCF/LEF activity in these cells mediated by an inducible dominant-negative TCF4 (DN-TCF4) inhibited both cell growth and the expression of Wnt target genes. Further, expression of TCF1 and LEF1, but not TCF4, stimulated TCF/LEF reporter activity in certain human cell lines independently of β-catenin. By a complementary approach in vivo, TCF1 mutants, which lacked the ability to bind to β-catenin, induced Xenopus embryo axis duplication, a hallmark of Wnt activation, and the expression of the Wnt target gene Xnr3. Through generation of different TCF1-TCF4 fusion proteins, we identified three distinct TCF1 domains that participate in the β-catenin-independent activity of this transcription factor. TCF1 and LEF1 physically interacted and functionally synergized with members of the activating transcription factor 2 (ATF2) family of transcription factors. Moreover, knockdown of ATF2 expression in lymphoma cells phenocopied the inhibitory effects of DN-TCF4 on the expression of target genes associated with the Wnt pathway and on cell growth. Together, our findings indicate that, through interaction with ATF2 factors, TCF1/LEF1 promote the growth of hematopoietic malignancies in the absence of β-catenin stabilization, thus establishing a new mechanism for TCF1/LEF1 transcriptional activity distinct from that associated with canonical Wnt signaling.
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