Sample records for icrf-193 involves atm

  1. Revised genetic requirements for the decatenation G2 checkpoint: the role of ATM

    PubMed Central

    Bower, Jacquelyn J.; Zhou, Yingchun; Zhou, Tong; Simpson, Dennis A.; Arlander, Sonnet J.; Paules, Richard S.; Cordeiro-Stone, Marila; Kaufmann, William K.

    2010-01-01

    The decatenation G2 checkpoint is proposed to delay cellular progression from G2 into mitosis when intertwined daughter chromatids are insufficiently decatenated. Previous studies indicated that the ATM- and Rad3-related (ATR) checkpoint kinase, but not the ataxia telangiectasia-mutated (ATM) kinase, was required for decatenation G2 checkpoint function. Here, we show that the method used to quantify decatenation G2 checkpoint function can influence the identification of genetic requirements for the checkpoint. Normal human diploid fibroblast (NHDF) lines responded to the topoisomerase II (topo II) catalytic inhibitor ICRF-193 with a stringent G2 arrest and a reduction in the mitotic index. While siRNA-mediated depletion of ATR and CHEK1 increased the mitotic index in ICRF-193 treated NHDF lines, depletion of these proteins did not affect the mitotic entry rate, indicating that the decatenation G2 checkpoint was functional. These results suggest that ATR and CHEK1 are not required for the decatenation G2 checkpoint, but may influence mitotic exit after inhibition of topo II. A re-evaluation of ataxia telangiectasia (AT) cell lines using the mitotic entry assay indicated that ATM was required for the decatenation G2 checkpoint. Three NHDF cell lines responded to ICRF-193 with a mean 98% inhibition of the mitotic entry rate. Examination of the mitotic entry rates in AT fibroblasts upon treatment with ICRF-193 revealed a significantly attenuated decatenation G2 checkpoint response, with a mean 59% inhibition of the mitotic entry rate. In addition, a normal lymphoblastoid line exhibited a 95% inhibition of the mitotic entry rate after incubation with ICRF-193, whereas two AT lymphoblastoid lines displayed only 36% and 20% inhibition of the mitotic entry rate. Stable depletion of ATM in normal human fibroblasts with short hairpin RNA also attenuated decatenation G2 checkpoint function by an average of 40%. Western immunoblot analysis demonstrated that treatment with ICRF

  2. An ATM-independent S-phase checkpoint response involves CHK1 pathway

    NASA Technical Reports Server (NTRS)

    Zhou, Xiang-Yang; Wang, Xiang; Hu, Baocheng; Guan, Jun; Iliakis, George; Wang, Ya

    2002-01-01

    After exposure to genotoxic stress, proliferating cells actively slow down the DNA replication through a S-phase checkpoint to provide time for repair. We report that in addition to the ataxia-telangiectasia mutated (ATM)-dependent pathway that controls the fast response, there is an ATM-independent pathway that controls the slow response to regulate the S-phase checkpoint after ionizing radiation in mammalian cells. The slow response of S-phase checkpoint, which is resistant to wortmannin, sensitive to caffeine and UCN-01, and related to cyclin-dependent kinase phosphorylation, is much stronger in CHK1 overexpressed cells, and it could be abolished by Chk1 antisense oligonucleotides. These results provide evidence that the ATM-independent slow response of S-phase checkpoint involves CHK1 pathway.

  3. Effects of ICRF power on SOL density profiles and LH coupling during simultaneous LH and ICRF operation on Alcator C-Mod

    NASA Astrophysics Data System (ADS)

    Lau, C.; Lin, Y.; Wallace, G.; Wukitch, S. J.; Hanson, G. R.; Labombard, B.; Ochoukov, R.; Shiraiwa, S.; Terry, J.

    2013-09-01

    A dedicated experiment during simultaneous lower hybrid (LH) and ion cyclotron range-of-frequencies (ICRF) operations is carried out to evaluate and understand the effects of ICRF power on the scrape-off-layer (SOL) density profiles and on the resultant LH coupling for a wide range of plasma parameters on Alcator C-Mod. Operation of the LH launcher with the adjacent ICRF antenna significantly degrades LH coupling while operation with the ICRF antenna that is not magnetically connected to the LH launcher minimally affects LH coupling. An X-mode reflectometer system at three poloidal locations adjacent to the LH launcher and a visible video camera imaging the LH launcher are used to measure local SOL density profile and emissivity modifications with the application of LH and LH + ICRF power. These measurements confirm that the density in front of the LH launcher depends strongly on the magnetic field line mapping of the active ICRF antenna. Reflectometer measurements also observe both ICRF-driven and LH-driven poloidal density profile asymmetries, especially a strong density depletion at certain poloidal locations in front of the LH launcher during operation with a magnetically connected ICRF antenna. The results indicate that understanding both LH-driven flows and ICRF sheath driven flows may be necessary to understand the observed density profile modifications and LH coupling results during simultaneous LH + ICRF operation.

  4. Aspects of ICRF-3

    NASA Astrophysics Data System (ADS)

    Ma, Chopo; MacMillan, Daniel; Le Bail, Karine; Gordon, David

    2016-12-01

    The Second Realization of the International Celestial Reference Frame (ICRF2) used dual-frequency VLBI data acquired for geodetic and astrometric purposes from 1979-2009 by organizations coordinated by the IVS and various precursor networks. Since 2009 the data set has been significantly broadened, especially by observations in the southern hemisphere. While the new southern data have ameliorated the north/south imbalance of observations, they appear to produce a systematic zonal declination change in the catalog positions. Over the 35 years of the ICRF data set the effect of galactic aberration may be significant. Geophysical and tropospheric models also may affect the source positions. All these effects need to be addressed in preparation for ICRF-3.

  5. Considerations for ICRF-3

    NASA Astrophysics Data System (ADS)

    Ma, Chopo; MacMillan, Daniel; Gordon, David

    2015-08-01

    The Second Realization of the International Celestial Reference Frame (ICRF) used dual-frequency VLBI data acquired for geodetic and astrometric purposes from 1979-2009 by organizations now coordinated by the International VLBI Service for Geodesy and Astrometry (IVS) and analyzed according to the Conventions of the International Earth Rotation and Reference Systems Service (IERS). Since 2009 the data set has been significantly broadened, especially by observations in the Southern Hemisphere, and modeling of astronomical, geophysical and tropospheric effects has progressed. The new southern data appear to cause a systematic zonal declination change in the catalog positions. Over the three decades of the ICRF data set the effect of galactic aberration may be significant. Geophysical and tropospheric models also may affect the source positions. All these effects need to be addressed in preparation for ICRF-3.

  6. Preservation of methane hydrate at 1 atm

    USGS Publications Warehouse

    Stern, L.A.; Circone, S.; Kirby, S.H.; Durham, W.B.

    2001-01-01

    A "pressure-release" method that enables reproducible bulk preservation of pure, porous, methane hydrate at conditions 50 to 75 K above its equilibrium T (193 K) at 1 atm is refined. The amount of hydrate preserved by this method appears to be greatly in excess of that reported in the previous citations, and is likely the result of a mechanism different from ice shielding.

  7. Towards a Future ICRF Realization

    NASA Technical Reports Server (NTRS)

    Ma, Chopo; Gordon, D.; MacMillan, D.; Petrov, L.; Smith, David E. (Technical Monitor)

    2001-01-01

    The data and analysis for the ICRF were completed in 1995 to define a frame to which the Hipparcos optical catalog could be fixed. Additional observations on most of the 608 sources in the overall ICRF catalog have been acquired using a small portion of geodetic observing time as well as astrometric sessions concentrating on the southern hemisphere. Positions of new sources have been determined, including approx.1200 from a VLBA phase calibrator survey. A future ICRF realization will require improved geophysical modeling, sophisticated treatment of position variations and/or source structure, optimized data selection and weighting, and reidentification of defining sources. The motivation for the next realization could be significant improvement in accuracy and density or preparation for optical extragalactic catalogs with microarcsecond precision.

  8. Towards a Future ICRF Realization

    NASA Technical Reports Server (NTRS)

    Ma, Chopo; Gordon, David; MacMillan, Daniel; Petrov, Leonid

    2002-01-01

    The data and analysis for the ICRF were completed in 1995 to define a frame to which the Hipparcos optical catalog could be fixed. Additional observations on most of the 608 sources in the overall ICRF catalog have been acquired using a small portion of geodetic observing time as well as astrometric sessions concentrating on the Southern Hemisphere. Positions of new sources have been determined, including approximately 1200 from a VLBA phase calibrator survey. A future ICRF realization will require improved geophysical modeling, sophisticated treatment of position variations and/or source structure, optimized data selection and weighting, and re-identification of defining sources. The motivation for the next realization could be significant improvement in accuracy and density or preparation for optical extragalactic catalogs with microarcsecond precision.

  9. ICRF-187 in clinical oncology.

    PubMed

    Poster, D S; Penta, J S; Bruno, S; Macdonald, J S

    1981-01-01

    Although the mechanism of action of ICRF-159 and 187 has not been clearly defined, it is evident from both preclinical and early clinical studies that these compounds are of interest. There are three distinct characteristics of these ICRF compounds that deserve careful clinical evaluation. First, these drugs are apparently alkylating agents with modest, predictable and noncumulative bone marrow toxicity that makes them good potential candidates for combination chemotherapy regimens. The second characteristic that should be investigated is the suggestion that combination of ICRF-187 with an anthracycline may ameliorate the cardiac toxicity of the latter. The third factor in the preclinical evaluation of the bis-diketopiperazines that may have clinical application is the evidence that suggests that these drugs have an antimetastatic effect.

  10. Refinement of the ICRF

    NASA Technical Reports Server (NTRS)

    Ma, Chopo

    2004-01-01

    Since the ICRF was generated in 1995, VLBI modeling and estimation, data quality: source position stability analysis, and supporting observational programs have improved markedly. There are developing and potential applications in the areas of space navigation Earth orientation monitoring and optical astrometry from space that would benefit from a refined ICRF with enhanced accuracy, stability and spatial distribution. The convergence of analysis, focused observations, and astrometric needs should drive the production of a new realization in the next few years.

  11. Extending the ICRF to Higher Radio Frequencies

    NASA Technical Reports Server (NTRS)

    Jacobs, C. S.; Jones, D. L.; Lanyi, G. E.; Lowe, S. T.; Naudet, C. J.; Resch, G. M.; Steppe, J. A.; Zhang, L. D.; Ulvestad, J. S.; Taylor, G. B.

    2002-01-01

    The ICRF forms the basis for all astrometry including use as the inertial coordinate system for navigating deep space missions. This frame was defined using S/X-band observations over the past 20+ years. In January 2002, the VLBA approved our proposal for observing time to extend the ICRF to K-band (24 GHz) and Q-band (43 GHz). The first step will be observations at K- and Q-bands on a subset of ICRF sources. Eventually, K- and Q-band multi-epoch observations will be used to estimate positions, flux density and source structure for a large fraction of the current S/X-band ICRF source list. This work will benefit the radio astronomy community by extending the VLBA calibrator list at these bands. In the longer term, we would also like to extend the ICRF to Ka-band (32 GHz). A celestial reference frame will be needed at this frequency to support deep space navigation. A navigation demonstration is being considered for NASA's Mars 2005 mission. The initial K- and Q-band work will serve to identify candidate sources at Ka-band for use with that mission.

  12. Toward the ICRF3: Astrometric Comparison of the USNO 2016A VLBI Solution with ICRF2 and Gaia DR1

    NASA Astrophysics Data System (ADS)

    Frouard, Julien; Johnson, Megan C.; Fey, Alan; Makarov, Valeri V.; Dorland, Bryan N.

    2018-06-01

    The VLBI USNO 2016A (U16A) solution is part of a work-in-progress effort by USNO toward the preparation of the ICRF3. Most of the astrometric improvement with respect to the ICRF2 is due to the re-observation of the VCS sources. Our objective in this paper is to assess U16A’s astrometry. A comparison with ICRF2 shows statistically significant offsets of size 0.1 mas between the two solutions. While Gaia DR1 positions are not precise enough to resolve these offsets, they are found to be significantly closer to U16A than ICRF2. In particular, the trend for typically larger errors for southern sources in VLBI solutions is decreased in U16A. Overall, the VLBI-Gaia offsets are reduced by 21%. The U16A list includes 718 sources not previously included in ICRF2. Twenty of those new sources have statistically significant radio-optical offsets. In two-thirds of the cases, these offsets can be explained from PanSTARRS images.

  13. Uses of the ICRF and implications for future VLBI

    NASA Technical Reports Server (NTRS)

    Ma, Chopo

    2006-01-01

    Since its inception on 1 Jan 1998, the fundamental ICRF has been set by the VLBI positions of 212 "defining" extragalactic radio sources. In all there are approx.3000 sources with usefully accurate (< few mas) positions consistent with the ICRF. The uses of the ICRF include fundamental astrometry, monitoring of Earth orientation, and spacecraft navigation. For fundamental astrometry, stability and accuracy are most important, and realizations at different frequencies must be in proper registration. However, there is no preferred frequency, and the GAIA mission has the potential for an optical ICRF with 500,000 objects at the 50 microarcsec level some time after the planned 2011 launch. The radio ICRF should be properly prepared for a transition to assure long term stability and consistency. Earth orientation monitoring requires objects attached to the solid Earth, and VLBI will continue to be the fundamental technique. For this purpose it is essential that the new VLBI stations contemplated in the VLBI20l0 report be capable of observing a sufficiently large and well-distributed set of stable sources, and identifying these sources is an on-going effort. Spacecraft navigation by differential VLBI is planned using the Ka-band telemetry signal, and work has begun towards an ICRF realization suitable for this purpose. The balancing of different needs related to the VLBI ICRF will be discussed.

  14. International Celestial Reference Frame (ICRF): mantenimiento y extensión

    NASA Astrophysics Data System (ADS)

    Ma, C.; Arias, E. F.; Eubanks, T.; Fey, A. L.; Gontier, A.-M.; Jacobs, C. S.; Sovers, O. J.; Archinal, B. A.; Charlot, P.

    A partir de enero de 1998 el sistema de referencia celeste convencional está representado por el International Celestial Reference System (ICRS) y materializado a través de las coordenadas VLBI del conjunto de radiofuentes extragalácticas que conforman el International Celestial Reference Frame (ICRF). La primera realización del ICRF, fue elaborada en 1995 por un grupo de expertos designado por la IAU, la que encomendó al International Earth Rotation Service el mantenimiento del ICRS, del ICRF y del vínculo con marcos de referencia en otras frecuencias. Una primera extensión del ICRF se realizó entre abril y junio de 1999, con el objetivo primario de proveer posiciones de radiofuentes extragalácticas observadas a partir de julio de 1995 y de mejorar las posiciones de las fuentes ``candidatas" con la inclusión de observaciones adicionales. Objetivos secundarios fueron monitorear a las radiofuentes para verificar que siguen siendo adecuadas para realizar al ICRF y mejorar las técnicas de análisis de datos. Como resultado del nuevo análisis se obtuvo una solución a partir de la cual se construyó la primera extensión del ICRF, denominada ICRF - Ext.1. Ella representa al ICRS, sus fuentes de definición se mantienen con las mismas posiciones y errores que en la primera realización del ICRF; las demás radiofuentes tienen coordenadas mejor determinadas que en ICRF; el marco de referencia se densificó con el agregado de 59 nuevas radiofuentes.

  15. The Second International Celestial Reference Frame (ICRF2)

    NASA Technical Reports Server (NTRS)

    Ma, Chopo

    2010-01-01

    The ICRF2 catalog was constructed by the IERS/IVS Working Group with oversight by the IAU Working Group. Derived using data from August 1979 through March 2009, it is a great improvement over the original ICRF with 3414 extragalactic radio source positions, a noise floor of 40 microarcsec, and axis stability of 10 microarcsec. Significant refinements were made in the selection of defining sources, modeling, and the integration of CRF, TRF, and EOP. The adoption of the ICRF2 was approved by the IAU in Resolution B3 at the XXVII IAU General Assembly and became effective 1 January 2010.

  16. Involvement of Atm and Trp53 in neural cell loss due to Terf2 inactivation during mouse brain development.

    PubMed

    Kim, Jusik; Choi, Inseo; Lee, Youngsoo

    2017-11-01

    Maintenance of genomic integrity is one of the critical features for proper neurodevelopment and inhibition of neurological diseases. The signals from both ATM and ATR to TP53 are well-known mechanisms to remove neural cells with DNA damage during neurogenesis. Here we examined the involvement of Atm and Atr in genomic instability due to Terf2 inactivation during mouse brain development. Selective inactivation of Terf2 in neural progenitors induced apoptosis, resulting in a complete loss of the brain structure. This neural loss was rescued partially in both Atm and Trp53 deficiency, but not in an Atr-deficient background in the mouse. Atm inactivation resulted in incomplete brain structures, whereas p53 deficiency led to the formation of multinucleated giant neural cells and the disruption of the brain structure. These giant neural cells disappeared in Lig4 deficiency. These data demonstrate ATM and TP53 are important for the maintenance of telomere homeostasis and the surveillance of telomere dysfunction during neurogenesis.

  17. VizieR Online Data Catalog: VLBI ICRF2 (Fey+, 2015)

    NASA Astrophysics Data System (ADS)

    Fey, A. L.; Gordon, D.; Jacobs, C. S.; Ma, C.; Gaume, R. A.; Arias, E. F.; Bianco, G.; Boboltz, D. A.; Bockmann, S.; Bolotin, S.; Charlot, P.; Collioud, A.; Engelhardt, G.; Gipson, J.; Gontier, A.-M.; Heinkelmann, R.; Kurdubov, S.; Lambert, S.; Lytvyn, S.; MacMillan, D. S.; Malkin, Z.; Nothnagel, A.; Ojha, R.; Skurikhina, E.; Sokolova, J.; Souchay, J.; Sovers, O. J.; Tesmer, V.; Titov, O.; Wang, G.; Zharov, V.

    2016-01-01

    We present the second realization of the International Celestial Reference Frame (ICRF2) at radio wavelengths using nearly 30 years of Very Long Baseline Interferometry observations. The earliest observations used are from 1979 August and the latest are from 2009 March. ICRF2 consists of accurate positions of 295 new "defining" sources and positions of 3119 additional compact radio sources to densify the frame. ICRF2 has more than 5 times as many sources as ICRF1 (Ma et al. 1997, cat. I/251), is roughly 5-6 times more accurate, and is nearly twice as stable in the orientation of its axes. (3 data files).

  18. Bulk ion heating with ICRF waves in tokamaks

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

    Mantsinen, M. J., E-mail: mervi.mantsinen@bsc.es; Barcelona Supercomputing Center, Barcelona; Bilato, R.

    2015-12-10

    Heating with ICRF waves is a well-established method on present-day tokamaks and one of the heating systems foreseen for ITER. However, further work is still needed to test and optimize its performance in fusion devices with metallic high-Z plasma facing components (PFCs) in preparation of ITER and DEMO operation. This is of particular importance for the bulk ion heating capabilities of ICRF waves. Efficient bulk ion heating with the standard ITER ICRF scheme, i.e. the second harmonic heating of tritium with or without {sup 3}He minority, was demonstrated in experiments carried out in deuterium-tritium plasmas on JET and TFTR andmore » is confirmed by ICRF modelling. This paper focuses on recent experiments with {sup 3}He minority heating for bulk ion heating on the ASDEX Upgrade (AUG) tokamak with ITER-relevant all-tungsten PFCs. An increase of 80% in the central ion temperature T{sub i} from 3 to 5.5 keV was achieved when 3 MW of ICRF power tuned to the central {sup 3}He ion cyclotron resonance was added to 4.5 MW of deuterium NBI. The radial gradient of the T{sub i} profile reached locally values up to about 50 keV/m and the normalized logarithmic ion temperature gradients R/LT{sub i} of about 20, which are unusually large for AUG plasmas. The large changes in the T{sub i} profiles were accompanied by significant changes in measured plasma toroidal rotation, plasma impurity profiles and MHD activity, which indicate concomitant changes in plasma properties with the application of ICRF waves. When the {sup 3}He concentration was increased above the optimum range for bulk ion heating, a weaker peaking of the ion temperature profile was observed, in line with theoretical expectations.« less

  19. Influence of ICRF heating on the stability of TAEs

    NASA Astrophysics Data System (ADS)

    Sears, J.; Burke, W.; Parker, R. R.; Snipes, J. A.; Wolfe, S.

    2007-11-01

    Unstable toroidicity-induced Alfv'en eigenmodes (TAEs) can appear spontaneously due to resonant interaction with fast particles such as fusion alphas, raising concern that TAEs may threaten ITER performance. This work investigates the progression of stable TAE damping rates toward instability during a scan of ICRF heating power up to 3.1 MW. Stable eigenmodes are identified in Alcator C-Mod by the Active MHD diagnostic. Unstable TAEs are observed to appear spontaneously in C-Mod limited L-mode plasmas at sufficient tail energies generated by >3 MW of ICRF heating. However preliminary analysis of experiments with moderate ICRF heating power show that TAE stability may not simply degrade with overall fast particle content. There are hints that the stability of some TAEs may be enhanced in the presence of fast particle distribution tails. Furthermore, the radial profile of the energetic particle distribution relative to the safety factor profile affects the ICRF power influence on TAE stability.

  20. The IAU Division A Working Group on the Third Realization of the ICRF: Background, Goals, Plans

    NASA Astrophysics Data System (ADS)

    Gaume, Ralph

    2015-08-01

    The XXVIII General Assembly of the IAU (Beijing, 2012) established the Division A Working Group on the Third Realization of the International Celestial Reference Frame (ICRF). The adopted charter of the ICRF3 Working Group includes a commitment to report on the implementation and execution plans for ICRF3 during the XXIX General Assembly of the IAU along with a targeted completion and presentation of ICRF3 in 2018 to the XXX General Assembly for adoption. This talk will discuss the background, purpose, and overall implementation plan for ICRF3, and motivate the concept, currently under consideration by the ICRF3 Working Group, that future realizations of the ICRF be based on multi-frequency astrometric data, starting with ICRF3.

  1. The Position/Structure Stability of Four ICRF2 Sources

    NASA Technical Reports Server (NTRS)

    Fomalont, Ed; Johnston, Kenneth; Fey, Alan; Boboltz, Dave; Oyama, Tomoaki; Honma, Mareki

    2010-01-01

    Four compact radio sources in the International Celestial Reference Frame (ICRF2) catalog were observed using phase referencing with the VLBA at 43, 23, and 8.6-GHz, and with VERA at 23-GHz over a one-year period. The goal was to determine the stability of the radio cores and to assess structure effects associated with positions in the ICRF2. Conclusions are: (1) 43-GHz VLBI high-resolution observations are often needed to determine the location of the radio core. (2) Over the observing period, the relative positions among the four radio cores were constant to 0.02 mas, suggesting that once the true radio core is identified, it remains stationary in the sky to this accuracy. (3) The emission in 0556+238, one of the four sources investigated and one of the 295 ICRF2 defining sources, was dominated by a strong component near the core and moved 0.1 mas during the year. (4) Comparison of the VLBA images at 43, 23, and 8.6-GHz with the ICRF2 positions suggests that the 8-GHz structure is often dominated by a bright non-core component. The measured ICRF2 position can be displaced more than 0.5 mas from the radio core and partake in the motion of the bright jet component.

  2. ATM Regulates Adipocyte Differentiation and Contributes to Glucose Homeostasis.

    PubMed

    Takagi, Masatoshi; Uno, Hatsume; Nishi, Rina; Sugimoto, Masataka; Hasegawa, Setsuko; Piao, Jinhua; Ihara, Norimasa; Kanai, Sayaka; Kakei, Saori; Tamura, Yoshifumi; Suganami, Takayoshi; Kamei, Yasutomi; Shimizu, Toshiaki; Yasuda, Akio; Ogawa, Yoshihiro; Mizutani, Shuki

    2015-02-11

    Ataxia-telangiectasia (A-T) patients occasionally develop diabetes mellitus. However, only limited attempts have been made to gain insight into the molecular mechanism of diabetes mellitus development in A-T patients. We found that Atm -/- mice were insulin resistant and possessed less subcutaneous adipose tissue as well as a lower level of serum adiponectin than Atm +/+ mice. Furthermore, in vitro studies revealed impaired adipocyte differentiation in Atm -/- cells caused by the lack of induction of C/EBPα and PPARγ, crucial transcription factors involved in adipocyte differentiation. Interestingly, ATM was activated by stimuli that induced differentiation, and the binding of ATM to C/EBPβ and p300 was involved in the transcriptional regulation of C/EBPα and adipocyte differentiation. Thus, our study sheds light on the poorly understood role of ATM in the pathogenesis of glucose intolerance in A-T patients and provides insight into the role of ATM in glucose metabolism. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Potential Refinement of the ICRF

    NASA Technical Reports Server (NTRS)

    Ma, Chopo

    2003-01-01

    The analysis and data used for the ICRF represented the state of the art in global, extragalactic, X/S band microwave astrometry in 1995. The same general analysis method was used to extend the ICRF with subsequent VLBI data in a manner consistent with the original catalog. Since 1995 there have been considerable advances in the geodetic/astrometric VLBI data set and in the analysis that would significantly improve the systematic errors, stability, and density of the next realization of the ICRS when the decision is made to take this step. In particular, data acquired since 1990, including extensive use of the VLBA, are of higher quality and astrometric utility because of changes in instrumentation, schedule design, and networks as well as specifically astrometric intent. The IVS (International VLBI Service for Geodesy and Astrometry) continues to devote a portion of its observing capability to systematic extension of the astrometric data set. Sufficient data distribution exists to select a better set of defining sources. Improvements in troposphere modeling will minimize known systematic astrometric errors while accurate modeling and estimation of station effects from loading and nonlinear motions will permit the reintegration of the celestial reference frame, terrestrial reference frame and Earth orientation parameters though a single VLBI solution. The differences between the current ICRF and the potential next realization will be described.

  4. Studies of ATM Kinase Activity Using Engineered ATM Sensitive to ATP Analogues (ATM-AS).

    PubMed

    Enari, Masato; Matsushima-Hibiya, Yuko; Miyazaki, Makoto; Otomo, Ryo

    2017-01-01

    Ataxia-telangiectasia mutated (ATM) protein is a member of the phosphatidylinositol 3-phosphate kinase (PI3-K)-related protein kinase (PIKK) family and is implicated in the initiation of signaling pathways following DNA double strand breaks (DSBs) elicited by exposure to ionizing irradiation (IR) or radiomimetic compounds. Loss of function of the ATM gene product results in the human genetic disorder ataxia-telangiectasia (A-T) characterized by neurodegeneration, immunodeficiency, genomic instability, and cancer predisposition. In response to DSBs, ATM is activated and phosphorylates Ser/Thr-Gln (S/T-Q) sequences on numerous proteins participating in DNA-damage responses. Among these proteins, phosphorylation of the tumor suppressor p53 at Ser15 is known as a target for ATM, which leads to the dissociation of MDM2, an E3 ubiquitin ligase, from p53 to prevent MDM2-dependent p53 degradation. Ser46 on p53 is phosphorylated in response to DSBs and contributes to the preferential transactivation of pro-apoptotic genes, such as p53AIP1, Noxa, and PUMA, to prevent tumor formation. Our group have shown that not only ATM preferentially phosphorylates S/T-Q sequences, but also Ser46, which is a noncanonical site with an S-P sequence for ATM. Ser46 on p53 is directly phosphorylated by ATM in a p53 conformation-dependent manner using the ATP analogue-accepting ATM mutant (ATM-AS) system. This protocol summarizes an approach to identify direct numerous targets for ATM kinase and is used to elucidate ATM signaling pathways in the DNA damage responses.

  5. IVS Observation of ICRF2-Gaia Transfer Sources

    NASA Astrophysics Data System (ADS)

    Le Bail, K.; Gipson, J. M.; Gordon, D.; MacMillan, D. S.; Behrend, D.; Thomas, C. C.; Bolotin, S.; Himwich, W. E.; Baver, K. D.; Corey, B. E.; Titus, M.; Bourda, G.; Charlot, P.; Collioud, A.

    2016-03-01

    The second realization of the International Celestial Reference Frame (ICRF2), which is the current fundamental celestial reference frame adopted by the International Astronomical Union, is based on Very Long Baseline Interferometry (VLBI) data at radio frequencies in X band and S band. The European Space Agency’s Gaia mission, launched on 2013 December 19, started routine scientific operations in 2014 July. By scanning the whole sky, it is expected to observe ∼500,000 Quasi Stellar Objects in the optical domain an average of 70 times each during the five years of the mission. This means that, in the future, two extragalactic celestial reference frames, at two different frequency domains, will coexist. It will thus be important to align them very accurately. In 2012, the Laboratoire d’Astrophysique de Bordeaux (LAB) selected 195 sources from ICRF2 that will be observed by Gaia and should be suitable for aligning the radio and optical frames: they are called ICRF2-Gaia transfer sources. The LAB submitted a proposal to the International VLBI Service (IVS) to regularly observe these ICRF2-Gaia transfer sources at the same rate as Gaia observes them in the optical realm, e.g., roughly once a month. We describe our successful effort to implement such a program and report on the results. Most observations of the ICRF2-Gaia transfer sources now occur automatically as part of the IVS source monitoring program, while a subset of 37 sources requires special attention. Beginning in 2013, we scheduled 25 VLBI sessions devoted in whole or in part to measuring these 37 sources. Of the 195 sources, all but one have been successfully observed in the 12 months prior to 2015 September 01. Of the sources, 87 met their observing target of 12 successful sessions per year. The position uncertainties of all of the ICRF2-Gaia transfer sources have improved since the start of this observing program. For a subset of 24 sources whose positions were very poorly known, the uncertainty

  6. 49 CFR 193.2304 - Corrosion control overview.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Corrosion control overview. 193.2304 Section 193... GAS FACILITIES: FEDERAL SAFETY STANDARDS Construction § 193.2304 Corrosion control overview. (a... materials specifications from a corrosion control viewpoint and determines that the materials involved will...

  7. 49 CFR 193.2304 - Corrosion control overview.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Corrosion control overview. 193.2304 Section 193... GAS FACILITIES: FEDERAL SAFETY STANDARDS Construction § 193.2304 Corrosion control overview. (a... materials specifications from a corrosion control viewpoint and determines that the materials involved will...

  8. 49 CFR 193.2304 - Corrosion control overview.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Corrosion control overview. 193.2304 Section 193... GAS FACILITIES: FEDERAL SAFETY STANDARDS Construction § 193.2304 Corrosion control overview. (a... materials specifications from a corrosion control viewpoint and determines that the materials involved will...

  9. 49 CFR 193.2304 - Corrosion control overview.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Corrosion control overview. 193.2304 Section 193... GAS FACILITIES: FEDERAL SAFETY STANDARDS Construction § 193.2304 Corrosion control overview. (a... materials specifications from a corrosion control viewpoint and determines that the materials involved will...

  10. Modelling of combined ICRF and NBI heating in JET hybrid plasmas

    NASA Astrophysics Data System (ADS)

    Gallart, Dani; Mantsinen, Mervi; Challis, Clive; Frigione, Domenico; Graves, Jonathan; Hobirk, Joerg; Belonohy, Eva; Czarnecka, Agata; Eriksson, Jacob; Goniche, Marc; Hellesen, Carl; Jacquet, Philippe; Joffrin, Emmanuel; Krawczyk, Natalia; King, Damian; Lennholm, Morten; Lerche, Ernesto; Pawelec, Ewa; Sips, George; Solano, Emilia; Tsalas, Maximos; Valisa, Marco

    2017-10-01

    During the 2015-2016 JET campaigns many efforts have been devoted to the exploration of high performance plasma scenarios envisaged for ITER operation. In this paper we model the combined ICRF+NBI heating in selected key hybrid discharges using PION. The antenna frequency was tuned to match the cyclotron frequency of minority hydrogen (H) at the center of the tokamak coinciding with the second harmonic cyclotron resonance of deuterium. The modelling takes into account the synergy between ICRF and NBI heating through the second harmonic cyclotron resonance of deuterium beam ions which allows us to assess its impact on the neutron rate RNT. We evaluate the influence of H concentration which was varied in different discharges in order to test their role in the heating performance. According to our modelling, the ICRF enhancement of RNT increases by decreasing the H concentration which increases the ICRF power absorbed by deuterons. We find that in the recent hybrid discharges this ICRF enhancement was in the range of 10-25%. Finally, we extrapolate the results to D-T and find that the best performing hybrid discharges correspond to an equivalent fusion power of ˜7.0 MW in D-T.

  11. The International Celestial Reference Frame (ICRF) and the Relationship Between Frames

    NASA Technical Reports Server (NTRS)

    Ma, Chopo

    2000-01-01

    The International Celestial Reference Frame (ICRF), a catalog of VLBI source positions, is now the basis for astrometry and geodesy. Its construction and extension/maintenance will be discussed as well as the relationship of the ICRF, ITRF, and EOP/nutation.

  12. Initial operation of high power ICRF system for long pulse in EAST

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

    Qin, C. M., E-mail: chmq@ipp.ac.cn; Zhao, Y. P.; Zhang, X. J.

    2015-12-10

    The ICRF heating system on EAST upgraded by active cooling aims for long pulse operation. In this paper, the main technical features of the ICRF system are described. One of a major challenges for long pulse operation is RF-edge interactions induced impurity production and heat loading. In EAST, ICRF antenna protections and Faraday screen bars damaged due to LH electron beam are found. Preliminary results for the analysis of the interaction between LHCD and ICRF antenna are discussed. Increase of metal impurities in the plasma during RF pulse and in a larger core radiation are also shown. These RF-edge interactionsmore » at EAST and some preliminary results for the optimizing RF performance will be presented.« less

  13. THE POSITION/STRUCTURE STABILITY OF FOUR ICRF2 SOURCES

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

    Fomalont, Ed; Johnston, Kenneth; Fey, Alan

    2011-03-15

    Four close radio sources in the International Celestial Reference Frame (ICRF) catalog were observed using phase referencing with the VLBA at 43, 23, and 8.6 GHz, and with VERA at 23 GHz over a one-year period. The goal was to determine the stability of the radio cores and to assess structure effects associated with positions in the ICRF. Although the four sources were compact at 8.6 GHz, the VLBA images at 43 GHz with 0.3 mas resolution showed that all were composed of several components. A component in each source was identified as the radio core using some or allmore » of the following emission properties: compactness, spectral index, location at the end of the extended emission region, and stationary in the sky. Over the observing period, the relative positions between the four radio cores were constant to 0.02 mas, the phase-referencing positional accuracy obtained at 23 and 43 GHz among the sources, suggesting that once a radio core is identified, it remains stationary in the sky to this accuracy. Other radio components in two of the four sources had detectable motion in the radio jet direction. Comparison of the 23 and 43 GHz VLBA images with the VLBA 8.6 GHz images and the ICRF positions suggests that some ICRF positions are dominated by a moving jet component; hence, they can be displaced up to 0.5 mas from the radio core and may also reflect the motion of the jet component. Future astrometric efforts to determine a more accurate quasar reference frame at 23 and 43 GHz and from the VLBI2010 project are discussed, and supporting VLBA or European VLBI Network observations of ICRF sources at 43 GHz are recommended in order to determine the internal structure of the sources. A future collaboration between the radio (ICRF) and the optical frame of GAIA is discussed.« less

  14. 49 CFR 193.2717 - Training: fire protection.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... under § 193.2801. (b) A written plan of continuing instruction, including plant fire drills, must be... 49 Transportation 3 2013-10-01 2013-10-01 false Training: fire protection. 193.2717 Section 193...: fire protection. (a) All personnel involved in maintenance and operations of an LNG plant, including...

  15. 49 CFR 193.2717 - Training: fire protection.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... under § 193.2801. (b) A written plan of continuing instruction, including plant fire drills, must be... 49 Transportation 3 2011-10-01 2011-10-01 false Training: fire protection. 193.2717 Section 193...: fire protection. (a) All personnel involved in maintenance and operations of an LNG plant, including...

  16. 49 CFR 193.2717 - Training: fire protection.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... under § 193.2801. (b) A written plan of continuing instruction, including plant fire drills, must be... 49 Transportation 3 2012-10-01 2012-10-01 false Training: fire protection. 193.2717 Section 193...: fire protection. (a) All personnel involved in maintenance and operations of an LNG plant, including...

  17. 49 CFR 193.2717 - Training: fire protection.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... under § 193.2801. (b) A written plan of continuing instruction, including plant fire drills, must be... 49 Transportation 3 2014-10-01 2014-10-01 false Training: fire protection. 193.2717 Section 193...: fire protection. (a) All personnel involved in maintenance and operations of an LNG plant, including...

  18. Acceleration of Dense Flowing Plasmas using ICRF Power in the VASIMR Experiment

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

    Squire, Jared P.

    2005-09-26

    ICRF power in the Variable Specific Impulse Magnetoplasma Rocket (VASIMR) concept energizes ions (> 100 eV) in a diverging magnetic field to accelerate a dense ({approx} 1019 m-3) flowing plasma to velocities useful for space propulsion ({approx}100 km/s). Theory predicts that an ICRF slow wave launched from the high field side of the resonance will propagate in the magnetic beach to absorb nearly all of the power at the resonance, thus efficiently converting the RF power to ion kinetic energy. The plasma flows through the resonance only once, so the ions are accelerated in a single pass. This process hasmore » proven efficient ({approx} 70%) with an ICRF power level of 1.5 kW at about 3.6 MHz in the VASIMR experiment, VX-30, using deuterium plasma created by a helicon operating in flowing mode. We have measured ICRF plasma loading up to 2 ohms, consistent with computational predictions made using Oak Ridge National Laboratory's EMIR code. Recent helicon power upgrades (20 kW at 13.56 MHz) have enabled a 5 cm diameter target plasma for ICRF with an ion flux of over 3x10 20 s-1 and a high degree of ionization. This paper summarizes our ICRF results and presents the latest helicon developments in VX-30.« less

  19. Anomalous preservation of pure methane hydrate at 1 atm

    USGS Publications Warehouse

    Stern, L.A.; Circone, S.; Kirby, S.H.; Durham, W.B.

    2001-01-01

    Direct measurement of decomposition rates of pure, polycrystalline methane hydrate reveals a thermal regime where methane hydrate metastably `preserves' in bulk by as much as 75 K above its nominal equilibrium temperature (193 K at 1 atm). Rapid release of the sample pore pressure at isothermal conditions between 242 and 271 K preserves up to 93% of the hydrate for at least 24 h, reflecting the greatly suppressed rates of dissociation that characterize this regime. Subsequent warming through the H2O ice point then induces rapid and complete dissociation, allowing controlled recovery of the total expected gas yield. This behavior is in marked contrast to that exhibited by methane hydrate at both colder (193-240 K) and warmer (272-290 K) test conditions, where dissociation rates increase monotonically with increasing temperature. Anomalous preservation has potential application for successful retrieval of natural gas hydrate or hydrate-bearing sediments from remote settings, as well as for temporary low-pressure transport and storage of natural gas.

  20. ATM encryption testing

    NASA Astrophysics Data System (ADS)

    Capell, Joyce; Deeth, David

    1996-01-01

    This paper describes why encryption was selected by Lockheed Martin Missiles & Space as the means for securing ATM networks. The ATM encryption testing program is part of an ATM network trial provided by Pacific Bell under the California Research Education Network (CalREN). The problem being addressed is the threat to data security which results when changing from a packet switched network infrastructure to a circuit switched ATM network backbone. As organizations move to high speed cell-based networks, there is a break down in the traditional security model which is designed to protect packet switched data networks from external attacks. This is due to the fact that most data security firewalls filter IP packets, restricting inbound and outbound protocols, e.g. ftp. ATM networks, based on cell-switching over virtual circuits, does not support this method for restricting access since the protocol information is not carried by each cell. ATM switches set up multiple virtual connections, thus there is no longer a single point of entry into the internal network. The problem is further complicated by the fact that ATM networks support high speed multi-media applications, including real time video and video teleconferencing which are incompatible with packet switched networks. The ability to restrict access to Lockheed Martin networks in support of both unclassified and classified communications is required before ATM network technology can be fully deployed. The Lockheed Martin CalREN ATM testbed provides the opportunity to test ATM encryption prototypes with actual applications to assess the viability of ATM encryption methodologies prior to installing large scale ATM networks. Two prototype ATM encryptors are being tested: (1) `MILKBUSH' a prototype encryptor developed by NSA for transmission of government classified data over ATM networks, and (2) a prototype ATM encryptor developed by Sandia National Labs in New Mexico, for the encryption of proprietary data.

  1. Modeling of the EAST ICRF antenna with ICANT Code

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

    Qin Chengming; Zhao Yanping; Colas, L.

    2007-09-28

    A Resonant Double Loop (RDL) antenna for ion-cyclotron range of frequencies (ICRF) on Experimental Advanced Superconducting Tokamak (EAST) is under construction. The new antenna is analyzed using the antenna coupling code ICANT which self-consistently determines the surface currents on all antenna parts. In this work, the modeling of the new ICRF antenna using this code is to assess the near-fields in front of the antenna and analysis its coupling capabilities. Moreover, the antenna reactive radiated power computed by ICANT and shows a good agreement with deduced from Transmission Line (TL) theory.

  2. Modeling of the EAST ICRF antenna with ICANT Code

    NASA Astrophysics Data System (ADS)

    Qin, Chengming; Zhao, Yanping; Colas, L.; Heuraux, S.

    2007-09-01

    A Resonant Double Loop (RDL) antenna for ion-cyclotron range of frequencies (ICRF) on Experimental Advanced Superconducting Tokamak (EAST) is under construction. The new antenna is analyzed using the antenna coupling code ICANT which self-consistently determines the surface currents on all antenna parts. In this work, the modeling of the new ICRF antenna using this code is to assess the near-fields in front of the antenna and analysis its coupling capabilities. Moreover, the antenna reactive radiated power computed by ICANT and shows a good agreement with deduced from Transmission Line (TL) theory.

  3. ICRF-Induced Changes in Floating Potential and Ion Saturation Current in the EAST Divertor

    NASA Astrophysics Data System (ADS)

    Perkins, Rory; Hosea, Joel; Taylor, Gary; Bertelli, Nicola; Kramer, Gerrit; Qin, Chengming; Wang, Liang; Yang, Jichan; Zhang, Xinjun

    2017-10-01

    Injection of waves in the ion cyclotron range of frequencies (ICRF) into a tokamak can potentially raise the plasma potential via RF rectification. Probes are affected both by changes in plasma potential and also by RF-averaging of the probe characteristic, with the latter tending to drop the floating potential. We present the effect of ICRF heating on divertor Langmuir probes in the EAST experiment. Over a scan of the outer gap, probes connected to the antennas have increases in floating potential with ICRF, but probes in between the outer-vessel strike point and flux surface tangent to the antenna have decreased floating potential. This behaviour is investigated using field-line mapping. Preliminary results show that mdiplane gas puffing can suppress the strong influence of ICRF on the probes' floating potential.

  4. Satellite ATM Networks: Architectures and Guidelines Developed

    NASA Technical Reports Server (NTRS)

    vonDeak, Thomas C.; Yegendu, Ferit

    1999-01-01

    An important element of satellite-supported asynchronous transfer mode (ATM) networking will involve support for the routing and rerouting of active connections. Work published under the auspices of the Telecommunications Industry Association (http://www.tiaonline.org), describes basic architectures and routing protocol issues for satellite ATM (SATATM) networks. The architectures and issues identified will serve as a basis for further development of technical specifications for these SATATM networks. Three ATM network architectures for bent pipe satellites and three ATM network architectures for satellites with onboard ATM switches were developed. The architectures differ from one another in terms of required level of mobility, supported data rates, supported terrestrial interfaces, and onboard processing and switching requirements. The documentation addresses low-, middle-, and geosynchronous-Earth-orbit satellite configurations. The satellite environment may require real-time routing to support the mobility of end devices and nodes of the ATM network itself. This requires the network to be able to reroute active circuits in real time. In addition to supporting mobility, rerouting can also be used to (1) optimize network routing, (2) respond to changing quality-of-service requirements, and (3) provide a fault tolerance mechanism. Traffic management and control functions are necessary in ATM to ensure that the quality-of-service requirements associated with each connection are not violated and also to provide flow and congestion control functions. Functions related to traffic management were identified and described. Most of these traffic management functions will be supported by on-ground ATM switches, but in a hybrid terrestrial-satellite ATM network, some of the traffic management functions may have to be supported by the onboard satellite ATM switch. Future work is planned to examine the tradeoffs of placing traffic management functions onboard a satellite as

  5. Sequential modelling of ICRF wave near RF fields and asymptotic RF sheaths description for AUG ICRF antennas

    NASA Astrophysics Data System (ADS)

    Jacquot, Jonathan; Tierens, Wouter; Zhang, Wei; Bobkov, Volodymyr; Colas, Laurent; Noterdaeme, Jean-Marie

    2017-10-01

    A sequence of simulations is performed with RAPLICASOL and SSWICH to compare two AUG ICRF antennas. RAPLICASOL outputs have been used as input to SSWICH-SW for the AUG ICRF antennas. Using parallel electric field maps and the scattering matrix produced by RAPLICASOL, SSWICH-SW, reduced to its asymptotic part, is able to produce a 2D radial/poloidal map of the DC plasma potential accounting for the antenna input settings (total power, power balance, phasing). Two models of antennas are compared: 2-strap antenna vs 3-strap antenna. The 2D DC potential structures are correlated to structures of the parallel electric field map for different phasing and power balance. The overall DC plasma potential on the 3-strap antenna is lower due to better global RF currents compensation. Spatial proximity between regions of high RF electric field and regions where high DC plasma potentials are observed is an important factor for sheath rectification.

  6. ATM facilitates mouse gammaherpesvirus reactivation from myeloid cells during chronic infection

    PubMed Central

    Kulinski, Joseph M.; Darrah, Eric J.; Broniowska, Katarzyna A.; Mboko, Wadzanai P.; Mounce, Bryan C.; Malherbe, Laurent P.; Corbett, John A; Gauld, Stephen B.; Tarakanova, Vera L.

    2015-01-01

    Gammaherpesviruses are cancer-associated pathogens that establish life-long infection in most adults. Insufficiency of Ataxia-Telangiectasia mutated (ATM) kinase leads to a poor control of chronic gammaherpesvirus infection via an unknown mechanism that likely involves a suboptimal antiviral response. In contrast to the phenotype in the intact host, ATM facilitates gammaherpesvirus reactivation and replication in vitro. We hypothesized that ATM mediates both pro- and antiviral activities to regulate chronic gammaherpesvirus infection in an immunocompetent host. To test the proposed proviral activity of ATM in vivo, we generated mice with ATM deficiency limited to myeloid cells. Myeloid-specific ATM deficiency attenuated gammaherpesvirus infection during the establishment of viral latency. The results of our study uncover a proviral role of ATM in the context of gammaherpesvirus infection in vivo and support a model where ATM combines pro- and antiviral functions to facilitate both gammaherpesvirus-specific T cell immune response and viral reactivation in vivo. PMID:26001649

  7. ATM facilitates mouse gammaherpesvirus reactivation from myeloid cells during chronic infection.

    PubMed

    Kulinski, Joseph M; Darrah, Eric J; Broniowska, Katarzyna A; Mboko, Wadzanai P; Mounce, Bryan C; Malherbe, Laurent P; Corbett, John A; Gauld, Stephen B; Tarakanova, Vera L

    2015-09-01

    Gammaherpesviruses are cancer-associated pathogens that establish life-long infection in most adults. Insufficiency of Ataxia-Telangiectasia mutated (ATM) kinase leads to a poor control of chronic gammaherpesvirus infection via an unknown mechanism that likely involves a suboptimal antiviral response. In contrast to the phenotype in the intact host, ATM facilitates gammaherpesvirus reactivation and replication in vitro. We hypothesized that ATM mediates both pro- and antiviral activities to regulate chronic gammaherpesvirus infection in an immunocompetent host. To test the proposed proviral activity of ATM in vivo, we generated mice with ATM deficiency limited to myeloid cells. Myeloid-specific ATM deficiency attenuated gammaherpesvirus infection during the establishment of viral latency. The results of our study uncover a proviral role of ATM in the context of gammaherpesvirus infection in vivo and support a model where ATM combines pro- and antiviral functions to facilitate both gammaherpesvirus-specific T cell immune response and viral reactivation in vivo. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. 49 CFR 193.2121-193.2153 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES: FEDERAL SAFETY STANDARDS Design Design of Components and Buildings §§ 193.2121-193...

  9. 49 CFR 193.2189-193.2233 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES: FEDERAL SAFETY STANDARDS Design Lng Storage Tanks §§ 193.2189-193.2233 [Reserved] ...

  10. Assessment of a field-aligned ICRF antenna

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

    Wukitch, S. J.; Brunner, D.; Ennever, P.

    Impurity contamination and localized heat loads associated with ion cyclotron range of frequency (ICRF) antenna operation are among the most challenging issues for ICRF utilization.. Another challenge is maintaining maximum coupled power through plasma variations including edge localized modes (ELMs) and confinement transitions. Here, we report on an experimental assessment of a field aligned (FA) antenna with respect to impurity contamination, impurity sources, RF enhanced heat flux and load tolerance. In addition, we compare the modification of the scrape of layer (SOL) plasma potential of the FA antenna to a conventional, toroidally aligned (TA) antenna, in order to explore themore » underlying physics governing impurity contamination linked to ICRF heating. The FA antenna is a 4-strap ICRF antenna where the current straps and antenna enclosure sides are perpendicular to and the Faraday screen rods are parallel to the total magnetic field. In principle, alignment with respect to the total magnetic field minimizes integrated E∥ (electric field along a magnetic field line) via symmetry. Consistent with expectations, we observed that the impurity contamination and impurity source at the FA antenna are reduced compared to the TA antenna. In both L and H-mode discharges, the radiated power is 20–30% lower for a FA-antenna heated discharge than a discharge heated with the TA-antennas. Further we observe that the fraction of RF energy deposited upon the antenna is less than 0.4 % of the total injected RF energy in dipole phasing. The total deposited energy increases significantly when the FA antenna is operated in monopole phasing. The FA antenna also exhibits an unexpected load tolerance for ELMs and confinement transitions compared to the TA antennas. However, inconsistent with expectations, we observe RF induced plasma potentials to be nearly identical for FA and TA antennas when operated in dipole phasing. In monopole phasing, the FA antenna has the highest

  11. ATM CMG/EPEA

    NASA Technical Reports Server (NTRS)

    Abramowitz, R.; Kovek, J.; Teimer, W.; Haddad, S. P.

    1975-01-01

    The Apollo Telescope mount double gimballed control moment gyro ATM CMG is described. Photographs of the CMG and its subassemblies are presented along with a functional block diagram of the CMG subsystem. Analog processing electronics for ATM vehicle pointing control and ATM experiment package pointing control are also described.

  12. Density Convection near Radiating ICRF Antennas and its Effect on the Coupling of Lower Hybrid Waves

    NASA Astrophysics Data System (ADS)

    Ekedahl, A.; Colas, L.; Mayoral, M.-L.; Beaumont, B.; Bibet, Ph.; Brémond, S.; Kazarian, F.; Mailloux, J.; Noterdaeme, J.-M.; Efda-Jet Contributors

    2003-12-01

    Combined operation of Lower Hybrid (LH) and Ion Cyclotron Resonance Frequency (ICRF) waves can result in a degradation of the LH wave coupling, as observed both in the Tore Supra and JET tokamaks. The reflection coefficient on the part of the LH launcher magnetically connected to the powered ICRF antenna increases, suggesting a local decrease in the electron density in the connecting flux tubes. This has been confirmed by Langmuir probe measurements on the LH launchers in the latest Tore Supra experiments. Moreover, recent experiments in JET indicate that the LH coupling degradation depends on the ICRF power and its launched k//-spectrum. The 2D density distribution around the Tore Supra ICRF antennas has been modelled with the CELLS-code, balancing parallel losses with diffusive transport and sheath induced E×B convection, obtained from RF field mapping using the ICANT-code. The calculations are in qualitative agreement with the experimental observations, i.e. density depletion is obtained, localised mainly in the antenna shadow, and dependent on ICRF power and antenna spectrum.

  13. 49 CFR 193.2183-193.2185 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES: FEDERAL SAFETY STANDARDS Design Impoundment Design and Capacity §§ 193.2183-193.2185 [Reserved] LNG Storage Tanks ...

  14. 49 CFR 193.2305-193.2319 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ....2319 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES: FEDERAL SAFETY STANDARDS Construction §§ 193.2305-193.2319 [Reserved] ...

  15. 49 CFR 193.2323-193.2329 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ....2329 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES: FEDERAL SAFETY STANDARDS Construction §§ 193.2323-193.2329 [Reserved] ...

  16. Immunoglobulin class switch recombination is impaired in Atm-deficient mice.

    PubMed

    Lumsden, Joanne M; McCarty, Thomas; Petiniot, Lisa K; Shen, Rhuna; Barlow, Carrolee; Wynn, Thomas A; Morse, Herbert C; Gearhart, Patricia J; Wynshaw-Boris, Anthony; Max, Edward E; Hodes, Richard J

    2004-11-01

    Immunoglobulin class switch recombination (Ig CSR) involves DNA double strand breaks (DSBs) at recombining switch regions and repair of these breaks by nonhomologous end-joining. Because the protein kinase ataxia telengiectasia (AT) mutated (ATM) plays a critical role in DSB repair and AT patients show abnormalities of Ig isotype expression, we assessed the role of ATM in CSR by examining ATM-deficient mice. In response to T cell-dependent antigen (Ag), Atm-/- mice secreted substantially less Ag-specific IgA, IgG1, IgG2b, and IgG3, and less total IgE than Atm+/+ controls. To determine whether Atm-/- B cells have an intrinsic defect in their ability to undergo CSR, we analyzed in vitro responses of purified B cells. Atm-/- cells secreted substantially less IgA, IgG1, IgG2a, IgG3, and IgE than wild-type (WT) controls in response to stimulation with lipopolysaccharide, CD40 ligand, or anti-IgD plus appropriate cytokines. Molecular analysis of in vitro responses indicated that WT and Atm-/- B cells produced equivalent amounts of germline IgG1 and IgE transcripts, whereas Atm-/- B cells produced markedly reduced productive IgG1 and IgE transcripts. The reduction in isotype switching by Atm-/- B cells occurs at the level of genomic DNA recombination as measured by digestion-circularization PCR. Analysis of sequences at CSR sites indicated that there is greater microhomology at the mu-gamma1 switch junctions in ATM B cells than in wild-type B cells, suggesting that ATM function affects the need or preference for sequence homology in the CSR process. These findings suggest a role of ATM in DNA DSB recognition and/or repair during CSR.

  17. Fast-ion distributions from third harmonic ICRF heating studied with neutron emission spectroscopy

    NASA Astrophysics Data System (ADS)

    Hellesen, C.; Gatu Johnson, M.; Andersson Sundén, E.; Conroy, S.; Ericsson, G.; Eriksson, J.; Sjöstrand, H.; Weiszflog, M.; Johnson, T.; Gorini, G.; Nocente, M.; Tardocchi, M.; Kiptily, V. G.; Pinches, S. D.; Sharapov, S. E.; EFDA Contributors, JET

    2013-11-01

    The fast-ion distribution from third harmonic ion cyclotron resonance frequency (ICRF) heating on the Joint European Torus is studied using neutron emission spectroscopy with the time-of-flight spectrometer TOFOR. The energy dependence of the fast deuteron distribution function is inferred from the measured spectrum of neutrons born in DD fusion reactions, and the inferred distribution is compared with theoretical models for ICRF heating. Good agreements between modelling and measurements are seen with clear features in the fast-ion distribution function, that are due to the finite Larmor radius of the resonating ions, replicated. Strong synergetic effects between ICRF and neutral beam injection heating were also seen. The total energy content of the fast-ion population derived from TOFOR data was in good agreement with magnetic measurements for values below 350 kJ.

  18. Downregulation of ATM Gene and Protein Expression in Canine Mammary Tumors.

    PubMed

    Raposo-Ferreira, T M M; Bueno, R C; Terra, E M; Avante, M L; Tinucci-Costa, M; Carvalho, M; Cassali, G D; Linde, S D; Rogatto, S R; Laufer-Amorim, R

    2016-11-01

    The ataxia telangiectasia mutated (ATM) gene encodes a protein associated with DNA damage repair and maintenance of genomic integrity. In women, ATM transcript and protein downregulation have been reported in sporadic breast carcinomas, and the absence of ATM protein expression has been associated with poor prognosis. The aim of this study was to evaluate ATM gene and protein expression in canine mammary tumors and their association with clinical outcome. ATM gene and protein expression was evaluated by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry, respectively, in normal mammary gland samples (n = 10), benign mammary tumors (n = 11), nonmetastatic mammary carcinomas (n = 19), and metastatic mammary carcinomas (n = 11). Lower ATM transcript levels were detected in benign mammary tumors and carcinomas compared with normal mammary glands (P = .011). Similarly, lower ATM protein expression was observed in benign tumors (P = .0003), nonmetastatic mammary carcinomas (P < .0001), and the primary sites of metastatic carcinomas (P < .0001) compared with normal mammary glands. No significant differences in ATM gene or protein levels were detected among benign tumors and nonmetastatic and metastatic mammary carcinomas (P > .05). The levels of ATM gene or protein expression were not significantly associated with clinical and pathological features or with survival. Similar to human breast cancer, the data in this study suggest that ATM gene and protein downregulation is involved in canine mammary gland tumorigenesis. © The Author(s) 2016.

  19. ATM technology and beyond

    NASA Technical Reports Server (NTRS)

    Cheung, Nim K.

    1993-01-01

    Networks based on Asynchronous Transfer Mode (ATM) are expected to provide cost-effective and ubiquitous infrastructure to support broadband and multimedia services. In this paper, we give an overview of the ATM standards and its associated physical layer transport technologies. We use the experimental HIPPI-ATM-SONET (HAS) interface in the Nectar Gigabit Testbed to illustrate how one can use the SONET/ATM public network to provide transport for bursty gigabit applications.

  20. Recent ICRF coupling experiments on EAST

    NASA Astrophysics Data System (ADS)

    Yuqing, YANG; Xinjun, ZHANG; Yanping, ZHAO; Chengming, QIN; Yan, CHENG; Yuzhou, MAO; Hua, YANG; Jianhua, WANG; Shuai, YUAN; Lei, WANG; Songqing, JU; Gen, CHEN; Xu, DENG; Kai, ZHANG; Baonian, WAN; Jiangang, LI; Yuntao, SONG; Xianzu, GONG; Jinping, QIAN; Tao, ZHANG

    2018-04-01

    Recent ion cyclotron resonance frequency (ICRF) coupling experiments for optimizing ICRF heating in high power discharge were performed on EAST. The coupling experiments were focus on antenna phasing and gas puffing, which were performed separately on two ports of the ion cyclotron resonance heating (ICRH) system of EAST. The antenna phasing was performed on the I-port antenna, which consists of four toroidally spaced radiating straps operating in multiple phasing cases; the coupling performance was better under low wave number | {k}\\parallel | (ranging from 4.5 to 6.5). By fuelling the plasma from gas injectors, placed as uniformly spaced array from top to bottom at each side limiter of the B-port antenna, which works in dipole phasing, the coupling resistance of the B-port antenna increased obviously. Furthermore, the coupling resistance of the I-port antenna was insensitive to a smaller rate of gas puffing but when the gas injection rate was more than a certain value (>1021s‑1), a sharp increase in the coupling resistance of the I-port antenna occurred, which was mainly caused by the toroidal asymmetric boundary density arising from gas puffing. A more specific analysis is given in the paper.

  1. The behavior of neutron emissions during ICRF minority heating of plasma at EAST

    NASA Astrophysics Data System (ADS)

    Zhong, Guoqiang; Cao, Hongrui; Hu, Liqun; Zhou, Ruijie; Xiao, Min; Li, Kai; Pu, Neng; Huang, Juan; Liu, Guangzhu; Lin, Shiyao; Lyu, Bo; Liu, Haiqing; Zhang, Xinjun; EAST Team

    2016-07-01

    Ion cyclotron radio frequency (ICRF) wave heating is a primary method to heat ions in the Experimental Advanced Superconducting Tokamak (EAST). Through neutron diagnostics, effective ion heating was observed in hydrogenminority heating (MH) scenarios. At present, investigation of deuterium-deuterium (DD) fusion neutrons is mostly based on time-resolved flux monitor and spectrometer measurements. When the ICRF was applied, the neutron intensity became one order higher. The H/H  +  D ratio was in the range of 5-10%, corresponding to the hydrogen MH dominated scenario, and a strong high energy tail was not displayed on the neutron spectrum that was measured by a liquid scintillator. Moreover, ion temperature in the plasma center (T i) was inversely calculated by the use of neutron source strength (S n) and the plasma density based on classical fusion reaction equations. This result indicates that T i increases by approximately 30% in L-mode plasma, and by more than 50% in H-mode plasma during ICRF heating, which shows good agreement with x-ray crystal spectrometer (XCS) diagnostics. Finally, the DD neutron source strength scaling law, with regard to plasma current (I P) and ICRF coupling power (P RF) on the typical minority heating condition, was obtained by statistical analysis.

  2. Gadd45a deletion aggravates hematopoietic stem cell dysfunction in ATM-deficient mice.

    PubMed

    Chen, Yulin; Yang, Runan; Guo, Peng; Ju, Zhenyu

    2014-01-01

    Ataxia telangiectasia mutated (ATM) kinase plays an essential role in the maintenance of genomic stability. ATM-deficient (ATM(-/-)) mice exhibit hematopoietic stem cell (HSC) dysfunction and a high incidence of lymphoma. Gadd45a controls cell cycle arrest, apoptosis and DNA repair, and is involved in the ATM-p53 mediated DNA damage response. However, the role of Gadd45a in regulating the functionality of ATM(-/-) HSCs is unknown. Here we report that Gadd45a deletion did not rescue the defects of T-cells and B-cells development in ATM(-/-) mice. Instead, ATM and Gadd45a double knockout (ATM(-/-) Gadd45a(-/-)) HSCs exhibited an aggravated defect in long-term self-renewal capacity compared to ATM(-/-) HSCs in HSC transplantation experiments. Further experiments revealed that the aggravated defect of ATM(-/-) Gadd45a(-/-) HSCs was due to a reduction of cell proliferation, associated with an accumulation of DNA damage and subsequent activation of DNA damage response including an up-regulation of p53-p21 signaling pathway. Additionally, ATM(-/-) Gadd45a(-/-) mice showed an increased incidence of hematopoietic malignancies, as well as an increased rate of metastasis than ATM(-/-) mice. In conclusion, Gadd45a deletion aggravated the DNA damage accumulation, which subsequently resulted in a further impaired self-renewal capacity and an increased malignant transformation in ATM(-/-) HSCs.

  3. Study of ICRF wave propagation and plasma coupling efficiency in a linear magnetic mirror device

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

    Peng, S.Y.

    1991-07-01

    Ion Cyclotron Range of Frequency (ICRF) wave propagation in an inhomogeneous axial magnetic field in a cylindrical plasma-vacuum system has historically been inadequately modelled. Previous works either sacrifice the cylindrical geometry in favor of a simpler slab geometry, concentrate on the resonance region, use a single mode to represent the entire field structure, or examine only radial propagation. This thesis performs both analytical and computational studies to model the ICRF wave-plasma coupling and propagation problem. Experimental analysis is also conducted to compare experimental results with theoretical predictions. Both theoretical as well as experimental analysis are undertaken as part of themore » thesis. The theoretical studies simulate the propagation of ICRF waves in an axially inhomogeneous magnetic field and in cylindrical geometry. Two theoretical analysis are undertaken - an analytical study and a computational study. The analytical study treats the inhomogeneous magnetic field by transforming the (r,z) coordinate into another coordinate system ({rho},{xi}) that allows the solution of the fields with much simpler boundaries. The plasma fields are then Fourier transformed into two coupled convolution-integral equations which are then differenced and solved for both the perpendicular mode number {alpha} as well as the complete EM fields. The computational study involves a multiple eigenmode computational analysis of the fields that exist within the plasma-vacuum system. The inhomogeneous axial field is treated by dividing the geometry into a series of transverse axial slices and using a constant dielectric tensor in each individual slice. The slices are then connected by longitudinal boundary conditions.« less

  4. ICRF operation with improved antennas in ASDEX Upgrade with W wall

    NASA Astrophysics Data System (ADS)

    Bobkov, V.; Balden, M.; Bilato, R.; Braun, F.; Dux, R.; Herrmann, A.; Faugel, H.; Fünfgelder, H.; Giannone, L.; Kallenbach, A.; Maier, H.; Müller, H. W.; Neu, R.; Noterdaeme, J.-M.; Pütterich, Th.; Rohde, V.; Tsujii, N.; Zeus, F.; Zohm, H.; the ASDEX Upgrade Team

    2013-09-01

    Experiments with boron-coated side limiters of two antennas operated together in 2012 showed that the side limiters are responsible for more than half of the increased W content in the plasma. Together with the contribution from the other limiter tiles, not replaced in 2012, the limiters account for at least two thirds of the W content. A modified test two-strap ion cyclotron range of frequency (ICRF) antennas in ASDEX Upgrade with broad limiters and narrow straps has shown an improved operation with full W wall in 2011/2012 campaigns with up to a 40% lower rise of W concentration allowing more stable operation at low deuterium gas injection rate. Limiter spectroscopy measurements indicate up to a 40% reduction of the rise of the W sputtering yield during ICRF power, measured under the assumption of negligible influence of geometry variations and reflections on the measurements. The boron limiters on two antennas together with the improved broad-limiter antenna allowed a successful ICRF operation in 2012. As a part of long-term strategy of antenna design development, two three-strap antennas with phase and power balance control for reduction of E‖ are planned for installation in the future.

  5. VizieR Online Data Catalog: Radio fluxes of 195 ICRF2-Gaia transfer sources (Le Bail+, 2016)

    NASA Astrophysics Data System (ADS)

    Le Bail, K.; Gipson, J. M.; Gordon, D.; MacMillan, D. S.; Behrend, D.; Thomas, C. C.; Bolotin, S.; Himwich, W. E.; Baver, K. D.; Corey, B. E.; Titus, M.; Bourda, G.; Charlot, P.; Collioud, A.

    2016-07-01

    The second realization of the International Celestial Reference Frame (ICRF2) is based on Very Long Baseline Interferometry (VLBI) data at radio frequencies in X band and S band. The European Space Agency's Gaia mission, launched on 2013 December 19, started routine scientific operations in 2014 July. By scanning the whole sky, it is expected to observe ~500000 Quasi Stellar Objects in the optical domain. This means that, in the future, two extragalactic celestial reference frames, at two different frequency domains, will coexist. It will thus be important to align them very accurately. In 2012, the Laboratoire d'Astrophysique de Bordeaux (LAB) selected 195 sources from ICRF2 that will be observed by Gaia and should be suitable for aligning the radio and optical frames: they are called ICRF2-Gaia transfer sources. The LAB submitted a proposal to the International VLBI Service (IVS) to regularly observe these ICRF2-Gaia transfer sources at the same rate as Gaia observes them in the optical realm, e.g., roughly once a month. Of the 195 sources, all but one have been successfully observed in the 12 months prior to 2015 September 01. Table1 lists the 195 ICRF2-Gaia transfer sources. Beginning in 2003 June, the Goddard VLBI group developed a program to purposefully monitor when sources were observed and to increase the observations of "under-observed" sources. In 2013 March, we added all 195 ICRF2-Gaia transfer sources to the IVS source monitoring program with an observation target of 12 successful sessions per year. (1 data file).

  6. Operation of ICRF antennas in a full tungsten environment in ASDEX Upgrade

    NASA Astrophysics Data System (ADS)

    Bobkov, Vl.; Braun, F.; Dux, R.; Giannone, L.; Herrmann, A.; Kallenbach, A.; Müller, H. W.; Neu, R.; Noterdaeme, J.-M.; Pütterich, Th.; Rohde, V.; ASDEX Upgrade Team

    2009-06-01

    In the 2007 and early part of 2008 experimental campaigns, ASDEX Upgrade operated with full tungsten (W) wall without boronization. Use of ICRF power results in a significant increase of W source. Low temperature conditions at the plasma facing components, achieved by a large clearance between the separatrix and the antenna (>6 cm) and by elevated gas puff rates (>5×1021 s) help to lower W sputtering yield during ICRF. Operation of neighboring ICRF antennas at the phase difference close to -90° can lead to a reduction in the W source. However, a reduction of parallel near-fields by antenna design is needed to further minimize the W source. A relation has been established between the HFSS code calculations predicting a dominant role of box currents in the formation of parallel antenna near-fields and the experiment. The shapes of the measured vertical profile of effective sputtering yields and the calculated sheath driving voltages show a qualitative agreement. This confirms that the existing tools are a good basis to design an improved antenna.

  7. Long-Term Variations of the EOP and ICRF2

    NASA Technical Reports Server (NTRS)

    Zharov, Vladimir; Sazhin, Mikhail; Sementsov, Valerian; Sazhina, Olga

    2010-01-01

    We analyzed the time series of the coordinates of the ICRF radio sources. We show that part of the radio sources, including the defining sources, shows a significant apparent motion. The stability of the celestial reference frame is provided by a no-net-rotation condition applied to the defining sources. In our case this condition leads to a rotation of the frame axes with time. We calculated the effect of this rotation on the Earth orientation parameters (EOP). In order to improve the stability of the celestial reference frame we suggest a new method for the selection of the defining sources. The method consists of two criteria: the first one we call cosmological and the second one kinematical. It is shown that a subset of the ICRF sources selected according to cosmological criteria provides the most stable reference frame for the next decade.

  8. ATM regulates Cdt1 stability during the unperturbed S phase to prevent re-replication

    PubMed Central

    Iwahori, Satoko; Kohmon, Daisuke; Kobayashi, Junya; Tani, Yuhei; Yugawa, Takashi; Komatsu, Kenshi; Kiyono, Tohru; Sugimoto, Nozomi; Fujita, Masatoshi

    2014-01-01

    Ataxia-telangiectasia mutated (ATM) plays crucial roles in DNA damage responses, especially with regard to DNA double-strand breaks (DSBs). However, it appears that ATM can be activated not only by DSB, but also by some changes in chromatin architecture, suggesting potential ATM function in cell cycle control. Here, we found that ATM is involved in timely degradation of Cdt1, a critical replication licensing factor, during the unperturbed S phase. At least in certain cell types, degradation of p27Kip1 was also impaired by ATM inhibition. The novel ATM function for Cdt1 regulation was dependent on its kinase activity and NBS1. Indeed, we found that ATM is moderately phosphorylated at Ser1981 during the S phase. ATM silencing induced partial reduction in levels of Skp2, a component of SCFSkp2 ubiquitin ligase that controls Cdt1 degradation. Furthermore, Skp2 silencing resulted in Cdt1 stabilization like ATM inhibition. In addition, as reported previously, ATM silencing partially prevented Akt phosphorylation at Ser473, indicative of its activation, and Akt inhibition led to modest stabilization of Cdt1. Therefore, the ATM-Akt-SCFSkp2 pathway may partly contribute to the novel ATM function. Finally, ATM inhibition rendered cells hypersensitive to induction of re-replication, indicating importance for maintenance of genome stability. PMID:24280901

  9. Traffic Management for Satellite-ATM Networks

    NASA Technical Reports Server (NTRS)

    Goyal, Rohit; Jain, Raj; Fahmy, Sonia; Vandalore, Bobby; Goyal, Mukul

    1998-01-01

    Various issues associated with "Traffic Management for Satellite-ATM Networks" are presented in viewgraph form. Specific topics include: 1) Traffic management issues for TCP/IP based data services over satellite-ATM networks; 2) Design issues for TCP/IP over ATM; 3) Optimization of the performance of TCP/IP over ATM for long delay networks; and 4) Evaluation of ATM service categories for TCP/IP traffic.

  10. Effect on the tritium breeding ratio for a distributed ICRF antenna in a DEMO reactor

    NASA Astrophysics Data System (ADS)

    Garcia, A.; Noterdaeme, J.-M.; Fischer, U.; Dies, J.

    2015-12-01

    The paper reports results of MCNP-5 calculations to assess the effect on the Tritium Breeding Ratio (TBR) when integrating a distributed Ion Cyclotron Range of Frequencies (ICRF) antenna in the blanket of DEMO fusion power reactor. The calculations consider different parameters such as the ICRF covering ratio and the type of breeding blanket including the Helium Cooled Pebble Bed (HCPB) and the Helium Cooled Lithium Lead (HCLL) concepts. For an antenna with a full toroidal circumference of 360°, located poloidally at 40° with a poloidal extension of 1 m, the reduction of the TBR is -0.349% for the HCPB blanket and -0.532% for the HCLL blanket. The distributed ICRF antenna is thus shown to have only a marginal effect on the TBR of the DEMO reactor.

  11. Recent progress on improving ICRF coupling and reducing RF-specific impurities in ASDEX Upgrade

    NASA Astrophysics Data System (ADS)

    Zhang, Wei; Bobkov, Volodymyr; Noterdaeme, Jean-Marie; Tierens, Wouter; Aguiam, Diogo; Bilato, Roberto; Coster, David; Colas, Laurent; Crombé, Kristel; Fuenfgelder, Helmut; Faugel, Helmut; Feng, Yuhe; Jacquot, Jonathan; Jacquet, Philippe; Kallenbach, Arne; Kostic, Ana; Lunt, Tilmann; Maggiora, Riccardo; Ochoukov, Roman; Silva, Antonio; Suárez, Guillermo; Tuccilo, Angelo A.; Tudisco, Onofrio; Usoltceva, Mariia; Van Eester, Dirk; Wang, Yongsheng; Yang, Qingxi

    2017-10-01

    The recent scientific research on ASDEX Upgrade (AUG) has greatly advanced solutions to two issues of Radio Frequency (RF) heating in the Ion Cyclotron Range of Frequencies (ICRF): (a) the coupling of ICRF power to the plasma is significantly improved by density tailoring with local gas puffing; (b) the release of RF-specific impurities is significantly reduced by minimizing the RF near field with 3-strap antennas. This paper summarizes the applied methods and reviews the associated achievements.

  12. Lyn tyrosine kinase promotes silencing of ATM-dependent checkpoint signaling during recovery from DNA double-strand breaks

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

    Fukumoto, Yasunori, E-mail: fukumoto@faculty.chiba-u.jp; Kuki, Kazumasa; Morii, Mariko

    2014-09-26

    Highlights: • Inhibition of Src family kinases decreased γ-H2AX signal. • Inhibition of Src family increased ATM-dependent phosphorylation of Chk2 and Kap1. • shRNA-mediated knockdown of Lyn increased phosphorylation of Kap1 by ATM. • Ectopic expression of Src family kinase suppressed ATM-mediated Kap1 phosphorylation. • Src is involved in upstream signaling for inactivation of ATM signaling. - Abstract: DNA damage activates the DNA damage checkpoint and the DNA repair machinery. After initial activation of DNA damage responses, cells recover to their original states through completion of DNA repair and termination of checkpoint signaling. Currently, little is known about the processmore » by which cells recover from the DNA damage checkpoint, a process called checkpoint recovery. Here, we show that Src family kinases promote inactivation of ataxia telangiectasia mutated (ATM)-dependent checkpoint signaling during recovery from DNA double-strand breaks. Inhibition of Src activity increased ATM-dependent phosphorylation of Chk2 and Kap1. Src inhibition increased ATM signaling both in G2 phase and during asynchronous growth. shRNA knockdown of Lyn increased ATM signaling. Src-dependent nuclear tyrosine phosphorylation suppressed ATM-mediated Kap1 phosphorylation. These results suggest that Src family kinases are involved in upstream signaling that leads to inactivation of the ATM-dependent DNA damage checkpoint.« less

  13. Global Confinement, Sawtooth Mixing, and Stochastic Diffusion Ripple Loss of Fast ICRF-driven H+ Minority Ions in TFTR

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

    Petrov, M.P.; Bell, R.; Budny, R.V.

    1998-07-01

    This paper presents studies of ICRF-driven H+ minority ions in TFTR (Tokamak Fusion Test Reator) deuterium plasmas using primarily passive Ho flux detection in the energy range of 0.2-1.0 MeV with some corroborating active (lithium pellet charge exchange) measurements. It is shown that in the passive mode the main donors for the neutralization of H+ ions in this energy range are C5+ ions. The measured effective H+ tail temperatures range from 0.15 MeV at an ICRF power of 2 MW to 0.35 MeV at 6 MW. Analysis of the ICRF-driven H+ ion energy balance has been performed on the basismore » of the dependence of effective H+ temperatures on the plasma parameters. The analysis showed that H+ confinement times are comparable with their slowing-down times and tended to decrease with increasing ICRF power. Radial redistribution of ICRF-driven H+ ions was detected when giant sawtooth crashes occurred during the ICRF heating. The redistribution affected ions with energy below 0.7-0.8 MeV. The sawtooth crashes displace H+ ions outward along the plasma major radius into the stochastic ripple diffusion domain were those ions are lost in about 10 milliseconds. These observations are consistent with the model of the redistribution of energetic particles developed previously to explain the results of deuterium-tritium alpha-particle redistribution due to sawteeth observed in TFTR. The experimental data are also consistent with ORBIT code simulations of H+ stochastic ripple diffusion losses.« less

  14. ATM over hybrid fiber-coaxial cable networks: practical issues in deploying residential ATM services

    NASA Astrophysics Data System (ADS)

    Laubach, Mark

    1996-11-01

    Residential broadband access network technology based on asynchronous transfer modem (ATM) will soon reach commercial availability. The capabilities provided by ATM access network promise integrated services bandwidth available in excess of those provided by traditional twisted pair copper wire public telephone networks. ATM to the side of the home placed need quality of service capability closest to the subscriber allowing immediate support for Internet services and traditional voice telephony. Other services such as desktop video teleconferencing and enhanced server-based application support can be added as part of future evolution of the network. Additionally, advanced subscriber home networks can be supported easily. This paper presents an updated summary of the standardization efforts for the ATM over HFC definition work currently taking place in the ATM forum's residential broadband working group and the standards progress in the IEEE 802.14 cable TV media access control and physical protocol working group. This update is fundamental for establishing the foundation for delivering ATM-based integrated services via a cable TV network. An economic model for deploying multi-tiered services is presenting showing that a single-tier service is insufficient for a viable cable operator business. Finally, the use of an ATM based system lends itself well to various deployment scenarios of synchronous optical networks (SONET).

  15. ICRF heating in a straight, helically symmetric stellarator

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

    Jaeger, E.F.; Weitzner, H.; Batchelor, D.B.

    1987-07-01

    Experimental observations of direct ion cyclotron resonant frequency (ICRF) heating at fundamental ion cyclotron resonance on the L-2 stellarator have stimulated interest in the theoretical basis for such heating. In this paper, global solutions for the ICRF wave fields in a helically symmetric, straight stellarator are calculated in the cold plasma limit. The component of the wave electric field parallel to B-vector is assumed zero. Helical symmetry allows Fourier decomposition in the longitudinal (z) direction. The two remaining partial differential equations in tau and phi identical to THETA - hz (h is the helical pitch) are solved by finite differencing.more » Energy absorption and antenna impedance are calculated from an ad hoc collision model. Results for parameters typical of the L-2 and Advanced Toroidal Facility (ATF) stellarators show that direct resonant absorption of the fundamental ion cyclotron resonance occurs mainly near the plasma edge. The magnitude of the absorption is about half that for minority heating at the two-ion hybrid resonance.« less

  16. Arc detection for the ICRF system on ITER

    NASA Astrophysics Data System (ADS)

    D'Inca, R.

    2011-12-01

    The ICRF system for ITER is designed to respect the high voltage breakdown limits. However arcs can still statistically happen and must be quickly detected and suppressed by shutting the RF power down. For the conception of a reliable and efficient detector, the analysis of the mechanism of arcs is necessary to find their unique signature. Numerous systems have been conceived to address the issues of arc detection. VSWR-based detectors, RF noise detectors, sound detectors, optical detectors, S-matrix based detectors. Until now, none of them has succeeded in demonstrating the fulfillment of all requirements and the studies for ITER now follow three directions: improvement of the existing concepts to fix their flaws, development of new theoretically fully compliant detectors (like the GUIDAR) and combination of several detectors to benefit from the advantages of each of them. Together with the physical and engineering challenges, the development of an arc detection system for ITER raises methodological concerns to extrapolate the results from basic experiments and present machines to the ITER scale ICRF system and to conduct a relevant risk analysis.

  17. Estimation of sheath potentials in front of ASDEX upgrade ICRF antenna with SSWICH asymptotic code

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

    Křivská, A., E-mail: alena.krivska@rma.ac.be; Bobkov, V.; Jacquot, J.

    Multi-megawatt Ion Cyclotron Range of Frequencies (ICRF) heating became problematic in ASDEX Upgrade (AUG) tokamak after coating of ICRF antenna limiters and other plasma facing components by tungsten. Strong impurity influx was indeed produced at levels of injected power markedly lower than in the previous experiments. It is assumed that the impurity production is mainly driven by parallel component of Radio-Frequency (RF) antenna electric near-field E// that is rectified in sheaths. In this contribution we estimate poloidal distribution of sheath Direct Current (DC) potential in front of the ICRF antenna and simulate its relative variations over the parametric scans performedmore » during experiments, trying to reproduce some of the experimental observations. In addition, relative comparison between two types of AUG ICRF antenna configurations, used for experiments in 2014, has been performed. For this purpose we use the Torino Polytechnic Ion Cyclotron Antenna (TOPICA) code and asymptotic version of the Self-consistent Sheaths and Waves for Ion Cyclotron Heating (SSWICH) code. Further, we investigate correlation between amplitudes of the calculated oscillating sheath voltages and the E// fields computed at the lateral side of the antenna box, in relation with a heuristic antenna design strategy at IPP Garching to mitigate RF sheaths.« less

  18. ATM-Dependent Phosphorylation of All Three Members of the MRN Complex: From Sensor to Adaptor.

    PubMed

    Lavin, Martin F; Kozlov, Sergei; Gatei, Magtouf; Kijas, Amanda W

    2015-10-23

    The recognition, signalling and repair of DNA double strand breaks (DSB) involves the participation of a multitude of proteins and post-translational events that ensure maintenance of genome integrity. Amongst the proteins involved are several which when mutated give rise to genetic disorders characterised by chromosomal abnormalities, cancer predisposition, neurodegeneration and other pathologies. ATM (mutated in ataxia-telangiectasia (A-T) and members of the Mre11/Rad50/Nbs1 (MRN complex) play key roles in this process. The MRN complex rapidly recognises and locates to DNA DSB where it acts to recruit and assist in ATM activation. ATM, in the company of several other DNA damage response proteins, in turn phosphorylates all three members of the MRN complex to initiate downstream signalling. While ATM has hundreds of substrates, members of the MRN complex play a pivotal role in mediating the downstream signalling events that give rise to cell cycle control, DNA repair and ultimately cell survival or apoptosis. Here we focus on the interplay between ATM and the MRN complex in initiating signaling of breaks and more specifically on the adaptor role of the MRN complex in mediating ATM signalling to downstream substrates to control different cellular processes.

  19. Effect on the tritium breeding ratio for a distributed ICRF antenna in a DEMO reactor

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

    Garcia, A., E-mail: albert.garcia.hp@gmail.com; Karlsruhe Institute of Technology; Polytechnic University of Catalonia

    The paper reports results of MCNP-5 calculations to assess the effect on the Tritium Breeding Ratio (TBR) when integrating a distributed Ion Cyclotron Range of Frequencies (ICRF) antenna in the blanket of DEMO fusion power reactor. The calculations consider different parameters such as the ICRF covering ratio and the type of breeding blanket including the Helium Cooled Pebble Bed (HCPB) and the Helium Cooled Lithium Lead (HCLL) concepts. For an antenna with a full toroidal circumference of 360°, located poloidally at 40° with a poloidal extension of 1 m, the reduction of the TBR is −0.349% for the HCPB blanket andmore » −0.532% for the HCLL blanket. The distributed ICRF antenna is thus shown to have only a marginal effect on the TBR of the DEMO reactor.« less

  20. Northern Hemisphere observations of ICRF sources on the USNO stellar catalogue frame

    NASA Astrophysics Data System (ADS)

    Fienga, A.; Andrei, A. H.

    2004-06-01

    The most recent USNO stellar catalogue, the USNO B1.0 (Monet et al. \\cite{Monet03}), provides positions for 1 042 618 261 objects, with a published astrometric accuracy of 200 mas and five-band magnitudes with a 0.3 mag accuracy. Its completeness is believed to be up to magnitude 21th in V-band. Such a catalogue would be a very good tool for astrometric reduction. This work investigates the accuracy of the USNO B1.0 link to ICRF and give an estimation of its internal and external accuracies by comparison with different catalogues, and by computation of ICRF sources using USNO B1.0 star positions.

  1. Implementation of the new multichannel X-mode edge density profile reflectometer for the ICRF antenna on ASDEX Upgrade

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

    Aguiam, D. E., E-mail: daguiam@ipfn.tecnico.ulisboa.pt; Silva, A.; Carvalho, P. J.

    A new multichannel frequency modulated continuous-wave reflectometry diagnostic has been successfully installed and commissioned on ASDEX Upgrade to measure the plasma edge electron density profile evolution in front of the Ion Cyclotron Range of Frequencies (ICRF) antenna. The design of the new three-strap ICRF antenna integrates ten pairs (sending and receiving) of microwave reflectometry antennas. The multichannel reflectometer can use three of these to measure the edge electron density profiles up to 2 × 10{sup 19} m{sup −3}, at different poloidal locations, allowing the direct study of the local plasma layers in front of the ICRF antenna. ICRF power coupling,more » operational effects, and poloidal variations of the plasma density profile can be consistently studied for the first time. In this work the diagnostic hardware architecture is described and the obtained density profile measurements were used to track outer radial plasma position and plasma shape.« less

  2. Security Services Discovery by ATM Endsystems

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

    Sholander, Peter; Tarman, Thomas

    This contribution proposes strawman techniques for Security Service Discovery by ATM endsystems in ATM networks. Candidate techniques include ILMI extensions, ANS extensions and new ATM anycast addresses. Another option is a new protocol based on an IETF service discovery protocol, such as Service Location Protocol (SLP). Finally, this contribution provides strawman requirements for Security-Based Routing in ATM networks.

  3. mda-7/IL-24 induces cell death in neuroblastoma through a novel mechanism involving AIF and ATM

    PubMed Central

    Bhoopathi, Praveen; Lee, Nathaniel; Pradhan, Anjan K.; Shen, Xue-Ning; Das, Swadesh K.; Sarkar, Devanand; Emdad, Luni; Fisher, Paul B.

    2016-01-01

    Advanced stages of neuroblastoma, the most common extracranial malignant solid tumor of the central nervous system in infants and children, are refractive to therapy. Ectopic expression of melanoma differentiation associated gene-7/Interleukin-24 (mda-7/IL-24) promotes broad-spectrum antitumor activity in vitro, in vivo in pre-clinical animal models and in a Phase I clinical trial in patients with advanced cancers, without harming normal cells. mda-7/IL-24 exerts cancer-specific toxicity (apoptosis or toxic autophagy) by promoting ER stress and modulating multiple signal transduction pathways regulating cancer cell growth, invasion, metastasis, survival and angiogenesis. To enhance cancer-selective expression and targeted anti-cancer activity of mda-7/IL-24 we created a tropism-modified Cancer Terminator Virus (Ad.5/3-CTV), which selectively replicates in cancer cells producing robust expression of mda-7/IL-24. We now show that Ad.5/3-CTV induces profound neuroblastoma anti-proliferative activity and apoptosis in a caspase 3/9-independent manner both in vitro and in vivo in a tumor xenograft model. Ad.5/3-CTV promotes these effects through a unique pathway involving apoptosis inducing factor (AIF) translocation into the nucleus. Inhibiting AIF rescued neuroblastoma cells from Ad.5/3-CTV-induced cell death, whereas pan-caspase inhibition failed to promote survival. Ad.5/3-CTV infection of neuroblastoma cells increased ATM phosphorylation instigating nuclear translocation and increased γ–H2AX, triggering nuclear translocation and intensified expression of AIF. These results were validated further using two ATM small molecule inhibitors that attenuated PARP cleavage by inhibiting γ–H2AX, which in turn inhibited AIF changes in Ad.5/3-CTV-infected neuroblastoma cells. Taken together, we elucidate a novel pathway for mda-7/IL-24-induced caspase-independent apoptosis in neuroblastoma cells mediated through modulation of AIF, ATM and γ–H2AX. PMID:27197168

  4. Gigabit ATM: another technical mistake?

    NASA Astrophysics Data System (ADS)

    Christ, Paul

    1998-09-01

    Once upon a time, or more precisely during February 1988 at the CCITT Seoul plenary, and definitely arriving as a revolution, ATM hit the hard-core B-ISDN circuit-switching gang. Initiated by the Telecoms' camp, but, surprisingly, soon to be pushed by computer minded people, ATM's generic technological history is somewhat richer than single-sided stories. Here are two classical elements of that history: Firstly, together with X.25, ATM suffers from the connection versus datagram dichotomy, well known for more than twenty years. Secondly, and lesser known, ATM's use of cells in support of the 'I' of B-ISDN was questioned from the very beginning by the packet switching camp. Furthermore, in this context, there are two other essential elements to be considered: Firstly, the exponential growth of the Internet and later intranets, using Internet technology, sparked by the success of the Web and the WINTEL alliance, resulted in a corresponding demand for both aggregate and end-system network bandwidth. Secondly, servers, historically restricted to the exclusive club of HIPPI-equipped supercomputers, suddenly become ordinary high-end PCs with 64-bit wide PCI busses -- definitely aiming at the Gigabit. Here, if your aim is for Gigabit ATM with 5000-transactions per second classical supercomputers, a 65K ATM MTU -- as implemented by Cray -- might be okay. Following Clark and others, another part of the story is the adoption and redefinition, by the IETF, of the Telecoms' notion of 'Integrated Services' and QoS mechanisms. The quest for low-delay IP packet forwarding, perhaps possible over ATM cut-throughs, has resulted in the switching versus/or integrated-with-routing movement. However, a blow for ATM may be the recent results concerning fast routing table lookup algorithms. This, by making Gigabit routing possible using ordinary Pentium processors may eventually render the much prophesized ATM switching performance unnecessary. Recently, with the rise of Gigabit Ethernet

  5. The ITER ICRF Antenna Design with TOPICA

    NASA Astrophysics Data System (ADS)

    Milanesio, Daniele; Maggiora, Riccardo; Meneghini, Orso; Vecchi, Giuseppe

    2007-11-01

    TOPICA (Torino Polytechnic Ion Cyclotron Antenna) code is an innovative tool for the 3D/1D simulation of Ion Cyclotron Radio Frequency (ICRF), i.e. accounting for antennas in a realistic 3D geometry and with an accurate 1D plasma model [1]. The TOPICA code has been deeply parallelized and has been already proved to be a reliable tool for antennas design and performance prediction. A detailed analysis of the 24 straps ITER ICRF antenna geometry has been carried out, underlining the strong dependence and asymmetries of the antenna input parameters due to the ITER plasma response. We optimized the antenna array geometry dimensions to maximize loading, lower mutual couplings and mitigate sheath effects. The calculated antenna input impedance matrices are TOPICA results of a paramount importance for the tuning and matching system design. Electric field distributions have been also calculated and they are used as the main input for the power flux estimation tool. The designed optimized antenna is capable of coupling 20 MW of power to plasma in the 40 -- 55 MHz frequency range with a maximum voltage of 45 kV in the feeding coaxial cables. [1] V. Lancellotti et al., Nuclear Fusion, 46 (2006) S476-S499

  6. Ataxia-telangiectasia mutated (ATM) silencing promotes neuroblastoma progression through a MYCN independent mechanism

    PubMed Central

    Mandriota, Stefano J.; Valentijn, Linda J.; Lesne, Laurence; Betts, David R.; Marino, Denis; Boudal-Khoshbeen, Mary; London, Wendy B.; Rougemont, Anne-Laure; Attiyeh, Edward F.; Maris, John M.; Hogarty, Michael D.; Koster, Jan; Molenaar, Jan J.; Versteeg, Rogier

    2015-01-01

    Neuroblastoma, a childhood cancer with highly heterogeneous biology and clinical behavior, is characterized by genomic aberrations including amplification of MYCN. Hemizygous deletion of chromosome 11q is a well-established, independent marker of poor prognosis. While 11q22-q23 is the most frequently deleted region, the neuroblastoma tumor suppressor in this region remains to be identified. Chromosome bands 11q22-q23 contain ATM, a cell cycle checkpoint kinase and tumor suppressor playing a pivotal role in the DNA damage response. Here, we report that haploinsufficiency of ATM in neuroblastoma correlates with lower ATM expression, event-free survival, and overall survival. ATM loss occurs in high stage neuroblastoma without MYCN amplification. In SK-N-SH, CLB-Ga and GI-ME-N human neuroblastoma cells, stable ATM silencing promotes neuroblastoma progression in soft agar assays, and in subcutaneous xenografts in nude mice. This effect is dependent on the extent of ATM silencing and does not appear to involve MYCN. Our findings identify ATM as a potential haploinsufficient neuroblastoma tumor suppressor, whose inactivation mirrors the increased aggressiveness associated with 11q deletion in neuroblastoma. PMID:26053094

  7. ATM CMG bearing failure analysis

    NASA Technical Reports Server (NTRS)

    1975-01-01

    The cause or causes for the failure of ATM CMG S/N 5 (Skylab 1) and the anomalies associated with ATM CMG S/N 6 (Skylab 2) were investigated. Skylab telemetry data were reviewed and presented in the form of parameter distributions. The theory that the problems were caused by marginal bearing lubrication was studied along with the effects of orbital conditions on lubricants. Bearing tests were performed to investigate the effect of lubricant or lack of lubricant in the ATM CMG bearings and the dispersion and migration of the lubricant. The vacuum and weightless conditions of space were simulated in the bearing tests. Analysis of the results of the tests conducted points to inadequate lubrication as the predominant factor causing the failure of ATM CMG S/N 5 (Skylab 1) and the anomalies associated with ATM CMG S/N 6 (Skylab 2).

  8. ATM-Dependent Phosphorylation of All Three Members of the MRN Complex: From Sensor to Adaptor

    PubMed Central

    Lavin, Martin F.; Kozlov, Sergei; Gatei, Magtouf; Kijas, Amanda W.

    2015-01-01

    The recognition, signalling and repair of DNA double strand breaks (DSB) involves the participation of a multitude of proteins and post-translational events that ensure maintenance of genome integrity. Amongst the proteins involved are several which when mutated give rise to genetic disorders characterised by chromosomal abnormalities, cancer predisposition, neurodegeneration and other pathologies. ATM (mutated in ataxia-telangiectasia (A-T) and members of the Mre11/Rad50/Nbs1 (MRN complex) play key roles in this process. The MRN complex rapidly recognises and locates to DNA DSB where it acts to recruit and assist in ATM activation. ATM, in the company of several other DNA damage response proteins, in turn phosphorylates all three members of the MRN complex to initiate downstream signalling. While ATM has hundreds of substrates, members of the MRN complex play a pivotal role in mediating the downstream signalling events that give rise to cell cycle control, DNA repair and ultimately cell survival or apoptosis. Here we focus on the interplay between ATM and the MRN complex in initiating signaling of breaks and more specifically on the adaptor role of the MRN complex in mediating ATM signalling to downstream substrates to control different cellular processes. PMID:26512707

  9. ICRF Mode Conversion Flow Drive Experiments on Alcator C-Mod

    NASA Astrophysics Data System (ADS)

    Lin, Y.; Reinke, M. L.; Rice, J. E.; Wukitch, S. J.; Granetz, R.; Greenwald, M.; Hubbard, A. E.; Marmar, E. S.; Podpaly, Y. A.; Porkolab, M.; Tsujii, N.; Wolfe, S.

    2011-12-01

    We have carried out a detailed study of the dependence of ICRF mode conversion flow drive (MCFD) on plasma and RF parameters. The flow drive efficiency is found to depend strongly on the 3He concentration in D(3He) plasmas, a key parameter separating the ICRF minority heating regime and mode conversion regime. At +90 ° antenna phasing (waves in the co-Ip direction) and dipole phasing, the driven flow is in the co-Ip direction, and the change of the rotation velocity increases with both PRF and Ip, and scales unfavorably vs. plasma density and antenna frequency. When MCFD is applied to I-mode plasmas, the plasma rotation increases until the onset of MHD modes triggered by large sawtooth crashes. Very high performance I-mode plasmas with HITER98,y2˜1.4 and Te0˜8 keV have been obtained in these experiments.

  10. Atm reactivation reverses ataxia telangiectasia phenotypes in vivo.

    PubMed

    Di Siena, Sara; Campolo, Federica; Gimmelli, Roberto; Di Pietro, Chiara; Marazziti, Daniela; Dolci, Susanna; Lenzi, Andrea; Nussenzweig, Andre; Pellegrini, Manuela

    2018-02-22

    Hereditary deficiencies in DNA damage signaling are invariably associated with cancer predisposition, immunodeficiency, radiation sensitivity, gonadal abnormalities, premature aging, and tissue degeneration. ATM kinase has been established as a central player in DNA double-strand break repair and its deficiency causes ataxia telangiectasia, a rare, multi-system disease with no cure. So ATM represents a highly attractive target for the development of novel types of gene therapy or transplantation strategies. Atm tamoxifen-inducible mouse models were generated to explore whether Atm reconstitution is able to restore Atm function in an Atm-deficient background. Body weight, immunodeficiency, spermatogenesis, and radioresistance were recovered in transgenic mice within 1 month from Atm induction. Notably, life span was doubled after Atm restoration, mice were protected from thymoma and no cerebellar defects were observed. Atm signaling was functional after DNA damage in vivo and in vitro. In summary, we propose a new Atm mouse model to investigate novel therapeutic strategies for ATM activation in ataxia telangiectasia disease.

  11. Novel targets for ATM-deficient malignancies

    PubMed Central

    Winkler, Johannes; Hofmann, Kay; Chen, Shuhua

    2014-01-01

    Conventional chemo- and radiotherapies for the treatment of cancer target rapidly dividing cells in both tumor and non-tumor tissues and can exhibit severe cytotoxicity in normal tissue and impair the patient's immune system. Novel targeted strategies aim for higher efficacy and tumor specificity. The role of ATM protein in the DNA damage response is well known and ATM deficiency frequently plays a role in tumorigenesis and development of malignancy. In addition to contributing to disease development, ATM deficiency also renders malignant cells heavily dependent on other pathways that cooperate with the ATM-mediated DNA damage response to ensure tumor cell survival. Disturbing those cooperative pathways by inhibiting critical protein components allows specific targeting of tumors while sparing healthy cells with normal ATM status. We review druggable candidate targets for the treatment of ATM-deficient malignancies and the mechanisms underlying such targeted therapies. PMID:27308314

  12. Existing and Required Modeling Capabilities for Evaluating ATM Systems and Concepts

    NASA Technical Reports Server (NTRS)

    Odoni, Amedeo R.; Bowman, Jeremy; Delahaye, Daniel; Deyst, John J.; Feron, Eric; Hansman, R. John; Khan, Kashif; Kuchar, James K.; Pujet, Nicolas; Simpson, Robert W.

    1997-01-01

    ATM systems throughout the world are entering a period of major transition and change. The combination of important technological developments and of the globalization of the air transportation industry has necessitated a reexamination of some of the fundamental premises of existing Air Traffic Management (ATM) concepts. New ATM concepts have to be examined, concepts that may place more emphasis on: strategic traffic management; planning and control; partial decentralization of decision-making; and added reliance on the aircraft to carry out strategic ATM plans, with ground controllers confined primarily to a monitoring and supervisory role. 'Free Flight' is a case in point. In order to study, evaluate and validate such new concepts, the ATM community will have to rely heavily on models and computer-based tools/utilities, covering a wide range of issues and metrics related to safety, capacity and efficiency. The state of the art in such modeling support is adequate in some respects, but clearly deficient in others. It is the objective of this study to assist in: (1) assessing the strengths and weaknesses of existing fast-time models and tools for the study of ATM systems and concepts and (2) identifying and prioritizing the requirements for the development of additional modeling capabilities in the near future. A three-stage process has been followed to this purpose: 1. Through the analysis of two case studies involving future ATM system scenarios, as well as through expert assessment, modeling capabilities and supporting tools needed for testing and validating future ATM systems and concepts were identified and described. 2. Existing fast-time ATM models and support tools were reviewed and assessed with regard to the degree to which they offer the capabilities identified under Step 1. 3 . The findings of 1 and 2 were combined to draw conclusions about (1) the best capabilities currently existing, (2) the types of concept testing and validation that can be carried

  13. 49 CFR 193.2101 - Scope.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... comply with requirements of this part and of NFPA 59A (2001) (incorporated by reference, see § 193.2013... comply with Section 7.2.2 of NFPA 59A (2006) (incorporated by reference, see § 193.2013) for seismic... (incorporated by reference, see § 193.2013) for seismic design. [Amdt. 193-22, 75 FR 48604, Aug. 11, 2010...

  14. Loss of tumour-specific ATM protein expression is an independent prognostic factor in early resected NSCLC

    PubMed Central

    Petersen, Lars F.; Klimowicz, Alexander C.; Otsuka, Shannon; Elegbede, Anifat A.; Petrillo, Stephanie K.; Williamson, Tyler; Williamson, Chris T.; Konno, Mie; Lees-Miller, Susan P.; Hao, Desiree; Morris, Don; Magliocco, Anthony M.; Bebb, D. Gwyn

    2017-01-01

    Ataxia-telangiectasia mutated (ATM) is critical in maintaining genomic integrity. In response to DNA double-strand breaks, ATM phosphorylates downstream proteins involved in cell-cycle checkpoint arrest, DNA repair, and apoptosis. Here we investigate the frequency, and influence of ATM deficiency on outcome, in early-resected non-small cell lung cancer (NSCLC). Tissue microarrays, containing 165 formalin-fixed, paraffin-embedded resected NSCLC tumours from patients diagnosed at the Tom Baker Cancer Centre, Calgary, Canada, between 2003 and 2006, were analyzed for ATM expression using quantitative fluorescence immunohistochemistry. Both malignant cell-specific ATM expression and the ratio of ATM expression within malignant tumour cells compared to that in the surrounding tumour stroma, defined as the ATM expression index (ATM-EI), were measured and correlated with clinical outcome. ATM loss was identified in 21.8% of patients, and was unaffected by clinical pathological variables. Patients with low ATM-EI tumours had worse survival outcomes compared to those with high ATM-EI (p < 0.01). This effect was pronounced in stage II/III patients, even after adjusting for other clinical co-variates (p < 0.001). Additionally, we provide evidence that ATM-deficient patients may derive greater benefit from guideline-recommended adjuvant chemotherapy following surgical resection. Taken together, these results indicate that ATM loss seems to be an early event in NSCLC carcinogenesis and is an independent prognostic factor associated with worse survival in stage II/III patients. PMID:28418844

  15. Loss of tumour-specific ATM protein expression is an independent prognostic factor in early resected NSCLC.

    PubMed

    Petersen, Lars F; Klimowicz, Alexander C; Otsuka, Shannon; Elegbede, Anifat A; Petrillo, Stephanie K; Williamson, Tyler; Williamson, Chris T; Konno, Mie; Lees-Miller, Susan P; Hao, Desiree; Morris, Don; Magliocco, Anthony M; Bebb, D Gwyn

    2017-06-13

    Ataxia-telangiectasia mutated (ATM) is critical in maintaining genomic integrity. In response to DNA double-strand breaks, ATM phosphorylates downstream proteins involved in cell-cycle checkpoint arrest, DNA repair, and apoptosis. Here we investigate the frequency, and influence of ATM deficiency on outcome, in early-resected non-small cell lung cancer (NSCLC). Tissue microarrays, containing 165 formalin-fixed, paraffin-embedded resected NSCLC tumours from patients diagnosed at the Tom Baker Cancer Centre, Calgary, Canada, between 2003 and 2006, were analyzed for ATM expression using quantitative fluorescence immunohistochemistry. Both malignant cell-specific ATM expression and the ratio of ATM expression within malignant tumour cells compared to that in the surrounding tumour stroma, defined as the ATM expression index (ATM-EI), were measured and correlated with clinical outcome. ATM loss was identified in 21.8% of patients, and was unaffected by clinical pathological variables. Patients with low ATM-EI tumours had worse survival outcomes compared to those with high ATM-EI (p < 0.01). This effect was pronounced in stage II/III patients, even after adjusting for other clinical co-variates (p < 0.001). Additionally, we provide evidence that ATM-deficient patients may derive greater benefit from guideline-recommended adjuvant chemotherapy following surgical resection. Taken together, these results indicate that ATM loss seems to be an early event in NSCLC carcinogenesis and is an independent prognostic factor associated with worse survival in stage II/III patients.

  16. Linking Deep Astrometric Standards to the ICRF

    NASA Astrophysics Data System (ADS)

    Frey, S.; Platais, I.; Fey, A. L.

    2007-07-01

    The next-generation large aperature and large field-of-view telescopes will address fundamantal questions of astrophysica and cosmology such as the nature of dark matter and dark energy. For a variety of applications, the CCD mosaic detectors in the focal plane arrays require astronomic calibrationat the milli-arcsecond (mas) level. The existing optical reference frames are insufficient to support such calibrations. To address this problem, deep optical astronomic fields are being established near the Galactic plane. In order to achiev a 5-10-mas or better positional accuracyfor the Deepp Astrometric Standards (DAS), and to obtain bsolute stellar proper motions for the study of Galactic structure, it is crucial to link these fields to the International Celestial Reference Frame (ICRF). To this end, we selected 15 candidate compact extragalactic radio sources in the Gemini-Orion-Taurus (GOT) field. These sources were observed with the European VLBI Network (EVN) at 5 GHz in phase-reference mode. The bright compact calibrator source J0603+2159 and seven other sources were detected and imaged at the angular resolution of -1.5-8 mas. Relative astrometric positions were derived for these sources at a milli-arcsecond accuracy level. The detection of the optical counterparts of these extragalactic radio sources will allow us to establish a direct link to the ICRF locally in the GOT field.

  17. Running TCP/IP over ATM Networks.

    ERIC Educational Resources Information Center

    Witt, Michael

    1995-01-01

    Discusses Internet protocol (IP) and subnets and describes how IP may operate over asynchronous transfer mode (ATM). Topics include TCP (transmission control protocol), ATM cells and adaptation layers, a basic architectural model for IP over ATM, address resolution, mapping IP to a subnet technology, and connection management strategy. (LRW)

  18. Experiences with the AEROnet/PSCN ATM Prototype

    NASA Technical Reports Server (NTRS)

    Kurak, Richard S.; Lisotta, Anthony J.; McCabe, James D.; Nothaft, Alfred E.; Russell, Kelly R.; Lasinski, T. A. (Technical Monitor)

    1995-01-01

    This paper discusses the experience gained by the AEROnet/PSCN networking team in deploying a prototype Asynchronous Transfer Mode (ATM) based network as part of the wide-area network for the Numerical Aerodynamic Simulation (NAS) Program at NASA Ames Research Center. The objectives of this prototype were to test concepts in using ATM over wide-area Internet Protocol (IP) networks and measure end-to-end system performance. This testbed showed that end-to-end ATM over a DS3 reaches approximately 80% of the throughput achieved from a FDDI to DS3 network. The 20% reduction in through-put can be attributed to the overhead associated with running ATM. As a result, we conclude that if the loss in capacity due to ATM overhead is balanced by the reduction in cost of ATM services, as compared to dedicated circuits, then ATM can be a viable alternative.

  19. 49 CFR 193.2911 - Security lighting.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Security lighting. 193.2911 Section 193.2911...: FEDERAL SAFETY STANDARDS Security § 193.2911 Security lighting. Where security warning systems are not provided for security monitoring under § 193.2913, the area around the facilities listed under § 193.2905(a...

  20. 49 CFR 193.2911 - Security lighting.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Security lighting. 193.2911 Section 193.2911...: FEDERAL SAFETY STANDARDS Security § 193.2911 Security lighting. Where security warning systems are not provided for security monitoring under § 193.2913, the area around the facilities listed under § 193.2905(a...

  1. 49 CFR 193.2911 - Security lighting.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Security lighting. 193.2911 Section 193.2911...: FEDERAL SAFETY STANDARDS Security § 193.2911 Security lighting. Where security warning systems are not provided for security monitoring under § 193.2913, the area around the facilities listed under § 193.2905(a...

  2. Theory and Practice in ICRF Antennas for Long Pulse Operation

    NASA Astrophysics Data System (ADS)

    Colas, L.; Faudot, E.; Brémond, S.; Heuraux, S.; Mitteau, R.; Chantant, M.; Goniche, M.; Basiuk, V.; Bosia, G.; Tore Supra Team

    2005-09-01

    Long plasma discharges on the Tore Supra (TS) tokamak were extended in 2004 towards higher powers and plasma densities by combined Lower Hybrid (LH) and Ion Cyclotron Range of Frequencies (ICRF) waves. RF pulses of 20s×8MW and 60s×4MW were produced. TS is equipped with 3 ICRF antennas, whose front faces are ready for CW operation. This paper reports on their behaviour over high power long pulses, as observed with infrared (IR) thermography and calorimetric measurements. Edge parasitic losses, although modest, are concentrated on a small surface and can raise surface temperatures close to operational limits. A complex hot spot pattern was revealed with at least 3 physical processes involved : convected power, electron acceleration in the LH near field, and a RF-specific phenomenon compatible with RF sheaths. LH coupling was also perturbed in the antenna shadow. This was attributed to RF-induced DC E×B0 convection. This motivated sheath modelling in two directions. First, the 2D topology of RF potentials was investigated in relation with the RF current distribution over the antenna, via a Green's function formalism and full-wave calculation using the ICANT code. In front of phased arrays of straps, convective cells were interpreted using the RF current profiles of strip line theory. Another class of convective cells, specific to antenna box corners, was evidenced for the first time. Within 1D sheath models assuming independent flux tubes, RF and rectified DC potentials are proportional. 2D fluid models couple nearby flux tubes via transverse polarisation currents. Unexpectedly this does not necessarily smooth RF potential maps. Peak DC potentials can even be enhanced. The experience gained on TS and the numerical tools are valuable for designing steady state high power antennas for next step devices. General rules to reduce RF potentials as well as concrete design options are discussed.

  3. Functional Characterization of ATM Kinase Using Acetylation-Specific Antibodies.

    PubMed

    Sun, Yingli; Du, Fengxia

    2017-01-01

    The activation of ATM is critical in the DNA double strand breaks repair pathway. Acetylation of ATM by Tip60 histone acetyltransferase (HAT) plays a key role in the activation of ATM kinase activity in response to DNA damage. ATM forms a stable complex with Tip60 through the FATC domain of ATM. Tip60 acetylates lysine3016 of ATM, and this acetylation induces the activation of ATM. Several techniques are included in the study of ATM acetylation by Tip60, such as in vitro kinase assay, systematic mutagenesis, western blots. Here, we describe how to study the acetylation of ATM using acetylation-specific antibodies.

  4. 40 CFR 19.3 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false [Reserved] 19.3 Section 19.3 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL ADJUSTMENT OF CIVIL MONETARY PENALTIES FOR INFLATION § 19.3 [Reserved] ...

  5. A pharmacological screen for compounds that rescue the developmental lethality of a Drosophila ATM mutant.

    PubMed

    Rimkus, Stacey A; Wassarman, David A

    2018-01-01

    Ataxia-telangiectasia (A-T) is a neurodegenerative disease caused by mutation of the A-T mutated (ATM) gene. ATM encodes a protein kinase that is activated by DNA damage and phosphorylates many proteins, including those involved in DNA repair, cell cycle control, and apoptosis. Characteristic biological and molecular functions of ATM observed in mammals are conserved in Drosophila melanogaster. As an example, conditional loss-of-function ATM alleles in flies cause progressive neurodegeneration through activation of the innate immune response. However, unlike in mammals, null alleles of ATM in flies cause lethality during development. With the goals of understanding biological and molecular roles of ATM in a whole animal and identifying candidate therapeutics for A-T, we performed a screen of 2400 compounds, including FDA-approved drugs, natural products, and bioactive compounds, for modifiers of the developmental lethality caused by a temperature-sensitive ATM allele (ATM8) that has reduced kinase activity at non-permissive temperatures. Ten compounds reproducibly suppressed the developmental lethality of ATM8 flies, including Ronnel, which is an organophosphate. Ronnel and other suppressor compounds are known to cause mitochondrial dysfunction or to inhibit the enzyme acetylcholinesterase, which controls the levels of the neurotransmitter acetylcholine, suggesting that detrimental consequences of reduced ATM kinase activity can be rescued by inhibiting the function of mitochondria or increasing acetylcholine levels. We carried out further studies of Ronnel because, unlike the other compounds that suppressed the developmental lethality of homozygous ATM8 flies, Ronnel was toxic to the development of heterozygous ATM8 flies. Ronnel did not affect the innate immune response of ATM8 flies, and it further increased the already high levels of DNA damage in brains of ATM8 flies, but its effects were not harmful to the lifespan of rescued ATM8 flies. These results provide

  6. Optical Spectra of Candidate International Celestial Reference Frame (ICRF) Flat-spectrum Radio Sources. III.

    NASA Astrophysics Data System (ADS)

    Titov, O.; Pursimo, T.; Johnston, Helen M.; Stanford, Laura M.; Hunstead, Richard W.; Jauncey, David L.; Zenere, Katrina A.

    2017-04-01

    In extending our spectroscopic program, which targets sources drawn from the International Celestial Reference Frame (ICRF) Catalog, we have obtained spectra for ˜160 compact, flat-spectrum radio sources and determined redshifts for 112 quasars and radio galaxies. A further 14 sources with featureless spectra have been classified as BL Lac objects. Spectra were obtained at three telescopes: the 3.58 m European Southern Observatory New Technology Telescope, and the two 8.2 m Gemini telescopes in Hawaii and Chile. While most of the sources are powerful quasars, a significant fraction of radio galaxies is also included from the list of non-defining ICRF radio sources.

  7. Optical Spectra of Candidate International Celestial Reference Frame (ICRF) Flat-spectrum Radio Sources. III

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

    Titov, O.; Stanford, Laura M.; Pursimo, T.

    In extending our spectroscopic program, which targets sources drawn from the International Celestial Reference Frame (ICRF) Catalog, we have obtained spectra for ∼160 compact, flat-spectrum radio sources and determined redshifts for 112 quasars and radio galaxies. A further 14 sources with featureless spectra have been classified as BL Lac objects. Spectra were obtained at three telescopes: the 3.58 m European Southern Observatory New Technology Telescope, and the two 8.2 m Gemini telescopes in Hawaii and Chile. While most of the sources are powerful quasars, a significant fraction of radio galaxies is also included from the list of non-defining ICRF radiomore » sources.« less

  8. Conditional abrogation of Atm in osteoclasts extends osteoclast lifespan and results in reduced bone mass.

    PubMed

    Hirozane, Toru; Tohmonda, Takahide; Yoda, Masaki; Shimoda, Masayuki; Kanai, Yae; Matsumoto, Morio; Morioka, Hideo; Nakamura, Masaya; Horiuchi, Keisuke

    2016-09-28

    Ataxia-telangiectasia mutated (ATM) kinase is a central component involved in the signal transduction of the DNA damage response (DDR) and thus plays a critical role in the maintenance of genomic integrity. Although the primary functions of ATM are associated with the DDR, emerging data suggest that ATM has many additional roles that are not directly related to the DDR, including the regulation of oxidative stress signaling, insulin sensitivity, mitochondrial homeostasis, and lymphocyte development. Patients and mice lacking ATM exhibit growth retardation and lower bone mass; however, the mechanisms underlying the skeletal defects are not fully understood. In the present study, we generated mutant mice in which ATM is specifically inactivated in osteoclasts. The mutant mice did not exhibit apparent developmental defects but showed reduced bone mass due to increased osteoclastic bone resorption. Osteoclasts lacking ATM were more resistant to apoptosis and showed a prolonged lifespan compared to the controls. Notably, the inactivation of ATM in osteoclasts resulted in enhanced NF-κB signaling and an increase in the expression of NF-κB-targeted genes. The present study reveals a novel function for ATM in regulating bone metabolism by suppressing the lifespan of osteoclasts and osteoclast-mediated bone resorption.

  9. Morphology and genomic hallmarks of breast tumours developed by ATM deleterious variant carriers.

    PubMed

    Renault, Anne-Laure; Mebirouk, Noura; Fuhrmann, Laetitia; Bataillon, Guillaume; Cavaciuti, Eve; Le Gal, Dorothée; Girard, Elodie; Popova, Tatiana; La Rosa, Philippe; Beauvallet, Juana; Eon-Marchais, Séverine; Dondon, Marie-Gabrielle; d'Enghien, Catherine Dubois; Laugé, Anthony; Chemlali, Walid; Raynal, Virginie; Labbé, Martine; Bièche, Ivan; Baulande, Sylvain; Bay, Jacques-Olivier; Berthet, Pascaline; Caron, Olivier; Buecher, Bruno; Faivre, Laurence; Fresnay, Marc; Gauthier-Villars, Marion; Gesta, Paul; Janin, Nicolas; Lejeune, Sophie; Maugard, Christine; Moutton, Sébastien; Venat-Bouvet, Laurence; Zattara, Hélène; Fricker, Jean-Pierre; Gladieff, Laurence; Coupier, Isabelle; Chenevix-Trench, Georgia; Hall, Janet; Vincent-Salomon, Anne; Stoppa-Lyonnet, Dominique; Andrieu, Nadine; Lesueur, Fabienne

    2018-04-17

    The ataxia telangiectasia mutated (ATM) gene is a moderate-risk breast cancer susceptibility gene; germline loss-of-function variants are found in up to 3% of hereditary breast and ovarian cancer (HBOC) families who undergo genetic testing. So far, no clear histopathological and molecular features of breast tumours occurring in ATM deleterious variant carriers have been described, but identification of an ATM-associated tumour signature may help in patient management. To characterise hallmarks of ATM-associated tumours, we performed systematic pathology review of tumours from 21 participants from ataxia-telangiectasia families and 18 participants from HBOC families, as well as copy number profiling on a subset of 23 tumours. Morphology of ATM-associated tumours was compared with that of 599 patients with no BRCA1 and BRCA2 mutations from a hospital-based series, as well as with data from The Cancer Genome Atlas. Absolute copy number and loss of heterozygosity (LOH) profiles were obtained from the OncoScan SNP array. In addition, we performed whole-genome sequencing on four tumours from ATM loss-of-function variant carriers with available frozen material. We found that ATM-associated tumours belong mostly to the luminal B subtype, are tetraploid and show LOH at the ATM locus at 11q22-23. Unlike tumours in which BRCA1 or BRCA2 is inactivated, tumours arising in ATM deleterious variant carriers are not associated with increased large-scale genomic instability as measured by the large-scale state transitions signature. Losses at 13q14.11-q14.3, 17p13.2-p12, 21p11.2-p11.1 and 22q11.23 were observed. Somatic alterations at these loci may therefore represent biomarkers for ATM testing and harbour driver mutations in potentially 'druggable' genes that would allow patients to be directed towards tailored therapeutic strategies. Although ATM is involved in the DNA damage response, ATM-associated tumours are distinct from BRCA1-associated tumours in terms of morphological

  10. 49 CFR 193.2709 - Security.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Security. 193.2709 Section 193.2709 Transportation...: FEDERAL SAFETY STANDARDS Personnel Qualifications and Training § 193.2709 Security. Personnel having security duties must be qualified to perform their assigned duties by successful completion of the training...

  11. 49 CFR 193.2709 - Security.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Security. 193.2709 Section 193.2709 Transportation...: FEDERAL SAFETY STANDARDS Personnel Qualifications and Training § 193.2709 Security. Personnel having security duties must be qualified to perform their assigned duties by successful completion of the training...

  12. 49 CFR 193.2709 - Security.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Security. 193.2709 Section 193.2709 Transportation...: FEDERAL SAFETY STANDARDS Personnel Qualifications and Training § 193.2709 Security. Personnel having security duties must be qualified to perform their assigned duties by successful completion of the training...

  13. 49 CFR 193.2709 - Security.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Security. 193.2709 Section 193.2709 Transportation...: FEDERAL SAFETY STANDARDS Personnel Qualifications and Training § 193.2709 Security. Personnel having security duties must be qualified to perform their assigned duties by successful completion of the training...

  14. 49 CFR 193.2709 - Security.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Security. 193.2709 Section 193.2709 Transportation...: FEDERAL SAFETY STANDARDS Personnel Qualifications and Training § 193.2709 Security. Personnel having security duties must be qualified to perform their assigned duties by successful completion of the training...

  15. High-power and steady-state operation of ICRF heating in the large helical device

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

    Mutoh, T., E-mail: mutoh@nifs.ac.jp; Seki, T.; Saito, K.

    2015-12-10

    Recent progress in an ion cyclotron range of frequencies (ICRF) heating system and experiment results in a Large Helical Device (LHD) are reported. Three kinds of ICRF antenna pairs were installed in the LHD, and the operation power regimes were extended up to 4.5 MW; also, the steady-state operation was extended for more than 45 min in LHD at a MW power level. We studied ICRF heating physics in heliotron configuration using a Hand Shake type (HAS) antenna, Field Aligned Impedance Transforming (FAIT) antenna, and Poloidal Array (PA) antenna, and established the optimum minority-ion heating scenario in an LHD. The FAITmore » antenna having a novel impedance transformer inside the vacuum chamber could reduce the VSWR and successfully injected a higher power to plasma. We tested the PA antennas completely removing the Faraday-shield pipes to avoid breakdown and to increase the plasma coupling. The heating performance was almost the same as other antennas; however, the heating efficiency was degraded when the gap between the antenna and plasma surface was large. Using these three kinds of antennas, ICRF heating could contribute to raising the plasma beta with the second- and third-harmonic cyclotron heating mode, and also to raising the ion temperature as discharge cleaning tools. In 2014, steady-state operation plasma with a line-averaged electron density of 1.2 × 10{sup 19} m{sup −3}, ion and electron temperature of 2 keV, and plasma sustainment time of 48 min was achieved with ICH and ECH heating power of 1.2 MW for majority helium with minority hydrogen. In 2015, the higher-power steady-state operation with a heating power of up to 3 MW was tested with higher density of 3 × 10{sup 19} m{sup −3}.« less

  16. 22 CFR 193.3 - Applications.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Applications. 193.3 Section 193.3 Foreign Relations DEPARTMENT OF STATE HOSTAGE RELIEF BENEFITS FOR HOSTAGES IN IRAQ, KUWAIT, OR LEBANON § 193.3.../Iraq/Lebanon Hostage Benefits Program, room 4817, Department of State, Washington, DC 20520-4818. (e...

  17. 22 CFR 193.2 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Definitions. 193.2 Section 193.2 Foreign Relations DEPARTMENT OF STATE HOSTAGE RELIEF BENEFITS FOR HOSTAGES IN IRAQ, KUWAIT, OR LEBANON § 193.2 Definitions. (a) For purposes of eligibility, the term covered family members shall be defined as prescribed...

  18. 46 CFR 193.50-1 - Application.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Application. 193.50-1 Section 193.50-1 Shipping COAST... EQUIPMENT Hand Portable Fire Extinguishers and Semiportable Fire Extinguishing Systems, Arrangements and Details § 193.50-1 Application. (a) The provisions of this subpart, with the exception of § 193.50-90...

  19. IShTAR ICRF antenna field characterization in vacuum and plasma by using probe diagnostic

    NASA Astrophysics Data System (ADS)

    Usoltceva, Mariia; Ochoukov, Roman; D'Inca, Rodolphe; Jacquot, Jonathan; Crombé, Kristel; Kostic, Ana; Heuraux, Stéphane; Faudot, Eric; Noterdaeme, Jean-Marie

    2017-10-01

    RF sheath physics is one of the key topics relevant for improvements of ICRF heating systems, which are present on nearly all modern magnetic fusion machines. This paper introduces developement and validation of a new approach to understanding general RF sheath physics. The presumed reason of enhanced plasma-antenna interactions, parallel electric field, is not measured directly, but proposed to be obtained from simulations in COMSOL Multiphysics® Modeling Software. Measurements of RF magnetic field components with B-dot probes are done on a linear device IShTAR (Ion cyclotron Sheath Test ARrangement) and then compared to simulations. Good resulting accordance is suggested to be the criterion for trustworthiness of parallel electric field estimation as a component of electromagnetic field in modeling. A comparison between simulation and experiment for one magnetic field component in vacuum has demonstrated a close match. An additional complication to this ICRF antenna field characterization study is imposed by the helicon antenna which is used as a plasma ignition tool in the test arrangement. The plasma case, in contrast to the vacuum case, must be approached carefully, since the overlapping of ICRF antenna and helicon antenna fields occurs. Distinguishing of the two fields is done by an analysis of correlation between measurements with both antennas together and with each one separately.

  20. 32 CFR 193.3 - Policy.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Policy. 193.3 Section 193.3 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS HIGHWAYS FOR NATIONAL DEFENSE § 193.3 Policy. In order to insure that the national defense is served by adequate, safe...

  1. 32 CFR 193.3 - Policy.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 2 2014-07-01 2014-07-01 false Policy. 193.3 Section 193.3 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS HIGHWAYS FOR NATIONAL DEFENSE § 193.3 Policy. In order to insure that the national defense is served by adequate, safe...

  2. 49 CFR 193.2119 - Records

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Records 193.2119 Section 193.2119 Transportation...: FEDERAL SAFETY STANDARDS Design Materials § 193.2119 Records Each operator shall keep a record of all... properties meet the requirements of this part. These records must be maintained for the life of the item...

  3. 49 CFR 193.2119 - Records

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Records 193.2119 Section 193.2119 Transportation...: FEDERAL SAFETY STANDARDS Design Materials § 193.2119 Records Each operator shall keep a record of all... properties meet the requirements of this part. These records must be maintained for the life of the item...

  4. 49 CFR 193.2119 - Records

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Records 193.2119 Section 193.2119 Transportation...: FEDERAL SAFETY STANDARDS Design Materials § 193.2119 Records Each operator shall keep a record of all... properties meet the requirements of this part. These records must be maintained for the life of the item...

  5. 49 CFR 193.2321 - Nondestructive tests.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., see § 193.2013), except that 100 percent of welds that are both longitudinal (or meridional) and... Vessel Code (Section VIII Division 1) (incorporated by reference, see § 193.2013). (b) For storage tanks... § 193.2013); (2) Appendices Q and C of API 620 Standard (incorporated by reference, see § 193.2013); (c...

  6. MiR-2964a-5p binding site SNP regulates ATM expression contributing to age-related cataract risk.

    PubMed

    Rong, Han; Gu, Shanshan; Zhang, Guowei; Kang, Lihua; Yang, Mei; Zhang, Junfang; Shen, Xinyue; Guan, Huaijin

    2017-10-17

    This study was to explore the involvement of DNA repair genes in the pathogenesis of age-related cataract (ARC). We genotyped nine single nucleotide polymorphisms (SNPs) of genes responsible to DNA double strand breaks (DSBs) in 804 ARC cases and 804 controls in a cohort of eye diseases in Chinese population and found that the ataxia telangiectasia mutated ( ATM ) gene-rs4585:G>T was significantly associated with ARC risk. An in vitro functional test found that miR-2964a-5p specifically down-regulated luciferase reporter expression and ATM expression in the cell lines transfected with rs4585 T allele compared to rs4585 G allele. The molecular assay on human tissue samples discovered that ATM expression was down-regulated in majority of ARC tissues and correlated with ATM genotypes. In addition, the Comet assay of cellular DNA damage of peripheral lymphocytes indicated that individuals carrying the G allele (GG/GT) of ATM -rs4585 had lower DNA breaks compared to individuals with TT genotype. These findings suggested that the SNP rs4585 in ATM might affect ARC risk through modulating the regulatory affinity of miR-2964a-5p. The reduced DSBs repair might be involved in ARC pathogenesis.

  7. Implementation of virtual LANs over ATM WANs

    NASA Astrophysics Data System (ADS)

    Braun, Torsten; Maehler, Martin

    1998-09-01

    Virtual LANs (VLANs) allow to interconnect users over campus or wide area networks and gives the users the impression as they would be connected to the same local area network (LAN). The implementation of VLANs is based on ATM Forum's LAN Emulation and LAN/ATM switches providing interconnection of emulated LANs over ATM and the LAN ports to which the user's end systems are attached to. The paper discusses possible implementation architectures and describes advanced features such as ATM short-cuts, QoS, and redundancy concepts.

  8. 46 CFR 193.15-10 - Controls.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Controls. 193.15-10 Section 193.15-10 Shipping COAST... EQUIPMENT Carbon Dioxide and Clean Agent Extinguishing Systems, Details § 193.15-10 Controls. (a) Except as noted in § 193.15-20(b), all controls and valves for the operation of the system shall be outside the...

  9. 46 CFR 193.15-10 - Controls.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Controls. 193.15-10 Section 193.15-10 Shipping COAST... EQUIPMENT Carbon Dioxide and Clean Agent Extinguishing Systems, Details § 193.15-10 Controls. (a) Except as noted in § 193.15-20(b), all controls and valves for the operation of the system shall be outside the...

  10. 46 CFR 193.15-10 - Controls.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Controls. 193.15-10 Section 193.15-10 Shipping COAST... EQUIPMENT Carbon Dioxide Extinguishing Systems, Details § 193.15-10 Controls. (a) Except as noted in § 193.15-20(b), all controls and valves for the operation of the system shall be outside the space...

  11. 46 CFR 193.15-10 - Controls.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Controls. 193.15-10 Section 193.15-10 Shipping COAST... EQUIPMENT Carbon Dioxide Extinguishing Systems, Details § 193.15-10 Controls. (a) Except as noted in § 193.15-20(b), all controls and valves for the operation of the system shall be outside the space...

  12. 46 CFR 193.15-10 - Controls.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Controls. 193.15-10 Section 193.15-10 Shipping COAST... EQUIPMENT Carbon Dioxide and Clean Agent Extinguishing Systems, Details § 193.15-10 Controls. (a) Except as noted in § 193.15-20(b), all controls and valves for the operation of the system shall be outside the...

  13. ICRF wall conditioning at TEXTOR-94 in the presence of a 2.25 T magnetic field

    NASA Astrophysics Data System (ADS)

    Esser, H. G.; Lyssoivan, A.; Freisinger, M.; Koch, R.; van Oost, G.; Weschenfelder, F.; Winter, J.; Textor-Icrh-Team

    1997-02-01

    To investigate alternative conditioning concepts for future fusion devices with permanent magnetic fields, plasmas produced by the coupling of ICRF power to He and gas mixtures of Helium + silane, have been analyzed in the presence of a 2.25 T toroidal magnetic field at TEXTOR-94. Their qualification for wall conditioning has been investigated for different He-pressures, PHe (1 × 10 -3 < PHe ( Pa) < 1 × 10 -1) and ICRF power, PICRF (100 < PICRF ( kW) < 800). Electron densities n e averaged along different radial lines of sight across the vacuum vessel from the top to the bottom have been obtained in the range 5 × 10 10 < ne ( cm-3) < 3 × 10 12. To study quantitatively the efficiency of hydrogen desorption from the first wall at different ICRF plasma conditions in a reproducible way, the first wall was presaturated by RG-glow discharges in H 2. The amount and the evolution of the H 2 desorption from rf discharge to rf discharge was determined by ion gauge measurements combined with mass spectrometry. To demonstrate the capability of the new method for plasma assisted thin film deposition, different amounts of silane (<50%) were added to the He gas. During the ICRF pulses, the silane molecules were dissociated in the plasma and the Si atoms stick to the wall. A good balance of the amount of Si disappearing from the gas phase and that measured by post mortem surface analyses of collector probes at the wall position was found.

  14. Atm knock-in mice harboring an in-frame deletion corresponding to the human ATM 7636del9 common mutation exhibit a variant phenotype.

    PubMed

    Spring, K; Cross, S; Li, C; Watters, D; Ben-Senior, L; Waring, P; Ahangari, F; Lu, S L; Chen, P; Misko, I; Paterson, C; Kay, G; Smorodinsky, N I; Shiloh, Y; Lavin, M F

    2001-06-01

    ATM, the gene mutated in the human immunodeficiency disorder ataxia-telangiectasia (A-T), plays a central role in recognizing ionizing radiation damage in DNA and in controlling several cell cycle checkpoints. We describe here a murine model in which a nine-nucleotide in-frame deletion has been introduced into the Atm gene by homologous recombination followed by removal of the selectable marker cassette by Cre-loxP site-specific, recombination-mediated excision. This mouse, Atm-DeltaSRI, was designed as a model of one of the most common deletion mutations (7636del9) found in A-T patients. The murine Atm deletion results in the loss of three amino acid residues (SRI; 2556-2558) but produces near full-length detectable Atm protein that lacks protein kinase activity. Radiosensitivity was observed in Atm-DeltaSRI mice, whereas the immunological profile of these mice showed greater heterogeneity of T-cell subsets than observed in Atm(-/-) mice. The life span of Atm-DeltaSRI mice was significantly longer than that of Atm(-/-) mice when maintained under nonspecific pathogen-free conditions. This can be accounted for by a lower incidence of thymic lymphomas in Atm-DeltaSRI mice up to 40 weeks, after which time the animals died of other causes. The thymic lymphomas in Atm-DeltaSRI mice were characterized by extensive apoptosis, which appears to be attributable to an increased number of cells expressing Fas ligand. A variety of other tumors including B-cell lymphomas, sarcomas, and carcinomas not seen in Atm(-/-) mice were observed in older Atm-DeltaSRI animals. Thus, expression of mutant protein in Atm-DeltaSRI knock-in mice gives rise to a discernibly different phenotype to Atm(-/-) mice, which may account for the heterogeneity seen in A-T patients with different mutations.

  15. Structure of the intact ATM/Tel1 kinase

    NASA Astrophysics Data System (ADS)

    Wang, Xuejuan; Chu, Huanyu; Lv, Mengjuan; Zhang, Zhihui; Qiu, Shuwan; Liu, Haiyan; Shen, Xuetong; Wang, Weiwu; Cai, Gang

    2016-05-01

    The ataxia-telangiectasia mutated (ATM) protein is an apical kinase that orchestrates the multifaceted DNA-damage response. Normally, ATM kinase is in an inactive, homodimer form and is transformed into monomers upon activation. Besides a conserved kinase domain at the C terminus, ATM contains three other structural modules, referred to as FAT, FATC and N-terminal helical solenoid. Here we report the first cryo-EM structure of ATM kinase, which is an intact homodimeric ATM/Tel1 from Schizosaccharomyces pombe. We show that two monomers directly contact head-to-head through the FAT and kinase domains. The tandem N-terminal helical solenoid tightly packs against the FAT and kinase domains. The structure suggests that ATM/Tel1 dimer interface and the consecutive HEAT repeats inhibit the binding of kinase substrates and regulators by steric hindrance. Our study provides a structural framework for understanding the mechanisms of ATM/Tel1 regulation as well as the development of new therapeutic agents.

  16. 53BP1 depletion causes PARP inhibitor resistance in ATM-deficient breast cancer cells.

    PubMed

    Hong, Ruoxi; Ma, Fei; Zhang, Weimin; Yu, Xiying; Li, Qing; Luo, Yang; Zhu, Changjun; Jiang, Wei; Xu, Binghe

    2016-09-09

    Mutations in DNA damage response factors BRCA1 and BRCA2 confer sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors in breast and ovarian cancers. BRCA1/BRCA2-defective tumors can exhibit resistance to PARP inhibitors via multiple mechanisms, one of which involves loss of 53BP1. Deficiency in the DNA damage response factor ataxia-telangiectasia mutated (ATM) can also sensitize tumors to PARP inhibitors, raising the question of whether the presence or absence of 53BP1 can predict sensitivity of ATM-deficient breast cancer to these inhibitors. Cytotoxicity of PARP inhibitor and ATM inhibitor in breast cancer cell lines was assessed by MTS, colony formation and apoptosis assays. ShRNA lentiviral vectors were used to knockdown 53BP1 expression in breast cancer cell lines. Phospho-ATM and 53BP1 protein expressions were determined in human breast cancer tissues by immunohistochemistry (IHC). We show that inhibiting ATM increased cytotoxicity of PARP inhibitor in triple-negative and non-triple-negative breast cancer cell lines, and depleting the cells of 53BP1 reduced this cytotoxicity. Inhibiting ATM abrogated homologous recombination induced by PARP inhibitor, and down-regulating 53BP1 partially reversed this effect. Further, overall survival was significantly better in triple-negative breast cancer patients with lower levels of phospho-ATM and tended to be better in patients with negative 53BP1. These results suggest that 53BP1 may be a predictor of PARP inhibitor resistance in patients with ATM-deficient tumors.

  17. Mobile phone signal exposure triggers a hormesis-like effect in Atm+/+ and Atm-/- mouse embryonic fibroblasts.

    PubMed

    Sun, Chuan; Wei, Xiaoxia; Fei, Yue; Su, Liling; Zhao, Xinyuan; Chen, Guangdi; Xu, Zhengping

    2016-11-18

    Radiofrequency electromagnetic fields (RF-EMFs) have been classified by the International Agency for Research on Cancer as possible carcinogens to humans; however, this conclusion is based on limited epidemiological findings and lacks solid support from experimental studies. In particular, there are no consistent data regarding the genotoxicity of RF-EMFs. Ataxia telangiectasia mutated (ATM) is recognised as a chief guardian of genomic stability. To address the debate on whether RF-EMFs are genotoxic, we compared the effects of 1,800 MHz RF-EMF exposure on genomic DNA in mouse embryonic fibroblasts (MEFs) with proficient (Atm +/+ ) or deficient (Atm -/- ) ATM. In Atm +/+ MEFs, RF-EMF exposure for 1 h at an average special absorption rate of 4.0 W/kg induced significant DNA single-strand breaks (SSBs) and activated the SSB repair mechanism. This effect reduced the DNA damage to less than that of the background level after 36 hours of exposure. In the Atm -/- MEFs, the same RF-EMF exposure for 12 h induced both SSBs and double-strand breaks and activated the two repair processes, which also reduced the DNA damage to less than the control level after prolonged exposure. The observed phenomenon is similar to the hormesis of a toxic substance at a low dose. To the best of our knowledge, this study is the first to report a hormesis-like effect of an RF-EMF.

  18. Phenotypic Analysis of ATM Protein Kinase in DNA Double-Strand Break Formation and Repair.

    PubMed

    Mian, Elisabeth; Wiesmüller, Lisa

    2017-01-01

    Ataxia telangiectasia mutated (ATM) encodes a serine/threonine protein kinase, which is involved in various regulatory processes in mammalian cells. Its best-known role is apical activation of the DNA damage response following generation of DNA double-strand breaks (DSBs). When DSBs appear, sensor and mediator proteins are recruited, activating transducers such as ATM, which in turn relay a widespread signal to a multitude of downstream effectors. ATM mutation causes Ataxia telangiectasia (AT), whereby the disease phenotype shows differing characteristics depending on the underlying ATM mutation. However, all phenotypes share progressive neurodegeneration and marked predisposition to malignancies at the organismal level and sensitivity to ionizing radiation and chromosome aberrations at the cellular level. Expression and localization of the ATM protein can be determined via western blotting and immunofluorescence microscopy; however, detection of subtle alterations such as resulting from amino acid exchanges rather than truncating mutations requires functional testing. Previous studies on the role of ATM in DSB repair, which connects with radiosensitivity and chromosomal stability, gave at first sight contradictory results. To systematically explore the effects of clinically relevant ATM mutations on DSB repair, we engaged a series of lymphoblastoid cell lines (LCLs) derived from AT patients and controls. To examine DSB repair both in a quantitative and qualitative manners, we used an EGFP-based assay comprising different substrates for distinct DSB repair mechanisms. In this way, we demonstrated that particular signaling defects caused by individual ATM mutations led to specific DSB repair phenotypes. To explore the impact of ATM on carcinogenic chromosomal aberrations, we monitored chromosomal breakage at a breakpoint cluster region hotspot within the MLL gene that has been associated with therapy-related leukemia. PCR-based MLL-breakage analysis of HeLa cells

  19. ATM supports gammaherpesvirus replication by attenuating type I interferon pathway.

    PubMed

    Darrah, Eric J; Stoltz, Kyle P; Ledwith, Mitchell; Tarakanova, Vera L

    2017-10-01

    Ataxia-Telangiectasia mutated (ATM) kinase participates in multiple networks, including DNA damage response, oxidative stress, and mitophagy. ATM also supports replication of diverse DNA and RNA viruses. Gammaherpesviruses are prevalent cancer-associated viruses that benefit from ATM expression during replication. This proviral role of ATM had been ascribed to its signaling within the DNA damage response network; other functions of ATM have not been considered. In this study increased type I interferon (IFN) responses were observed in ATM deficient gammaherpesvirus-infected macrophages. Using a mouse model that combines ATM and type I IFN receptor deficiencies we show that increased type I IFN response in the absence of ATM fully accounts for the proviral role of ATM during gammaherpesvirus replication. Further, increased type I IFN response rendered ATM deficient macrophages more susceptible to antiviral effects of type II IFN. This study identifies attenuation of type I IFN responses as the primary mechanism underlying proviral function of ATM during gammaherpesvirus infection. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Mode conversion in three ion species ICRF heating scenario

    NASA Astrophysics Data System (ADS)

    Lin, Y.; Edlund, E.; Ennever, P.; Porkolab, M.; Wright, J.; Wukitch, S.

    2016-10-01

    Three-ion species ICRF heating has been studied on Alcator C-Mod and on JET. It has been shown to heat the plasma and generate energetic particles. In a typical three-ion scenario, the plasma consists of 60-70% D, 30-40% H and a trace level (1% or less) of 3He. This species mixture creates two hybrid resonances (D-3He and 3He-H) in the plasma, in the vicinity of the 3He IC resonance (on both sides). The fast wave can undergo mode conversion (MC) to ion Bernstein waves and ion cyclotron waves at the two hybrid resonances. A phase contrast imaging (PCI) system has been used to measure the RF waves in the three-ion heating experiment. The experimentally measured MC locations and the separating distance between the two MC regions help to determine the concentration of the three species. The PCI signal amplitudes for the RF waves are found to be sensitive to RF and plasma parameters, including PRF, Te, ne and also the species mix concentration. The parameter dependences found in the experiment will be compared with ICRF code simulations. Supported by USDoE Awards DE-FC02-99ER54512 and DE-FG02-94-ER54235.

  1. NOTCH1 Inhibits Activation of ATM by Impairing the Formation of an ATM-FOXO3a-KAT5/Tip60 Complex.

    PubMed

    Adamowicz, Marek; Vermezovic, Jelena; d'Adda di Fagagna, Fabrizio

    2016-08-23

    The DNA damage response (DDR) signal transduction pathway is responsible for sensing DNA damage and further relaying this signal into the cell. ATM is an apical DDR kinase that orchestrates the activation and the recruitment of downstream DDR factors to induce cell-cycle arrest and repair. We have previously shown that NOTCH1 inhibits ATM activation upon DNA damage, but the underlying mechanism remains unclear. Here, we show that NOTCH1 does not impair ATM recruitment to DNA double-strand breaks (DSBs). Rather, NOTCH1 prevents binding of FOXO3a and KAT5/Tip60 to ATM through a mechanism in which NOTCH1 competes with FOXO3a for ATM binding. Lack of FOXO3a binding to ATM leads to the loss of KAT5/Tip60 association with ATM. Moreover, expression of NOTCH1 or depletion of ATM impairs the formation of the FOXO3a-KAT5/Tip60 protein complex. Finally, we show that pharmacological induction of FOXO3a nuclear localization sensitizes NOTCH1-driven cancers to DNA-damage-induced cell death. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Apigenin induces DNA damage through the PKCδ-dependent activation of ATM and H2AX causing down-regulation of genes involved in cell cycle control and DNA repair

    PubMed Central

    Arango, Daniel; Parihar, Arti; Villamena, Frederick A.; Wang, Liwen; Freitas, Michael A.; Grotewold, Erich; Doseff, Andrea I.

    2014-01-01

    Apigenin, an abundant plant flavonoid, exhibits anti-proliferative and anti-carcinogenic activities through mechanisms yet not fully defined. In the present study, we show that the treatment of leukemia cells with apigenin resulted in the induction of DNA damage preceding the activation of the apoptotic program. Apigenin-induced DNA damage was mediated by p38 and protein kinase C-delta (PKCδ), yet was independent of reactive oxygen species or caspase activity. Treatment of monocytic leukemia cells with apigenin induced the phosphorylation of the ataxia-telangiectasia mutated (ATM) kinase and histone H2AX, two key regulators of the DNA damage response, without affecting the ataxia-telangiectasia mutated and Rad-3-related (ATR) kinase. Silencing and pharmacological inhibition of PKCδ abrogated ATM and H2AX phosphorylation, whereas inhibition of p38 reduced H2AX phosphorylation independently of ATM. We established that apigenin delayed cell cycle progression at G1/S and increased the number of apoptotic cells. In addition, genome-wide mRNA analyses showed that apigenin-induced DNA damage led to down-regulation of genes involved in cell-cycle control and DNA repair. Taken together, the present results show that the PKCδ-dependent activation of ATM and H2AX define the signaling networks responsible for the regulation of DNA damage promoting genome-wide mRNA alterations that result in cell cycle arrest, hence contributing to the anti-carcinogenic activities of this flavonoid. PMID:22985621

  3. ATM activation in normal human tissues and testicular cancer.

    PubMed

    Bartkova, Jirina; Bakkenist, Christopher J; Rajpert-De Meyts, Ewa; Skakkebaek, Niels E; Sehested, Maxwell; Lukas, Jiri; Kastan, Michael B; Bartek, Jiri

    2005-06-01

    The ATM kinase is a tumor suppressor and key regulator of biological responses to DNA damage. Cultured cells respond to genotoxic insults that induce DNA double-strand breaks by prompt activation of ATM through its autophosphorylation on serine 1981. However, whether ATM-S1981 becomes phosphorylated in vivo, for example during physiological processes that generate DSBs, is unknown. Here we produced phospho-specific monoclonal antibodies against S1981-phosphorylated ATM (pS-ATM), and applied them to immunohistochemical analyses of a wide range of normal human tissues and testicular tumors. Our data show that regardless of proliferation and differentiation, most human tissues contain only the S1981-nonphosphorylated, inactive form of ATM. In contrast, nuclear staining for pS-ATM was detected in subsets of bone-marrow lymphocytes and primary spermatocytes in the adult testes, cell types in which DSBs are generated during physiological V(D)J recombination and meiotic recombination, respectively. Among testicular germ-cell tumors, an aberrant constitutive pS-ATM was observed especially in embryonal carcinomas, less in seminomas, and only modestly in teratomas and the pre-invasive carcinoma-in-situ stage. Compared with pS-ATM, phosphorylated histone H2AX (gammaH2AX), another DNA damage marker and ATM substrate, was detected in a higher proportion of cancer cells, and also in normal fetal gonocytes, and a wider range of adult spermatocyte differentiation stages. Collectively, our results strongly support the physiological relevance of the recently proposed model of ATM autoactivation, and provide further evidence for constitutive activation of the DNA damage machinery during cancer development. The new tools characterized here should facilitate monitoring of ATM activation in clinical specimens, and help develop future treatment strategies.

  4. Theory and Practice in ICRF Antennas for Long Pulse Operation

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

    Colas, L.; Bremond, S.; Mitteau, R.

    2005-09-26

    Long plasma discharges on the Tore Supra (TS) tokamak were extended in 2004 towards higher powers and plasma densities by combined Lower Hybrid (LH) and Ion Cyclotron Range of Frequencies (ICRF) waves. RF pulses of 20sx8MW and 60sx4MW were produced. TS is equipped with 3 ICRF antennas, whose front faces are ready for CW operation. This paper reports on their behaviour over high power long pulses, as observed with infrared (IR) thermography and calorimetric measurements. Edge parasitic losses, although modest, are concentrated on a small surface and can raise surface temperatures close to operational limits. A complex hot spot patternmore » was revealed with at least 3 physical processes involved : convected power, electron acceleration in the LH near field, and a RF-specific phenomenon compatible with RF sheaths. LH coupling was also perturbed in the antenna shadow. This was attributed to RF-induced DC ExB0 convection. This motivated sheath modelling in two directions. First, the 2D topology of RF potentials was investigated in relation with the RF current distribution over the antenna, via a Green's function formalism and full-wave calculation using the ICANT code. In front of phased arrays of straps, convective cells were interpreted using the RF current profiles of strip line theory. Another class of convective cells, specific to antenna box corners, was evidenced for the first time. Within 1D sheath models assuming independent flux tubes, RF and rectified DC potentials are proportional. 2D fluid models couple nearby flux tubes via transverse polarisation currents. Unexpectedly this does not necessarily smooth RF potential maps. Peak DC potentials can even be enhanced. The experience gained on TS and the numerical tools are valuable for designing steady state high power antennas for next step devices. General rules to reduce RF potentials as well as concrete design options are discussed.« less

  5. Asynchronous Transfer Mode (ATM) Switch Technology and Vendor Survey

    NASA Technical Reports Server (NTRS)

    Berry, Noemi

    1995-01-01

    Asynchronous Transfer Mode (ATM) switch and software features are described and compared in order to make switch comparisons meaningful. An ATM switch's performance cannot be measured solely based on its claimed switching capacity; traffic management and congestion control are emerging as the determining factors in an ATM network's ultimate throughput. Non-switch ATM products and experiences with actual installations of ATM networks are described. A compilation of select vendor offerings as of October 1994 is provided in chart form.

  6. 49 CFR 193.2711 - Personnel health.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Personnel health. 193.2711 Section 193.2711 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY...: FEDERAL SAFETY STANDARDS Personnel Qualifications and Training § 193.2711 Personnel health. Each operator...

  7. 49 CFR 193.2711 - Personnel health.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Personnel health. 193.2711 Section 193.2711 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY...: FEDERAL SAFETY STANDARDS Personnel Qualifications and Training § 193.2711 Personnel health. Each operator...

  8. 49 CFR 193.2711 - Personnel health.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Personnel health. 193.2711 Section 193.2711 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY...: FEDERAL SAFETY STANDARDS Personnel Qualifications and Training § 193.2711 Personnel health. Each operator...

  9. 49 CFR 193.2711 - Personnel health.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Personnel health. 193.2711 Section 193.2711 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY...: FEDERAL SAFETY STANDARDS Personnel Qualifications and Training § 193.2711 Personnel health. Each operator...

  10. 49 CFR 193.2711 - Personnel health.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Personnel health. 193.2711 Section 193.2711 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY...: FEDERAL SAFETY STANDARDS Personnel Qualifications and Training § 193.2711 Personnel health. Each operator...

  11. Assessment of compatibility of ICRF antenna operation with full W wall in ASDEX Upgrade

    NASA Astrophysics Data System (ADS)

    Bobkov, Vl. V.; Braun, F.; Dux, R.; Herrmann, A.; Giannone, L.; Kallenbach, A.; Krivska, A.; Müller, H. W.; Neu, R.; Noterdaeme, J.-M.; Pütterich, T.; Rohde, V.; Schweinzer, J.; Sips, A.; Zammuto, I.; ASDEX Upgrade Team

    2010-03-01

    The compatibility of ICRF (ion cyclotron range of frequencies) antenna operation with high-Z plasma facing components is assessed in ASDEX Upgrade (AUG) with its tungsten (W) first wall. The mechanism of ICRF-related W sputtering was studied by various diagnostics including the local spectroscopic measurements of W sputtering yield YW on antenna limiters. Modification of one antenna with triangular shields, which cover the locations where long magnetic field lines pass only one out of two (0π)-phased antenna straps, did not influence the locally measured YW values markedly. In the experiments with antennas powered individually, poloidal profiles of YW on limiters of powered antennas show high YW close to the equatorial plane and at the very edge of the antenna top. The YW-profile on an unpowered antenna limiter peaks at the location projecting to the top of the powered antenna. An interpretation of the YW measurements is presented, assuming a direct link between the W sputtering and the sheath driving RF voltages deduced from parallel electric near-field (E||) calculations and this suggests a strong E|| at the antenna limiters. However, uncertainties are too large to describe the YW poloidal profiles. In order to reduce ICRF-related rise in W concentration CW, an operational approach and an approach based on calculations of parallel electric fields with new antenna designs are considered. In the operation, a noticeable reduction in YW and CW in the plasma during ICRF operation with W wall can be achieved by (a) increasing plasma-antenna clearance; (b) strong gas puffing; (c) decreasing the intrinsic light impurity content (mainly oxygen and carbon in AUG). In calculations, which take into account a realistic antenna geometry, the high E|| fields at the antenna limiters are reduced in several ways: (a) by extending the antenna box and the surrounding structures parallel to the magnetic field; (b) by increasing the average strap-box distance, e.g. by increasing the

  12. 49 CFR 193.2609 - Support systems.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Support systems. 193.2609 Section 193.2609 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY...: FEDERAL SAFETY STANDARDS Maintenance § 193.2609 Support systems. Each support system or foundation of each...

  13. 49 CFR 193.2609 - Support systems.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Support systems. 193.2609 Section 193.2609 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY...: FEDERAL SAFETY STANDARDS Maintenance § 193.2609 Support systems. Each support system or foundation of each...

  14. 49 CFR 193.2609 - Support systems.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Support systems. 193.2609 Section 193.2609 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY...: FEDERAL SAFETY STANDARDS Maintenance § 193.2609 Support systems. Each support system or foundation of each...

  15. 49 CFR 193.2917 - Warning signs.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Warning signs. 193.2917 Section 193.2917 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY...: FEDERAL SAFETY STANDARDS Security § 193.2917 Warning signs. (a) Warning signs must be conspicuously placed...

  16. 49 CFR 193.2917 - Warning signs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Warning signs. 193.2917 Section 193.2917 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY...: FEDERAL SAFETY STANDARDS Security § 193.2917 Warning signs. (a) Warning signs must be conspicuously placed...

  17. 49 CFR 193.2917 - Warning signs.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Warning signs. 193.2917 Section 193.2917 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY...: FEDERAL SAFETY STANDARDS Security § 193.2917 Warning signs. (a) Warning signs must be conspicuously placed...

  18. 49 CFR 193.2917 - Warning signs.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Warning signs. 193.2917 Section 193.2917 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY...: FEDERAL SAFETY STANDARDS Security § 193.2917 Warning signs. (a) Warning signs must be conspicuously placed...

  19. 49 CFR 193.2917 - Warning signs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Warning signs. 193.2917 Section 193.2917 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY...: FEDERAL SAFETY STANDARDS Security § 193.2917 Warning signs. (a) Warning signs must be conspicuously placed...

  20. 49 CFR 193.2303 - Construction acceptance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Construction acceptance. 193.2303 Section 193.2303 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY...: FEDERAL SAFETY STANDARDS Construction § 193.2303 Construction acceptance. No person may place in service...

  1. 49 CFR 193.2303 - Construction acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Construction acceptance. 193.2303 Section 193.2303 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY...: FEDERAL SAFETY STANDARDS Construction § 193.2303 Construction acceptance. No person may place in service...

  2. 49 CFR 193.2607 - Foreign material.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Foreign material. 193.2607 Section 193.2607 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY...: FEDERAL SAFETY STANDARDS Maintenance § 193.2607 Foreign material. (a) The presence of foreign material...

  3. 49 CFR 193.2625 - Corrosion protection.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Corrosion protection. 193.2625 Section 193.2625...: FEDERAL SAFETY STANDARDS Maintenance § 193.2625 Corrosion protection. (a) Each operator shall determine which metallic components could, unless corrosion is controlled, have their integrity or reliability...

  4. 49 CFR 193.2321 - Nondestructive tests.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Nondestructive tests. 193.2321 Section 193.2321 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY...: FEDERAL SAFETY STANDARDS Construction § 193.2321 Nondestructive tests. (a) The butt welds in metal shells...

  5. 49 CFR 193.2625 - Corrosion protection.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Corrosion protection. 193.2625 Section 193.2625...: FEDERAL SAFETY STANDARDS Maintenance § 193.2625 Corrosion protection. (a) Each operator shall determine which metallic components could, unless corrosion is controlled, have their integrity or reliability...

  6. 49 CFR 193.2625 - Corrosion protection.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Corrosion protection. 193.2625 Section 193.2625...: FEDERAL SAFETY STANDARDS Maintenance § 193.2625 Corrosion protection. (a) Each operator shall determine which metallic components could, unless corrosion is controlled, have their integrity or reliability...

  7. 49 CFR 193.2625 - Corrosion protection.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Corrosion protection. 193.2625 Section 193.2625...: FEDERAL SAFETY STANDARDS Maintenance § 193.2625 Corrosion protection. (a) Each operator shall determine which metallic components could, unless corrosion is controlled, have their integrity or reliability...

  8. 49 CFR 193.2909 - Security communications.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Security communications. 193.2909 Section 193.2909...: FEDERAL SAFETY STANDARDS Security § 193.2909 Security communications. A means must be provided for: (a) Prompt communications between personnel having supervisory security duties and law enforcement officials...

  9. 49 CFR 193.2909 - Security communications.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Security communications. 193.2909 Section 193.2909...: FEDERAL SAFETY STANDARDS Security § 193.2909 Security communications. A means must be provided for: (a) Prompt communications between personnel having supervisory security duties and law enforcement officials...

  10. 49 CFR 193.2909 - Security communications.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Security communications. 193.2909 Section 193.2909...: FEDERAL SAFETY STANDARDS Security § 193.2909 Security communications. A means must be provided for: (a) Prompt communications between personnel having supervisory security duties and law enforcement officials...

  11. 49 CFR 193.2607 - Foreign material.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Foreign material. 193.2607 Section 193.2607 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY...: FEDERAL SAFETY STANDARDS Maintenance § 193.2607 Foreign material. (a) The presence of foreign material...

  12. MSFC institutional area network and ATM technology

    NASA Technical Reports Server (NTRS)

    Amin, Ashok T.

    1994-01-01

    The New Institutional Area Network (NEWIAN) at Marshall supports over 5000 end users with access to 26 file servers providing work presentation services. It is comprised of some 150 Ethernet LAN's interconnected by bridges/routers which are in turn connected to servers over two dual FDDI rings. The network supports various higher level protocols such as IP, IPX, AppleTalk (AT), and DECNet. At present IPX and AT protocols packets are routed, and IP protocol packets are bridged; however, work is in progress to route all IP packets. The impact of routing IP packets on network operation is examined. Broadband Integrated Services Data Network (BISDN), presently at various stages of development, is intended to provide voice, video, and data transfer services over a single network. BISDN will use asynchronous transfer mode (ATM) as a data transfer technique which provides for transmission, multiplexing, switching, and relaying of small size data units called cells. Limited ATM Wide Area Network (WAN) services are offered by Wiltel, AT&T, Sprint, and others. NASA is testing a pilot ATM WAN with a view to provide Program Support Communication Network services using ATM. ATM supports wide range of data rates and quality of service requirements. It is expected that ATM switches will penetrate campus networks as well. However, presently products in these areas are at various stages of development and standards are not yet complete. We examine development of ATM to help assess its role in the evolution of NEWIAN.

  13. Contribution of canonical nonhomologous end joining to chromosomal rearrangements is enhanced by ATM kinase deficiency.

    PubMed

    Bhargava, Ragini; Carson, Caree R; Lee, Gabriella; Stark, Jeremy M

    2017-01-24

    A likely mechanism of chromosomal rearrangement formation involves joining the ends from two different chromosomal double-strand breaks (DSBs). These events could potentially be mediated by either of two end-joining (EJ) repair pathways [canonical nonhomologous end joining (C-NHEJ) or alternative end joining (ALT-EJ)], which cause distinct rearrangement junction patterns. The relative role of these EJ pathways during rearrangement formation has remained controversial. Along these lines, we have tested whether the DNA damage response mediated by the Ataxia Telangiectasia Mutated (ATM) kinase may affect the relative influence of C-NHEJ vs. ALT-EJ on rearrangement formation. We developed a reporter in mouse cells for a 0.4-Mbp deletion rearrangement that is formed by EJ between two DSBs induced by the Cas9 endonuclease. We found that disruption of the ATM kinase causes an increase in the frequency of the rearrangement as well as a shift toward rearrangement junctions that show hallmarks of C-NHEJ. Furthermore, ATM suppresses rearrangement formation in an experimental condition, in which C-NHEJ is the predominant EJ repair event (i.e., expression of the 3' exonuclease Trex2). Finally, several C-NHEJ factors are required for the increase in rearrangement frequency caused by inhibition of the ATM kinase. We also examined ATM effectors and found that H2AX shows a similar influence as ATM, whereas the influence of ATM on this rearrangement seems independent of 53BP1. We suggest that the contribution of the C-NHEJ pathway to the formation of a 0.4-Mbp deletion rearrangement is enhanced in ATM-deficient cells.

  14. 49 CFR 193.2719 - Training: records.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Training: records. 193.2719 Section 193.2719...: FEDERAL SAFETY STANDARDS Personnel Qualifications and Training § 193.2719 Training: records. (a) Each operator shall maintain a system of records which— (1) Provide evidence that the training programs required...

  15. 49 CFR 193.2719 - Training: records.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Training: records. 193.2719 Section 193.2719...: FEDERAL SAFETY STANDARDS Personnel Qualifications and Training § 193.2719 Training: records. (a) Each operator shall maintain a system of records which— (1) Provide evidence that the training programs required...

  16. 49 CFR 193.2519 - Communication systems.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Communication systems. 193.2519 Section 193.2519...: FEDERAL SAFETY STANDARDS Operations § 193.2519 Communication systems. (a) Each LNG plant must have a primary communication system that provides for verbal communications between all operating personnel at...

  17. 49 CFR 193.2519 - Communication systems.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Communication systems. 193.2519 Section 193.2519...: FEDERAL SAFETY STANDARDS Operations § 193.2519 Communication systems. (a) Each LNG plant must have a primary communication system that provides for verbal communications between all operating personnel at...

  18. 49 CFR 193.2173 - Water removal.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Water removal. 193.2173 Section 193.2173...: FEDERAL SAFETY STANDARDS Design Impoundment Design and Capacity § 193.2173 Water removal. (a) Impoundment areas must be constructed such that all areas drain completely to prevent water collection. Drainage...

  19. 49 CFR 193.2173 - Water removal.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Water removal. 193.2173 Section 193.2173...: FEDERAL SAFETY STANDARDS Design Impoundment Design and Capacity § 193.2173 Water removal. (a) Impoundment areas must be constructed such that all areas drain completely to prevent water collection. Drainage...

  20. 49 CFR 193.2519 - Communication systems.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...: FEDERAL SAFETY STANDARDS Operations § 193.2519 Communication systems. (a) Each LNG plant must have a primary communication system that provides for verbal communications between all operating personnel at... 49 Transportation 3 2011-10-01 2011-10-01 false Communication systems. 193.2519 Section 193.2519...

  1. 46 CFR 193.30-1 - Application.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Application. 193.30-1 Section 193.30-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS FIRE PROTECTION EQUIPMENT Automatic Sprinkler Systems § 193.30-1 Application. Automatic sprinkling systems shall comply with...

  2. 46 CFR 193.30-1 - Application.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Application. 193.30-1 Section 193.30-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS FIRE PROTECTION EQUIPMENT Automatic Sprinkler Systems § 193.30-1 Application. Automatic sprinkling systems shall comply with...

  3. 46 CFR 193.30-1 - Application.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Application. 193.30-1 Section 193.30-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS FIRE PROTECTION EQUIPMENT Automatic Sprinkler Systems § 193.30-1 Application. Automatic sprinkling systems shall comply with...

  4. 46 CFR 193.30-1 - Application.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Application. 193.30-1 Section 193.30-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS FIRE PROTECTION EQUIPMENT Automatic Sprinkler Systems § 193.30-1 Application. Automatic sprinkling systems shall comply with...

  5. 46 CFR 193.30-1 - Application.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Application. 193.30-1 Section 193.30-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS FIRE PROTECTION EQUIPMENT Automatic Sprinkler Systems § 193.30-1 Application. Automatic sprinkling systems shall comply with...

  6. 49 CFR 193.2633 - Interference currents.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...: FEDERAL SAFETY STANDARDS Maintenance § 193.2633 Interference currents. (a) Each component that is subject to electrical current interference must be protected by a continuing program to minimize the... 49 Transportation 3 2012-10-01 2012-10-01 false Interference currents. 193.2633 Section 193.2633...

  7. 49 CFR 193.2633 - Interference currents.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...: FEDERAL SAFETY STANDARDS Maintenance § 193.2633 Interference currents. (a) Each component that is subject to electrical current interference must be protected by a continuing program to minimize the... 49 Transportation 3 2014-10-01 2014-10-01 false Interference currents. 193.2633 Section 193.2633...

  8. 49 CFR 193.2633 - Interference currents.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...: FEDERAL SAFETY STANDARDS Maintenance § 193.2633 Interference currents. (a) Each component that is subject to electrical current interference must be protected by a continuing program to minimize the... 49 Transportation 3 2013-10-01 2013-10-01 false Interference currents. 193.2633 Section 193.2633...

  9. 49 CFR 193.2633 - Interference currents.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...: FEDERAL SAFETY STANDARDS Maintenance § 193.2633 Interference currents. (a) Each component that is subject to electrical current interference must be protected by a continuing program to minimize the... 49 Transportation 3 2011-10-01 2011-10-01 false Interference currents. 193.2633 Section 193.2633...

  10. 49 CFR 193.2173 - Water removal.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Water removal. 193.2173 Section 193.2173...: FEDERAL SAFETY STANDARDS Design Impoundment Design and Capacity § 193.2173 Water removal. (a) Impoundment areas must be constructed such that all areas drain completely to prevent water collection. Drainage...

  11. 49 CFR 193.2173 - Water removal.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Water removal. 193.2173 Section 193.2173...: FEDERAL SAFETY STANDARDS Design Impoundment Design and Capacity § 193.2173 Water removal. (a) Impoundment areas must be constructed such that all areas drain completely to prevent water collection. Drainage...

  12. 49 CFR 193.2173 - Water removal.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Water removal. 193.2173 Section 193.2173...: FEDERAL SAFETY STANDARDS Design Impoundment Design and Capacity § 193.2173 Water removal. (a) Impoundment areas must be constructed such that all areas drain completely to prevent water collection. Drainage...

  13. Susceptibility of ATM-deficient pancreatic cancer cells to radiation.

    PubMed

    Ayars, Michael; Eshleman, James; Goggins, Michael

    2017-05-19

    Ataxia telangiectasia mutated (ATM) is inactivated in a significant minority of pancreatic ductal adenocarcinomas and may be predictor of treatment response. We determined if ATM deficiency renders pancreatic cancer cells more sensitive to fractionated radiation or commonly used chemotherapeutics. ATM expression was knocked down in three pancreatic cancer cell lines using ATM-targeting shRNA. Isogenic cell lines were tested for sensitivity to several chemotherapeutic agents and radiation. DNA repair kinetics were analyzed in irradiated cells using the comet assay. We find that while rendering pancreatic cancer cells ATM-deficient did not significantly change their sensitivity to several chemotherapeutics, it did render them exquisitely sensitized to radiation. Pancreatic cancer ATM status may help predict response to radiotherapy.

  14. Functional and nonfunctional testing of ATM networks

    NASA Astrophysics Data System (ADS)

    Ricardo, Manuel; Ferreira, M. E. P.; Guimaraes, Francisco E.; Mamede, J.; Henriques, M.; da Silva, Jorge A.; Carrapatoso, E.

    1995-02-01

    ATM network will support new multimedia services that will require new protocols, those services and protocols will need different test strategies and tools. In this paper, the concepts of functional and non-functional testers of ATM networks are discussed, a multimedia service and its requirements are presented and finally, a summary description of an ATM network and of the test tool that will be used to validate it are presented.

  15. Traffic Management in ATM Networks Over Satellite Links

    NASA Technical Reports Server (NTRS)

    Goyal, Rohit; Jain, Raj; Goyal, Mukul; Fahmy, Sonia; Vandalore, Bobby; vonDeak, Thomas

    1999-01-01

    This report presents a survey of the traffic management Issues in the design and implementation of satellite Asynchronous Transfer Mode (ATM) networks. The report focuses on the efficient transport of Transmission Control Protocol (TCP) traffic over satellite ATM. First, a reference satellite ATM network architecture is presented along with an overview of the service categories available in ATM networks. A delay model for satellite networks and the major components of delay and delay variation are described. A survey of design options for TCP over Unspecified Bit Rate (UBR), Guaranteed Frame Rate (GFR) and Available Bit Rate (ABR) services in ATM is presented. The main focus is on traffic management issues. Several recommendations on the design options for efficiently carrying data services over satellite ATM networks are presented. Most of the results are based on experiments performed on Geosynchronous (GEO) latencies. Some results for Low Earth Orbits (LEO) and Medium Earth Orbit (MEO) latencies are also provided.

  16. 49 CFR 193.2167 - Covered systems.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Covered systems. 193.2167 Section 193.2167...: FEDERAL SAFETY STANDARDS Design Impoundment Design and Capacity § 193.2167 Covered systems. A covered impounding system is prohibited except for concrete wall designed tanks where the concrete wall is an outer...

  17. 49 CFR 193.2167 - Covered systems.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Covered systems. 193.2167 Section 193.2167...: FEDERAL SAFETY STANDARDS Design Impoundment Design and Capacity § 193.2167 Covered systems. A covered impounding system is prohibited except for concrete wall designed tanks where the concrete wall is an outer...

  18. 49 CFR 193.2167 - Covered systems.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Covered systems. 193.2167 Section 193.2167...: FEDERAL SAFETY STANDARDS Design Impoundment Design and Capacity § 193.2167 Covered systems. A covered impounding system is prohibited except for concrete wall designed tanks where the concrete wall is an outer...

  19. 49 CFR 193.2067 - Wind forces.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Wind forces. 193.2067 Section 193.2067...: FEDERAL SAFETY STANDARDS Siting Requirements § 193.2067 Wind forces. (a) LNG facilities must be designed to withstand without loss of structural or functional integrity: (1) The direct effect of wind forces...

  20. 49 CFR 193.2067 - Wind forces.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Wind forces. 193.2067 Section 193.2067...: FEDERAL SAFETY STANDARDS Siting Requirements § 193.2067 Wind forces. (a) LNG facilities must be designed to withstand without loss of structural or functional integrity: (1) The direct effect of wind forces...

  1. 49 CFR 193.2067 - Wind forces.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Wind forces. 193.2067 Section 193.2067...: FEDERAL SAFETY STANDARDS Siting Requirements § 193.2067 Wind forces. (a) LNG facilities must be designed to withstand without loss of structural or functional integrity: (1) The direct effect of wind forces...

  2. 49 CFR 193.2067 - Wind forces.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Wind forces. 193.2067 Section 193.2067...: FEDERAL SAFETY STANDARDS Siting Requirements § 193.2067 Wind forces. (a) LNG facilities must be designed to withstand without loss of structural or functional integrity: (1) The direct effect of wind forces...

  3. 49 CFR 193.2503 - Operating procedures.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...: FEDERAL SAFETY STANDARDS Operations § 193.2503 Operating procedures. Each operator shall follow one or more manuals of written procedures to provide safety in normal operation and in responding to an... 49 Transportation 3 2013-10-01 2013-10-01 false Operating procedures. 193.2503 Section 193.2503...

  4. 49 CFR 193.2503 - Operating procedures.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...: FEDERAL SAFETY STANDARDS Operations § 193.2503 Operating procedures. Each operator shall follow one or more manuals of written procedures to provide safety in normal operation and in responding to an... 49 Transportation 3 2011-10-01 2011-10-01 false Operating procedures. 193.2503 Section 193.2503...

  5. 49 CFR 193.2503 - Operating procedures.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...: FEDERAL SAFETY STANDARDS Operations § 193.2503 Operating procedures. Each operator shall follow one or more manuals of written procedures to provide safety in normal operation and in responding to an... 49 Transportation 3 2014-10-01 2014-10-01 false Operating procedures. 193.2503 Section 193.2503...

  6. 49 CFR 193.2503 - Operating procedures.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...: FEDERAL SAFETY STANDARDS Operations § 193.2503 Operating procedures. Each operator shall follow one or more manuals of written procedures to provide safety in normal operation and in responding to an... 49 Transportation 3 2012-10-01 2012-10-01 false Operating procedures. 193.2503 Section 193.2503...

  7. 49 CFR 193.2715 - Training: security.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Training: security. 193.2715 Section 193.2715...: FEDERAL SAFETY STANDARDS Personnel Qualifications and Training § 193.2715 Training: security. (a) Personnel responsible for security at an LNG plant must be trained in accordance with a written plan of...

  8. 49 CFR 193.2913 - Security monitoring.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Security monitoring. 193.2913 Section 193.2913...: FEDERAL SAFETY STANDARDS Security § 193.2913 Security monitoring. Each protective enclosure and the area.... Monitoring must be by visual observation in accordance with the schedule in the security procedures under...

  9. 49 CFR 193.2903 - Security procedures.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Security procedures. 193.2903 Section 193.2903...: FEDERAL SAFETY STANDARDS Security § 193.2903 Security procedures. Each operator shall prepare and follow one or more manuals of written procedures to provide security for each LNG plant. The procedures must...

  10. 49 CFR 193.2903 - Security procedures.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Security procedures. 193.2903 Section 193.2903...: FEDERAL SAFETY STANDARDS Security § 193.2903 Security procedures. Each operator shall prepare and follow one or more manuals of written procedures to provide security for each LNG plant. The procedures must...

  11. 49 CFR 193.2715 - Training: security.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Training: security. 193.2715 Section 193.2715...: FEDERAL SAFETY STANDARDS Personnel Qualifications and Training § 193.2715 Training: security. (a) Personnel responsible for security at an LNG plant must be trained in accordance with a written plan of...

  12. 49 CFR 193.2913 - Security monitoring.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Security monitoring. 193.2913 Section 193.2913...: FEDERAL SAFETY STANDARDS Security § 193.2913 Security monitoring. Each protective enclosure and the area.... Monitoring must be by visual observation in accordance with the schedule in the security procedures under...

  13. 49 CFR 193.2903 - Security procedures.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Security procedures. 193.2903 Section 193.2903...: FEDERAL SAFETY STANDARDS Security § 193.2903 Security procedures. Each operator shall prepare and follow one or more manuals of written procedures to provide security for each LNG plant. The procedures must...

  14. 49 CFR 193.2913 - Security monitoring.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Security monitoring. 193.2913 Section 193.2913...: FEDERAL SAFETY STANDARDS Security § 193.2913 Security monitoring. Each protective enclosure and the area.... Monitoring must be by visual observation in accordance with the schedule in the security procedures under...

  15. 49 CFR 193.2715 - Training: security.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Training: security. 193.2715 Section 193.2715...: FEDERAL SAFETY STANDARDS Personnel Qualifications and Training § 193.2715 Training: security. (a) Personnel responsible for security at an LNG plant must be trained in accordance with a written plan of...

  16. 49 CFR 193.2067 - Wind forces.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Wind forces. 193.2067 Section 193.2067...: FEDERAL SAFETY STANDARDS Siting Requirements § 193.2067 Wind forces. (a) LNG facilities must be designed to withstand without loss of structural or functional integrity: (1) The direct effect of wind forces...

  17. 46 CFR 193.60-10 - Location.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Location. 193.60-10 Section 193.60-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS FIRE PROTECTION EQUIPMENT Fire Axes § 193.60-10 Location. (a) Fire axes shall be distributed throughout the spaces available...

  18. 46 CFR 193.10-1 - Application.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Application. 193.10-1 Section 193.10-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS FIRE PROTECTION EQUIPMENT Fire Main System, Details § 193.10-1 Application. (a) The provisions of this subpart, with the...

  19. 49 CFR 193.2441 - Control center.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Control center. 193.2441 Section 193.2441...: FEDERAL SAFETY STANDARDS Equipment Vaporization Equipment § 193.2441 Control center. Each LNG plant must have a control center from which operations and warning devices are monitored as required by this part...

  20. 49 CFR 193.2441 - Control center.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Control center. 193.2441 Section 193.2441...: FEDERAL SAFETY STANDARDS Equipment Vaporization Equipment § 193.2441 Control center. Each LNG plant must have a control center from which operations and warning devices are monitored as required by this part...

  1. 49 CFR 193.2441 - Control center.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Control center. 193.2441 Section 193.2441...: FEDERAL SAFETY STANDARDS Equipment Vaporization Equipment § 193.2441 Control center. Each LNG plant must have a control center from which operations and warning devices are monitored as required by this part...

  2. 49 CFR 193.2441 - Control center.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Control center. 193.2441 Section 193.2441...: FEDERAL SAFETY STANDARDS Equipment Vaporization Equipment § 193.2441 Control center. Each LNG plant must have a control center from which operations and warning devices are monitored as required by this part...

  3. 49 CFR 193.2441 - Control center.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Control center. 193.2441 Section 193.2441...: FEDERAL SAFETY STANDARDS Equipment Vaporization Equipment § 193.2441 Control center. Each LNG plant must have a control center from which operations and warning devices are monitored as required by this part...

  4. NPP ATMS Snowfall Rate Product

    NASA Technical Reports Server (NTRS)

    Meng, Huan; Ferraro, Ralph; Kongoli, Cezar; Wang, Nai-Yu; Dong, Jun; Zavodsky, Bradley; Yan, Banghua

    2015-01-01

    Passive microwave measurements at certain high frequencies are sensitive to the scattering effect of snow particles and can be utilized to retrieve snowfall properties. Some of the microwave sensors with snowfall sensitive channels are Advanced Microwave Sounding Unit (AMSU), Microwave Humidity Sounder (MHS) and Advance Technology Microwave Sounder (ATMS). ATMS is the follow-on sensor to AMSU and MHS. Currently, an AMSU and MHS based land snowfall rate (SFR) product is running operationally at NOAA/NESDIS. Based on the AMSU/MHS SFR, an ATMS SFR algorithm has been developed recently. The algorithm performs retrieval in three steps: snowfall detection, retrieval of cloud properties, and estimation of snow particle terminal velocity and snowfall rate. The snowfall detection component utilizes principal component analysis and a logistic regression model. The model employs a combination of temperature and water vapor sounding channels to detect the scattering signal from falling snow and derive the probability of snowfall (Kongoli et al., 2015). In addition, a set of NWP model based filters is also employed to improve the accuracy of snowfall detection. Cloud properties are retrieved using an inversion method with an iteration algorithm and a two-stream radiative transfer model (Yan et al., 2008). A method developed by Heymsfield and Westbrook (2010) is adopted to calculate snow particle terminal velocity. Finally, snowfall rate is computed by numerically solving a complex integral. NCEP CMORPH analysis has shown that integration of ATMS SFR has improved the performance of CMORPH-Snow. The ATMS SFR product is also being assessed at several NWS Weather Forecast Offices for its usefulness in weather forecast.

  5. 19 CFR 10.193 - Imported directly.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Imported directly. 10.193 Section 10.193 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. Caribbean Basin Initiative § 10.193 Imported...

  6. 46 CFR 193.60-1 - Application.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Application. 193.60-1 Section 193.60-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS FIRE PROTECTION EQUIPMENT Fire Axes § 193.60-1 Application. (a) The provisions of this subpart shall apply to all vessels...

  7. Introduction to multiprotocol over ATM (MPOA)

    NASA Astrophysics Data System (ADS)

    Fredette, Andre N.

    1997-10-01

    Multiprotocol over ATM (MPOA) is a new protocol specified by the ATM Forum. MPOA provides a framework for effectively synthesizing bridging and routing with ATM in an environment of diverse protocols and network technologies. The primary goal of MPOA is the efficient transfer of inter-subnet unicast data in a LAN Emulation (LANE) environment. MPOA integrates LANE and the next hop resolution protocol (NHRP) to preserve the benefits of LAN Emulation, while allowing inter-subnet, internetwork layer protocol communication over ATM VCCs without requiring routers in the data path. It reduces latency and the internetwork layer forwarding load on backbone routers by enabling direct connectivity between ATM-attached edge devices (i.e., shortcuts). To establish these shortcuts, MPOA uses both routing and bridging information to locate the edge device closest to the addressed end station. By integrating LANE and NHRP, MPOA allows the physical separation of internetwork layer route calculation and forwarding, a technique known as virtual routing. This separation provides a number of key benefits including enhanced manageability and reduced complexity of internetwork layer capable edge devices. This paper provides an overview of MPOA that summarizes the goals, architecture, and key attributes of the protocol. In presenting this overview, the salient attributes of LANE and NHRP are described as well.

  8. Activation of ATM by DNA Damaging Agents

    DTIC Science & Technology

    2004-09-01

    risk for breast cancer . Since many anti-tumor chemotherapeutics used in breast cancer treatment have the capacity to induce DNA DSBs, I have...of a subset of downstream effectors of ATM in two human breast cancer cell lines. Studies are now underway to identify proteins that interact with ATM...implications for the treatment of breast cancer patients harboring mutations in ATM. 14. SUBJECT TERMS 15. NUMBER OF PAGES signal transduction, DNA damage and

  9. ATM protein is deficient in over 40% of lung adenocarcinomas.

    PubMed

    Villaruz, Liza C; Jones, Helen; Dacic, Sanja; Abberbock, Shira; Kurland, Brenda F; Stabile, Laura P; Siegfried, Jill M; Conrads, Thomas P; Smith, Neil R; O'Connor, Mark J; Pierce, Andrew J; Bakkenist, Christopher J

    2016-09-06

    Lung cancer is the leading cause of cancer-related mortality in the USA and worldwide, and of the estimated 1.2 million new cases of lung cancer diagnosed every year, over 30% are lung adenocarcinomas. The backbone of 1st-line systemic therapy in the metastatic setting, in the absence of an actionable oncogenic driver, is platinum-based chemotherapy. ATM and ATR are DNA damage signaling kinases activated at DNA double-strand breaks (DSBs) and stalled and collapsed replication forks, respectively. ATM protein is lost in a number of cancer cell lines and ATR kinase inhibitors synergize with cisplatin to resolve xenograft models of ATM-deficient lung cancer. We therefore sought to determine the frequency of ATM loss in a tissue microarray (TMA) of lung adenocarcinoma. Here we report the validation of a commercial antibody (ab32420) for the identification of ATM by immunohistochemistry and estimate that 61 of 147 (41%, 95% CI 34%-50%) cases of lung adenocarcinoma are negative for ATM protein expression. As a positive control for ATM staining, nuclear ATM protein was identified in stroma and immune infiltrate in all evaluable cases. ATM loss in lung adenocarcinoma was not associated with overall survival. However, our preclinical findings in ATM-deficient cell lines suggest that ATM could be a predictive biomarker for synergy of an ATR kinase inhibitor with standard-of-care cisplatin. This could improve clinical outcome in 100,000's of patients with ATM-deficient lung adenocarcinoma every year.

  10. ATM protein is deficient in over 40% of lung adenocarcinomas

    PubMed Central

    Villaruz, Liza C.; Jones, Helen; Dacic, Sanja; Abberbock, Shira; Kurland, Brenda F.; Stabile, Laura P.; Siegfried, Jill M.; Conrads, Thomas P.; Smith, Neil R.; O'Connor, Mark J.; Pierce, Andrew J.; Bakkenist, Christopher J.

    2016-01-01

    Lung cancer is the leading cause of cancer-related mortality in the USA and worldwide, and of the estimated 1.2 million new cases of lung cancer diagnosed every year, over 30% are lung adenocarcinomas. The backbone of 1st-line systemic therapy in the metastatic setting, in the absence of an actionable oncogenic driver, is platinum-based chemotherapy. ATM and ATR are DNA damage signaling kinases activated at DNA double-strand breaks (DSBs) and stalled and collapsed replication forks, respectively. ATM protein is lost in a number of cancer cell lines and ATR kinase inhibitors synergize with cisplatin to resolve xenograft models of ATM-deficient lung cancer. We therefore sought to determine the frequency of ATM loss in a tissue microarray (TMA) of lung adenocarcinoma. Here we report the validation of a commercial antibody (ab32420) for the identification of ATM by immunohistochemistry and estimate that 61 of 147 (41%, 95% CI 34%-50%) cases of lung adenocarcinoma are negative for ATM protein expression. As a positive control for ATM staining, nuclear ATM protein was identified in stroma and immune infiltrate in all evaluable cases. ATM loss in lung adenocarcinoma was not associated with overall survival. However, our preclinical findings in ATM-deficient cell lines suggest that ATM could be a predictive biomarker for synergy of an ATR kinase inhibitor with standard-of-care cisplatin. This could improve clinical outcome in 100,000's of patients with ATM-deficient lung adenocarcinoma every year. PMID:27259260

  11. Tumor protein D52 represents a negative regulator of ATM protein levels

    PubMed Central

    Chen, Yuyan; Kamili, Alvin; Hardy, Jayne R; Groblewski, Guy E; Khanna, Kum Kum; Byrne, Jennifer A

    2013-01-01

    Tumor protein D52 (TPD52) is a coiled-coil motif bearing hydrophilic polypeptide known to be overexpressed in cancers of diverse cellular origins. Increased TPD52 expression is associated with increased proliferation and invasive capacity in different cell types. Recent studies have reported a correlation between TPD52 transcript levels and G2 chromosomal radiosensitivity in lymphocytes of women at risk of hereditary breast cancer, and that TPD52 knockdown significantly reduced the radiation sensitivity of multiple cancer cell lines. In this study, we investigated possible roles for TPD52 in DNA damage response, and found that increased TPD52 expression in breast cancer and TPD52-expressing BALB/c 3T3 cells compromised ATM-mediated cellular responses to DNA double-strand breaks induced by γ-ray irradiation, which was associated with downregulation of steady-state ATM protein, but not transcript levels, regardless of irradiation status. TPD52-expressing 3T3 cells also showed significantly increased radiation sensitivity compared with vector cells evaluated by clonogenic assays. Furthermore, direct interactions between exogenous and endogenous ATM and TPD52 were detected by GST pull-down and co-immunoprecipitation assays. We also identified the interaction domains involved in this binding as TPD52 residues 111–131, and ATM residues 1–245 and 772–1102. Taken together, our results suggest that TPD52 may represent a novel negative regulator of ATM protein levels. PMID:23974097

  12. Buffer Management Simulation in ATM Networks

    NASA Technical Reports Server (NTRS)

    Yaprak, E.; Xiao, Y.; Chronopoulos, A.; Chow, E.; Anneberg, L.

    1998-01-01

    This paper presents a simulation of a new dynamic buffer allocation management scheme in ATM networks. To achieve this objective, an algorithm that detects congestion and updates the dynamic buffer allocation scheme was developed for the OPNET simulation package via the creation of a new ATM module.

  13. Mitochondria are required for ATM activation by extranuclear oxidative stress in cultured human hepatoblastoma cell line Hep G2 cells

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

    Morita, Akinori, E-mail: morita@tokushima-u.ac.jp; Department of Radiological Science, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8509; Tanimoto, Keiji

    2014-01-24

    Highlights: • Oxidative ATM activation can occur in the absence of nuclear DNA damage response. • The oxidized Hep G2 cells were subjected to subcellular fractionation. • The obtained results suggest that the ATM activation occurs in mitochondria. • ATM failed to respond to oxidative stress in mitochondria-depleted Hep G2 cells. • Mitochondria are required for the oxidative activation of ATM. - Abstract: Ataxia–telangiectasia mutated (ATM) is a serine/threonine protein kinase that plays a central role in DNA damage response (DDR). A recent study reported that oxidized ATM can be active in the absence of DDR. However, the issue ofmore » where ATM is activated by oxidative stress remains unclear. Regarding the localization of ATM, two possible locations, namely, mitochondria and peroxisomes are possible. We report herein that ATM can be activated when exposed to hydrogen peroxide without inducing nuclear DDR in Hep G2 cells, and the oxidized cells could be subjected to subcellular fractionation. The first detergent-based fractionation experiment revealed that active, phosphorylated ATM was located in the second fraction, which also contained both mitochondria and peroxisomes. An alternative fractionation method involving homogenization and differential centrifugation, which permits the light membrane fraction containing peroxisomes to be produced, but not mitochondria, revealed that the light membrane fraction contained only traces of ATM. In contrast, the heavy membrane fraction, which mainly contained mitochondrial components, was enriched in ATM and active ATM, suggesting that the oxidative activation of ATM occurs in mitochondria and not in peroxisomes. In Rho 0-Hep G2 cells, which lack mitochondrial DNA and functional mitochondria, ATM failed to respond to hydrogen peroxide, indicating that mitochondria are required for the oxidative activation of ATM. These findings strongly suggest that ATM can be activated in response to oxidative stress in

  14. ATM Card Cloning and Ethical Considerations.

    PubMed

    Kaur, Paramjit; Krishan, Kewal; Sharma, Suresh K; Kanchan, Tanuj

    2018-05-01

    With the advent of modern technology, the way society handles and performs monetary transactions has changed tremendously. The world is moving swiftly towards the digital arena. The use of Automated Teller Machine (ATM) cards (credit and debit) has led to a "cash-less society" and has fostered digital payments and purchases. In addition to this, the trust and reliance of the society upon these small pieces of plastic, having numbers engraved upon them, has increased immensely over the last two decades. In the past few years, the number of ATM fraud cases has increased exponentially. With the money of the people shifting towards the digital platform, ATM skimming has become a problem that has eventually led to a global outcry. The present review discusses the serious repercussions of ATM card cloning and the associated privacy, ethical and legal concerns. The preventive measures which need to be taken and adopted by the government authorities to mitigate the problem have also been discussed.

  15. 32 CFR 193.2 - Applicability.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 2 2014-07-01 2014-07-01 false Applicability. 193.2 Section 193.2 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS... the Department of Defense. ...

  16. 32 CFR 193.2 - Applicability.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Applicability. 193.2 Section 193.2 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS... the Department of Defense. ...

  17. ATM/cable arch and beam structural test program

    NASA Technical Reports Server (NTRS)

    Housley, J. A.

    1972-01-01

    The structural testing is described of an Apollo Telescope Mount (ATM) cable arch and beam assembly, using static loads to simulate the critical conditions expected during transportation and launch of the ATM. All test objectives were met. Stress and deflection data show that the assembly is structurally adequate for use in the ATM.

  18. Almost 2% of Spanish breast cancer families are associated to germline pathogenic mutations in the ATM gene.

    PubMed

    Tavera-Tapia, A; Pérez-Cabornero, L; Macías, J A; Ceballos, M I; Roncador, G; de la Hoya, M; Barroso, A; Felipe-Ponce, V; Serrano-Blanch, R; Hinojo, C; Miramar-Gallart, M D; Urioste, M; Caldés, T; Santillan-Garzón, S; Benitez, J; Osorio, A

    2017-02-01

    There is still a considerable percentage of hereditary breast and ovarian cancer (HBOC) cases not explained by BRCA1 and BRCA2 genes. In this report, next-generation sequencing (NGS) techniques were applied to identify novel variants and/or genes involved in HBOC susceptibility. Using whole exome sequencing, we identified a novel germline mutation in the moderate-risk gene ATM (c.5441delT; p.Leu1814Trpfs*14) in a family negative for mutations in BRCA1/2 (BRCAX). A case-control association study was performed to establish its prevalence in Spanish population, in a series of 1477 BRCAX families and 589 controls further screened, and NGS panels were used for ATM mutational screening in a cohort of 392 HBOC Spanish BRCAX families and 350 patients affected with diseases not related to breast cancer. Although the interrogated mutation was not prevalent in case-control association study, a comprehensive mutational analysis of the ATM gene revealed 1.78% prevalence of mutations in the ATM gene in HBOC and 1.94% in breast cancer-only BRCAX families in Spanish population, where data about ATM mutations were very limited. ATM mutation prevalence in Spanish population highlights the importance of considering ATM pathogenic variants linked to breast cancer susceptibility.

  19. Tunable biasing magnetic field design of ferrite tuner for ICRF heating system in EAST

    NASA Astrophysics Data System (ADS)

    Manman, XU; Yuntao, SONG; Gen, CHEN; Yanping, ZHAO; Yuzhou, MAO; Guang, LIU; Zhen, PENG

    2017-11-01

    Ion cyclotron range of frequency (ICRF) heating has been used in tokamaks as one of the most successful auxiliary heating tools and has been adopted in the EAST. However, the antenna load will fluctuate with the change of plasma parameters in the ICRF heating process. To ensure the steady operation of the ICRF heating system in the EAST, fast ferrite tuner (FFT) has been carried out to achieve real-time impedance matching. For the requirements of the FFT impedance matching system, the magnet system of the ferrite tuner (FT) was designed by numerical simulations and experimental analysis, where the biasing magnetic circuit and alternating magnetic circuit were the key researched parts of the ferrite magnet. The integral design goal of the FT magnetic circuit is that DC bias magnetic field is 2000 Gs and alternating magnetic field is ±400 Gs. In the FTT, E-type magnetic circuit was adopted. Ferrite material is NdFeB with a thickness of 30 mm by setting the working point of NdFeB, and the ampere turn of excitation coil is 25 through the theoretical calculation and simulation analysis. The coil inductance to generate alternating magnetic field is about 7 mH. Eddy-current effect has been analyzed, while the magnetic field distribution has been measured by a Hall probe in the medium plane of the biasing magnet. Finally, the test results show the good performance of the biasing magnet satisfying the design and operating requirements of the FFT.

  20. 46 CFR 193.50-5 - Classification.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Classification. 193.50-5 Section 193.50-5 Shipping COAST... Details § 193.50-5 Classification. (a) Hand portable fire extinguishers and semiportable fire...) Classification Type Size Soda-acid and water, gals. Foam, gals. Carbon dioxide, lbs. Dry chemical, lbs. A II 21/2...

  1. 46 CFR 193.50-5 - Classification.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Classification. 193.50-5 Section 193.50-5 Shipping COAST... Details § 193.50-5 Classification. (a) Hand portable fire extinguishers and semiportable fire...) Classification Type Size Soda-acid and water, gals. Foam, gals. Carbon dioxide, lbs. Dry chemical, lbs. A II 21/2...

  2. 46 CFR 193.50-5 - Classification.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Classification. 193.50-5 Section 193.50-5 Shipping COAST... Details § 193.50-5 Classification. (a) Hand portable fire extinguishers and semiportable fire...) Classification Type Size Soda-acid and water, gals. Foam, gals. Carbon dioxide, lbs. Dry chemical, lbs. A II 21/2...

  3. 46 CFR 193.50-5 - Classification.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Classification. 193.50-5 Section 193.50-5 Shipping COAST... Details § 193.50-5 Classification. (a) Hand portable fire extinguishers and semiportable fire...) Classification Type Size Soda-acid and water, gals. Foam, gals. Carbon dioxide, lbs. Dry chemical, lbs. A II 21/2...

  4. 46 CFR 193.50-5 - Classification.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Classification. 193.50-5 Section 193.50-5 Shipping COAST... Details § 193.50-5 Classification. (a) Hand portable fire extinguishers and semiportable fire...) Classification Type Size Soda-acid and water, gals. Foam, gals. Carbon dioxide, lbs. Dry chemical, lbs. A II 21/2...

  5. 49 CFR 193.2801 - Fire protection.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Fire protection. 193.2801 Section 193.2801...: FEDERAL SAFETY STANDARDS Fire Protection § 193.2801 Fire protection. Each operator must provide and maintain fire protection at LNG plants according to sections 9.1 through 9.7 and section 9.9 of NFPA 59A...

  6. 49 CFR 193.2619 - Control systems.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Control systems. 193.2619 Section 193.2619...: FEDERAL SAFETY STANDARDS Maintenance § 193.2619 Control systems. (a) Each control system must be properly adjusted to operate within design limits. (b) If a control system is out of service for 30 days or more, it...

  7. 49 CFR 193.2619 - Control systems.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Control systems. 193.2619 Section 193.2619...: FEDERAL SAFETY STANDARDS Maintenance § 193.2619 Control systems. (a) Each control system must be properly adjusted to operate within design limits. (b) If a control system is out of service for 30 days or more, it...

  8. 49 CFR 193.2619 - Control systems.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Control systems. 193.2619 Section 193.2619...: FEDERAL SAFETY STANDARDS Maintenance § 193.2619 Control systems. (a) Each control system must be properly adjusted to operate within design limits. (b) If a control system is out of service for 30 days or more, it...

  9. 49 CFR 193.2619 - Control systems.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Control systems. 193.2619 Section 193.2619...: FEDERAL SAFETY STANDARDS Maintenance § 193.2619 Control systems. (a) Each control system must be properly adjusted to operate within design limits. (b) If a control system is out of service for 30 days or more, it...

  10. 49 CFR 193.2619 - Control systems.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Control systems. 193.2619 Section 193.2619...: FEDERAL SAFETY STANDARDS Maintenance § 193.2619 Control systems. (a) Each control system must be properly adjusted to operate within design limits. (b) If a control system is out of service for 30 days or more, it...

  11. ATM test and integration. [Skylab Apollo Telescope Mount

    NASA Technical Reports Server (NTRS)

    Moore, J. W.; Mitchell, J. R.

    1974-01-01

    The test and checkout philosophy of the test program for the Skylab ATM module and the overall test flow including in-process, post-manufacturing, vibration, thermal vacuum, and prelaunch checkout activities are described. Capabilities and limitations of the test complex and its use of automation are discussed. Experiences with the organizational principle of using a dedicated test team for all checkout activities are reported. Material on the development of the ATM subsystems, the experimental program and the requirements of the scientific community, and the integration and verification of the complex systems/subsystems of the ATM are presented. The performance of the ATM test program in such areas as alignment, systems and subsystems, contamination control, and experiment operation is evaluated. The conclusions and recommendations resulting from the ATM test program are enumerated.

  12. 46 CFR 193.60-5 - Number required.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Number required. 193.60-5 Section 193.60-5 Shipping... EQUIPMENT Fire Axes § 193.60-5 Number required. (a) All vessels shall carry at least the minimum number of... necessary for the proper protection of the vessel. Table 193.60-5(a) Gross tons Over Not over Number of axes...

  13. 46 CFR 193.60-5 - Number required.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Number required. 193.60-5 Section 193.60-5 Shipping... EQUIPMENT Fire Axes § 193.60-5 Number required. (a) All vessels shall carry at least the minimum number of... necessary for the proper protection of the vessel. Table 193.60-5(a) Gross tons Over Not over Number of axes...

  14. 46 CFR 193.60-5 - Number required.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Number required. 193.60-5 Section 193.60-5 Shipping... EQUIPMENT Fire Axes § 193.60-5 Number required. (a) All vessels shall carry at least the minimum number of... necessary for the proper protection of the vessel. Table 193.60-5(a) Gross tons Over Not over Number of axes...

  15. 46 CFR 193.60-5 - Number required.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Number required. 193.60-5 Section 193.60-5 Shipping... EQUIPMENT Fire Axes § 193.60-5 Number required. (a) All vessels shall carry at least the minimum number of... necessary for the proper protection of the vessel. Table 193.60-5(a) Gross tons Over Not over Number of axes...

  16. 46 CFR 193.60-5 - Number required.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Number required. 193.60-5 Section 193.60-5 Shipping... EQUIPMENT Fire Axes § 193.60-5 Number required. (a) All vessels shall carry at least the minimum number of... necessary for the proper protection of the vessel. Table 193.60-5(a) Gross tons Over Not over Number of axes...

  17. European project RETAIN: new approach for IBC in teleradiology and PACS based on full ATM network

    NASA Astrophysics Data System (ADS)

    Cordonnier, Emmanuel; Jensch, Peter F.; Piqueras, Joachim; Gandon, Yves

    1995-05-01

    This paper describes the RETAIN project (radiological examination transfer on ATM Integrated Network), which is supported by the European Community, in the frame of the TEN-IBC program (trans-European networks integrated broad band communication). It links together three European sites in France (Rennes), Spain (Barcelona), and Germany (Oldenburg) and involves a partnership between the public national operators France Telecom, Telefonica, and Telekom. One important reason to explicitly consider asynchronous transfer mode (ATM) for medical imaging is that multimedia applications on such networks allow integration of digital data and person-to-person communication. The RETAIN project includes trials of teleworking sessions between radiologists of Rennes and Barcelona within a clinical and/or scientific context based on ATM equipments performing DICOM transfer on examination, digital remote manipulation within a comprehensive dialogue, and high quality visiophony on ATM adaptation layer (AAL) type 1. The project includes also visiophony trials with Oldenburg and preparation of harmonized regional experimentation within an emergency context. The network used is a full 10 Mbits/s ATM network directly connected to local PACSs.

  18. Functional link between DNA damage responses and transcriptional regulation by ATM in response to a histone deacetylase inhibitor TSA.

    PubMed

    Lee, Jong-Soo

    2007-09-01

    Mutations in the ATM (ataxia-telangiectasia mutated) gene, which encodes a 370 kd protein with a kinase catalytic domain, predisposes people to cancers, and these mutations are also linked to ataxia-telangiectasia (A-T). The histone acetylaion/deacetylation- dependent chromatin remodeling can activate the ATM kinase-mediated DNA damage signal pathway (in an accompanying work, Lee, 2007). This has led us to study whether this modification can impinge on the ATM-mediated DNA damage response via transcriptional modulation in order to understand the function of ATM in the regulation of gene transcription. To identify the genes whose expression is regulated by ATM in response to histone deaceylase (HDAC) inhibition, we performed an analysis of oligonucleotide microarrays with using the appropriate cell lines, isogenic A-T (ATM(-)) and control (ATM(+)) cells, following treatment with a HDAC inhibitor TSA. Treatment with TSA reprograms the differential gene expression profile in response to HDAC inhibition in ATM(-) cells and ATM(+) cells. We analyzed the genes that are regulated by TSA in the ATM-dependent manner, and we classified these genes into different functional categories, including those involved in cell cycle/DNA replication, DNA repair, apoptosis, growth/differentiation, cell- cell adhesion, signal transduction, metabolism and transcription. We found that while some genes are regulated by TSA without regard to ATM, the patterns of gene regulation are differentially regulated in an ATM-dependent manner. Taken together, these finding indicate that ATM can regulate the transcription of genes that play critical roles in the molecular response to DNA damage, and this response is modulated through an altered HDAC inhibition-mediated gene expression.

  19. Using ATM over SATCOM links

    NASA Technical Reports Server (NTRS)

    Comparetto, Gary M.

    1995-01-01

    The Asynchronous Transfer Mode (ATM) protocol is studied from the standpoint of determining what limitations, if any, exist in using it over satellite links. It is concluded that, while there is nothing intrinsic about ATM that would generally preclude its use over satellite links, there are, however, several intrinsic characteristics of satellite links, as well as some satellite system configuration-specific issues, that must be taken into account.

  20. Study of ATM Phosphorylation by Cdk5 in Neuronal Cells.

    PubMed

    She, Hua; Mao, Zixu

    2017-01-01

    The phosphatidylinositol-3-kinase-like kinase ATM (ataxia-telangiectasia mutated) plays a central role in coordinating the DNA damage responses including cell cycle checkpoint control, DNA repair, and apoptosis. Mutations of ATM cause a spectrum of defects ranging from neurodegeneration to cancer predisposition. We previously showed that Cdk5 (cyclin-dependent kinase 5) is activated by DNA damage and directly phosphorylates ATM at serine 794 in postmitotic neurons. Phosphorylation at serine 794 precedes and is required for ATM autophosphorylation at serine 1981, and activates ATM kinase activity. Cdk5-ATM pathway plays a crucial role in DNA damage-induced neuronal injury. This chapter describes protocols used in analyzing ATM phosphorylation by Cdk5 in CGNs (cerebellar granule neurons) and its effects on neuronal survival.

  1. Management of ATM-based networks supporting multimedia medical information systems

    NASA Astrophysics Data System (ADS)

    Whitman, Robert A.; Blaine, G. James; Fritz, Kevin; Goodgold, Ken; Heisinger, Patrick

    1997-05-01

    Medical information systems are acquiring the ability to collect and deliver many different types of medical information. In support of the increased network demands necessitated by these expanded capabilities, asynchronous transfer mode (ATM) based networks are being deployed in medical care systems. While ATM supplies a much greater line rate than currently deployed networks, the management and standards surrounding ATM are yet to mature. This paper explores the management and control issues surrounding an ATM network supporting medical information systems, and examines how management impacts network performance and robustness. A multivendor ATM network at the BJC Health System/Washington University and the applications using the network are discussed. Performance information for specific applications is presented and analyzed. Network management's influence on application reliability is outlined. The information collected is used to show how ATM network standards and management tools influence network reliability and performance. Performance of current applications using the ATM network is discussed. Special attention is given to issues encountered in implementation of hypertext transfer protocol over ATM internet protocol (IP) communications. A classical IP ATM implementation yields greater than twenty percent higher network performance over LANE. Maximum performance for a host's suite of applications can be obtained by establishing multiple individually engineered IP links through its ATM network connection.

  2. 49 CFR 193.2003 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false [Reserved] 193.2003 Section 193.2003 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES...

  3. 49 CFR 193.2617 - Repairs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Repairs. 193.2617 Section 193.2617 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES...

  4. 49 CFR 193.2015 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false [Reserved] 193.2015 Section 193.2015 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES...

  5. 49 CFR 193.2517 - Purging.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Purging. 193.2517 Section 193.2517 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES...

  6. 49 CFR 193.2401 - Scope.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Scope. 193.2401 Section 193.2401 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES...

  7. 49 CFR 193.2603 - General.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false General. 193.2603 Section 193.2603 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES...

  8. 49 CFR 193.2505 - Cooldown.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Cooldown. 193.2505 Section 193.2505 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES...

  9. 49 CFR 193.2501 - Scope.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Scope. 193.2501 Section 193.2501 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES...

  10. 49 CFR 193.2301 - Scope.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Scope. 193.2301 Section 193.2301 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES...

  11. 49 CFR 193.2601 - Scope.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Scope. 193.2601 Section 193.2601 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES...

  12. 49 CFR 193.2011 - Reporting.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Reporting. 193.2011 Section 193.2011 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES...

  13. Hyperoxia activates ATM independent from mitochondrial ROS and dysfunction.

    PubMed

    Resseguie, Emily A; Staversky, Rhonda J; Brookes, Paul S; O'Reilly, Michael A

    2015-08-01

    High levels of oxygen (hyperoxia) are often used to treat individuals with respiratory distress, yet prolonged hyperoxia causes mitochondrial dysfunction and excessive reactive oxygen species (ROS) that can damage molecules such as DNA. Ataxia telangiectasia mutated (ATM) kinase is activated by nuclear DNA double strand breaks and delays hyperoxia-induced cell death through downstream targets p53 and p21. Evidence for its role in regulating mitochondrial function is emerging, yet it has not been determined if mitochondrial dysfunction or ROS activates ATM. Because ATM maintains mitochondrial homeostasis, we hypothesized that hyperoxia induces both mitochondrial dysfunction and ROS that activate ATM. In A549 lung epithelial cells, hyperoxia decreased mitochondrial respiratory reserve capacity at 12h and basal respiration by 48 h. ROS were significantly increased at 24h, yet mitochondrial DNA double strand breaks were not detected. ATM was not required for activating p53 when mitochondrial respiration was inhibited by chronic exposure to antimycin A. Also, ATM was not further activated by mitochondrial ROS, which were enhanced by depleting manganese superoxide dismutase (SOD2). In contrast, ATM dampened the accumulation of mitochondrial ROS during exposure to hyperoxia. Our findings suggest that hyperoxia-induced mitochondrial dysfunction and ROS do not activate ATM. ATM more likely carries out its canonical response to nuclear DNA damage and may function to attenuate mitochondrial ROS that contribute to oxygen toxicity. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  14. ATM loss leads to synthetic lethality in BRCA1 BRCT mutant mice associated with exacerbated defects in homology-directed repair

    PubMed Central

    Chen, Chun-Chin; Kass, Elizabeth M.; Yen, Wei-Feng; Ludwig, Thomas; Moynahan, Mary Ellen; Chaudhuri, Jayanta; Jasin, Maria

    2017-01-01

    BRCA1 is essential for homology-directed repair (HDR) of DNA double-strand breaks in part through antagonism of the nonhomologous end-joining factor 53BP1. The ATM kinase is involved in various aspects of DNA damage signaling and repair, but how ATM participates in HDR and genetically interacts with BRCA1 in this process is unclear. To investigate this question, we used the Brca1S1598F mouse model carrying a mutation in the BRCA1 C-terminal domain of BRCA1. Whereas ATM loss leads to a mild HDR defect in adult somatic cells, we find that ATM inhibition leads to severely reduced HDR in Brca1S1598F cells. Consistent with a critical role for ATM in HDR in this background, loss of ATM leads to synthetic lethality of Brca1S1598F mice. Whereas both ATM and BRCA1 promote end resection, which can be regulated by 53BP1, 53bp1 deletion does not rescue the HDR defects of Atm mutant cells, in contrast to Brca1 mutant cells. These results demonstrate that ATM has a role in HDR independent of the BRCA1–53BP1 antagonism and that its HDR function can become critical in certain contexts. PMID:28659469

  15. ATM loss leads to synthetic lethality in BRCA1 BRCT mutant mice associated with exacerbated defects in homology-directed repair.

    PubMed

    Chen, Chun-Chin; Kass, Elizabeth M; Yen, Wei-Feng; Ludwig, Thomas; Moynahan, Mary Ellen; Chaudhuri, Jayanta; Jasin, Maria

    2017-07-18

    BRCA1 is essential for homology-directed repair (HDR) of DNA double-strand breaks in part through antagonism of the nonhomologous end-joining factor 53BP1. The ATM kinase is involved in various aspects of DNA damage signaling and repair, but how ATM participates in HDR and genetically interacts with BRCA1 in this process is unclear. To investigate this question, we used the Brca1 S1598F mouse model carrying a mutation in the BRCA1 C-terminal domain of BRCA1. Whereas ATM loss leads to a mild HDR defect in adult somatic cells, we find that ATM inhibition leads to severely reduced HDR in Brca1 S1598F cells. Consistent with a critical role for ATM in HDR in this background, loss of ATM leads to synthetic lethality of Brca1 S1598F mice. Whereas both ATM and BRCA1 promote end resection, which can be regulated by 53BP1, 53bp1 deletion does not rescue the HDR defects of Atm mutant cells, in contrast to Brca1 mutant cells. These results demonstrate that ATM has a role in HDR independent of the BRCA1-53BP1 antagonism and that its HDR function can become critical in certain contexts.

  16. 40 CFR 408.193 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true [Reserved] 408.193 Section 408.193 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS CANNED AND PRESERVED SEAFOOD PROCESSING POINT SOURCE CATEGORY West Coast Mechanized Salmon Processing...

  17. 40 CFR 408.193 - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 29 2011-07-01 2009-07-01 true [Reserved] 408.193 Section 408.193 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS CANNED AND PRESERVED SEAFOOD PROCESSING POINT SOURCE CATEGORY West Coast Mechanized Salmon Processing...

  18. ATM Quality of Service Tests for Digitized Video Using ATM Over Satellite: Laboratory Tests

    NASA Technical Reports Server (NTRS)

    Ivancic, William D.; Brooks, David E.; Frantz, Brian D.

    1997-01-01

    A digitized video application was used to help determine minimum quality of service parameters for asynchronous transfer mode (ATM) over satellite. For these tests, binomially distributed and other errors were digitally inserted in an intermediate frequency link via a satellite modem and a commercial gaussian noise generator. In this paper, the relation- ship between the ATM cell error and cell loss parameter specifications is discussed with regard to this application. In addition, the video-encoding algorithms, test configurations, and results are presented in detail.

  19. A Managerial Analysis of ATM in Facilitating Distance Education.

    ERIC Educational Resources Information Center

    Littman, Marlyn Kemper

    In this paper, the fundamental characteristics and capabilities of ATM (Asynchronous Transfer Mode) networks in a distance learning environment are examined. Current and projected ATM applications are described, and issues and challenges associated with developing ATM networking solutions for instructional delivery are explored. Other topics…

  20. Ataxia telangiectasia mutated (ATM) interacts with p400 ATPase for an efficient DNA damage response.

    PubMed

    Smith, Rebecca J; Savoian, Matthew S; Weber, Lauren E; Park, Jeong Hyeon

    2016-11-04

    Ataxia telangiectasia mutated (ATM) and TRRAP proteins belong to the phosphatidylinositol 3-kinase-related kinase family and are involved in DNA damage repair and chromatin remodeling. ATM is a checkpoint kinase that is recruited to sites of DNA double-strand breaks where it phosphorylates a diverse range of proteins that are part of the chromatin and DNA repair machinery. As an integral subunit of the TRRAP-TIP60 complexes, p400 ATPase is a chromatin remodeler that is also targeted to DNA double-strand break sites. While it is understood that DNA binding transcriptional activators recruit p400 ATPase into a regulatory region of the promoter, how p400 recognises and moves to DNA double-strand break sites is far less clear. Here we investigate a possibility whether ATM serves as a shuttle to deliver p400 to break sites. Our data indicate that p400 co-immunoprecipitates with ATM independently of DNA damage state and that the N-terminal domain of p400 is vital for this interaction. Heterologous expression studies using Sf9 cells revealed that the ATM-p400 complex can be reconstituted without other mammalian bridging proteins. Overexpression of ATM-interacting p400 regions in U2OS cells induced dominant negative effects including the inhibition of both DNA damage repair and cell proliferation. Consistent with the dominant negative effect, the stable expression of an N-terminal p400 fragment showed a decrease in the association of p400 with ATM, but did not alter the association of p400 with TRRAP. Taken together, our findings suggest that a protein-protein interaction between ATM and p400 ATPase occurs independently of DNA damage and contributes to efficient DNA damage response and repair.

  1. ATM: Restructing Learning for Deaf Students.

    ERIC Educational Resources Information Center

    Keefe, Barbara; Stockford, David

    Governor Baxter School for the Deaf is one of six Maine pilot sites chosen by NYNEX to showcase asynchronous transfer mode (ATM) technology. ATM is a network connection that allows high bandwidth transmission of data, voice, and video. Its high speed capability allows for high quality two-way full-motion video, which is especially beneficial to a…

  2. ATM and KAT5 safeguard replicating chromatin against formaldehyde damage

    PubMed Central

    Ortega-Atienza, Sara; Wong, Victor C.; DeLoughery, Zachary; Luczak, Michal W.; Zhitkovich, Anatoly

    2016-01-01

    Many carcinogens damage both DNA and protein constituents of chromatin, and it is unclear how cells respond to this compound injury. We examined activation of the main DNA damage-responsive kinase ATM and formation of DNA double-strand breaks (DSB) by formaldehyde (FA) that forms histone adducts and replication-blocking DNA-protein crosslinks (DPC). We found that low FA doses caused a strong and rapid activation of ATM signaling in human cells, which was ATR-independent and restricted to S-phase. High FA doses inactivated ATM via its covalent dimerization and formation of larger crosslinks. FA-induced ATM signaling showed higher CHK2 phosphorylation but much lower phospho-KAP1 relative to DSB inducers. Replication blockage by DPC did not produce damaged forks or detectable amounts of DSB during the main wave of ATM activation, which did not require MRE11. Chromatin-monitoring KAT5 (Tip60) acetyltransferase was responsible for acetylation and activation of ATM by FA. KAT5 and ATM were equally important for triggering of intra-S-phase checkpoint and ATM signaling promoted recovery of normal human cells after low-dose FA. Our results revealed a major role of the KAT5-ATM axis in protection of replicating chromatin against damage by the endogenous carcinogen FA. PMID:26420831

  3. 49 CFR 193.2915 - Alternative power sources.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Alternative power sources. 193.2915 Section 193.2915 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS... GAS FACILITIES: FEDERAL SAFETY STANDARDS Security § 193.2915 Alternative power sources. An alternative...

  4. 49 CFR 193.2515 - Investigations of failures.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Investigations of failures. 193.2515 Section 193.2515 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS... GAS FACILITIES: FEDERAL SAFETY STANDARDS Operations § 193.2515 Investigations of failures. (a) Each...

  5. 49 CFR 193.2515 - Investigations of failures.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Investigations of failures. 193.2515 Section 193.2515 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS... GAS FACILITIES: FEDERAL SAFETY STANDARDS Operations § 193.2515 Investigations of failures. (a) Each...

  6. 49 CFR 193.2515 - Investigations of failures.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Investigations of failures. 193.2515 Section 193.2515 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS... GAS FACILITIES: FEDERAL SAFETY STANDARDS Operations § 193.2515 Investigations of failures. (a) Each...

  7. 49 CFR 193.2515 - Investigations of failures.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Investigations of failures. 193.2515 Section 193.2515 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS... GAS FACILITIES: FEDERAL SAFETY STANDARDS Operations § 193.2515 Investigations of failures. (a) Each...

  8. Tyrosine 370 phosphorylation of ATM positively regulates DNA damage response

    PubMed Central

    Lee, Hong-Jen; Lan, Li; Peng, Guang; Chang, Wei-Chao; Hsu, Ming-Chuan; Wang, Ying-Nai; Cheng, Chien-Chia; Wei, Leizhen; Nakajima, Satoshi; Chang, Shih-Shin; Liao, Hsin-Wei; Chen, Chung-Hsuan; Lavin, Martin; Ang, K Kian; Lin, Shiaw-Yih; Hung, Mien-Chie

    2015-01-01

    Ataxia telangiectasia mutated (ATM) mediates DNA damage response by controling irradiation-induced foci formation, cell cycle checkpoint, and apoptosis. However, how upstream signaling regulates ATM is not completely understood. Here, we show that upon irradiation stimulation, ATM associates with and is phosphorylated by epidermal growth factor receptor (EGFR) at Tyr370 (Y370) at the site of DNA double-strand breaks. Depletion of endogenous EGFR impairs ATM-mediated foci formation, homologous recombination, and DNA repair. Moreover, pretreatment with an EGFR kinase inhibitor, gefitinib, blocks EGFR and ATM association, hinders CHK2 activation and subsequent foci formation, and increases radiosensitivity. Thus, we reveal a critical mechanism by which EGFR directly regulates ATM activation in DNA damage response, and our results suggest that the status of ATM Y370 phosphorylation has the potential to serve as a biomarker to stratify patients for either radiotherapy alone or in combination with EGFR inhibition. PMID:25601159

  9. ATM function and its relationship with ATM gene mutations in chronic lymphocytic leukemia with the recurrent deletion (11q22.3-23.2).

    PubMed

    Jiang, Y; Chen, H-C; Su, X; Thompson, P A; Liu, X; Do, K-A; Wierda, W; Keating, M J; Plunkett, W

    2016-09-02

    Approximately 10-20% of chronic lymphocytic leukemia (CLL) patients exhibit del(11q22-23) before treatment, this cohort increases to over 40% upon progression following chemoimmunotherapy. The coding sequence of the DNA damage response gene, ataxia-telangiectasia-mutated (ATM), is contained in this deletion. The residual ATM allele is frequently mutated, suggesting a relationship between gene function and clinical response. To investigate this possibility, we sought to develop and validate an assay for the function of ATM protein in these patients. SMC1 (structural maintenance of chromosomes 1) and KAP1 (KRAB-associated protein 1) were found to be unique substrates of ATM kinase by immunoblot detection following ionizing radiation. Using a pool of eight fluorescence in situ hybridization-negative CLL samples as a standard, the phosphorylation of SMC1 and KAP1 from 46 del (11q22-23) samples was analyzed using normal mixture model-based clustering. This identified 13 samples (28%) that were deficient in ATM function. Targeted sequencing of the ATM gene of these samples, with reference to genomic DNA, revealed 12 somatic mutations and 15 germline mutations in these samples. No strong correlation was observed between ATM mutation and function. Therefore, mutation status may not be taken as an indicator of ATM function. Rather, a direct assay of the kinase activity should be used in the development of therapies.

  10. 49 CFR 193.2635 - Monitoring corrosion control.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Monitoring corrosion control. 193.2635 Section 193... GAS FACILITIES: FEDERAL SAFETY STANDARDS Maintenance § 193.2635 Monitoring corrosion control. Corrosion protection provided as required by this subpart must be periodically monitored to give early...

  11. 49 CFR 193.2635 - Monitoring corrosion control.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Monitoring corrosion control. 193.2635 Section 193... GAS FACILITIES: FEDERAL SAFETY STANDARDS Maintenance § 193.2635 Monitoring corrosion control. Corrosion protection provided as required by this subpart must be periodically monitored to give early...

  12. 49 CFR 193.2635 - Monitoring corrosion control.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Monitoring corrosion control. 193.2635 Section 193... GAS FACILITIES: FEDERAL SAFETY STANDARDS Maintenance § 193.2635 Monitoring corrosion control. Corrosion protection provided as required by this subpart must be periodically monitored to give early...

  13. 49 CFR 193.2635 - Monitoring corrosion control.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Monitoring corrosion control. 193.2635 Section 193... GAS FACILITIES: FEDERAL SAFETY STANDARDS Maintenance § 193.2635 Monitoring corrosion control. Corrosion protection provided as required by this subpart must be periodically monitored to give early...

  14. 49 CFR 37.193 - Interim service requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Interim service requirements. 37.193 Section 37.193 Transportation Office of the Secretary of Transportation TRANSPORTATION SERVICES FOR INDIVIDUALS WITH DISABILITIES (ADA) Over-the-Road Buses (OTRBs) § 37.193 Interim service requirements. (a) Until...

  15. 49 CFR 193.2057 - Thermal radiation protection.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Thermal radiation protection. 193.2057 Section 193... GAS FACILITIES: FEDERAL SAFETY STANDARDS Siting Requirements § 193.2057 Thermal radiation protection...) The thermal radiation distances must be calculated using Gas Technology Institute's (GTI) report or...

  16. 49 CFR 193.2057 - Thermal radiation protection.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Thermal radiation protection. 193.2057 Section 193... GAS FACILITIES: FEDERAL SAFETY STANDARDS Siting Requirements § 193.2057 Thermal radiation protection...) The thermal radiation distances must be calculated using Gas Technology Institute's (GTI) report or...

  17. 49 CFR 193.2057 - Thermal radiation protection.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Thermal radiation protection. 193.2057 Section 193... GAS FACILITIES: FEDERAL SAFETY STANDARDS Siting Requirements § 193.2057 Thermal radiation protection...) The thermal radiation distances must be calculated using Gas Technology Institute's (GTI) report or...

  18. ATM Is Required for the Prolactin-Induced HSP90-Mediated Increase in Cellular Viability and Clonogenic Growth After DNA Damage.

    PubMed

    Karayazi Atici, Ödül; Urbanska, Anna; Gopinathan, Sesha Gopal; Boutillon, Florence; Goffin, Vincent; Shemanko, Carrie S

    2018-02-01

    Prolactin (PRL) acts as a survival factor for breast cancer cells, but the PRL signaling pathway and the mechanism are unknown. Previously, we identified the master chaperone, heat shock protein 90 (HSP90) α, as a prolactin-Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) target gene involved in survival, and here we investigated the role of HSP90 in the mechanism of PRL-induced viability in response to DNA damage. The ataxia-telangiectasia mutated kinase (ATM) protein plays a critical role in the cellular response to double-strand DNA damage. We observed that PRL increased viability of breast cancer cells treated with doxorubicin or etoposide. The increase in cellular resistance is specific to the PRL receptor, because the PRL receptor antagonist, Δ1-9-G129R-hPRL, prevented the increase in viability. Two different HSP90 inhibitors, 17-allylamino-17-demethoxygeldanamycin and BIIB021, reduced the PRL-mediated increase in cell viability of doxorubicin-treated cells and led to a decrease in JAK2, ATM, and phosphorylated ATM protein levels. Inhibitors of JAK2 (G6) and ATM (KU55933) abolished the PRL-mediated increase in cell viability of DNA-damaged cells, supporting the involvement of each, as well as the crosstalk of ATM with the PRL pathway in the context of DNA damage. Drug synergism was detected between the ATM inhibitor (KU55933) and doxorubicin and between the HSP90 inhibitor (BIIB021) and doxorubicin. Short interfering RNA directed against ATM prevented the PRL-mediated increase in cell survival in two-dimensional cell culture, three-dimensional collagen gel cultures, and clonogenic cell survival, after doxorubicin treatment. Our results indicate that ATM contributes to the PRL-JAK2-STAT5-HSP90 pathway in mediating cellular resistance to DNA-damaging agents. Copyright © 2018 Endocrine Society.

  19. An HTRF® Assay for the Protein Kinase ATM.

    PubMed

    Adams, Phillip; Clark, Jonathan; Hawdon, Simon; Hill, Jennifer; Plater, Andrew

    2017-01-01

    Ataxia telangiectasia mutated (ATM) is a serine/threonine kinase that plays a key role in the regulation of DNA damage pathways and checkpoint arrest. In recent years, there has been growing interest in ATM as a therapeutic target due to its association with cancer cell survival following genotoxic stress such as radio- and chemotherapy. Large-scale targeted drug screening campaigns have been hampered, however, by technical issues associated with the production of sufficient quantities of purified ATM and the availability of a suitable high-throughput assay. Using a purified, functionally active recombinant ATM and one of its physiological substrates, p53, we have developed an in vitro FRET-based activity assay that is suitable for high-throughput drug screening.

  20. 28 CFR 115.193 - Audits of standards.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Audits of standards. 115.193 Section 115.193 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PRISON RAPE ELIMINATION ACT NATIONAL STANDARDS Standards for Lockups Audits § 115.193 Audits of standards. The agency shall conduct audits...

  1. 28 CFR 115.193 - Audits of standards.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Audits of standards. 115.193 Section 115.193 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PRISON RAPE ELIMINATION ACT NATIONAL STANDARDS Standards for Lockups Audits § 115.193 Audits of standards. The agency shall conduct audits...

  2. 28 CFR 115.193 - Audits of standards.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Audits of standards. 115.193 Section 115.193 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PRISON RAPE ELIMINATION ACT NATIONAL STANDARDS Standards for Lockups Audits § 115.193 Audits of standards. The agency shall conduct audits...

  3. 46 CFR 193.15-25 - Discharge outlets.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Discharge outlets. 193.15-25 Section 193.15-25 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS FIRE PROTECTION EQUIPMENT Carbon Dioxide Extinguishing Systems, Details § 193.15-25 Discharge outlets. (a) Discharge outlets...

  4. 46 CFR 193.15-25 - Discharge outlets.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Discharge outlets. 193.15-25 Section 193.15-25 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS FIRE PROTECTION EQUIPMENT Carbon Dioxide Extinguishing Systems, Details § 193.15-25 Discharge outlets. (a) Discharge outlets...

  5. 49 CFR 193.2631 - Internal corrosion control.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Internal corrosion control. 193.2631 Section 193... GAS FACILITIES: FEDERAL SAFETY STANDARDS Maintenance § 193.2631 Internal corrosion control. Each component that is subject to internal corrosive attack must be protected from internal corrosion by— (a...

  6. Absence of Wip1 partially rescues Atm deficiency phenotypes in mice

    PubMed Central

    Darlington, Yolanda; Nguyen, Thuy-Ai; Moon, Sung-Hwan; Herron, Alan; Rao, Pulivarthi; Zhu, Chengming; Lu, Xiongbin; Donehower, Lawrence A.

    2011-01-01

    Wildtype p53-Induced Phosphatase 1 (WIP1) is a serine/threonine phosphatase that dephosphorylates proteins in the ataxia telangiectasia mutated (ATM)-initiated DNA damage response pathway. WIP1 may play a homeostatic role in ATM signaling by returning the cell to a normal pre-stress state following completion of DNA repair. To better understand the effects of WIP1 on ATM signaling, we crossed Atm-deficient mice to Wip1-deficient mice and characterized phenotypes of the double knockout progeny. We hypothesized that the absence of Wip1 might rescue Atm deficiency phenotypes. Atm null mice, like ATM-deficient humans with the inherited syndrome ataxia telangiectasia, exhibit radiation sensitivity, fertility defects, and are T-cell lymphoma prone. Most double knockout mice were largely protected from lymphoma development and had a greatly extended lifespan compared to Atm null mice. Double knockout mice had increased p53 and H2AX phosphorylation and p21 expression compared to their Atm null counterparts, indicating enhanced p53 and DNA damage responses. Additionally, double knockout splenocytes displayed reduced chromosomal instability compared to Atm null mice. Finally, doubly null mice were partially rescued from infertility defects observed in Atm null mice. These results indicate that inhibition of WIP1 may represent a useful strategy for cancer treatment in general and A-T patients in particular. PMID:21765465

  7. 46 CFR 193.15-25 - Discharge outlets.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Discharge outlets. 193.15-25 Section 193.15-25 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS FIRE PROTECTION EQUIPMENT Carbon Dioxide and Clean Agent Extinguishing Systems, Details § 193.15-25 Discharge outlets. (a...

  8. 46 CFR 193.15-25 - Discharge outlets.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Discharge outlets. 193.15-25 Section 193.15-25 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS FIRE PROTECTION EQUIPMENT Carbon Dioxide and Clean Agent Extinguishing Systems, Details § 193.15-25 Discharge outlets. (a...

  9. 49 CFR 193.2703 - Design and fabrication.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Design and fabrication. 193.2703 Section 193.2703...: FEDERAL SAFETY STANDARDS Personnel Qualifications and Training § 193.2703 Design and fabrication. For the design and fabrication of components, each operator shall use— (a) With respect to design, persons who...

  10. 49 CFR 193.2613 - Auxiliary power sources.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... test must take into account the power needed to start up and simultaneously operate equipment that... 49 Transportation 3 2011-10-01 2011-10-01 false Auxiliary power sources. 193.2613 Section 193.2613...: FEDERAL SAFETY STANDARDS Maintenance § 193.2613 Auxiliary power sources. Each auxiliary power source must...

  11. 32 CFR 193.4 - Authorities and responsibilities.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 2 2013-07-01 2013-07-01 false Authorities and responsibilities. 193.4 Section 193.4 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS HIGHWAYS FOR NATIONAL DEFENSE § 193.4 Authorities and responsibilities. (a) The Secretary of the...

  12. 32 CFR 193.4 - Authorities and responsibilities.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 2 2011-07-01 2011-07-01 false Authorities and responsibilities. 193.4 Section 193.4 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS HIGHWAYS FOR NATIONAL DEFENSE § 193.4 Authorities and responsibilities. (a) The Secretary of the...

  13. 32 CFR 193.4 - Authorities and responsibilities.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 2 2012-07-01 2012-07-01 false Authorities and responsibilities. 193.4 Section 193.4 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS HIGHWAYS FOR NATIONAL DEFENSE § 193.4 Authorities and responsibilities. (a) The Secretary of the...

  14. ATM directs DNA damage responses and proteostasis via genetically separable pathways

    PubMed Central

    Lee, Ji-Hoon; Mand, Michael R.; Kao, Chung-Hsuan; Zhou, Yi; Ryu, Seung W.; Richards, Alicia L.; Coon, Joshua J.; Paull, Tanya T.

    2018-01-01

    The protein kinase ATM is a master regulator of the DNA damage response but also responds directly to oxidative stress. Loss of ATM causes Ataxia telangiectasia, a neurodegenerative disorder with pleiotropic symptoms that include cerebellar dysfunction, cancer, diabetes, and premature aging. Here, we genetically separated DNA damage activation of ATM from oxidative activation using separation-of-function mutations. We found that deficiency in ATM activation by Mre11-Rad50-Nbs1 and DNA double-strand breaks resulted in loss of cell viability, checkpoint activation, and DNA end resection in response to DNA damage. In contrast, loss of oxidative activation of ATM had minimal effects on DNA damage-related outcomes but blocked ATM-mediated initiation of checkpoint responses after oxidative stress and resulted in deficiencies in mitochondrial function and autophagy. In addition, expression of ATM lacking oxidative activation generates widespread protein aggregation. These results indicate a direct relationship between the mechanism of ATM activation and its effects on cellular metabolism and DNA damage responses in human cells and implicates ATM in the control of protein homeostasis. PMID:29317520

  15. Identification of ATM Protein Kinase Phosphorylation Sites by Mass Spectrometry.

    PubMed

    Graham, Mark E; Lavin, Martin F; Kozlov, Sergei V

    2017-01-01

    ATM (ataxia-telangiectasia mutated) protein kinase is a key regulator of cellular responses to DNA damage and oxidative stress. DNA damage triggers complex cascade of signaling events leading to numerous posttranslational modification on multitude of proteins. Understanding the regulation of ATM kinase is therefore critical not only for understanding the human genetic disorder ataxia-telangiectasia and potential treatment strategies, but essential for deciphering physiological responses of cells to stress. These responses play an important role in carcinogenesis, neurodegeneration, and aging. We focus here on the identification of DNA damage inducible ATM phosphorylation sites to understand the importance of autophosphorylation in the mechanism of ATM kinase activation. We demonstrate the utility of using immunoprecipitated ATM in quantitative LC-MS/MS workflow with stable isotope dimethyl labeling of ATM peptides for identification of phosphorylation sites.

  16. Prevalence of deleterious ATM germline mutations in gastric cancer patients.

    PubMed

    Huang, Dong-Sheng; Tao, Hou-Quan; He, Xu-Jun; Long, Ming; Yu, Sheng; Xia, Ying-Jie; Wei, Zhang; Xiong, Zikai; Jones, Sian; He, Yiping; Yan, Hai; Wang, Xiaoyue

    2015-12-01

    Besides CDH1, few hereditary gastric cancer predisposition genes have been previously reported. In this study, we discovered two germline ATM mutations (p.Y1203fs and p.N1223S) in a Chinese family with a history of gastric cancer by screening 83 cancer susceptibility genes. Using a published exome sequencing dataset, we found deleterious germline mutations of ATM in 2.7% of 335 gastric cancer patients of different ethnic origins. The frequency of deleterious ATM mutations in gastric cancer patients is significantly higher than that in general population (p=0.0000435), suggesting an association of ATM mutations with gastric cancer predisposition. We also observed biallelic inactivation of ATM in tumors of two gastric cancer patients. Further evaluation of ATM mutations in hereditary gastric cancer will facilitate genetic testing and risk assessment.

  17. 46 CFR 193.10-5 - Fire pumps.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Fire pumps. 193.10-5 Section 193.10-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS FIRE PROTECTION EQUIPMENT Fire Main System, Details § 193.10-5 Fire pumps. (a) Vessels shall be equipped with independently...

  18. ICRF fast wave current drive and mode conversion current drive in EAST tokamak

    NASA Astrophysics Data System (ADS)

    Yin, L.; Yang, C.; Gong, X. Y.; Lu, X. Q.; Du, D.; Chen, Y.

    2017-10-01

    Fast wave in the ion-cyclotron resonance frequency (ICRF) range is a promising candidate for non-inductive current drive (CD), which is essential for long pulse and high performance operation of tokamaks. A numerical study on the ICRF fast wave current drive (FWCD) and mode-conversion current drive (MCCD) in the Experimental Advanced Superconducting Tokamak (EAST) is carried out by means of the coupled full wave and Ehst-Karney parameterization methods. The results show that FWCD efficiency is notable in two frequency regimes, i.e., f ≥ 85 MHz and f = 50-65 MHz, where ion cyclotron absorption is effectively avoided, and the maximum on-axis driven current per unit power can reach 120 kA/MW. The sensitivity of the CD efficiency to the minority ion concentration is confirmed, owing to fast wave mode conversion, and the peak MCCD efficiency is reached for 22% minority-ion concentration. The effects of the wave-launch position and the toroidal wavenumber on the efficiency of current drive are also investigated.

  19. Multimedia Applications in Heterogeneous Internet/ATM Environments.

    ERIC Educational Resources Information Center

    Wolf, Lars C.

    1999-01-01

    Discussion of multimedia systems focuses on interaction approaches for the quality of service (QoS) architectures developed for the Internet and for asynchronous transfer mode (ATM). Highlights include interactions, videoconferencing, video on demand, a comparison of the ATM and IntServ QoS architectures, interaction models, and subordination…

  20. Quantitative and Dynamic Imaging of ATM Kinase Activity.

    PubMed

    Nyati, Shyam; Young, Grant; Ross, Brian Dale; Rehemtulla, Alnawaz

    2017-01-01

    Ataxia telangiectasia mutated (ATM) is a serine/threonine kinase critical to the cellular DNA-damage response, including DNA double-strand breaks (DSBs). ATM activation results in the initiation of a complex cascade of events facilitating DNA damage repair, cell cycle checkpoint control, and survival. Traditionally, protein kinases have been analyzed in vitro using biochemical methods (kinase assays using purified proteins or immunological assays) requiring a large number of cells and cell lysis. Genetically encoded biosensors based on optical molecular imaging such as fluorescence or bioluminescence have been developed to enable interrogation of kinase activities in live cells with a high signal to background. We have genetically engineered a hybrid protein whose bioluminescent activity is dependent on the ATM-mediated phosphorylation of a substrate. The engineered protein consists of the split luciferase-based protein complementation pair with a CHK2 (a substrate for ATM kinase activity) target sequence and a phospho-serine/threonine-binding domain, FHA2, derived from yeast Rad53. Phosphorylation of the serine residue within the target sequence by ATM would lead to its interaction with the phospho-serine-binding domain, thereby preventing complementation of the split luciferase pair and loss of reporter activity. Bioluminescence imaging of reporter expressing cells in cultured plates or as mouse xenografts provides a quantitative surrogate for ATM kinase activity and therefore the cellular DNA damage response in a noninvasive, dynamic fashion.

  1. Early deployment of ATMS/ATIS for metropolitan Detroit

    DOT National Transportation Integrated Search

    1994-09-26

    The Michigan Department of Transportation (MDOT) is currently planning for the expansion of their current Advanced Traffic Management and Advanced Traveler Information Systems (ATMS and ATIS, respectively). Current ATMS and ATIS coverage include 3...

  2. TP53 and ATM mRNA expression in skin and skeletal muscle after low-level laser exposure.

    PubMed

    Guedes de Almeida, Luciana; Sergio, Luiz Philippe da Silva; de Paoli, Flavia; Mencalha, Andre Luiz; da Fonseca, Adenilson de Souza

    2017-08-01

    Low-level lasers are widespread in regenerative medicine, but the molecular mechanisms involved in their biological effects are not fully understood, particularly those on DNA stability. Therefore, this study aimed to investigate mRNA expression of genes related to DNA genomic stability in skin and skeletal muscle tissue from Wistar rats exposed to low-level red and infrared lasers. For this, TP53 (Tumor Protein 53) and ATM (Ataxia Telangiectasia Mutated gene) mRNA expressions were evaluated by real-time quantitative PCR (RT-qPCR) technique 24 hours after low-level red and infrared laser exposure. Our data showed that relative TP53 mRNA expression was not significantly altered in both tissues exposed to lasers. For ATM, relative mRNA expression in skin tissue was not significantly altered, but in muscle tissue, laser exposure increased relative ATM mRNA expression. Low-level red and infrared laser radiations alter ATM mRNA expression related to DNA stability in skeletal muscle tissue.

  3. Absence of ERK5/MAPK7 delays tumorigenesis in Atm-/- mice.

    PubMed

    Granados-Jaén, Alba; Angulo-Ibáñez, Maria; Rovira-Clavé, Xavier; Gamez, Celina Paola Vasquez; Soriano, Francesc X; Reina, Manuel; Espel, Enric

    2016-11-15

    Ataxia-telangiectasia mutated (ATM) is a cell cycle checkpoint kinase that upon activation by DNA damage leads to cell cycle arrest and DNA repair or apoptosis. The absence of Atm or the occurrence of loss-of-function mutations in Atm predisposes to tumorigenesis. MAPK7 has been implicated in numerous types of cancer with pro-survival and pro-growth roles in tumor cells, but its functional relation with tumor suppressors is not clear. In this study, we show that absence of MAPK7 delays death due to spontaneous tumor development in Atm-/- mice. Compared with Atm-/- thymocytes, Mapk7-/-Atm-/- thymocytes exhibited an improved response to DNA damage (increased phosphorylation of H2AX) and a restored apoptotic response after treatment of mice with ionizing radiation. These findings define an antagonistic function of ATM and MAPK7 in the thymocyte response to DNA damage, and suggest that the lack of MAPK7 inhibits thymic lymphoma growth in Atm-/- mice by partially restoring the DNA damage response in thymocytes.

  4. 46 CFR 193.10-5 - Fire pumps.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... pressures specified in § 193.10-5(i)(1)(i). (2) Remote control of fire pumps. (i) At least one fire pump must be capable of remote activation and control. (ii) If the fire pump is in a continuously manned... 46 Shipping 7 2011-10-01 2011-10-01 false Fire pumps. 193.10-5 Section 193.10-5 Shipping COAST...

  5. ATM directs DNA damage responses and proteostasis via genetically separable pathways.

    PubMed

    Lee, Ji-Hoon; Mand, Michael R; Kao, Chung-Hsuan; Zhou, Yi; Ryu, Seung W; Richards, Alicia L; Coon, Joshua J; Paull, Tanya T

    2018-01-09

    The protein kinase ATM is a master regulator of the DNA damage response but also responds directly to oxidative stress. Loss of ATM causes ataxia telangiectasia, a neurodegenerative disorder with pleiotropic symptoms that include cerebellar dysfunction, cancer, diabetes, and premature aging. We genetically separated the activation of ATM by DNA damage from that by oxidative stress using separation-of-function mutations. We found that deficient activation of ATM by the Mre11-Rad50-Nbs1 complex and DNA double-strand breaks resulted in loss of cell viability, checkpoint activation, and DNA end resection in response to DNA damage. In contrast, loss of oxidative activation of ATM had minimal effects on DNA damage-related outcomes but blocked ATM-mediated initiation of checkpoint responses after oxidative stress and resulted in deficiencies in mitochondrial function and autophagy. In addition, expression of a variant ATM incapable of activation by oxidative stress resulted in widespread protein aggregation. These results indicate a direct relationship between the mechanism of ATM activation and its effects on cellular metabolism and DNA damage responses in human cells and implicate ATM in the control of protein homeostasis. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  6. Kinase-dead ATM protein causes genomic instability and early embryonic lethality in mice.

    PubMed

    Yamamoto, Kenta; Wang, Yunyue; Jiang, Wenxia; Liu, Xiangyu; Dubois, Richard L; Lin, Chyuan-Sheng; Ludwig, Thomas; Bakkenist, Christopher J; Zha, Shan

    2012-08-06

    Ataxia telangiectasia (A-T) mutated (ATM) kinase orchestrates deoxyribonucleic acid (DNA) damage responses by phosphorylating numerous substrates implicated in DNA repair and cell cycle checkpoint activation. A-T patients and mouse models that express no ATM protein undergo normal embryonic development but exhibit pleiotropic DNA repair defects. In this paper, we report that mice carrying homozygous kinase-dead mutations in Atm (Atm(KD/KD)) died during early embryonic development. Atm(KD/-) cells exhibited proliferation defects and genomic instability, especially chromatid breaks, at levels higher than Atm(-/-) cells. Despite this increased genomic instability, Atm(KD/-) lymphocytes progressed through variable, diversity, and joining recombination and immunoglobulin class switch recombination, two events requiring nonhomologous end joining, at levels comparable to Atm(-/-) lymphocytes. Together, these results reveal an essential function of ATM during embryogenesis and an important function of catalytically inactive ATM protein in DNA repair.

  7. Scenarios for control and data flows in multiprotocol over ATM

    NASA Astrophysics Data System (ADS)

    Kujoory, Ali

    1997-10-01

    The multiprotocol over ATM (MPOA), specified by the ATM Forum, provides an architecture for transfer of Internetwork layer packets (Layer 3 datagram such as IP, IPX) over ATM subnets or across the emulated LANs. MPOA provides shortcuts that bypass routers to avoid router bottlenecks. It is a grand union of some of the existing standards such as LANE by the ATM Forum, NHRP by the IETF, and the Q.2931 by ITU. The intent of this paper is to clarify the data flows between pairs of source and destination hosts in an MPOA system. It includes scenarios for both the intra- and inter-subnet flows between different pairs of MPOA end-systems. The intrasubnet flows simply use LANE for address resolution or data transfer. The inter-subnet flows may use a default path for short-lived flows or a shortcut for long-lived flows. The default path uses the LANE and router capabilities. The shortcut path uses LANE plus NHRP for ATM address resoluton. An ATM virtual circuit is established before the data transfer. This allows efficient transfer of internetwork layer packets over ATM for real-time applications.

  8. 49 CFR 193.2321 - Nondestructive tests.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Nondestructive tests. 193.2321 Section 193.2321 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES...

  9. 49 CFR 193.2509 - Emergency procedures.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Emergency procedures. 193.2509 Section 193.2509 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES...

  10. 49 CFR 193.2633 - Interference currents.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Interference currents. 193.2633 Section 193.2633 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES...

  11. 49 CFR 193.2303 - Construction acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Construction acceptance. 193.2303 Section 193.2303 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES...

  12. 49 CFR 193.2609 - Support systems.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Support systems. 193.2609 Section 193.2609 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES...

  13. 49 CFR 193.2611 - Fire protection.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Fire protection. 193.2611 Section 193.2611 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES...

  14. 49 CFR 193.2521 - Operating records.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Operating records. 193.2521 Section 193.2521 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES...

  15. 49 CFR 193.2637 - Remedial measures.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Remedial measures. 193.2637 Section 193.2637 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES...

  16. 49 CFR 193.2625 - Corrosion protection.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Corrosion protection. 193.2625 Section 193.2625 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES...

  17. 49 CFR 193.2607 - Foreign material.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Foreign material. 193.2607 Section 193.2607 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES...

  18. 49 CFR 193.2605 - Maintenance procedures.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Maintenance procedures. 193.2605 Section 193.2605 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES...

  19. 49 CFR 193.2519 - Communication systems.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Communication systems. 193.2519 Section 193.2519 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES...

  20. Simplified management of ATM traffic

    NASA Astrophysics Data System (ADS)

    Luoma, Marko; Ilvesmaeki, Mika

    1997-10-01

    ATM has been under a thorough standardization process for more than ten years. Looking at it now, what have we achieved during this time period? Originally ATM was meant to be an easy and efficient protocol enabling varying services over a single network. What it is turning to be it `yet another ISDN'--network full of hopes and promises but too difficult to implement and expensive to market. The fact is that more and more `nice features' are implemented on the cost of overloading network with hard management procedures. Therefore we need to adopt a new approach. This approach keeps a strong reminder on `what is necessary.' This paper presents starting points for an alternative approach to the traffic management. We refer to this approach as `the minimum management principle.' Choosing of the suitable service classes for the ATM network is made difficult by the fact that the more services one implements the more management he needs. This is especially true for the variable bit rate connections that are usually treated based on the stochastic models. Stochastic model, at its best, can only reveal momentary characteristics in the traffic stream not the long range behavior of it. Our assumption is that ATM will move towards Internet in the sense that strict values for quality make little or no sense in the future. Therefore stochastic modeling of variable bit rate connections seems to be useless. Nevertheless we see that some traffic needs to have strict guarantees and that the only economic way of doing so is to use PCR allocation.

  1. A Complete Bank of Optical Images of the ICRF QSOs

    NASA Astrophysics Data System (ADS)

    Humberto Andrei, Alexandre; Taris, Francois; Anton, Sonia; Bourda, Geraldine; Damljanovic, Goran; Souchay, Jean; Vieira Martins, Roberto; Pursimo, Tapio; Barache, Christophe; Nepomuceno da Silva Neto, Dario; Fernandes Coelho, Bruno David

    2015-08-01

    We have been developing a systematic effort to collect good quality images of the optical counterpart of ICRF sources, in particular for those that have been regularly radio surveyed either for future implementation at high frequencies and/or those that will be the link sources between the ICRF and the Gaia CRF. Observations have been taken at the LNA/Brazil, CASLEO/Argentina, NOT/Spain, LFOA/Austria, Rozhen/Bulgária, and ASV/Serbia. In complement images were collected from the SDSS. As a step to implement such image data bank and make it publicly available through the IERS service we present its description, that comprises for each source the number of measurements, filter, pixel scale, size of field, and seeing at each observation. The photometry analysis is centered on the morphology, since there remain still cases in which the host galaxy is overwhelming, and many cases in which the host asks for a non-stellar PSF modeling. On basis of the neighbor stars we assign magnitudes and variability whenever possible. Finally, assisted by previous literature, the redshift and luminosity are used to derive astrophysical quantities, in special the absolute magnitude, SED and spectral index. Moreover, since Gaia will not obtain direct images of the observed sources, the morphology and magnitude becomes useful as templates onto which assembling and interpreting the one-dimensional and uncontinuous line spread function samplings that will be delivered by Gaia for each QSO.

  2. 49 CFR 193.2321 - Nondestructive tests.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Nondestructive tests. 193.2321 Section 193.2321 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES: FEDERAL SAFETY STANDARDS...

  3. 49 CFR 193.2321 - Nondestructive tests.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Nondestructive tests. 193.2321 Section 193.2321 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES: FEDERAL SAFETY STANDARDS...

  4. Measurement of fast minority /sub 3/He/sup + +/ energy distribution during ICRF heating

    DOEpatents

    Post, D.E. Jr.; Grisham, L.R.; Medley, S.S.

    A method and means for measuring the fast /sub 3/He/sup + +/ distribution during /sub 3/He/sup + +/ minority Ion Cyclotron Resonance Frequency (ICRF) heating is disclosed. The present invention involves the use of 10 to 100 keV beams of neutral helium atoms to neutralize the fast /sub 3/He/sup + +/ ions in a heated plasma by double charge exchange (/sub 3/He/sup + +/ + /sub 4/He/sup 0/ ..-->.. /sub 3/He/sup 0/ + /sub 4/He/sup + +/). The neutralized fast /sub 3/He/sup 0/ atoms then escape from the hot plasma confined by a magnetic field and are detected by conventional neutral particle analyzing means. This technique permits the effectiveness of the coupling of the ion cyclotron waves to the /sub 3/He/sup + +/ minority ions to be accurately measured. The present invention is particularly adapted for use in evaluating the effectiveness of the intermediate coupling between the RF heating and the /sub 3/He/sup + +/ in an energetic toroidal plasma.

  5. ATM-Deficient Colorectal Cancer Cells Are Sensitive to the PARP Inhibitor Olaparib.

    PubMed

    Wang, Chen; Jette, Nicholas; Moussienko, Daniel; Bebb, D Gwyn; Lees-Miller, Susan P

    2017-04-01

    The ataxia telangiectasia mutated (ATM) protein kinase plays a central role in the cellular response to DNA damage. Loss or inactivation of both copies of the ATM gene (ATM) leads to ataxia telangiectasia, a devastating childhood condition characterized by neurodegeneration, immune deficiencies, and cancer predisposition. ATM is also absent in approximately 40% of mantle cell lymphomas (MCLs), and we previously showed that MCL cell lines with loss of ATM are sensitive to poly-ADP ribose polymerase (PARP) inhibitors. Next-generation sequencing of patient tumors has revealed that ATM is altered in many human cancers including colorectal, lung, prostate, and breast. Here, we show that the colorectal cancer cell line SK-CO-1 lacks detectable ATM protein expression and is sensitive to the PARP inhibitor olaparib. Similarly, HCT116 colorectal cancer cells with shRNA depletion of ATM are sensitive to olaparib, and depletion of p53 enhances this sensitivity. Moreover, HCT116 cells are sensitive to olaparib in combination with the ATM inhibitor KU55933, and sensitivity is enhanced by deletion of p53. Together our studies suggest that PARP inhibitors may have potential for treating colorectal cancer with ATM dysfunction and/or colorectal cancer with mutation of p53 when combined with an ATM kinase inhibitor. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. ATM LAN Emulation: Getting from Here to There.

    ERIC Educational Resources Information Center

    Learn, Larry L., Ed.

    1995-01-01

    Discusses current LAN (local area network) configuration and explains ATM (asynchronous transfer mode) as the future telecommunications transport. Highlights include LAN emulation, which enables the interconnection of legacy LANs and the new ATM environment; virtual LANs; broadcast servers; and standards. (LRW)

  7. ATM, radiation, and the risk of second primary breast cancer.

    PubMed

    Bernstein, Jonine L; Concannon, Patrick

    2017-10-01

    It was first suggested more than 40 years ago that heterozygous carriers for the human autosomal recessive disorder Ataxia-Telangiectasia (A-T) might also be at increased risk for cancer. Subsequent studies have identified the responsible gene, Ataxia-Telangiectasia Mutated (ATM), characterized genetic variation at this locus in A-T and a variety of different cancers, and described the functions of the ATM protein with regard to cellular DNA damage responses. However, an overall model of how ATM contributes to cancer risk, and in particular, the role of DNA damage in this process, remains lacking. This review considers these questions in the context of contralateral breast cancer (CBC). Heterozygous carriers of loss of function mutations in ATM that are A-T causing, are at increased risk of breast cancer. However, examination of a range of genetic variants, both rare and common, across multiple cancers, suggests that ATM may have additional effects on cancer risk that are allele-dependent. In the case of CBC, selected common alleles at ATM are associated with a reduced incidence of CBC, while other rare and predicted deleterious variants may act jointly with radiation exposure to increase risk. Further studies that characterize germline and somatic ATM mutations in breast cancer and relate the detected genetic changes to functional outcomes, particularly with regard to radiation responses, are needed to gain a complete picture of the complex relationship between ATM, radiation and breast cancer.

  8. Regulation of the DNA damage response by DNA-PKcs inhibitory phosphorylation of ATM

    PubMed Central

    Zhou, Yi; Lee, Ji-Hoon; Jiang, Wenxia; Crowe, Jennie L; Zha, Shan; Paull, Tanya T.

    2017-01-01

    SUMMARY Ataxia-Telangiectasia Mutated (ATM) regulates the DNA damage response as well as DNA double-strand break repair through homologous recombination. Here we show that ATM is hyperactive when the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is chemically inhibited or when the DNA-PKcs gene is deleted in human cells. Pre-incubation of ATM protein with active DNA-PKcs also significantly reduces ATM activity in vitro. We characterize several phosphorylation sites in ATM that are targets of DNA-PKcs and show that phospho-mimetic mutations at these residues significantly inhibit ATM activity and impair ATM signaling upon DNA damage. In contrast, phospho-blocking mutations at one cluster of sites increase the frequency of apoptosis during normal cell growth. DNA-PKcs, which is integral to the non-homologous end joining pathway, thus negatively regulates ATM activity through phosphorylation of ATM. These observations illuminate an important regulatory mechanism for ATM that also controls DNA repair pathway choice. PMID:27939942

  9. Regulation of the DNA Damage Response by DNA-PKcs Inhibitory Phosphorylation of ATM.

    PubMed

    Zhou, Yi; Lee, Ji-Hoon; Jiang, Wenxia; Crowe, Jennie L; Zha, Shan; Paull, Tanya T

    2017-01-05

    Ataxia-telangiectasia mutated (ATM) regulates the DNA damage response as well as DNA double-strand break repair through homologous recombination. Here we show that ATM is hyperactive when the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is chemically inhibited or when the DNA-PKcs gene is deleted in human cells. Pre-incubation of ATM protein with active DNA-PKcs also significantly reduces ATM activity in vitro. We characterize several phosphorylation sites in ATM that are targets of DNA-PKcs and show that phospho-mimetic mutations at these residues significantly inhibit ATM activity and impair ATM signaling upon DNA damage. In contrast, phospho-blocking mutations at one cluster of sites increase the frequency of apoptosis during normal cell growth. DNA-PKcs, which is integral to the non-homologous end joining pathway, thus negatively regulates ATM activity through phosphorylation of ATM. These observations illuminate an important regulatory mechanism for ATM that also controls DNA repair pathway choice. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Health ATMs in Saudi Arabia: A Perspective.

    PubMed

    Aldosari, Bakheet

    2017-06-01

    Health ATMs are terminals which are connected to a centrally located database storing patients' electronic healthcare records (EHR). These machines are capable of collecting information in a far superior fashion than humans and are also able to rectify obsolete data in a manner that humans are generally not inclined to. The main goal of this study is to assess the importance of adopting health ATMs in the Kingdom of Saudi Arabia (KSA), which can improve the confidence of patients, reward health self-management, and achieve positive health outcomes through their easy-to-use applications that are secure and accessible through various devices. Strength, Weakness, Opportunity, and Threat (SWOT) analysis was used to assess the efficiency of adopting health ATMs in KSA and reveal the said characteristics. Three focus groups assembled in the cities of Riyadh, Jeddah and Dammam during the period 2013-2014. The groups consisted of individuals experienced in the function of health ATMs. It was found that the sector possessed a number of strengths that would help it in reaching the goals outlined therein, thereby achieving successful outcomes. Health ATMs could be a promising new advancement in the field of health if the project were to be planned and implemented correctly. Their benefits would consequently reach organizational and national levels. It is, therefore, crucial to educate the project managers about the benefits of learning from others as well as educating them about the needs and the requirements of the concerned organization.

  11. FACET: Future ATM Concepts Evaluation Tool

    NASA Technical Reports Server (NTRS)

    Bilmoria, Karl D.; Banavar, Sridhar; Chatterji, Gano B.; Sheth, Kapil S.; Grabbe, Shon

    2000-01-01

    FACET (Future ATM Concepts Evaluation Tool) is an Air Traffic Management research tool being developed at the NASA Ames Research Center. This paper describes the design, architecture and functionalities of FACET. The purpose of FACET is to provide E simulation environment for exploration, development and evaluation of advanced ATM concepts. Examples of these concepts include new ATM paradigms such as Distributed Air-Ground Traffic Management, airspace redesign and new Decision Support Tools (DSTs) for controllers working within the operational procedures of the existing air traffic control system. FACET is currently capable of modeling system-wide en route airspace operations over the contiguous United States. Airspace models (e.g., Center/sector boundaries, airways, locations of navigation aids and airports) are available from databases. A core capability of FACET is the modeling of aircraft trajectories. Using round-earth kinematic equations, aircraft can be flown along flight plan routes or great circle routes as they climb, cruise and descend according to their individual aircraft-type performance models. Performance parameters (e.g., climb/descent rates and speeds, cruise speeds) are obtained from data table lookups. Heading, airspeed and altitude-rate dynamics are also modeled. Additional functionalities will be added as necessary for specific applications. FACET software is written in Java and C programming languages. It is platform-independent, and can be run on a variety of computers. FACET has been designed with a modular software architecture to enable rapid integration of research prototype implementations of new ATM concepts. There are several advanced ATM concepts that are currently being implemented in FACET airborne separation assurance, dynamic density predictions, airspace redesign (re-sectorization), benefits of a controller DST for direct-routing, and the integration of commercial space transportation system operations into the U.S. National

  12. ATM regulates NF-κB-dependent immediate-early genes via RelA Ser 276 phosphorylation coupled to CDK9 promoter recruitment

    PubMed Central

    Fang, Ling; Choudhary, Sanjeev; Zhao, Yingxin; Edeh, Chukwudi B; Yang, Chunying; Boldogh, Istvan; Brasier, Allan R.

    2014-01-01

    Ataxia-telangiectasia mutated (ATM), a member of the phosphatidylinositol 3 kinase-like kinase family, is a master regulator of the double strand DNA break-repair pathway after genotoxic stress. Here, we found ATM serves as an essential regulator of TNF-induced NF-kB pathway. We observed that TNF exposure of cells rapidly induced DNA double strand breaks and activates ATM. TNF-induced ROS promote nuclear IKKγ association with ubiquitin and its complex formation with ATM for nuclear export. Activated cytoplasmic ATM is involved in the selective recruitment of the E3-ubiquitin ligase β-TrCP to phospho-IκBα proteosomal degradation. Importantly, ATM binds and activates the catalytic subunit of protein kinase A (PKAc), ribosmal S6 kinase that controls RelA Ser 276 phosphorylation. In ATM knockdown cells, TNF-induced RelA Ser 276 phosphorylation is significantly decreased. We further observed decreased binding and recruitment of the transcriptional elongation complex containing cyclin dependent kinase-9 (CDK9; a kinase necessary for triggering transcriptional elongation) to promoters of NF-κB-dependent immediate-early cytokine genes, in ATM knockdown cells. We conclude that ATM is a nuclear damage-response signal modulator of TNF-induced NF-κB activation that plays a key scaffolding role in IκBα degradation and RelA Ser 276 phosphorylation. Our study provides a mechanistic explanation of decreased innate immune response associated with A-T mutation. PMID:24957606

  13. 46 CFR 193.15-20 - Carbon dioxide storage.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Carbon dioxide storage. 193.15-20 Section 193.15-20 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS FIRE PROTECTION EQUIPMENT Carbon Dioxide Extinguishing Systems, Details § 193.15-20 Carbon dioxide storage. (a...

  14. 46 CFR 193.15-20 - Carbon dioxide storage.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Carbon dioxide storage. 193.15-20 Section 193.15-20 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS FIRE PROTECTION EQUIPMENT Carbon Dioxide Extinguishing Systems, Details § 193.15-20 Carbon dioxide storage. (a...

  15. IP over fiber technologies: ATM/POS/SDL

    NASA Astrophysics Data System (ADS)

    Jin, Depeng; Zeng, Lieguang

    2001-10-01

    The explosive growth of Internet traffic has created the need to transport IP over high-speed links such as fiber. Three main IP over fiber technologies have been developed: ATM, POS and SDL. As ATM has been widely researched and developed, this paper mainly discusses the POS and SDL. POS is a traditional mapping method of packets, and this paper presents the realization state machine of POS and analyzes the Probability of Packet Loss. SDL is a new framing protocol for variable/fixed length of packet, which extends the HEC-liking framing mechanism used in ATM. This paper analyzes this new protocol and gives the performance results such as MTTF and PFP. Finally, the comparison of POS and SDL is provided.

  16. 21 CFR 133.193 - Spiced, flavored standardized cheeses.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Spiced, flavored standardized cheeses. 133.193 Section 133.193 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Standardized Cheese and Related Products § 133.193 Spiced, flavored standardized cheeses. (a) Except as...

  17. 46 CFR 193.15-30 - Alarms.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Alarms. 193.15-30 Section 193.15-30 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS FIRE PROTECTION EQUIPMENT Carbon..., and the alarm shall depend on no source of power other than the carbon dioxide. ...

  18. Role of ATM in bystander signaling between human monocytes and lung adenocarcinoma cells.

    PubMed

    Ghosh, Somnath; Ghosh, Anu; Krishna, Malini

    2015-12-01

    The response of a cell or tissue to ionizing radiation is mediated by direct damage to cellular components and indirect damage mediated by radiolysis of water. Radiation affects both irradiated cells and the surrounding cells and tissues. The radiation-induced bystander effect is defined by the presence of biological effects in cells that were not themselves in the field of irradiation. To establish the contribution of the bystander effect in the survival of the neighboring cells, lung carcinoma A549 cells were exposed to gamma-irradiation, 2Gy. The medium from the irradiated cells was transferred to non-irradiated A549 cells. Irradiated A549 cells as well as non-irradiated A549 cells cultured in the presence of medium from irradiated cells showed decrease in survival and increase in γ-H2AX and p-ATM foci, indicating a bystander effect. Bystander signaling was also observed between different cell types. Phorbol-12-myristate-13-acetate (PMA)-stimulated and gamma-irradiated U937 (human monocyte) cells induced a bystander response in non-irradiated A549 (lung carcinoma) cells as shown by decreased survival and increased γ-H2AX and p-ATM foci. Non-stimulated and/or irradiated U937 cells did not induce such effects in non-irradiated A549 cells. Since ATM protein was activated in irradiated cells as well as bystander cells, it was of interest to understand its role in bystander effect. Suppression of ATM with siRNA in A549 cells completely inhibited bystander effect in bystander A549 cells. On the other hand suppression of ATM with siRNA in PMA stimulated U937 cells caused only a partial inhibition of bystander effect in bystander A549 cells. These results indicate that apart from ATM, some additional factor may be involved in bystander effect between different cell types. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. 49 CFR 193.2623 - Inspecting LNG storage tanks.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Inspecting LNG storage tanks. 193.2623 Section 193... GAS FACILITIES: FEDERAL SAFETY STANDARDS Maintenance § 193.2623 Inspecting LNG storage tanks. Each LNG storage tank must be inspected or tested to verify that each of the following conditions does not impair...

  20. 49 CFR 193.2623 - Inspecting LNG storage tanks.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Inspecting LNG storage tanks. 193.2623 Section 193... GAS FACILITIES: FEDERAL SAFETY STANDARDS Maintenance § 193.2623 Inspecting LNG storage tanks. Each LNG storage tank must be inspected or tested to verify that each of the following conditions does not impair...

  1. 49 CFR 193.2623 - Inspecting LNG storage tanks.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Inspecting LNG storage tanks. 193.2623 Section 193... GAS FACILITIES: FEDERAL SAFETY STANDARDS Maintenance § 193.2623 Inspecting LNG storage tanks. Each LNG storage tank must be inspected or tested to verify that each of the following conditions does not impair...

  2. Neurodegeneration in ataxia-telangiectasia: Multiple roles of ATM kinase in cellular homeostasis.

    PubMed

    Choy, Kay Rui; Watters, Dianne J

    2018-01-01

    Ataxia-telangiectasia (A-T) is characterized by neuronal degeneration, cancer, diabetes, immune deficiency, and increased sensitivity to ionizing radiation. A-T is attributed to the deficiency of the protein kinase coded by the ATM (ataxia-telangiectasia mutated) gene. ATM is a sensor of DNA double-strand breaks (DSBs) and signals to cell cycle checkpoints and the DNA repair machinery. ATM phosphorylates numerous substrates and activates many cell-signaling pathways. There has been considerable debate about whether a defective DNA damage response is causative of the neurological aspects of the disease. In proliferating cells, ATM is localized mainly in the nucleus; however, in postmitotic cells such as neurons, ATM is mostly cytoplasmic. Recent studies reveal an increasing number of roles for ATM in the cytoplasm, including activation by oxidative stress. ATM associates with organelles including mitochondria and peroxisomes, both sources of reactive oxygen species (ROS), which have been implicated in neurodegenerative diseases and aging. ATM is also associated with synaptic vesicles and has a role in regulating cellular homeostasis and autophagy. The cytoplasmic roles of ATM provide a new perspective on the neurodegenerative process in A-T. This review will examine the expanding roles of ATM in cellular homeostasis and relate these functions to the complex A-T phenotype. Developmental Dynamics 247:33-46, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  3. miR-193b Regulates Mcl-1 in Melanoma

    PubMed Central

    Chen, Jiamin; Zhang, Xiao; Lentz, Cindy; Abi-Daoud, Marie; Paré, Geneviève C.; Yang, Xiaolong; Feilotter, Harriet E.; Tron, Victor A.

    2011-01-01

    MicroRNAs play important roles in gene regulation, and their expression is frequently dysregulated in cancer cells. In a previous study, we reported that miR-193b represses cell proliferation and regulates cyclin D1 in melanoma cells, suggesting that miR-193b could act as a tumor suppressor. Herein, we demonstrate that miR-193b also down-regulates myeloid cell leukemia sequence 1 (Mcl-1) in melanoma cells. MicroRNA microarray profiling revealed that miR-193b is expressed at a significantly lower level in malignant melanoma than in benign nevi. Consistent with this, Mcl-1 is detected at a higher level in malignant melanoma than in benign nevi. In a survey of melanoma samples, the level of Mcl-1 is inversely correlated with the level of miR-193b. Overexpression of miR-193b in melanoma cells represses Mcl-1 expression. Previous studies showed that Mcl-1 knockdown cells are hypersensitive to ABT-737, a small-molecule inhibitor of Bcl-2, Bcl-XL, and Bcl-w. Similarly, overexpression of miR-193b restores ABT-737 sensitivity to ABT-737–resistant cells. Furthermore, the effect of miR-193b on the expression of Mcl-1 seems to be mediated by direct interaction between miR-193b and seed and seedless pairing sequences in the 3′ untranslated region of Mcl-1 mRNA. Thus, this study provides evidence that miR-193b directly regulates Mcl-1 and that down-regulation of miR-193b in vivo could be an early event in melanoma progression. PMID:21893020

  4. ATM Technology Adoption in U.S. Campus Networking.

    ERIC Educational Resources Information Center

    Yao, Engui; Perry, John F.; Anderson, Larry S.; Brook, R. Dan; Hare, R. Dwight; Moore, Arnold J.; Xu, Xiaohe

    This study examined the relationships between ATM (asynchronous transfer mode) adoption in universities and four organizational variables: university size, type, finances, and information processing maturity. Another purpose of the study was to identify the current status of ATM adoption in campus networking. Subjects were university domain LAN…

  5. 27 CFR 41.193 - Corporate documents.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2012-04-01 2011-04-01 true Corporate documents. 41.193... PROCESSED TOBACCO Tobacco Products Importers § 41.193 Corporate documents. Every corporation, before..., required by § 41.191, a true copy of the corporate charter or a certificate of corporate existence or...

  6. Characterisation of ATM mutations in Slavic Ataxia telangiectasia patients.

    PubMed

    Soukupova, Jana; Pohlreich, Petr; Seemanova, Eva

    2011-09-01

    Ataxia telangiectasia (AT) is a genomic instability syndrome characterised, among others, by progressive cerebellar degeneration, oculocutaneous telangiectases, immunodeficiency, elevated serum alpha-phetoprotein level, chromosomal breakage, hypersensitivity to ionising radiation and increased cancer risk. This autosomal recessive disorder is caused by mutations in the ataxia telangiectasia mutated (ATM) gene coding for serine/threonine protein kinase with a crucial role in response to DNA double-strand breaks. We characterised genotype and phenotype of 12 Slavic AT patients from 11 families. Mutation analysis included sequencing of the entire coding sequence, adjacent intron regions, 3'UTR and 5'UTR of the ATM gene and multiplex ligation-dependent probe amplification (MLPA) for the detection of large deletions/duplications at the ATM locus. The high incidence of new and individual mutations demonstrates a marked mutational heterogeneity of AT in the Czech Republic. Our data indicate that sequence analysis of the entire coding region of ATM is sufficient for a high detection rate of mutations in ATM and that MLPA analysis for the detection of deletions/duplications seems to be redundant in the Slavic population.

  7. 27 CFR 26.193 - Notification of tax liability.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Notification of tax liability. 26.193 Section 26.193 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE... Rico § 26.193 Notification of tax liability. (a) If the chemist of the Treasury of Puerto Rico finds...

  8. 27 CFR 24.193 - Conversion into still wine.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Conversion into still wine. 24.193 Section 24.193 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS WINE Production of Effervescent Wine § 24.193 Conversion into still wine...

  9. 27 CFR 24.193 - Conversion into still wine.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Conversion into still wine. 24.193 Section 24.193 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS WINE Production of Effervescent Wine § 24.193 Conversion into still wine...

  10. Health ATMs in Saudi Arabia: A Perspective

    PubMed Central

    Aldosari, Bakheet

    2017-01-01

    Background: Health ATMs are terminals which are connected to a centrally located database storing patients’ electronic healthcare records (EHR). These machines are capable of collecting information in a far superior fashion than humans and are also able to rectify obsolete data in a manner that humans are generally not inclined to. Objectives: The main goal of this study is to assess the importance of adopting health ATMs in the Kingdom of Saudi Arabia (KSA), which can improve the confidence of patients, reward health self-management, and achieve positive health outcomes through their easy-to-use applications that are secure and accessible through various devices. Methods: Strength, Weakness, Opportunity, and Threat (SWOT) analysis was used to assess the efficiency of adopting health ATMs in KSA and reveal the said characteristics. Three focus groups assembled in the cities of Riyadh, Jeddah and Dammam during the period 2013-2014. The groups consisted of individuals experienced in the function of health ATMs. Results: It was found that the sector possessed a number of strengths that would help it in reaching the goals outlined therein, thereby achieving successful outcomes. Conclusions: Health ATMs could be a promising new advancement in the field of health if the project were to be planned and implemented correctly. Their benefits would consequently reach organizational and national levels. It is, therefore, crucial to educate the project managers about the benefits of learning from others as well as educating them about the needs and the requirements of the concerned organization. PMID:28883680

  11. 50 CFR 19.3 - Relation to other laws.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 8 2011-10-01 2011-10-01 false Relation to other laws. 19.3 Section 19.3... PLANTS (CONTINUED) AIRBORNE HUNTING Introduction § 19.3 Relation to other laws. The exemptions to general... subpart B of this part) do not supersede, or authorize the violation of, other laws designed for the...

  12. 50 CFR 19.3 - Relation to other laws.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 9 2013-10-01 2013-10-01 false Relation to other laws. 19.3 Section 19.3... PLANTS (CONTINUED) AIRBORNE HUNTING Introduction § 19.3 Relation to other laws. The exemptions to general... subpart B of this part) do not supersede, or authorize the violation of, other laws designed for the...

  13. 46 CFR 193.15-20 - Carbon dioxide storage.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Carbon dioxide storage. 193.15-20 Section 193.15-20 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS FIRE PROTECTION EQUIPMENT Carbon Dioxide and Clean Agent Extinguishing Systems, Details § 193.15-20 Carbon dioxide storage. (a) Except as provided in...

  14. Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes

    PubMed Central

    Zhou, Kaixin; Bellenguez, Celine; Spencer, Chris CA; Bennett, Amanda J; Coleman, Ruth L; Tavendale, Roger; Hawley, Simon A.; Donnelly, Louise A; Schofield, Chris; Groves, Christopher J; Burch, Lindsay; Carr, Fiona; Strange, Amy; Freeman, Colin; Blackwell, Jenefer M; Bramon, Elvira; Brown, Matthew A; Casas, Juan P; Corvin, Aiden; Craddock, Nicholas; Deloukas, Panos; Dronov, Serge; Duncanson, Audrey; Edkins, Sarah; Gray, Emma; Hunt, Sarah; Jankowski, Janusz; Langford, Cordelia; Markus, Hugh S; Mathew, Christopher G; Plomin, Robert; Rautanen, Anna; Sawcer, Stephen J; Samani, Nilesh J; Trembath, Richard; Viswanathan, Ananth C; Wood, Nicholas W; Harries, Lorna W; Hattersley, Andrew T; Doney, Alex SF; Colhoun, Helen; Morris, Andrew D; Sutherland, Calum; Hardie, D. Grahame; Peltonen, Leena; McCarthy, Mark I; Holman, Rury R.; Palmer, Colin N.A.; Donnelly, Peter; Pearson, Ewan R

    2010-01-01

    Metformin is the most commonly used pharmacological therapy for type 2 diabetes. We carried out a GWA study on glycaemic response to metformin in 1024 Scottish patients with type 2 diabetes. Replication was in two cohorts consisting of 1783 Scottish patients and 1113 patients from the UK Prospective Diabetes Study. In a meta-analysis (n=3920) we observed an association (P=2.9 *10−9) for a SNP rs11212617 at a locus containing the ataxia telangiectasia mutated (ATM) gene with an odds ratio of 1.35 (95% CI 1.22 to 1.49) for treatment success. In a rat hepatoma cell line, inhibition of ATM with KU-55933 attenuated the phosphorylation and activation of AMPK in response to metformin. We conclude that ATM, a gene known to be involved in DNA repair and cell cycle control, plays a role in the effect of metformin upstream of AMPK, and variation in this gene alters glycaemic response to metformin. PMID:21186350

  15. miR-193b Regulates Mcl-1 in Melanoma.

    PubMed

    Chen, Jiamin; Zhang, Xiao; Lentz, Cindy; Abi-Daoud, Marie; Paré, Geneviève C; Yang, Xiaolong; Feilotter, Harriet E; Tron, Victor A

    2011-11-01

    MicroRNAs play important roles in gene regulation, and their expression is frequently dysregulated in cancer cells. In a previous study, we reported that miR-193b represses cell proliferation and regulates cyclin D1 in melanoma cells, suggesting that miR-193b could act as a tumor suppressor. Herein, we demonstrate that miR-193b also down-regulates myeloid cell leukemia sequence 1 (Mcl-1) in melanoma cells. MicroRNA microarray profiling revealed that miR-193b is expressed at a significantly lower level in malignant melanoma than in benign nevi. Consistent with this, Mcl-1 is detected at a higher level in malignant melanoma than in benign nevi. In a survey of melanoma samples, the level of Mcl-1 is inversely correlated with the level of miR-193b. Overexpression of miR-193b in melanoma cells represses Mcl-1 expression. Previous studies showed that Mcl-1 knockdown cells are hypersensitive to ABT-737, a small-molecule inhibitor of Bcl-2, Bcl-X(L), and Bcl-w. Similarly, overexpression of miR-193b restores ABT-737 sensitivity to ABT-737-resistant cells. Furthermore, the effect of miR-193b on the expression of Mcl-1 seems to be mediated by direct interaction between miR-193b and seed and seedless pairing sequences in the 3' untranslated region of Mcl-1 mRNA. Thus, this study provides evidence that miR-193b directly regulates Mcl-1 and that down-regulation of miR-193b in vivo could be an early event in melanoma progression. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  16. ATM is required for SOD2 expression and homeostasis within the mammary gland.

    PubMed

    Dyer, Lisa M; Kepple, Jessica D; Ai, Lingbao; Kim, Wan-Ju; Stanton, Virginia L; Reinhard, Mary K; Backman, Lindsey R F; Streitfeld, W Scott; Babu, Nivetha Ramesh; Treiber, Nicolai; Scharffetter-Kochanek, Karin; McKinnon, Peter J; Brown, Kevin D

    2017-12-01

    ATM activates the NF-κB transcriptional complex in response to genotoxic and oxidative stress. The purpose of this study was to examine if the NF-κB target gene and critical antioxidant SOD2 (MnSOD) in cultured mammary epithelium is also ATM-dependent, and what phenotypes arise from deletion of ATM and SOD2 within the mammary gland. SOD2 expression was studied in human mammary epithelial cells and MCF10A using RNAi to knockdown ATM or the NF-κB subunit RelA. To study ATM and SOD2 function in mammary glands, mouse lines containing Atm or Sod2 genes containing LoxP sites were mated with mice harboring Cre recombinase under the control of the whey acidic protein promoter. Quantitative PCR was used to measure gene expression, and mammary gland structure was studied using histology. SOD2 expression is ATM- and RelA-dependent, ATM knockdown renders cells sensitive to pro-oxidant exposure, and SOD mimetics partially rescue this sensitivity. Mice with germline deletion of Atm fail to develop mature mammary glands, but using a conditional knockout approach, we determined that Atm deletion significantly diminished the expression of Sod2. We also observed that these mice (termed Atm Δ/Δ ) displayed a progressive lactation defect as judged by reduced pup growth rate, aberrant lobulo-alveolar structure, diminished milk protein gene expression, and increased apoptosis within lactating glands. This phenotype appears to be linked to dysregulated Sod2 expression as mammary gland-specific deletion of Sod2 phenocopies defects observed in Atm Δ/Δ dams. We conclude that ATM is required to promote expression of SOD2 within the mammary epithelium, and that both ATM and SOD2 play a crucial role in mammary gland homeostasis.

  17. 49 CFR 193.2627 - Atmospheric corrosion control.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 193.2627 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES: FEDERAL SAFETY STANDARDS Maintenance § 193.2627 Atmospheric corrosion...

  18. Advisor-Teller Money Manager (ATM) Therapy for Substance Use Disorders

    PubMed Central

    Rosen, Marc I.; Rounsaville, Bruce J.; Ablondi, Karen; Black, Anne C.; Rosenheck, Robert A.

    2011-01-01

    Objective Patients with concomitant psychiatric and substance use disorders are commonly assigned representative payees or case managers to help manage their funds, but money management has not been conceptualized as a theory-based treatment. This randomized clinical trial was conducted to determine the effect of a money management–based therapy, advisor-teller money manager (ATM), on substance abuse or dependence. Methods Ninety patients at a community mental health center who had a history of cocaine or alcohol abuse or dependence were assessed after random assignment to 36 weeks of ATM (N=47) or a control condition in which use of a financial workbook was reviewed (N=43). Patients assigned to ATM were encouraged to deposit their funds into a third-party account, plan weekly expenditures, and negotiate monthly budgets. Substance use calendars and urine toxicology tests were collected every other week for 36 weeks and again 52 weeks after randomization. Results Patients assigned to ATM had significantly more negative toxicologies for cocaine metabolite over time than patients in the control group, and treating clinicians rated ATM patients as significantly more likely to be abstinent from illicit drugs. Self-reported abstinence from alcohol did not significantly differ between groups. Unexpectedly, patients assigned to ATM were more likely to be assigned a representative payee or a conservator than control participants during the follow-up period (ten of 47 versus two of 43). One patient in ATM assaulted the therapist when his check had not arrived. Conclusions ATM is an efficacious therapy for the treatment of cocaine abuse or dependence among people with concomitant psychiatric illness but requires protection of patient autonomy and staff safety. PMID:20592006

  19. Advisor-Teller Money Manager (ATM) therapy for substance use disorders.

    PubMed

    Rosen, Marc I; Rounsaville, Bruce J; Ablondi, Karen; Black, Anne C; Rosenheck, Robert A

    2010-07-01

    Patients with concomitant psychiatric and substance use disorders are commonly assigned representative payees or case managers to help manage their funds, but money management has not been conceptualized as a theory-based treatment. This randomized clinical trial was conducted to determine the effect of a money management-based therapy, advisor-teller money manager (ATM), on substance abuse or dependence. Ninety patients at a community mental health center who had a history of cocaine or alcohol abuse or dependence were assessed after random assignment to 36 weeks of ATM (N=47) or a control condition in which use of a financial workbook was reviewed (N=43). Patients assigned to ATM were encouraged to deposit their funds into a third-party account, plan weekly expenditures, and negotiate monthly budgets. Substance use calendars and urine toxicology tests were collected every other week for 36 weeks and again 52 weeks after randomization. Patients assigned to ATM had significantly more negative toxicologies for cocaine metabolite over time than patients in the control group, and treating clinicians rated ATM patients as significantly more likely to be abstinent from illicit drugs. Self-reported abstinence from alcohol did not significantly differ between groups. Unexpectedly, patients assigned to ATM were more likely to be assigned a representative payee or a conservator than control participants during the follow-up period (ten of 47 versus two of 43). One patient in ATM assaulted the therapist when his check had not arrived. ATM is an efficacious therapy for the treatment of cocaine abuse or dependence among people with concomitant psychiatric illness but requires protection of patient autonomy and staff safety.

  20. Loss of ATM kinase activity leads to embryonic lethality in mice.

    PubMed

    Daniel, Jeremy A; Pellegrini, Manuela; Lee, Baeck-Seung; Guo, Zhi; Filsuf, Darius; Belkina, Natalya V; You, Zhongsheng; Paull, Tanya T; Sleckman, Barry P; Feigenbaum, Lionel; Nussenzweig, André

    2012-08-06

    Ataxia telangiectasia (A-T) mutated (ATM) is a key deoxyribonucleic acid (DNA) damage signaling kinase that regulates DNA repair, cell cycle checkpoints, and apoptosis. The majority of patients with A-T, a cancer-prone neurodegenerative disease, present with null mutations in Atm. To determine whether the functions of ATM are mediated solely by its kinase activity, we generated two mouse models containing single, catalytically inactivating point mutations in Atm. In this paper, we show that, in contrast to Atm-null mice, both D2899A and Q2740P mutations cause early embryonic lethality in mice, without displaying dominant-negative interfering activity. Using conditional deletion, we find that the D2899A mutation in adult mice behaves largely similar to Atm-null cells but shows greater deficiency in homologous recombination (HR) as measured by hypersensitivity to poly (adenosine diphosphate-ribose) polymerase inhibition and increased genomic instability. These results may explain why missense mutations with no detectable kinase activity are rarely found in patients with classical A-T. We propose that ATM kinase-inactive missense mutations, unless otherwise compensated for, interfere with HR during embryogenesis.

  1. ATM Coastal Topography-Alabama 2001

    USGS Publications Warehouse

    Nayegandhi, Amar; Yates, Xan; Brock, John C.; Sallenger, A.H.; Bonisteel, Jamie M.; Klipp, Emily S.; Wright, C. Wayne

    2009-01-01

    These remotely sensed, geographically referenced elevation measurements of Lidar-derived first surface (FS) topography were produced collaboratively by the U.S. Geological Survey (USGS), Florida Integrated Science Center (FISC), St. Petersburg, FL, and the National Aeronautics and Space Administration (NASA), Wallops Flight Facility, VA. This project provides highly detailed and accurate datasets of the Alabama coastline, acquired October 3-4, 2001. The datasets are made available for use as a management tool to research scientists and natural resource managers. An innovative scanning Lidar instrument originally developed by NASA, and known as the Airborne Topographic Mapper (ATM), was used during data acquisition. The ATM system is a scanning Lidar system that measures high-resolution topography of the land surface, and incorporates a green-wavelength laser operating at pulse rates of 2 to 10 kilohertz. Measurements from the laser ranging device are coupled with data acquired from inertial navigation system (INS) attitude sensors and differentially corrected global positioning system (GPS) receivers to measure topography of the surface at accuracies of +/-15 centimeters. The nominal ATM platform is a Twin Otter or P-3 Orion aircraft, but the instrument may be deployed on a range of light aircraft. Elevation measurements were collected over the survey area using the ATM system, and the resulting data were then processed using the Airborne Lidar Processing System (ALPS), a custom-built processing system developed in a NASA-USGS collaboration. ALPS supports the exploration and processing of Lidar data in an interactive or batch mode. Modules for pre-survey flight line definition, flight path plotting, Lidar raster and waveform investigation, and digital camera image playback have been developed. Processing algorithms have been developed to extract the range to the first and last significant return within each waveform. ALPS is routinely used to create maps that

  2. ATM Coastal Topography-Mississippi, 2001

    USGS Publications Warehouse

    Nayegandhi, Amar; Yates, Xan; Brock, John C.; Sallenger, A.H.; Klipp, Emily S.; Wright, C. Wayne

    2009-01-01

    These remotely sensed, geographically referenced elevation measurements of lidar-derived first-surface (FS) topography were produced collaboratively by the U.S. Geological Survey (USGS), Florida Integrated Science Center (FISC), St. Petersburg, FL, and the National Aeronautics and Space Administration (NASA), Wallops Flight Facility, VA. This project provides highly detailed and accurate datasets of the Mississippi coastline, from Lakeshore to Petit Bois Island, acquired September 9-10, 2001. The datasets are made available for use as a management tool to research scientists and natural-resource managers. An innovative scanning lidar instrument originally developed by NASA, and known as the Airborne Topographic Mapper (ATM), was used during data acquisition. The ATM system is a scanning lidar system that measures high-resolution topography of the land surface and incorporates a green-wavelength laser operating at pulse rates of 2 to 10 kilohertz. Measurements from the laser-ranging device are coupled with data acquired from inertial navigation system (INS) attitude sensors and differentially corrected global positioning system (GPS) receivers to measure topography of the surface at accuracies of +/-15 centimeters. The nominal ATM platform is a Twin Otter or P-3 Orion aircraft, but the instrument may be deployed on a range of light aircraft. Elevation measurements were collected over the survey area using the ATM system, and the resulting data were then processed using the Airborne Lidar Processing System (ALPS), a custom-built processing system developed in a NASA-USGS collaboration. ALPS supports the exploration and processing of lidar data in an interactive or batch mode. Modules for presurvey flight-line definition, flight-path plotting, lidar raster and waveform investigation, and digital camera image playback have been developed. Processing algorithms have been developed to extract the range to the first and last significant return within each waveform. ALPS

  3. NPP After Launch: Characterizing ATMS Performance

    NASA Technical Reports Server (NTRS)

    Lambrigtsen, Bjorn

    2011-01-01

    The NPOESS Preparatory Project (NPP) mission is scheduled to launch in the fall of 2011. Although several teams from the government and the instrument contractor will be assessing and characterizing the performance of the Advanced Technology Microwave Sounder (ATMS) and the Cross-track Infrared Sounder (CrIS) sounding suite, the NASA NPP Science Team will be paying particular attention to the aspects of these sensors that affect their utility for atmospheric and climate research. In this talk we discuss relevant aspects of ATMS and our post launch analysis approach.

  4. 27 CFR 28.193 - Export marks.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export marks. 28.193... Drawback Filing of Notice and Removal § 28.193 Export marks. In addition to the marks and brands required... chapter, the exporter shall mark the word “Export” on the Government side of each case or Government head...

  5. ATM regulation of IL-8 links oxidative stress to cancer cell migration and invasion.

    PubMed

    Chen, Wei-Ta; Ebelt, Nancy D; Stracker, Travis H; Xhemalce, Blerta; Van Den Berg, Carla L; Miller, Kyle M

    2015-06-01

    Ataxia-telangiectasia mutated (ATM) protein kinase regulates the DNA damage response (DDR) and is associated with cancer suppression. Here we report a cancer-promoting role for ATM. ATM depletion in metastatic cancer cells reduced cell migration and invasion. Transcription analyses identified a gene network, including the chemokine IL-8, regulated by ATM. IL-8 expression required ATM and was regulated by oxidative stress. IL-8 was validated as an ATM target by its ability to rescue cell migration and invasion defects in ATM-depleted cells. Finally, ATM-depletion in human breast cancer cells reduced lung tumors in a mouse xenograft model and clinical data validated IL-8 in lung metastasis. These findings provide insights into how ATM activation by oxidative stress regulates IL-8 to sustain cell migration and invasion in cancer cells to promote metastatic potential. Thus, in addition to well-established roles in tumor suppression, these findings identify a role for ATM in tumor progression.

  6. ORNL diagnostic and modeling development for LAPD ICRF experiments

    NASA Astrophysics Data System (ADS)

    Isler, R. C.; Caughman, J. B. O.; Lau, C.; Martin, E. H.; Perkins, R. J.; Compernolle, B. Van; Vincena, S.; Tripathi, S. K. P.; Gekelman, W.

    2017-10-01

    PPPL, UCLA, and ORNL scientists have recently collaborated on a three week ICRF campaign at the upgraded LAPD device to study near field-plasma interactions associated with a single strap antenna driven at 2.38 MHz with 100 kW of RF power. This poster highlights ORNL involvement through implementation of the following diagnostics: an optical emission probe to measure neutral density, a retarding field energy analyzer to measure fast ions, phase locked imaging to measure line integrated RF-driven optical emission fluctuations, and an RF compensated triple Langmuir probe to measure density and temperature. To interpret the results of the experimental campaign a 3D cold plasma finite element model with realistic antenna and vacuum vessel geometry was developed in COMSOL. A summary of these results will be discussed. Highlights include a proof of principle localized and spatially resolved measurement of the neutral density, a strong increase in RF-driven optical emission fluctuations directly in front of the RF antenna strap, a shift in fast ion energies near the plasma edge, and qualitative agreement between the COMSOL cold plasma model with the various diagnostics. Funded by the DOE OFES (DE-AC05-00OR22725, DE-AC02-09CH11466, and DE-FC02-07ER54918) and the Univ. of California (12-LR-237124).

  7. GNSS real time performance monitoring and CNS/ATM implementation

    DOT National Transportation Integrated Search

    2006-07-01

    The global transition to communications, navigation, surveillance / air traffic management (CNS/ATM) technology is moving forward at an increasing pace. A critical part of the CNS/ATM concept is the ability to monitor, analyze, and distribute aeronau...

  8. 49 CFR 193.2013 - Incorporation by reference.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Thermal Radiation Model for LNG Fires (March 2004) § 193.2057(a). (2) GTI-04/0049 (April 2004) “LNG Vapor... FEM3A for LNG Accident Consequence Analyses” (April 1997) § 193.2059. F. National Fire Protection...

  9. 49 CFR 193.2013 - Incorporation by reference.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Thermal Radiation Model for LNG Fires (March 2004) § 193.2057(a). (2) GTI-04/0049 (April 2004) “LNG Vapor... FEM3A for LNG Accident Consequence Analyses” (April 1997) § 193.2059. F. National Fire Protection...

  10. 49 CFR 193.2013 - Incorporation by reference.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Thermal Radiation Model for LNG Fires (March 2004) § 193.2057(a). (2) GTI-04/0049 (April 2004) “LNG Vapor... FEM3A for LNG Accident Consequence Analyses” (April 1997) § 193.2059. F. National Fire Protection...

  11. 49 CFR 193.2057 - Thermal radiation protection.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... section 2.2.3.2 of NFPA 59A (incorporated by reference, see § 193.2013) with the following exceptions: (a..., see § 193.2013). The use of other alternate models which take into account the same physical factors...

  12. 49 CFR 193.2057 - Thermal radiation protection.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... section 2.2.3.2 of NFPA 59A (incorporated by reference, see § 193.2013) with the following exceptions: (a..., see § 193.2013). The use of other alternate models which take into account the same physical factors...

  13. Dissecting cellular responses to irradiation via targeted disruptions of the ATM-CHK1-PP2A circuit

    PubMed Central

    Palii, Stela S.; Cui, Yuxia; Innes, Cynthia L.; Paules, Richard S.

    2013-01-01

    Exposure of proliferating cells to genotoxic stresses activates a cascade of signaling events termed the DNA damage response (DDR). The DDR preserves genetic stability by detecting DNA lesions, activating cell cycle checkpoints and promoting DNA damage repair. The phosphoinositide 3-kinase-related kinases (PIKKs) ataxia telangiectasia-mutated (ATM), ATM and Rad 3-related kinase (ATR) and DNA-dependent protein kinase (DNA-PK) are crucial for sensing lesions and signal transduction. The checkpoint kinase 1 (CHK1) is a traditional ATR target involved in DDR and normal cell cycle progression and represents a pharmacological target for anticancer regimens. This study employed cell lines stably depleted for CHK1, ATM or both for dissecting cross-talk and compensatory effects on G₂/M checkpoint in response to ionizing radiation (IR). We show that a 90% depletion of CHK1 renders cells radiosensitive without abrogating their IR-mediated G₂/M checkpoint arrest. ATM phosphorylation is enhanced in CHK1-deficient cells compared with their wild-type counterparts. This correlates with lower nuclear abundance of the PP2A catalytic subunit in CHK1-depleted cells. Stable depletion of CHK1 in an ATM-deficient background showed only a 50% reduction from wild-type CHK1 protein expression levels and resulted in an additive attenuation of the G₂/M checkpoint response compared with the individual knockdowns. ATM inhibition and 90% CHK1 depletion abrogated the early G₂/M checkpoint and precluded the cells from mounting an efficient compensatory response to IR at later time points. Our data indicates that dual targeting of ATM and CHK1 functionalities disrupts the compensatory response to DNA damage and could be exploited for developing efficient anti-neoplastic treatments. PMID:23462183

  14. A PIC-MCC code RFdinity1d for simulation of discharge initiation by ICRF antenna

    NASA Astrophysics Data System (ADS)

    Tripský, M.; Wauters, T.; Lyssoivan, A.; Bobkov, V.; Schneider, P. A.; Stepanov, I.; Douai, D.; Van Eester, D.; Noterdaeme, J.-M.; Van Schoor, M.; ASDEX Upgrade Team; EUROfusion MST1 Team

    2017-12-01

    Discharges produced and sustained by ion cyclotron range of frequency (ICRF) waves in absence of plasma current will be used on ITER for (ion cyclotron-) wall conditioning (ICWC, Te = 3{-}5 eV, ne < 1018 m-3 ). In this paper, we present the 1D particle-in-cell Monte Carlo collision (PIC-MCC) RFdinity1d for the study the breakdown phase of ICRF discharges, and its dependency on the RF discharge parameters (i) antenna input power P i , (ii) RF frequency f, (iii) shape of the electric field and (iv) the neutral gas pressure pH_2 . The code traces the motion of both electrons and ions in a narrow bundle of magnetic field lines close to the antenna straps. The charged particles are accelerated in the parallel direction with respect to the magnetic field B T by two electric fields: (i) the vacuum RF field of the ICRF antenna E_z^RF and (ii) the electrostatic field E_zP determined by the solution of Poisson’s equation. The electron density evolution in simulations follows exponential increase, {\\dot{n_e} ∼ ν_ion t } . The ionization rate varies with increasing electron density as different mechanisms become important. The charged particles are affected solely by the antenna RF field E_z^RF at low electron density ({ne < 1011} m-3 , {≤ft \\vert E_z^RF \\right \\vert \\gg ≤ft \\vert E_zP \\right \\vert } ). At higher densities, when the electrostatic field E_zP is comparable to the antenna RF field E_z^RF , the ionization frequency reaches the maximum. Plasma oscillations propagating toroidally away from the antenna are observed. The simulated energy distributions of ions and electrons at {ne ∼ 1015} m-3 correspond a power-law Kappa energy distribution. This energy distribution was also observed in NPA measurements at ASDEX Upgrade in ICWC experiments.

  15. Generation and Sustainment of Plasma Rotation by ICRF Heating

    NASA Astrophysics Data System (ADS)

    Perkins, F. W.

    2000-10-01

    When tokamak plasmas are heated by the fundamental minority ion-cyclotron process, they are observed to rotate toroidally, even though this heating process introduces negligable angular momentum. This work proposes and evaluates a physics mechanism which resolves this apparent conflict. The argument has two elements. First, it is assumed that angular momentum transport is governed by a diffusion equation with a v_tor = 0 boundary condition at the plasma surface and a torque-density source. When the source consists of separated regions of positive and negative torque density, a finite central rotation velocity results, even though the volume integrated torque density - the angular momentum input - vanishes. Secondly, ions energized by the ICRF process can generate separated regions of positive and negative torque density. Heating increases their banana widths which leads to radial energetic-particle transport that must be balanced by neutralizing radial currents and a j_rB_pR torque density in the bulk plasma. Additional, comparable torque density results from collisional transfer of mechanical angular momentum from energetic particles to the bulk plasma and particle loss through banana particles impacting the wall. Monte-Carlo calculations utilizing the ORBIT code evaluate all sources of torque density and rigorously assure that no net angular momentum is introduced. Two models of ICRF heating, diffusive and instantaneous, give similar results. When the resonance location is on the LFS, the calculated rotation has the magnitude, profile, and co-current sense of Alcator C-Mod observations. For HFS resonance locations, the model predicts counter-current rotation. Scans of rotational profiles vs. resonance location, initial energy, particle loss, pitch, and qm will be presented as will the location of the velocity shear layer its scaling to a reactor.

  16. Development of the Advanced Technology Microwave Sounder (ATMS) for NPOESS C1

    NASA Astrophysics Data System (ADS)

    Brann, C.; Kunkee, D.

    2008-12-01

    The National Polar-orbiting Operational Environmental Satellite System's Advanced Technology Microwave Sounder (ATMS) is planned for flight on the first NPOESS mission (C1) in 2013. The C1 ATMS will be the second instrument of the ATMS series and will provide along with the companion Cross-track Infrared Sounder (CrIS), atmospheric temperature and moisture profiles for NPOESS. The first flight of the ATMS is scheduled in 2010 on the NPOESS Preparatory Project (NPP) satellite, which is an early instrument risk reduction component of the NPOESS mission. This poster will focus on the development of the ATMS for C1 including aspects of the sensor calibration, antenna beam and RF characteristics and scanning. New design aspects of the C1 ATMS, required primarily by parts obsolescence, will also be addressed in this poster.

  17. Identification and chromosomal localization of Atm, the mouse homolog of the ataxia-telangiectasia gene.

    PubMed

    Pecker, I; Avraham, K B; Gilbert, D J; Savitsky, K; Rotman, G; Harnik, R; Fukao, T; Schröck, E; Hirotsune, S; Tagle, D A; Collins, F S; Wynshaw-Boris, A; Ried, T; Copeland, N G; Jenkins, N A; Shiloh, Y; Ziv, Y

    1996-07-01

    Atm, the mouse homolog of the human ATM gene defective in ataxia-telangiectasia (A-T), has been identified. The entire coding sequence of the Atm transcript was cloned and found to contain an open reading frame encoding a protein of 3066 amino acids with 84% overall identity and 91% similarity to the human ATM protein. Variable levels of expression of Atm were observed in different tissues. Fluorescence in situ hybridization and linkage analysis located the Atm gene on mouse chromosome 9, band 9C, in a region homologous to the ATM region on human chromosome 11q22-q23.

  18. 49 CFR 193.2615 - Isolating and purging.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Isolating and purging. 193.2615 Section 193.2615 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES...

  19. 49 CFR 193.2613 - Auxiliary power sources.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Auxiliary power sources. 193.2613 Section 193.2613 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES...

  20. 49 CFR 193.2621 - Testing transfer hoses.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Testing transfer hoses. 193.2621 Section 193.2621 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES...

  1. ATM regulation of IL-8 links oxidative stress to cancer cell migration and invasion

    PubMed Central

    Chen, Wei-Ta; Ebelt, Nancy D; Stracker, Travis H; Xhemalce, Blerta; Van Den Berg, Carla L; Miller, Kyle M

    2015-01-01

    Ataxia-telangiectasia mutated (ATM) protein kinase regulates the DNA damage response (DDR) and is associated with cancer suppression. Here we report a cancer-promoting role for ATM. ATM depletion in metastatic cancer cells reduced cell migration and invasion. Transcription analyses identified a gene network, including the chemokine IL-8, regulated by ATM. IL-8 expression required ATM and was regulated by oxidative stress. IL-8 was validated as an ATM target by its ability to rescue cell migration and invasion defects in ATM-depleted cells. Finally, ATM-depletion in human breast cancer cells reduced lung tumors in a mouse xenograft model and clinical data validated IL-8 in lung metastasis. These findings provide insights into how ATM activation by oxidative stress regulates IL-8 to sustain cell migration and invasion in cancer cells to promote metastatic potential. Thus, in addition to well-established roles in tumor suppression, these findings identify a role for ATM in tumor progression. DOI: http://dx.doi.org/10.7554/eLife.07270.001 PMID:26030852

  2. Calcium dysregulation and Cdk5-ATM pathway involved in a mouse model of fragile X-associated tremor/ataxia syndrome.

    PubMed

    Robin, Gaëlle; López, José R; Espinal, Glenda M; Hulsizer, Susan; Hagerman, Paul J; Pessah, Isaac N

    2017-07-15

    Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurological disorder that affects premutation carriers with 55-200 CGG-expansion repeats (preCGG) in FMR1, presenting with early alterations in neuronal network formation and function that precede neurodegeneration. Whether intranuclear inclusions containing DNA damage response (DDR) proteins are causally linked to abnormal synaptic function, neuronal growth and survival are unknown. In a mouse that harbors a premutation CGG expansion (preCGG), cortical and hippocampal FMRP expression is moderately reduced from birth through adulthood, with greater FMRP reductions in the soma than in the neurite, despite several-fold elevation of Fmr1 mRNA levels. Resting cytoplasmic calcium concentration ([Ca2+]i) in cultured preCGG hippocampal neurons is chronically elevated, 3-fold compared to Wt; elevated ROS and abnormal glutamatergic responses are detected at 14 DIV. Elevated µ-calpain activity and a higher p25/p35 ratio in the cortex of preCGG young adult mice indicate abnormal Cdk5 regulation. In support, the Cdk5 substrate, ATM, is upregulated by 1.5- to 2-fold at P0 and 6 months in preCGG brain, as is p-Ser1981-ATM. Bax:Bcl-2 is 30% higher in preCGG brain, indicating a greater vulnerability to apoptotic activation. Elevated [Ca2+]i, ROS, and DDR signals are normalized with dantrolene. Chronic [Ca2+]i dysregulation amplifies Cdk5-ATM signaling, possibly linking impaired glutamatergic signaling and DDR to neurodegeneration in preCGG brain. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Reinstated JET ICRF ILA: Overview and Results

    NASA Astrophysics Data System (ADS)

    Dumortier, Pierre; Durodié, Frédéric; Blackman, Trevor; Helou, Walid; Jacquet, Philippe; Lerche, Ernesto; Monakhov, Igor; Noble, Craig; Bobkov, Volodymyr; Goulding, Richard; Kaufman, Michael; Van Eester, Dirk

    2017-10-01

    The works undertaken to reinstate the JET ICRF ILA are reviewed. The vacuum matching capacitors were replaced, an extensive calibration of all the measurements in the RF circuit was carried out, new simulation tools were created and new control algorithms were implemented for the - toroidal and poloidal - phase control of the array as well as for the matching of the second stage. A review of the contribution of the reinstated ILA to the JET programme during the last campaigns is given showing namely that the new controls allowed extending the range of the operation to lower (29MHz) and higher (51MHz) frequencies than previously achieved and allowed more flexible and reliable operation. Operation with coupled power levels up to 2.8MW and voltages up to 40kV was achieved. ILA results on plasma are discussed and emphasis is given to the features of interest for ITER.

  4. Experience with PACS in an ATM/Ethernet switched network environment.

    PubMed

    Pelikan, E; Ganser, A; Kotter, E; Schrader, U; Timmermann, U

    1998-03-01

    Legacy local area network (LAN) technologies based on shared media concepts are not adequate for the growth of a large-scale picture archiving and communication system (PACS) in a client-server architecture. First, an asymmetric network load, due to the requests of a large number of PACS clients for only a few main servers, should be compensated by communication links to the servers with a higher bandwidth compared to the clients. Secondly, as the number of PACS nodes increases, the network throughout should not measurably cut production. These requirements can easily be fulfilled using switching technologies. Here asynchronous transfer mode (ATM) is clearly one of the hottest topics in networking because the ATM architecture provides integrated support for a variety of communication services, and it supports virtual networking. On the other hand, most of the imaging modalities are not yet ready for integration into a native ATM network. For a lot of nodes already joining an Ethernet, a cost-effective and pragmatic way to benefit from the switching concept would be a combined ATM/Ethernet switching environment. This incorporates an incremental migration strategy with the immediate benefits of high-speed, high-capacity ATM (for servers and high-sophisticated display workstations), while preserving elements of the existing network technologies. In addition, Ethernet switching instead of shared media Ethernet improves the performance considerably. The LAN emulation (LANE) specification by the ATM forum defines mechanisms that allow ATM networks to coexist with legacy systems using any data networking protocol. This paper points out the suitability of this network architecture in accordance with an appropriate system design.

  5. 42 CFR 84.193 - Cartridges; color and markings; requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Cartridges; color and markings; requirements. 84.193 Section 84.193 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Chemical Cartridge Respirators § 84.193 Cartridges; color and markings; requirements. The color and...

  6. 42 CFR 84.193 - Cartridges; color and markings; requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Cartridges; color and markings; requirements. 84.193 Section 84.193 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Chemical Cartridge Respirators § 84.193 Cartridges; color and markings; requirements. The color and...

  7. 42 CFR 84.193 - Cartridges; color and markings; requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Cartridges; color and markings; requirements. 84.193 Section 84.193 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Chemical Cartridge Respirators § 84.193 Cartridges; color and markings; requirements. The color and...

  8. 42 CFR 84.193 - Cartridges; color and markings; requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Cartridges; color and markings; requirements. 84.193 Section 84.193 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Chemical Cartridge Respirators § 84.193 Cartridges; color and markings; requirements. The color and...

  9. 42 CFR 84.193 - Cartridges; color and markings; requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Cartridges; color and markings; requirements. 84.193 Section 84.193 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Chemical Cartridge Respirators § 84.193 Cartridges; color and markings; requirements. The color and...

  10. 14 CFR 21.193 - Experimental certificates: general.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Experimental certificates: general. 21.193 Section 21.193 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... instructions for the aircraft that meet an applicable consensus standard. (5) The aircraft's flight training...

  11. 49 CFR 193.2627 - Atmospheric corrosion control.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Atmospheric corrosion control. 193.2627 Section... LIQUEFIED NATURAL GAS FACILITIES: FEDERAL SAFETY STANDARDS Maintenance § 193.2627 Atmospheric corrosion control. Each exposed component that is subject to atmospheric corrosive attack must be protected from...

  12. 49 CFR 193.2627 - Atmospheric corrosion control.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Atmospheric corrosion control. 193.2627 Section... LIQUEFIED NATURAL GAS FACILITIES: FEDERAL SAFETY STANDARDS Maintenance § 193.2627 Atmospheric corrosion control. Each exposed component that is subject to atmospheric corrosive attack must be protected from...

  13. 49 CFR 193.2627 - Atmospheric corrosion control.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Atmospheric corrosion control. 193.2627 Section... LIQUEFIED NATURAL GAS FACILITIES: FEDERAL SAFETY STANDARDS Maintenance § 193.2627 Atmospheric corrosion control. Each exposed component that is subject to atmospheric corrosive attack must be protected from...

  14. 49 CFR 193.2627 - Atmospheric corrosion control.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Atmospheric corrosion control. 193.2627 Section... LIQUEFIED NATURAL GAS FACILITIES: FEDERAL SAFETY STANDARDS Maintenance § 193.2627 Atmospheric corrosion... atmospheric corrosion by— (a) Material that has been designed and selected to resist the corrosive atmosphere...

  15. 49 CFR 193.2703 - Design and fabrication.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Design and fabrication. 193.2703 Section 193.2703 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES: FEDERAL SAFETY STANDARDS...

  16. 49 CFR 193.2631 - Internal corrosion control.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Internal corrosion control. 193.2631 Section 193.2631 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES: FEDERAL SAFETY STANDARDS...

  17. 49 CFR 193.2631 - Internal corrosion control.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Internal corrosion control. 193.2631 Section 193.2631 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES: FEDERAL SAFETY STANDARDS...

  18. 49 CFR 193.2631 - Internal corrosion control.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Internal corrosion control. 193.2631 Section 193.2631 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES: FEDERAL SAFETY STANDARDS...

  19. 13 CFR 120.193 - Reconsideration after denial.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Reconsideration after denial. 120.193 Section 120.193 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS... original request. To prevail, the applicant must demonstrate that it has overcome all legitimate reasons...

  20. Organic antireflective coatings for 193-nm lithography

    NASA Astrophysics Data System (ADS)

    Trefonas, Peter, III; Blacksmith, Robert F.; Szmanda, Charles R.; Kavanagh, Robert J.; Adams, Timothy G.; Taylor, Gary N.; Coley, Suzanne; Pohlers, Gerd

    1999-06-01

    Organic anti-reflective coatings (ARCs) continue to play an important role in semiconductor manufacturing. These materials provide a convenient means of greatly reducing the resist photospeed swing and reflective notching. In this paper, we describe a novel class of ARC materials optimized for lithographic applications using 193 nm exposure tools. These ARCs are based upon polymers containing hydroxyl-alkyl methacrylate monomers for crosslinkable sites, styrene for a chromophore at 193 nm, and additional alkyl-methacrylate monomers as property modifiers. A glycouril crosslinker and a thermally-activated acidic catalyst provide a route to forming an impervious crosslinked film activate data high bake temperatures. ARC compositions can be adjusted to optimize the film's real and imaginary refractive indices. Selection of optimal target indices for 193 nm lithographic processing through simulations is described. Potential chromophores for 193 nm were explored using ZNDO modeling. We show how these theoretical studies were combined with material selection criteria to yield a versatile organic anti-reflectant film, Shipley 193 G0 ARC. Lithographic process data indicates the materials is capable of supporting high resolution patterning, with the line features displaying a sharp resist/ARC interface with low line edge roughness. The resist Eo swing is successfully reduced from 43 percent to 6 percent.

  1. The over expression of long non-coding RNA ANRIL promotes epithelial-mesenchymal transition by activating the ATM-E2F1 signaling pathway in pancreatic cancer: An in vivo and in vitro study.

    PubMed

    Chen, Shi; Zhang, Jia-Qiang; Chen, Jiang-Zhi; Chen, Hui-Xing; Qiu, Fu-Nan; Yan, Mao-Lin; Chen, Yan-Ling; Peng, Cheng-Hong; Tian, Yi-Feng; Wang, Yao-Dong

    2017-09-01

    This study aims to investigate the roles of lncRNA ANRIL in epithelial-mesenchymal transition (EMT) by regulating the ATM-E2F1 signaling pathway in pancreatic cancer (PC). PC rat models were established and ANRIL overexpression and interference plasmids were transfected. The expression of ANRIL, EMT markers (E-cadherin, N-cadherin and Vimentin) and ATM-E2F1 signaling pathway-related proteins (ATM, E2F1, INK4A, INK4B and ARF) were detected. Small molecule drugs were applied to activate and inhibit the ATM-E2F1 signaling pathway. Transwell assay and the scratch test were adopted to detect cell invasion and migration abilities. ANRIL expression in the PC cells was higher than in normal pancreatic duct epithelial cells. In the PC rat models and PC cells, ANRIL interference promoted the expressions of INK4B, INK4A, ARF and E-cadherin, while reduced N-cadherin and Vimentin expression. Over-expressed ANRIL decreased the expression of INK4B, INK4A, ARF and E-cadherin, but raised N-cadherin and Vimentin expressions. By inhibiting the ATM-E2F1 signaling pathway in PC cells, E-cadherin expression increased but N-cadherin and Vimentin expressions decreased. After ANRIL was silenced or the ATM-E2F1 signaling pathway inhibited, PC cell migration and invasion abilities were decreased. In conclusion, over-expression of lncRNA ANRIL can promote EMT of PC cells by activating the ATM-E2F1 signaling pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Detection of OH on photolysis of styrene oxide at 193 nm in gas phase

    NASA Astrophysics Data System (ADS)

    Kumar, Awadhesh; SenGupta, Sumana; Pushpa, K. K.; Naik, P. D.; Bajaj, P. N.

    2006-10-01

    Photodissociation of styrene oxide at 193 nm in gas phase generates OH, as detected by laser-induced fluorescence technique. Under similar conditions, OH was not observed from ethylene and propylene oxides, primarily because of their low absorption cross-sections at 193 nm. Mechanism of OH formation involves first opening of the three-membered ring from the ground electronic state via cleavage of either of two C sbnd O bonds, followed by isomerization to enolic forms of phenylacetaldehyde and acetophenone, and finally scission of the C sbnd OH bond of enols. Ab initio molecular orbital calculations support the proposed mechanism.

  3. 14 CFR 61.193 - Flight instructor privileges.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 2 2012-01-01 2012-01-01 false Flight instructor privileges. 61.193... (CONTINUED) AIRMEN CERTIFICATION: PILOTS, FLIGHT INSTRUCTORS, AND GROUND INSTRUCTORS Flight Instructors Other than Flight Instructors With a Sport Pilot Rating § 61.193 Flight instructor privileges. A person who...

  4. 14 CFR 61.193 - Flight instructor privileges.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 2 2013-01-01 2013-01-01 false Flight instructor privileges. 61.193... (CONTINUED) AIRMEN CERTIFICATION: PILOTS, FLIGHT INSTRUCTORS, AND GROUND INSTRUCTORS Flight Instructors Other than Flight Instructors With a Sport Pilot Rating § 61.193 Flight instructor privileges. A person who...

  5. 14 CFR 61.193 - Flight instructor privileges.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Flight instructor privileges. 61.193 Section 61.193 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... recency of experience requirement of this part; (h) A practical test; and (i) A knowledge test. [Doc. No...

  6. 14 CFR 61.193 - Flight instructor privileges.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 2 2011-01-01 2011-01-01 false Flight instructor privileges. 61.193 Section 61.193 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... recency of experience requirement of this part; (h) A practical test; and (i) A knowledge test. [Doc. No...

  7. Lead (Pb) induced ATM-dependent mitophagy via PINK1/Parkin pathway.

    PubMed

    Gu, Xueyan; Qi, Yongmei; Feng, Zengxiu; Ma, Lin; Gao, Ke; Zhang, Yingmei

    2018-07-01

    Lead (Pb), a widely distributed environmental pollutant, is known to induce mitochondrial damage as well as autophagy in vitro and in vivo. In this study, we found that Pb could trigger mitophagy in both HEK293 cells and the kidney cortex of male Kunming mice. However, whether ataxia telangiectasis mutated (ATM) which is reported to be linked with PTEN-induced putative kinase 1 (PINK1)/Parkin pathway (a well-characterized mitophagic pathway) participates in the regulation of Pb-induced mitophagy and its exact role remains enigmatic. Our results indicated that Pb activated ATM in vitro and in vivo, and further in vitro studies showed that ATM could co-localize with PINK1 and Parkin in cytosol and interact with PINK1. Knockdown of ATM by siRNA blocked Pb-induced mitophagy even under the circumstance of enhanced accumulation of PINK1 and mitochondrial Parkin. Intriguingly, elevation instead of reduction in phosphorylation level of PINK1 and Parkin was observed in response to ATM knockdown and Pb did not contribute to the further increase of their phosphorylation level, implying that ATM indirectly regulated PINK1/Parkin pathway. These findings reveal a novel mechanism for Pb toxicity and suggest the regulatory importance of ATM in PINK1/Parkin-mediated mitophagy. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Integrated Service Provisioning in an Ipv6 over ATM Research Network

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

    Eli Dart; Helen Chen; Jerry Friesen

    1999-02-01

    During the past few years, the worldwide Internet has grown at a phenomenal rate, which has spurred the proposal of innovative network technologies to support the fast, efficient and low-latency transport of a wide spectrum of multimedia traffic types. Existing network infrastructures have been plagued by their inability to provide for real-time application traffic as well as their general lack of resources and resilience to congestion. This work proposes to address these issues by implementing a prototype high-speed network infrastructure consisting of Internet Protocol Version 6 (IPv6) on top of an Asynchronous Transfer Mode (ATM) transport medium. Since ATM ismore » connection-oriented whereas IP uses a connection-less paradigm, the efficient integration of IPv6 over ATM is especially challenging and has generated much interest in the research community. We propose, in collaboration with an industry partner, to implement IPv6 over ATM using a unique approach that integrates IP over fast A TM hardware while still preserving IP's connection-less paradigm. This is achieved by replacing ATM's control software with IP's routing code and by caching IP's forwarding decisions in ATM's VPI/VCI translation tables. Prototype ''VR'' and distributed-parallel-computing applications will also be developed to exercise the realtime capability of our IPv6 over ATM network.« less

  9. Inactivation of the ATMIN/ATM pathway protects against glioblastoma formation

    PubMed Central

    Blake, Sophia M; Stricker, Stefan H; Halavach, Hanna; Poetsch, Anna R; Cresswell, George; Kelly, Gavin; Kanu, Nnennaya; Marino, Silvia; Luscombe, Nicholas M; Pollard, Steven M; Behrens, Axel

    2016-01-01

    Glioblastoma multiforme (GBM) is the most aggressive human primary brain cancer. Using a Trp53-deficient mouse model of GBM, we show that genetic inactivation of the Atm cofactor Atmin, which is dispensable for embryonic and adult neural development, strongly suppresses GBM formation. Mechanistically, expression of several GBM-associated genes, including Pdgfra, was normalized by Atmin deletion in the Trp53-null background. Pharmacological ATM inhibition also reduced Pdgfra expression, and reduced the proliferation of Trp53-deficient primary glioma cells from murine and human tumors, while normal neural stem cells were unaffected. Analysis of GBM datasets showed that PDGFRA expression is also significantly increased in human TP53-mutant compared with TP53-wild-type tumors. Moreover, combined treatment with ATM and PDGFRA inhibitors efficiently killed TP53-mutant primary human GBM cells, but not untransformed neural stem cells. These results reveal a new requirement for ATMIN-dependent ATM signaling in TP53-deficient GBM, indicating a pro-tumorigenic role for ATM in the context of these tumors. DOI: http://dx.doi.org/10.7554/eLife.08711.001 PMID:26984279

  10. Structures of closed and open conformations of dimeric human ATM

    PubMed Central

    Baretić, Domagoj; Pollard, Hannah K.; Fisher, David I.; Johnson, Christopher M.; Santhanam, Balaji; Truman, Caroline M.; Kouba, Tomas; Fersht, Alan R.; Phillips, Christopher; Williams, Roger L.

    2017-01-01

    ATM (ataxia-telangiectasia mutated) is a phosphatidylinositol 3-kinase–related protein kinase (PIKK) best known for its role in DNA damage response. ATM also functions in oxidative stress response, insulin signaling, and neurogenesis. Our electron cryomicroscopy (cryo-EM) suggests that human ATM is in a dynamic equilibrium between closed and open dimers. In the closed state, the PIKK regulatory domain blocks the peptide substrate–binding site, suggesting that this conformation may represent an inactive or basally active enzyme. The active site is held in this closed conformation by interaction with a long helical hairpin in the TRD3 (tetratricopeptide repeats domain 3) domain of the symmetry-related molecule. The open dimer has two protomers with only a limited contact interface, and it lacks the intermolecular interactions that block the peptide-binding site in the closed dimer. This suggests that the open conformation may be more active. The ATM structure shows the detailed topology of the regulator-interacting N-terminal helical solenoid. The ATM conformational dynamics shown by the structures represent an important step in understanding the enzyme regulation. PMID:28508083

  11. The ATM signaling network in development and disease.

    PubMed

    Stracker, Travis H; Roig, Ignasi; Knobel, Philip A; Marjanović, Marko

    2013-01-01

    The DNA damage response (DDR) rapidly recognizes DNA lesions and initiates the appropriate cellular programs to maintain genome integrity. This includes the coordination of cell cycle checkpoints, transcription, translation, DNA repair, metabolism, and cell fate decisions, such as apoptosis or senescence (Jackson and Bartek, 2009). DNA double-strand breaks (DSBs) represent one of the most cytotoxic DNA lesions and defects in their metabolism underlie many human hereditary diseases characterized by genomic instability (Stracker and Petrini, 2011; McKinnon, 2012). Patients with hereditary defects in the DDR display defects in development, particularly affecting the central nervous system, the immune system and the germline, as well as aberrant metabolic regulation and cancer predisposition. Central to the DDR to DSBs is the ataxia-telangiectasia mutated (ATM) kinase, a master controller of signal transduction. Understanding how ATM signaling regulates various aspects of the DDR and its roles in vivo is critical for our understanding of human disease, its diagnosis and its treatment. This review will describe the general roles of ATM signaling and highlight some recent advances that have shed light on the diverse roles of ATM and related proteins in human disease.

  12. The ATM signaling network in development and disease

    PubMed Central

    Stracker, Travis H.; Roig, Ignasi; Knobel, Philip A.; Marjanović, Marko

    2013-01-01

    The DNA damage response (DDR) rapidly recognizes DNA lesions and initiates the appropriate cellular programs to maintain genome integrity. This includes the coordination of cell cycle checkpoints, transcription, translation, DNA repair, metabolism, and cell fate decisions, such as apoptosis or senescence (Jackson and Bartek, 2009). DNA double-strand breaks (DSBs) represent one of the most cytotoxic DNA lesions and defects in their metabolism underlie many human hereditary diseases characterized by genomic instability (Stracker and Petrini, 2011; McKinnon, 2012). Patients with hereditary defects in the DDR display defects in development, particularly affecting the central nervous system, the immune system and the germline, as well as aberrant metabolic regulation and cancer predisposition. Central to the DDR to DSBs is the ataxia-telangiectasia mutated (ATM) kinase, a master controller of signal transduction. Understanding how ATM signaling regulates various aspects of the DDR and its roles in vivo is critical for our understanding of human disease, its diagnosis and its treatment. This review will describe the general roles of ATM signaling and highlight some recent advances that have shed light on the diverse roles of ATM and related proteins in human disease. PMID:23532176

  13. 32 CFR 193.1 - Purpose and scope.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 2 2014-07-01 2014-07-01 false Purpose and scope. 193.1 Section 193.1 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS... authority in matters pertaining to Department of Defense highway needs and, when appropriate, to the highway...

  14. 32 CFR 193.1 - Purpose and scope.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Purpose and scope. 193.1 Section 193.1 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS... authority in matters pertaining to Department of Defense highway needs and, when appropriate, to the highway...

  15. Kinase-dead ATM protein is highly oncogenic and can be preferentially targeted by Topo-isomerase I inhibitors.

    PubMed

    Yamamoto, Kenta; Wang, Jiguang; Sprinzen, Lisa; Xu, Jun; Haddock, Christopher J; Li, Chen; Lee, Brian J; Loredan, Denis G; Jiang, Wenxia; Vindigni, Alessandro; Wang, Dong; Rabadan, Raul; Zha, Shan

    2016-06-15

    Missense mutations in ATM kinase, a master regulator of DNA damage responses, are found in many cancers, but their impact on ATM function and implications for cancer therapy are largely unknown. Here we report that 72% of cancer-associated ATM mutations are missense mutations that are enriched around the kinase domain. Expression of kinase-dead ATM (Atm(KD/-)) is more oncogenic than loss of ATM (Atm(-/-)) in mouse models, leading to earlier and more frequent lymphomas with Pten deletions. Kinase-dead ATM protein (Atm-KD), but not loss of ATM (Atm-null), prevents replication-dependent removal of Topo-isomerase I-DNA adducts at the step of strand cleavage, leading to severe genomic instability and hypersensitivity to Topo-isomerase I inhibitors. Correspondingly, Topo-isomerase I inhibitors effectively and preferentially eliminate Atm(KD/-), but not Atm-proficientor Atm(-/-) leukemia in animal models. These findings identify ATM kinase-domain missense mutations as a potent oncogenic event and a biomarker for Topo-isomerase I inhibitor based therapy.

  16. The Landscape of Somatic Genetic Alterations in Breast Cancers From ATM Germline Mutation Carriers.

    PubMed

    Weigelt, Britta; Bi, Rui; Kumar, Rahul; Blecua, Pedro; Mandelker, Diana L; Geyer, Felipe C; Pareja, Fresia; James, Paul A; Couch, Fergus J; Eccles, Diana M; Blows, Fiona; Pharoah, Paul; Li, Anqi; Selenica, Pier; Lim, Raymond S; Jayakumaran, Gowtham; Waddell, Nic; Shen, Ronglai; Norton, Larry; Wen, Hannah Y; Powell, Simon N; Riaz, Nadeem; Robson, Mark E; Reis-Filho, Jorge S; Chenevix-Trench, Georgia

    2018-02-28

    Pathogenic germline variants in ataxia-telangiectasia mutated (ATM), a gene that plays a role in DNA damage response and cell cycle checkpoints, confer an increased breast cancer (BC) risk. Here, we investigated the phenotypic characteristics and landscape of somatic genetic alterations in 24 BCs from ATM germline mutation carriers by whole-exome and targeted sequencing. ATM-associated BCs were consistently hormone receptor positive and largely displayed minimal immune infiltrate. Although 79.2% of these tumors exhibited loss of heterozygosity of the ATM wild-type allele, none displayed high activity of mutational signature 3 associated with defective homologous recombination DNA (HRD) repair. No TP53 mutations were found in the ATM-associated BCs. Analysis of an independent data set confirmed that germline ATM variants and TP53 somatic mutations are mutually exclusive. Our findings indicate that ATM-associated BCs often harbor bi-allelic inactivation of ATM, are phenotypically distinct from BRCA1/2-associated BCs, lack HRD-related mutational signatures, and that TP53 and ATM genetic alterations are likely epistatic.

  17. ATM/RB1 mutations predict shorter overall survival in urothelial cancer.

    PubMed

    Yin, Ming; Grivas, Petros; Emamekhoo, Hamid; Mendiratta, Prateek; Ali, Siraj; Hsu, JoAnn; Vasekar, Monali; Drabick, Joseph J; Pal, Sumanta; Joshi, Monika

    2018-03-30

    Mutations of DNA repair genes, e.g. ATM/RB1 , are frequently found in urothelial cancer (UC) and have been associated with better response to cisplatin-based chemotherapy. Further external validation of the prognostic value of ATM/RB1 mutations in UC can inform clinical decision making and trial designs. In the discovery dataset, ATM/RB1 mutations were present in 24% of patients and were associated with shorter OS (adjusted HR 2.67, 95% CI, 1.45-4.92, p = 0.002). There was a higher mutation load in patients carrying ATM/RB1 mutations (median mutation load: 6.7 versus 5.5 per Mb, p = 0.072). In the validation dataset, ATM/RB1 mutations were present in 22.2% of patients and were non-significantly associated with shorter OS (adjusted HR 1.87, 95% CI, 0.97-3.59, p = 0.06) and higher mutation load (median mutation load: 8.1 versus 7.2 per Mb, p = 0.126). Exome sequencing data of 130 bladder UC patients from The Cancer Genome Atlas (TCGA) dataset were analyzed as a discovery cohort to determine the prognostic value of ATM/RB1 mutations. Results were validated in an independent cohort of 81 advanced UC patients. Cox proportional hazard regression analysis was performed to calculate the hazard ratio (HR) and 95% confidence interval (CI) to compare overall survival (OS). ATM/RB1 mutations may be a biomarker of poor prognosis in unselected UC patients and may correlate with higher mutational load. Further studies are required to determine factors that can further stratify prognosis and evaluate predictive role of ATM/RB1 mutation status to immunotherapy and platinum-based chemotherapy.

  18. ATM-dependent pathways of chromatin remodelling and oxidative DNA damage responses.

    PubMed

    Berger, N Daniel; Stanley, Fintan K T; Moore, Shaun; Goodarzi, Aaron A

    2017-10-05

    Ataxia-telangiectasia mutated (ATM) is a serine/threonine protein kinase with a master regulatory function in the DNA damage response. In this role, ATM commands a complex biochemical network that signals the presence of oxidative DNA damage, including the dangerous DNA double-strand break, and facilitates subsequent repair. Here, we review the current state of knowledge regarding ATM-dependent chromatin remodelling and epigenomic alterations that are required to maintain genomic integrity in the presence of DNA double-strand breaks and/or oxidative stress. We will focus particularly on the roles of ATM in adjusting nucleosome spacing at sites of unresolved DNA double-strand breaks within complex chromatin environments, and the impact of ATM on preserving the health of cells within the mammalian central nervous system.This article is part of the themed issue 'Chromatin modifiers and remodellers in DNA repair and signalling'. © 2017 The Author(s).

  19. Tug of War between Survival and Death: Exploring ATM Function in Cancer

    PubMed Central

    Stagni, Venturina; Oropallo, Veronica; Fianco, Giulia; Antonelli, Martina; Cinà, Irene; Barilà, Daniela

    2014-01-01

    Ataxia-telangiectasia mutated (ATM) kinase is a one of the main guardian of genome stability and plays a central role in the DNA damage response (DDR). The deregulation of these pathways is strongly linked to cancer initiation and progression as well as to the development of therapeutic approaches. These observations, along with reports that identify ATM loss of function as an event that may promote tumor initiation and progression, point to ATM as a bona fide tumor suppressor. The identification of ATM as a positive modulator of several signalling networks that sustain tumorigenesis, including oxidative stress, hypoxia, receptor tyrosine kinase and AKT serine-threonine kinase activation, raise the question of whether ATM function in cancer may be more complex. This review aims to give a complete overview on the work of several labs that links ATM to the control of the balance between cell survival, proliferation and death in cancer. PMID:24681585

  20. 10 CFR 205.193 - Notice of Objection.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Appeals. The Notice shall be filed in duplicate, shall briefly describe how the person would be aggrieved... 10 Energy 3 2010-01-01 2010-01-01 false Notice of Objection. 205.193 Section 205.193 Energy DEPARTMENT OF ENERGY OIL ADMINISTRATIVE PROCEDURES AND SANCTIONS Notice of Probable Violation, Remedial Order...

  1. 10 CFR 205.193 - Notice of Objection.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Appeals. The Notice shall be filed in duplicate, shall briefly describe how the person would be aggrieved... 10 Energy 3 2011-01-01 2011-01-01 false Notice of Objection. 205.193 Section 205.193 Energy DEPARTMENT OF ENERGY OIL ADMINISTRATIVE PROCEDURES AND SANCTIONS Notice of Probable Violation, Remedial Order...

  2. ATM photoheliograph. [at a solar observatory

    NASA Technical Reports Server (NTRS)

    Prout, R. A.

    1975-01-01

    The design and fabrication are presented of a 65 cm photoheliograph functional verification unit (FVU) installed in a major solar observatory. The telescope is used in a daily program of solar observation while serving as a test bed for the development of instrumentation to be included in early space shuttle launched solar telescopes. The 65 cm FVU was designed to be mechanically compatible with the ATM spar/canister and would be adaptable to a second ATM flight utilizing the existing spar/canister configuration. An image motion compensation breadboard and a space-hardened, remotely tuned H alpha filter, as well as solar telescopes of different optical configurations or increased aperture are discussed.

  3. DNA damage checkpoint kinase ATM regulates germination and maintains genome stability in seeds

    PubMed Central

    Waterworth, Wanda M.; Footitt, Steven; Bray, Clifford M.; Finch-Savage, William E.; West, Christopher E.

    2016-01-01

    Genome integrity is crucial for cellular survival and the faithful transmission of genetic information. The eukaryotic cellular response to DNA damage is orchestrated by the DNA damage checkpoint kinases ATAXIA TELANGIECTASIA MUTATED (ATM) and ATM AND RAD3-RELATED (ATR). Here we identify important physiological roles for these sensor kinases in control of seed germination. We demonstrate that double-strand breaks (DSBs) are rate-limiting for germination. We identify that desiccation tolerant seeds exhibit a striking transcriptional DSB damage response during germination, indicative of high levels of genotoxic stress, which is induced following maturation drying and quiescence. Mutant atr and atm seeds are highly resistant to aging, establishing ATM and ATR as determinants of seed viability. In response to aging, ATM delays germination, whereas atm mutant seeds germinate with extensive chromosomal abnormalities. This identifies ATM as a major factor that controls germination in aged seeds, integrating progression through germination with surveillance of genome integrity. Mechanistically, ATM functions through control of DNA replication in imbibing seeds. ATM signaling is mediated by transcriptional control of the cell cycle inhibitor SIAMESE-RELATED 5, an essential factor required for the aging-induced delay to germination. In the soil seed bank, seeds exhibit increased transcript levels of ATM and ATR, with changes in dormancy and germination potential modulated by environmental signals, including temperature and soil moisture. Collectively, our findings reveal physiological functions for these sensor kinases in linking genome integrity to germination, thereby influencing seed quality, crucial for plant survival in the natural environment and sustainable crop production. PMID:27503884

  4. DNA damage checkpoint kinase ATM regulates germination and maintains genome stability in seeds.

    PubMed

    Waterworth, Wanda M; Footitt, Steven; Bray, Clifford M; Finch-Savage, William E; West, Christopher E

    2016-08-23

    Genome integrity is crucial for cellular survival and the faithful transmission of genetic information. The eukaryotic cellular response to DNA damage is orchestrated by the DNA damage checkpoint kinases ATAXIA TELANGIECTASIA MUTATED (ATM) and ATM AND RAD3-RELATED (ATR). Here we identify important physiological roles for these sensor kinases in control of seed germination. We demonstrate that double-strand breaks (DSBs) are rate-limiting for germination. We identify that desiccation tolerant seeds exhibit a striking transcriptional DSB damage response during germination, indicative of high levels of genotoxic stress, which is induced following maturation drying and quiescence. Mutant atr and atm seeds are highly resistant to aging, establishing ATM and ATR as determinants of seed viability. In response to aging, ATM delays germination, whereas atm mutant seeds germinate with extensive chromosomal abnormalities. This identifies ATM as a major factor that controls germination in aged seeds, integrating progression through germination with surveillance of genome integrity. Mechanistically, ATM functions through control of DNA replication in imbibing seeds. ATM signaling is mediated by transcriptional control of the cell cycle inhibitor SIAMESE-RELATED 5, an essential factor required for the aging-induced delay to germination. In the soil seed bank, seeds exhibit increased transcript levels of ATM and ATR, with changes in dormancy and germination potential modulated by environmental signals, including temperature and soil moisture. Collectively, our findings reveal physiological functions for these sensor kinases in linking genome integrity to germination, thereby influencing seed quality, crucial for plant survival in the natural environment and sustainable crop production.

  5. Kinase-dead ATM protein is highly oncogenic and can be preferentially targeted by Topo-isomerase I inhibitors

    PubMed Central

    Yamamoto, Kenta; Wang, Jiguang; Sprinzen, Lisa; Xu, Jun; Haddock, Christopher J; Li, Chen; Lee, Brian J; Loredan, Denis G; Jiang, Wenxia; Vindigni, Alessandro; Wang, Dong; Rabadan, Raul; Zha, Shan

    2016-01-01

    Missense mutations in ATM kinase, a master regulator of DNA damage responses, are found in many cancers, but their impact on ATM function and implications for cancer therapy are largely unknown. Here we report that 72% of cancer-associated ATM mutations are missense mutations that are enriched around the kinase domain. Expression of kinase-dead ATM (AtmKD/-) is more oncogenic than loss of ATM (Atm-/-) in mouse models, leading to earlier and more frequent lymphomas with Pten deletions. Kinase-dead ATM protein (Atm-KD), but not loss of ATM (Atm-null), prevents replication-dependent removal of Topo-isomerase I-DNA adducts at the step of strand cleavage, leading to severe genomic instability and hypersensitivity to Topo-isomerase I inhibitors. Correspondingly, Topo-isomerase I inhibitors effectively and preferentially eliminate AtmKD/-, but not Atm-proficientor Atm-/- leukemia in animal models. These findings identify ATM kinase-domain missense mutations as a potent oncogenic event and a biomarker for Topo-isomerase I inhibitor based therapy. DOI: http://dx.doi.org/10.7554/eLife.14709.001 PMID:27304073

  6. 49 CFR 193.2013 - Incorporation by reference.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Association (AGA), 400 North Capitol Street, NW., Washington, DC 20001. B. American Society of Civil Engineers...), Three Park Avenue, New York, NY 10016-5990. D. Gas Technology Institute (GTI), 1700 S. Mount Prospect... 2008, addendum 1, March 2009) §§ 193.2101(b); 193.2321(b)(2). C. American Society of Civil Engineers...

  7. 49 CFR 193.2009 - Rules of regulatory construction.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 193.2009 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES: FEDERAL SAFETY STANDARDS General § 193.2009 Rules of regulatory...

  8. Experiences with ATM in a multivendor pilot system at Forschungszentrum Julich

    NASA Astrophysics Data System (ADS)

    Kleines, H.; Ziemons, K.; Zwoll, K.

    1998-08-01

    The ATM technology for high speed serial transmission provides a new quality of communication by introducing novel features in a LAN environment, especially support of real time communication, of both LAN and WAN communication and of multimedia streams. In order to evaluate ATM for future DAQ systems and remote control systems as well as for a high speed picture archiving and communications system for medical images, Forschungszentrum Julich has build up a pilot system for the evaluation of ATM and standard low cost multimedia systems. It is a heterogeneous multivendor system containing a variety of switches and desktop solutions, employing different protocol options of ATM. The tests conducted in the pilot system revealed major difficulties regarding stability, interoperability and performance. The paper presents motivations, layout and results of the pilot system. Discussion of results concentrates on performance issues relevant for realistic applications, e.g., connection to a RAID system via NFS over ATM.

  9. ATM Protein Physically and Functionally Interacts with Proliferating Cell Nuclear Antigen to Regulate DNA Synthesis*

    PubMed Central

    Gamper, Armin M.; Choi, Serah; Matsumoto, Yoshihiro; Banerjee, Dibyendu; Tomkinson, Alan E.; Bakkenist, Christopher J.

    2012-01-01

    Ataxia telangiectasia (A-T) is a pleiotropic disease, with a characteristic hypersensitivity to ionizing radiation that is caused by biallelic mutations in A-T mutated (ATM), a gene encoding a protein kinase critical for the induction of cellular responses to DNA damage, particularly to DNA double strand breaks. A long known characteristic of A-T cells is their ability to synthesize DNA even in the presence of ionizing radiation-induced DNA damage, a phenomenon termed radioresistant DNA synthesis. We previously reported that ATM kinase inhibition, but not ATM protein disruption, blocks sister chromatid exchange following DNA damage. We now show that ATM kinase inhibition, but not ATM protein disruption, also inhibits DNA synthesis. Investigating a potential physical interaction of ATM with the DNA replication machinery, we found that ATM co-precipitates with proliferating cell nuclear antigen (PCNA) from cellular extracts. Using bacterially purified ATM truncation mutants and in vitro translated PCNA, we showed that the interaction is direct and mediated by the C terminus of ATM. Indeed, a 20-amino acid region close to the kinase domain is sufficient for strong binding to PCNA. This binding is specific to ATM, because the homologous regions of other PIKK members, including the closely related kinase A-T and Rad3-related (ATR), did not bind PCNA. ATM was found to bind two regions in PCNA. To examine the functional significance of the interaction between ATM and PCNA, we tested the ability of ATM to stimulate DNA synthesis by DNA polymerase δ, which is implicated in both DNA replication and DNA repair processes. ATM was observed to stimulate DNA polymerase activity in a PCNA-dependent manner. PMID:22362778

  10. High-Performance Computational Modeling of ICRF Physics and Plasma-Surface Interactions in Alcator C-Mod

    NASA Astrophysics Data System (ADS)

    Jenkins, Thomas; Smithe, David

    2016-10-01

    Inefficiencies and detrimental physical effects may arise in conjunction with ICRF heating of tokamak plasmas. Large wall potential drops, associated with sheath formation near plasma-facing antenna hardware, give rise to high-Z impurity sputtering from plasma-facing components and subsequent radiative cooling. Linear and nonlinear wave excitations in the plasma edge/SOL also dissipate injected RF power and reduce overall antenna efficiency. Recent advances in finite-difference time-domain (FDTD) modeling techniques allow the physics of localized sheath potentials, and associated sputtering events, to be modeled concurrently with the physics of antenna near- and far-field behavior and RF power flow. The new methods enable time-domain modeling of plasma-surface interactions and ICRF physics in realistic experimental configurations at unprecedented spatial resolution. We present results/animations from high-performance (10k-100k core) FDTD/PIC simulations spanning half of Alcator C-Mod at mm-scale resolution, exploring impurity production due to localized sputtering (in response to self-consistent sheath potentials at antenna surfaces) and the physics of parasitic slow wave excitation near the antenna hardware and SOL. Supported by US DoE (Award DE-SC0009501) and the ALCC program.

  11. ICRF antenna-plasma interactions and its influence on W sputtering in ASDEX upgrade

    NASA Astrophysics Data System (ADS)

    ASDEX Upgrade Team Bobkov, Vl.; Braun, F.; Colas, L.; Dux, R.; Faugel, H.; Giannone, L.; Herrmann, A.; Kallenbach, A.; Müller, H. W.; Neu, R.; Noterdaeme, J.-M.; Pütterich, Th.; Siegl, G.; Wolfrum, E.

    2011-08-01

    Analysis of the W concentration during ICRF over AUG experimental campaigns confirms the critical role of W antenna limiters for the W content in plasma, though other structures connected to antennas along magnetic field lines cannot be neglected as W sources.Abrupt changes of spectroscopically measured W sputtering patterns are observed which correlate with step-wise changes of connection lengths at antenna limiters. Analysis of discharges with the reversed direction of toroidal magnetic field shows less W release compared to identical discharges with the normal direction. The lower W release is accompanied by lower intensity of fluctuations of reflected ICRF power in the 1-60 kHz range. The observations suggest that local magnetic geometry and density convection at the antennas are at least as important for the W sputtering as the distribution of RF near-fields at the antenna.Measurements of DC currents flowing through the antenna limiters show that the limiters at the active antenna collect predominantly negative DC currents whereas those distant from the active antenna collect predominantly positive DC currents. The latter decrease and become more negative when the intensity of the RF pickup measured at the limiters increases. The mutual compensation between the positive and negative currents can lead to lower values of the DC current than those expected from simplified theoretical models of the RF/DC circuit.

  12. ICRF antenna-plasma interactions and its influence on W sputtering in ASDEX upgrade

    NASA Astrophysics Data System (ADS)

    Bobkov, Vl.; Braun, F.; Colas, L.; Dux, R.; Faugel, H.; Giannone, L.; Herrmann, A.; Kallenbach, A.; Müller, H. W.; Neu, R.; Noterdaeme, J.-M.; Pütterich, Th.; Siegl, G.; Wolfrum, E.; ASDEX Upgrade Team

    2011-08-01

    Analysis of the W concentration during ICRF over AUG experimental campaigns confirms the critical role of W antenna limiters for the W content in plasma, though other structures connected to antennas along magnetic field lines cannot be neglected as W sources. Abrupt changes of spectroscopically measured W sputtering patterns are observed which correlate with step-wise changes of connection lengths at antenna limiters. Analysis of discharges with the reversed direction of toroidal magnetic field shows less W release compared to identical discharges with the normal direction. The lower W release is accompanied by lower intensity of fluctuations of reflected ICRF power in the 1-60 kHz range. The observations suggest that local magnetic geometry and density convection at the antennas are at least as important for the W sputtering as the distribution of RF near-fields at the antenna. Measurements of DC currents flowing through the antenna limiters show that the limiters at the active antenna collect predominantly negative DC currents whereas those distant from the active antenna collect predominantly positive DC currents. The latter decrease and become more negative when the intensity of the RF pickup measured at the limiters increases. The mutual compensation between the positive and negative currents can lead to lower values of the DC current than those expected from simplified theoretical models of the RF/DC circuit.

  13. Phase-shift/transmittance measurements in a micro pattern using MPM193EX

    NASA Astrophysics Data System (ADS)

    Nozawa, Hiroto; Ishida, Takayuki; Kato, Satoru; Sato, Osamu; Miyazaki, Koji; Takehisa, Kiwamu; Awamura, Naoki; Takizawa, Hideo; Kusunose, Hal

    2009-04-01

    A new direct Phase-shift/Transmittance measurement tool "MPM193EX" has been developed to respond to the growing demand for higher precision measurements of finer patterns in ArF Lithography. Specifications of MPM193EX are listed below along with corresponding specifications of the conventional tool MPM193. 1) Phase-shift [3 Sigma]: 0.5 deg. (MPM193) => 0.2 deg. (MPM193EX) 2) Transmittance [3 Sigma]: 0.20 % (MPM193) => 0.04 % (MPM193EX) 3) Minimum measurement pattern width: 7.5 μm (MPM193) => 1.0 μm (MPM193EX) Furthermore, new design optics using an ArF Laser and an objective lens with long working distance allows measurements of masks with pellicles. The new method for improving the measurement repeatability is based on elimination of influence from instantaneous fluctuation in interferometer fringes by scanning two adjacent areas simultaneously. Also, MPM193EX is equipped with high-resolution and stable optics. The newly employed auto-focus system in MPM193EX accurately adjusts, by a new image processing method using high-resolution optics, the focus height that is one of the most important factors for measurements in a micro pattern.

  14. 193-nm multilayer imaging systems

    NASA Astrophysics Data System (ADS)

    Meador, James D.; Holmes, Doug; DiMenna, William; Nagatkina, Mariya I.; Rich, Michael D.; Flaim, Tony D.; Bennett, Randy; Kobayashi, Ichiro

    2003-06-01

    This paper highlights the performance of new materials that have been developed for use in 193-nm trilayer microlithography. The products are embedded etch masking layers (EMLs) and bottom antireflective coatings (BARCs). Both coatings are spin applied from organic solvent(s) and then thermoset during a hot plate bake. The EMLs (middle layers) are imaging compatible with JSR, Sumitomo, and TOK 193-nm photoresists. Best-case trilayer film stacks have given 100-nm dense and semi-dense L/S. Plasma etching, selectivities and solution compatibility performance of the EMLs meet or exceed proposed product targets. In addition, the EMLs exhibit both solution and plasma etching properties that should lead to successful rework processes for photoresists. The multiplayer BARCs offer good thick film coating quality and contribute to excellent images when used in trilayer applications. Combining the EMLs, which are nearly optically transparent (k=0.04) at 193-nm, with the new trilayer BARCs results in outstanding Prolith simulated reflectance control. In one modeling example, reflectance is a flat line at 0.5% on five different substrates for BARC thicknesses between 300 and 700-nm.

  15. ATM QoS Experiments Using TCP Applications: Performance of TCP/IP Over ATM in a Variety of Errored Links

    NASA Technical Reports Server (NTRS)

    Frantz, Brian D.; Ivancic, William D.

    2001-01-01

    Asynchronous Transfer Mode (ATM) Quality of Service (QoS) experiments using the Transmission Control Protocol/Internet Protocol (TCP/IP) were performed for various link delays. The link delay was set to emulate a Wide Area Network (WAN) and a Satellite Link. The purpose of these experiments was to evaluate the ATM QoS requirements for applications that utilize advance TCP/IP protocols implemented with large windows and Selective ACKnowledgements (SACK). The effects of cell error, cell loss, and random bit errors on throughput were reported. The detailed test plan and test results are presented herein.

  16. ATM: The Key To Harnessing the Power of Networked Multimedia.

    ERIC Educational Resources Information Center

    Gross, Rod

    1996-01-01

    ATM (Asynchronous Transfer Mode) network technology handles the real-time continuous traffic flow necessary to support desktop multimedia applications. Describes network applications already used: desktop video collaboration, distance learning, and broadcasting video delivery. Examines the architecture of ATM technology, video delivery and sound…

  17. Extending the ICRF into the Infrared: 2MASS - UCAC Astrometry

    NASA Technical Reports Server (NTRS)

    Zacharias, Norbert; McCallon, Howard L.; Kopan, Eugene; Cutri, Roc M.

    2000-01-01

    An external comparison between the infrared 2MASS and the optical UCAC positions was performed, both being on the same system, the ICRS. About 48 million sources in common were identified. Random errors of the 2MASS catalog positions are about 60 to 70 mas per coordinate for the Ks = 4 to 14 range, increasing to about 100 to 150 mas for saturated and very faint stars. Systematic position differences between the 2 catalogs are very small, about 5 to 10 mas as a function of magnitude and color, with somewhat larger errors as a function of right ascension and declination. The extension of the ICRF into the infrared has become a reality.

  18. 47 CFR 95.193 - (FRS Rule 3) Types of communications.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false (FRS Rule 3) Types of communications. 95.193 Section 95.193 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PERSONAL RADIO SERVICES Family Radio Service (FRS) General Provisions § 95.193 (FRS Rule 3) Types...

  19. ASCIZ/ATMIN is dispensable for ATM signaling in response to replication stress.

    PubMed

    Liu, Rui; King, Ashleigh; Hoch, Nicolas C; Chang, Catherine; Kelly, Gemma L; Deans, Andrew J; Heierhorst, Jörg

    2017-09-01

    The ATM kinase plays critical roles in the response to DNA double-strand breaks, and can also be activated by prolonged DNA replication blocks. It has recently been proposed that replication stress-dependent ATM activation is mediated by ASCIZ (also known as ATMIN, ZNF822), an essential developmental transcription factor. In contrast, we show here that ATM activation, and phosphorylation of its substrates KAP1, p53 and H2AX in response to the replication blocking agent aphidicolin was unaffected in both immortalized and primary ASCIZ/ATMIN-deficient murine embryonic fibroblasts compared to control cells. Similar results were also obtained in human ASCIZ/ATMIN-deleted lymphoma cells. The results demonstrate that ASCIZ/ATMIN is dispensable for ATM activation, and contradict the previously reported dependence of ATM on ASCIZ/ATMIN. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  20. Role of ataxia-telangiectasia mutated (ATM) in porcine oocyte in vitro maturation.

    PubMed

    Lin, Zi-Li; Kim, Nam-Hyung

    2015-06-01

    Ataxia-telangiectasia mutated (ATM) is critical for the DNA damage response, cell cycle checkpoints, and apoptosis. Significant effort has focused on elucidating the relationship between ATM and other nuclear signal transducers; however, little is known about the connection between ATM and oocyte meiotic maturation. We investigated the function of ATM in porcine oocytes. ATM was expressed at all stages of oocyte maturation and localized predominantly in the nucleus. Furthermore, the ATM-specific inhibitor KU-55933 blocked porcine oocyte maturation, reducing the percentages of oocytes that underwent germinal vesicle breakdown (GVBD) and first polar body extrusion. KU-55933 also decreased the expression of DNA damage-related genes (breast cancer 1, budding uninhibited by benzimidazoles 1, and P53) and reduced the mRNA and protein levels of AKT and other cell cycle-regulated genes that are predominantly expressed during G2/M phase, including bone morphogenetic protein 15, growth differentiation factor 9, cell division cycle protein 2, cyclinB1, and AKT. KU-55933 treatment decreased the developmental potential of blastocysts following parthenogenetic activation and increased the level of apoptosis. Together, these data suggested that ATM influenced the meiotic and cytoplasmic maturation of porcine oocytes, potentially by decreasing their sensitivity to DNA strand breaks, stimulating the AKT pathway, and/or altering the expression of other maternal genes. © 2015 International Federation for Cell Biology.

  1. ATMS Step By Step.

    ERIC Educational Resources Information Center

    National Library of Australia, Canberra.

    This manual is designed to provide an introduction and basic guide to the use of IBM's Advanced Text Management System (ATMS), the text processing system to be used for the creation of Australian data bases within AUSINET. Instructions are provided for using the system to enter, store, retrieve, and modify data, which may then be displayed at the…

  2. ATR- and ATM-Mediated DNA Damage Response Is Dependent on Excision Repair Assembly during G1 but Not in S Phase of Cell Cycle.

    PubMed

    Ray, Alo; Blevins, Chessica; Wani, Gulzar; Wani, Altaf A

    2016-01-01

    Cell cycle checkpoint is mediated by ATR and ATM kinases, as a prompt early response to a variety of DNA insults, and culminates in a highly orchestrated signal transduction cascade. Previously, we defined the regulatory role of nucleotide excision repair (NER) factors, DDB2 and XPC, in checkpoint and ATR/ATM-dependent repair pathway via ATR and ATM phosphorylation and recruitment to ultraviolet radiation (UVR)-induced damage sites. Here, we have dissected the molecular mechanisms of DDB2- and XPC- mediated regulation of ATR and ATM recruitment and activation upon UVR exposures. We show that the ATR and ATM activation and accumulation to UVR-induced damage not only depends on DDB2 and XPC, but also on the NER protein XPA, suggesting that the assembly of an active NER complex is essential for ATR and ATM recruitment. ATR and ATM localization and H2AX phosphorylation at the lesion sites occur as early as ten minutes in asynchronous as well as G1 arrested cells, showing that repair and checkpoint-mediated by ATR and ATM starts early upon UV irradiation. Moreover, our results demonstrated that ATR and ATM recruitment and H2AX phosphorylation are dependent on NER proteins in G1 phase, but not in S phase. We reasoned that in G1 the UVR-induced ssDNA gaps or processed ssDNA, and the bound NER complex promote ATR and ATM recruitment. In S phase, when the UV lesions result in stalled replication forks with long single-stranded DNA, ATR and ATM recruitment to these sites is regulated by different sets of proteins. Taken together, these results provide evidence that UVR-induced ATR and ATM recruitment and activation differ in G1 and S phases due to the existence of distinct types of DNA lesions, which promote assembly of different proteins involved in the process of DNA repair and checkpoint activation.

  3. Quantitative and Dynamic Imaging of ATM Kinase Activity by Bioluminescence Imaging.

    PubMed

    Nyati, Shyam; Young, Grant; Ross, Brian Dale; Rehemtulla, Alnawaz

    2017-01-01

    Ataxia telangiectasia mutated (ATM) is a serine/threonine kinase critical to the cellular DNA damage response, including DNA double strand breaks (DSBs). ATM activation results in the initiation of a complex cascade of events facilitating DNA damage repair, cell cycle checkpoint control, and survival. Traditionally, protein kinases have been analyzed in vitro using biochemical methods (kinase assays using purified proteins or immunological assays) requiring a large number of cells and cell lysis. Genetically encoded biosensors based on optical molecular imaging such as fluorescence or bioluminescence have been developed to enable interrogation of kinase activities in live cells with a high signal to background. We have genetically engineered a hybrid protein whose bioluminescent activity is dependent on the ATM-mediated phosphorylation of a substrate. The engineered protein consists of the split luciferase-based protein complementation pair with a CHK2 (a substrate for ATM kinase activity) target sequence and a phospho-serine/threonine-binding domain, FHA2, derived from yeast Rad53. Phosphorylation of the serine residue within the target sequence by ATM would lead to its interaction with the phospho-serine-binding domain, thereby preventing complementation of the split luciferase pair and loss of reporter activity. Bioluminescence imaging of reporter-expressing cells in cultured plates or as mouse xenografts provides a quantitative surrogate for ATM kinase activity and therefore the cellular DNA damage response in a noninvasive, dynamic fashion.

  4. A predictive transport modeling code for ICRF-heated tokamaks

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

    Phillips, C.K.; Hwang, D.Q.; Houlberg, W.

    In this report, a detailed description of the physic included in the WHIST/RAZE package as well as a few illustrative examples of the capabilities of the package will be presented. An in depth analysis of ICRF heating experiments using WHIST/RAZE will be discussed in a forthcoming report. A general overview of philosophy behind the structure of the WHIST/RAZE package, a summary of the features of the WHIST code, and a description of the interface to the RAZE subroutines are presented in section 2 of this report. Details of the physics contained in the RAZE code are examined in section 3.more » Sample results from the package follow in section 4, with concluding remarks and a discussion of possible improvements to the package discussed in section 5.« less

  5. A predictive transport modeling code for ICRF-heated tokamaks

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

    Phillips, C.K.; Hwang, D.Q.; Houlberg, W.

    1992-02-01

    In this report, a detailed description of the physic included in the WHIST/RAZE package as well as a few illustrative examples of the capabilities of the package will be presented. An in depth analysis of ICRF heating experiments using WHIST/RAZE will be discussed in a forthcoming report. A general overview of philosophy behind the structure of the WHIST/RAZE package, a summary of the features of the WHIST code, and a description of the interface to the RAZE subroutines are presented in section 2 of this report. Details of the physics contained in the RAZE code are examined in section 3.more » Sample results from the package follow in section 4, with concluding remarks and a discussion of possible improvements to the package discussed in section 5.« less

  6. The Role of Combined ICRF and NBI Heating in JET Hybrid Plasmas in Quest for High D-T Fusion Yield

    NASA Astrophysics Data System (ADS)

    Mantsinen, Mervi; Challis, Clive; Frigione, Domenico; Graves, Jonathan; Hobirk, Joerg; Belonohy, Eva; Czarnecka, Agata; Eriksson, Jacob; Gallart, Dani; Goniche, Marc; Hellesen, Carl; Jacquet, Philippe; Joffrin, Emmanuel; King, Damian; Krawczyk, Natalia; Lennholm, Morten; Lerche, Ernesto; Pawelec, Ewa; Sips, George; Solano, Emilia R.; Tsalas, Maximos; Valisa, Marco

    2017-10-01

    Combined ICRF and NBI heating played a key role in achieving the world-record fusion yield in the first deuterium-tritium campaign at the JET tokamak in 1997. The current plans for JET include new experiments with deuterium-tritium (D-T) plasmas with more ITER-like conditions given the recently installed ITER-like wall (ILW). In the 2015-2016 campaigns, significant efforts have been devoted to the development of high-performance plasma scenarios compatible with ILW in preparation of the forthcoming D-T campaign. Good progress was made in both the inductive (baseline) and the hybrid scenario: a new record JET ILW fusion yield with a significantly extended duration of the high-performance phase was achieved. This paper reports on the progress with the hybrid scenario which is a candidate for ITER longpulse operation (˜1000 s) thanks to its improved normalized confinement, reduced plasma current and higher plasma beta with respect to the ITER reference baseline scenario. The combined NBI+ICRF power in the hybrid scenario was increased to 33 MW and the record fusion yield, averaged over 100 ms, to 2.9x1016 neutrons/s from the 2014 ILW fusion record of 2.3x1016 neutrons/s. Impurity control with ICRF waves was one of the key means for extending the duration of the high-performance phase. The main results are reviewed covering both key core and edge plasma issues.

  7. Radiation induces genomic instability and mammary ductal dysplasia in Atm heterozygous mice

    NASA Technical Reports Server (NTRS)

    Weil, M. M.; Kittrell, F. S.; Yu, Y.; McCarthy, M.; Zabriskie, R. C.; Ullrich, R. L.

    2001-01-01

    Ataxia-telangiectasia (AT) is a genetic syndrome resulting from the inheritance of two defective copies of the ATM gene that includes among its stigmata radiosensitivity and cancer susceptibility. Epidemiological studies have demonstrated that although women with a single defective copy of ATM (AT heterozygotes) appear clinically normal, they may never the less have an increased relative risk of developing breast cancer. Whether they are at increased risk for radiation-induced breast cancer from medical exposures to ionizing radiation is unknown. We have used a murine model of AT to investigate the effect of a single defective Atm allele, the murine homologue of ATM, on the susceptibility of mammary epithelial cells to radiation-induced transformation. Here we report that mammary epithelial cells from irradiated mice with one copy of Atm truncated in the PI-3 kinase domain were susceptible to radiation-induced genomic instability and generated a 10% incidence of dysplastic mammary ducts when transplanted into syngenic recipients, whereas cells from Atm(+/+) mice were stable and formed only normal ducts. Since radiation-induced ductal dysplasia is a precursor to mammary cancer, the results indicate that AT heterozygosity increases susceptibility to radiogenic breast cancer in this murine model system.

  8. ATM-Mediated Transcriptional and Developmental Responses to γ-rays in Arabidopsis

    PubMed Central

    Renou, Jean-Pierre; Pichon, Olivier; Fochesato, Sylvain; Ortet, Philippe; Montané, Marie-Hélène

    2007-01-01

    ATM (Ataxia Telangiectasia Mutated) is an essential checkpoint kinase that signals DNA double-strand breaks in eukaryotes. Its depletion causes meiotic and somatic defects in Arabidopsis and progressive motor impairment accompanied by several cell deficiencies in patients with ataxia telangiectasia (AT). To obtain a comprehensive view of the ATM pathway in plants, we performed a time-course analysis of seedling responses by combining confocal laser scanning microscopy studies of root development and genome-wide expression profiling of wild-type (WT) and homozygous ATM-deficient mutants challenged with a dose of γ-rays (IR) that is sublethal for WT plants. Early morphologic defects in meristematic stem cells indicated that AtATM, an Arabidopsis homolog of the human ATM gene, is essential for maintaining the quiescent center and controlling the differentiation of initial cells after exposure to IR. Results of several microarray experiments performed with whole seedlings and roots up to 5 h post-IR were compiled in a single table, which was used to import gene information and extract gene sets. Sequence and function homology searches; import of spatio-temporal, cell cycling, and mutant-constitutive expression characteristics; and a simplified functional classification system were used to identify novel genes in all functional classes. The hundreds of radiomodulated genes identified were not a random collection, but belonged to functional pathways such as those of the cell cycle; cell death and repair; DNA replication, repair, and recombination; and transcription; translation; and signaling, indicating the strong cell reprogramming and double-strand break abrogation functions of ATM checkpoints. Accordingly, genes in all functional classes were either down or up-regulated concomitantly with downregulation of chromatin deacetylases or upregulation of acetylases and methylases, respectively. Determining the early transcriptional indicators of prolonged S-G2 phases that

  9. ATM-mediated transcriptional and developmental responses to gamma-rays in Arabidopsis.

    PubMed

    Ricaud, Lilian; Proux, Caroline; Renou, Jean-Pierre; Pichon, Olivier; Fochesato, Sylvain; Ortet, Philippe; Montané, Marie-Hélène

    2007-05-09

    ATM (Ataxia Telangiectasia Mutated) is an essential checkpoint kinase that signals DNA double-strand breaks in eukaryotes. Its depletion causes meiotic and somatic defects in Arabidopsis and progressive motor impairment accompanied by several cell deficiencies in patients with ataxia telangiectasia (AT). To obtain a comprehensive view of the ATM pathway in plants, we performed a time-course analysis of seedling responses by combining confocal laser scanning microscopy studies of root development and genome-wide expression profiling of wild-type (WT) and homozygous ATM-deficient mutants challenged with a dose of gamma-rays (IR) that is sublethal for WT plants. Early morphologic defects in meristematic stem cells indicated that AtATM, an Arabidopsis homolog of the human ATM gene, is essential for maintaining the quiescent center and controlling the differentiation of initial cells after exposure to IR. Results of several microarray experiments performed with whole seedlings and roots up to 5 h post-IR were compiled in a single table, which was used to import gene information and extract gene sets. Sequence and function homology searches; import of spatio-temporal, cell cycling, and mutant-constitutive expression characteristics; and a simplified functional classification system were used to identify novel genes in all functional classes. The hundreds of radiomodulated genes identified were not a random collection, but belonged to functional pathways such as those of the cell cycle; cell death and repair; DNA replication, repair, and recombination; and transcription; translation; and signaling, indicating the strong cell reprogramming and double-strand break abrogation functions of ATM checkpoints. Accordingly, genes in all functional classes were either down or up-regulated concomitantly with downregulation of chromatin deacetylases or upregulation of acetylases and methylases, respectively. Determining the early transcriptional indicators of prolonged S-G2 phases

  10. The Advanced Technology Microwave Sounder (ATMS): A New Operational Sensor Series

    NASA Technical Reports Server (NTRS)

    Kim, Edward; Lyu, Cheng-H Joseph; Leslie, R. Vince; Baker, Neal; Mo, Tsan; Sun, Ninghai; Bi, Li; Anderson, Mike; Landrum, Mike; DeAmici, Giovanni; hide

    2012-01-01

    ATMS is a new satellite microwave sounding sensor designed to provide operational weather agencies with atmospheric temperature and moisture profile information for global weather forecasting and climate applications. ATMS will continue the microwave sounding capabilities first provided by its predecessors, the Microwave Sounding Unit (MSU) and Advanced Microwave Sounding Unit (AMSU). The first ATMS was launched October 28, 2011 on board the Suomi National Polar-orbiting Partnership (S-NPP) satellite. Microwave soundings by themselves are the highest-impact input data used by Numerical Weather Prediction (NWP) models; and ATMS, when combined with the Cross-track Infrared Sounder (CrIS), forms the Cross-track Infrared and Microwave Sounding Suite (CrIMSS). The microwave soundings help meet NWP sounding requirements under cloudy sky conditions and provide key profile information near the surface

  11. 27 CFR 479.193 - Arms Export Control Act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2010-04-01 2010-04-01 false Arms Export Control Act. 479.193 Section 479.193 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND...

  12. 27 CFR 479.193 - Arms Export Control Act.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2012-04-01 2010-04-01 true Arms Export Control Act. 479.193 Section 479.193 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND...

  13. 27 CFR 479.193 - Arms Export Control Act.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2011-04-01 2010-04-01 true Arms Export Control Act. 479.193 Section 479.193 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND...

  14. 27 CFR 479.193 - Arms Export Control Act.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2013-04-01 2013-04-01 false Arms Export Control Act. 479.193 Section 479.193 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND...

  15. 27 CFR 479.193 - Arms Export Control Act.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2014-04-01 2014-04-01 false Arms Export Control Act. 479.193 Section 479.193 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND...

  16. 21 CFR 133.193 - Spiced, flavored standardized cheeses.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Spiced, flavored standardized cheeses. 133.193... (CONTINUED) FOOD FOR HUMAN CONSUMPTION CHEESES AND RELATED CHEESE PRODUCTS Requirements for Specific Standardized Cheese and Related Products § 133.193 Spiced, flavored standardized cheeses. (a) Except as...

  17. 38 CFR 17.193 - Prerequisites for payments to State homes.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... payments to State homes. 17.193 Section 17.193 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS MEDICAL Aid to States for Care of Veterans in State Homes § 17.193 Prerequisites for payments to State homes. No payment or grant may be made to any State home unless the State home meets the...

  18. Snowfall Rate Retrieval using NPP ATMS Passive Microwave Measurements

    NASA Technical Reports Server (NTRS)

    Meng, Huan; Ferraro, Ralph; Kongoli, Cezar; Wang, Nai-Yu; Dong, Jun; Zavodsky, Bradley; Yan, Banghua; Zhao, Limin

    2014-01-01

    Passive microwave measurements at certain high frequencies are sensitive to the scattering effect of snow particles and can be utilized to retrieve snowfall properties. Some of the microwave sensors with snowfall sensitive channels are Advanced Microwave Sounding Unit (AMSU), Microwave Humidity Sounder (MHS) and Advance Technology Microwave Sounder (ATMS). ATMS is the follow-on sensor to AMSU and MHS. Currently, an AMSU and MHS based land snowfall rate (SFR) product is running operationally at NOAA/NESDIS. Based on the AMSU/MHS SFR, an ATMS SFR algorithm has been developed recently. The algorithm performs retrieval in three steps: snowfall detection, retrieval of cloud properties, and estimation of snow particle terminal velocity and snowfall rate. The snowfall detection component utilizes principal component analysis and a logistic regression model. The model employs a combination of temperature and water vapor sounding channels to detect the scattering signal from falling snow and derive the probability of snowfall (Kongoli et al., 2014). In addition, a set of NWP model based filters is also employed to improve the accuracy of snowfall detection. Cloud properties are retrieved using an inversion method with an iteration algorithm and a two-stream radiative transfer model (Yan et al., 2008). A method developed by Heymsfield and Westbrook (2010) is adopted to calculate snow particle terminal velocity. Finally, snowfall rate is computed by numerically solving a complex integral. The ATMS SFR product is validated against radar and gauge snowfall data and shows that the ATMS algorithm outperforms the AMSU/MHS SFR.

  19. ATM-deficiency increases genomic instability and metastatic potential in a mouse model of pancreatic cancer.

    PubMed

    Drosos, Yiannis; Escobar, David; Chiang, Ming-Yi; Roys, Kathryn; Valentine, Virginia; Valentine, Marc B; Rehg, Jerold E; Sahai, Vaibhav; Begley, Lesa A; Ye, Jianming; Paul, Leena; McKinnon, Peter J; Sosa-Pineda, Beatriz

    2017-09-11

    Germline mutations in ATM (encoding the DNA-damage signaling kinase, ataxia-telangiectasia-mutated) increase Familial Pancreatic Cancer (FPC) susceptibility, and ATM somatic mutations have been identified in resected human pancreatic tumors. Here we investigated how Atm contributes to pancreatic cancer by deleting this gene in a murine model of the disease expressing oncogenic Kras (Kras G12D ). We show that partial or total ATM deficiency cooperates with Kras G12D to promote highly metastatic pancreatic cancer. We also reveal that ATM is activated in pancreatic precancerous lesions in the context of DNA damage and cell proliferation, and demonstrate that ATM deficiency leads to persistent DNA damage in both precancerous lesions and primary tumors. Using low passage cultures from primary tumors and liver metastases we show that ATM loss accelerates Kras-induced carcinogenesis without conferring a specific phenotype to pancreatic tumors or changing the status of the tumor suppressors p53, p16 Ink4a and p19 Arf . However, ATM deficiency markedly increases the proportion of chromosomal alterations in pancreatic primary tumors and liver metastases. More importantly, ATM deficiency also renders murine pancreatic tumors highly sensitive to radiation. These and other findings in our study conclusively establish that ATM activity poses a major barrier to oncogenic transformation in the pancreas via maintaining genomic stability.

  20. SIDON: A simulator of radio-frequency networks. Application to WEST ICRF launchers

    NASA Astrophysics Data System (ADS)

    Helou, Walid; Dumortier, Pierre; Durodié, Frédéric; Goniche, Marc; Hillairet, Julien; Mollard, Patrick; Berger-By, Gilles; Bernard, Jean-Michel; Colas, Laurent; Lombard, Gilles; Maggiora, Riccardo; Magne, Roland; Milanesio, Daniele; Moreau, Didier

    2015-12-01

    SIDON (SImulator of raDiO-frequency Networks) is an in-house developed Radio-Frequency (RF) network solver that has been implemented to cross-validate the design of WEST ICRF launchers and simulate their impedance matching algorithm while considering all mutual couplings and asymmetries. In this paper, the authors illustrate the theory of SIDON as well as results of its calculations. The authors have built time-varying plasma scenarios (a sequence of launchers front-faces L-mode and H-mode Z-matrices), where at each time step (1 millisecond here), SIDON solves the RF network. At the same time, when activated, the impedance matching algorithm controls the matching elements (vacuum capacitors) and thus their corresponding S-matrices. Typically a 1-second pulse requires around 10 seconds of computational time on a desktop computer. These tasks can be hardly handled by commercial RF software. This innovative work allows identifying strategies for the launchers future operation while insuring the limitations on the currents, voltages and electric fields, matching and Load-Resilience, as well as the required straps voltage amplitude/phase balance. In this paper, a particular attention is paid to the simulation of the launchers behavior when arcs appear at several locations of their circuits using SIDON calculator. This latter work shall confirm or identify strategies for the arc detection using various RF electrical signals. One shall note that the use of such solvers in not limited to ICRF launchers simulations but can be employed, in principle, to any linear or linearized RF problem.

  1. 46 CFR 193.15-20 - Carbon dioxide storage.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Carbon dioxide storage. 193.15-20 Section 193.15-20 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS FIRE... storage. (a) Except as provided in paragraph (b) of this section, the cylinders shall be located outside...

  2. 46 CFR 193.15-20 - Carbon dioxide storage.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Carbon dioxide storage. 193.15-20 Section 193.15-20 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS FIRE... storage. (a) Except as provided in paragraph (b) of this section, the cylinders shall be located outside...

  3. 12 CFR 193.3 - Qualification of public accountant.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 1 2013-01-01 2013-01-01 false Qualification of public accountant. 193.3... REQUIREMENTS Form and Content of Financial Statements § 193.3 Qualification of public accountant. The term “qualified public accountant” means a certified public accountant or licensed public accountant certified or...

  4. 12 CFR 193.3 - Qualification of public accountant.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 1 2014-01-01 2014-01-01 false Qualification of public accountant. 193.3... REQUIREMENTS Form and Content of Financial Statements § 193.3 Qualification of public accountant. The term “qualified public accountant” means a certified public accountant or licensed public accountant certified or...

  5. 12 CFR 193.3 - Qualification of public accountant.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 1 2012-01-01 2012-01-01 false Qualification of public accountant. 193.3... REQUIREMENTS Form and Content of Financial Statements § 193.3 Qualification of public accountant. The term “qualified public accountant” means a certified public accountant or licensed public accountant certified or...

  6. Neural-tree call admission controller for ATM networks

    NASA Astrophysics Data System (ADS)

    Rughooputh, Harry C. S.

    1999-03-01

    Asynchronous Transfer Mode (ATM) has been recommended by ITU-T as the transport method for broadband integrated services digital networks. In high-speed ATM networks different types of multimedia traffic streams with widely varying traffic characteristics and Quality of Service (QoS) are asynchronously multiplexed on transmission links and switched without window flow control as found in X.25. In such an environment, a traffic control scheme is required to manage the required QoS of each class individually. To meet the QoS requirements, Bandwidth Allocation and Call Admission Control (CAC) in ATM networks must be able to adapt gracefully to the dynamic behavior of traffic and the time-varying nature of the network condition. In this paper, a Neural Network approach for CAC is proposed. The call admission problem is addressed by designing controllers based on Neural Tree Networks. Simulations reveal that the proposed scheme is not only simple but it also offers faster response than conventional neural/neuro-fuzzy controllers.

  7. ATM kinase is required for telomere elongation in mouse and human cells

    PubMed Central

    Lee, Stella Suyong; Bohrson, Craig; Pike, Alexandra Mims; Wheelan, Sarah Jo; Greider, Carol Widney

    2015-01-01

    Summary Short telomeres induce a DNA damage response, senescence and apoptosis; thus, maintaining telomere length equilibrium is essential for cell viability. Telomerase addition of telomere repeats is tightly regulated in cells. To probe pathways that regulate telomere addition, we developed the ADDIT assay to measure new telomere addition at a single telomere in vivo. Sequence analysis showed telomerase specific addition of repeats onto a new telomere occurred in just 48 hr. Using the ADDIT assay, we found that ATM is required for addition of new repeats onto telomeres in mouse cells. Evaluation of bulk telomeres, in both human and mouse cells, showed that blocking ATM inhibited telomere elongation. Finally, the activation of ATM through the inhibition of PARP1 resulted in increased telomere elongation, supporting the central role of the ATM pathway in regulating telomere addition. Understanding this role of ATM may yield new areas for possible therapeutic intervention in telomere-mediated disease. PMID:26586427

  8. Application of Computer Simulation to Teach ATM Access to Individuals with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Davies, Daniel K.; Stock, Steven E.; Wehmeyer, Michael L.

    2003-01-01

    This study investigates use of computer simulation for teaching ATM use to adults with intellectual disabilities. ATM-SIM is a computer-based trainer used for teaching individuals with intellectual disabilities how to use an automated teller machine (ATM) to access their personal bank accounts. In the pilot evaluation, a prototype system was…

  9. Ataxia-telangiectasia gene (ATM) mutation heterozygosity in breast cancer: a narrative review.

    PubMed

    Jerzak, K J; Mancuso, T; Eisen, A

    2018-04-01

    Despite the fact that heterozygosity for a pathogenic ATM variant is present in 1%-2% of the adult population, clinical guidelines to inform physicians and genetic counsellors about optimal management in that population are lacking. In this narrative review, we describe the challenges and controversies in the management of women who are heterozygous for a pathogenic ATM variant with respect to screening for breast and other malignancies, to choices for systemic therapy, and to decisions about radiation therapy. Given that the lifetime risk for breast cancer in women who are heterozygous for a pathogenic ATM variant is likely greater than 25%, those women should undergo annual mammographic screening starting at least by 40 years of age. For women in this group who have a strong family history of breast cancer, earlier screening with both magnetic resonance imaging and mammography should be considered. High-quality data to inform the management of established breast cancer in carriers of pathogenic ATM variants are lacking. Although deficiency in the ATM gene product might confer sensitivity to dna-damaging pharmaceuticals such as inhibitors of poly (adp-ribose) polymerase or platinum agents, prospective clinical trials have not been conducted in the relevant patient population. Furthermore, the evidence with respect to radiation therapy is mixed; some data suggest increased toxicity, and other data suggest improved clinical benefit from radiation in women who are carriers of a pathogenic ATM variant. As in the 2017 U.S. National Comprehensive Cancer Network guidelines, we recommend high-risk imaging for women in Ontario who are heterozygous for a pathogenic ATM variant. Currently, ATM carrier status should not influence decisions about systemic or radiation therapy in the setting of an established breast cancer diagnosis.

  10. 40 CFR 60.193 - Standard for visible emissions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Section 60.193 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... Reduction Plants § 60.193 Standard for visible emissions. (a) On and after the date on which the performance... which exhibit 10 percent opacity or greater, or (2) From any anode bake plant any gases which exhibit 20...

  11. Promoter Hypermethylation of the ATM Gene as a Novel Biomarker for Breast Cancer

    PubMed

    Begam, Nasrin; Jamil, Kaiser; Raju, Suryanarayana G

    2017-11-26

    Background: Breast cancer may be induced by activation of protooncogenes to oncogenes and in many cases inactivation of tumor suppressor genes. Ataxia telangiectasia mutated (ATM) is an important tumor suppressor gene which plays central roles in the maintenance of genomic integrity by activating cell cycle checkpoints and promoting repair of double-strand breaks of DNA. In breast cancer, decrease ATM expression correlates with a poor outcome; however, the molecular mechanisms underlying downregulation are still unclear. Promoter hypermethylation may contribute in downregulation. Hence the present investigation was designed to evaluate promoter methylation and expression of the ATM gene in breast cancer cases, and to determine links with clinical and demographic manifestations, in a South Indian population. Methods: Tumor biopsy samples were collected from 50 pathologically confirmed sporadic breast cancer cases. DNA was isolated from tumor and adjacent non-tumorous regions, and sodium bisulfite conversion and methylation-specific PCR were performed using MS-PCR primers for the ATM promoter region. In addition, ATM mRNA expression was also analyzed for all samples using real-time PCR. Results: Fifty eight percent (58%) of cancer tissue samples showed promoter hypermethylation for the ATM gene, in contrast to only 4.44% of normal tissues (p= 0.0001). Furthermore, ATM promoter methylation was positively associated with age (p = 0.01), tumor size (p=0.045) and advanced stage of disease i.e. stages III and IV (p =0.019). An association between promoter hypermethylation and lower expression of ATM mRNA was also found (p=0.035). Conclusion: We report for the first time that promoter hypermethylation of ATM gene may be useful as a potential new biomarker for breast cancer, especially in the relatively young patients. Creative Commons Attribution License

  12. Analysis of Chromosomal Aberrations after Low and High Dose Rate Gamma Irradiation in ATM or NBS Suppressed Human Fibroblast Cells

    NASA Technical Reports Server (NTRS)

    Hada, M.; Huff, J. L.; Patel, Z.; Pluth, J. M.; George, K. A.; Cucinotta, F. A.

    2009-01-01

    A detailed understanding of the biological effects of heavy nuclei is needed for space radiation protection and for cancer therapy. High-LET radiation produces more complex DNA lesions that may be non-repairable or that may require additional processing steps compared to endogenous DSBs, increasing the possibility of misrepair. Interplay between radiation sensitivity, dose, and radiation quality has not been studied extensively. Previously we studied chromosome aberrations induced by low- and high- LET radiation in several cell lines deficient in ATM (ataxia telangactasia mutated; product of the gene that is mutated in ataxia telangiectasia patients) or NBS (nibrin; product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase (DNA-PK) activity. We found that the yields of both simple and complex chromosomal aberrations were significantly increased in the DSB repair defective cells compared to normal cells. The increased aberrations observed for the ATM and NBS defective lines was due to a significantly larger quadratic dose-response term compared to normal fibroblasts for both simple and complex aberrations, while the linear dose-response term was significantly higher in NBS cells only for simple exchanges. These results point to the importance of the functions of ATM and NBS in chromatin modifications that function to facilitate correct DSB repair and minimize aberration formation. To further understand the sensitivity differences that were observed in ATM and NBS deficient cells, in this study, chromosomal aberration analysis was performed in normal lung fibroblast cells treated with KU-55933, a specific ATM kinase inhibitor, or Mirin, an MRN complex inhibitor involved in activation of ATM. We are also testing siRNA knockdown of these proteins. Normal and ATM or NBS suppressed cells were irradiated with gamma-rays and chromosomes were collected with a premature chromosome

  13. RF current distribution and topology of RF sheath potentials in front of ICRF antennae

    NASA Astrophysics Data System (ADS)

    Colas, L.; Heuraux, S.; Brémond, S.; Bosia, G.

    2005-08-01

    The 2D (radial/poloidal) spatial topology of RF-induced convective cells developing radially in front of ion cyclotron range of frequency (ICRF) antennae is investigated, in relation to the spatial distribution of RF currents over the metallic structure of the antenna. This is done via a Green's function, determined from the ICRF wave coupling equations, and well-suited to open field lines extending toroidally far away on both sides of the antenna. Using such formalism, combined with a full-wave calculation using the 3D antenna code ICANT (Pécoul S. et al 2000 Comput. Phys. Commun. 146 166-87), two classes of convective cells are analysed. The first one appears in front of phased arrays of straps, and depending on the strap phasing, its topology is interpreted using the poloidal profiles of either the RF current or the RF voltage of the strip line theory. The other class of convective cells is specific to antenna box corners and is evidenced for the first time. Based on such analysis, general design rules are worked out in order to reduce the RF-sheath potentials, which generalize those proposed in the earlier literature, and concrete antenna design options are tested numerically. The merits of aligning all strap centres on the same (tilted) flux tube, and of reducing the antenna box toroidal conductivity in its lower and upper parts, are discussed.

  14. Spectral Calculation of ICRF Wave Propagation and Heating in 2-D Using Massively Parallel Computers

    NASA Astrophysics Data System (ADS)

    Jaeger, E. F.; D'Azevedo, E.; Berry, L. A.; Carter, M. D.; Batchelor, D. B.

    2000-10-01

    Spectral calculations of ICRF wave propagation in plasmas have the natural advantage that they require no assumption regarding the smallness of the ion Larmor radius ρ relative to wavelength λ. Results are therefore applicable to all orders in k_bot ρ where k_bot = 2π/λ. But because all modes in the spectral representation are coupled, the solution requires inversion of a large dense matrix. In contrast, finite difference algorithms involve only matrices that are sparse and banded. Thus, spectral calculations of wave propagation and heating in tokamak plasmas have so far been limited to 1-D. In this paper, we extend the spectral method to 2-D by taking advantage of new matrix inversion techniques that utilize massively parallel computers. By spreading the dense matrix over 576 processors on the ORNL IBM RS/6000 SP supercomputer, we are able to solve up to 120,000 coupled complex equations requiring 230 GBytes of memory and achieving over 500 Gflops/sec. Initial results for ASDEX and NSTX will be presented using up to 200 modes in both the radial and vertical dimensions.

  15. Satellite Communications for ATM

    NASA Technical Reports Server (NTRS)

    Shamma, Mohammed A.

    2003-01-01

    This presentation is an overview on Satellite Communication for the Aeronautical Telecommunication Management (ATM) research. Satellite Communications are being considered by the FAA and NASA as a possible alternative to the present and future ground systems supporting Air Traffic Communications. The international Civil Aviation Organization (ICAO) have in place Standards and Recommended Practices (SARPS) for the Aeronautical Mobile Satellite Services (AMSS) which is mainly derived from the pre-existing Inmarsat service that has been in service since the 1980s. The Working Group A of the Aeronautical Mobile Communication Panel of ICAO has also been investigating SARPS for what is called the Next Generation Satellite Service (NGSS) which conforms less to the Inmarsat based architecture and explores wider options in terms of satellite architectures. Several designs are being proposed by Firms such as Boeing, ESA, NASA that are geared toward full or secondary usage of satellite communications for ATM. Satellite communications for ATM can serve several purposes ranging from primary usage where ground services would play a minimal backup role, to an integrated solution where it will be used to cover services, or areas that are less likely to be supported by the proposed and existing ground infrastructure. Such Integrated roles can include usage of satellite communications for oceanic and remote land areas for example. It also can include relieving the capacity of the ground network by providing broadcast based services of Traffic Information Services messages (TIS-B), or Flight Information Services (FIS-B) which can take a significant portion of the ground system capacity. Additionally, satellite communication can play a backup role to support any needs for ground replacement, or additional needed capacity even after the new digital systems are in place. The additional bandwidth that can be provided via satellite communications can also open the door for many new

  16. The ATM protein kinase and cellular redox signaling: beyond the DNA damage response

    PubMed Central

    Ditch, Scott; Paull, Tanya T.

    2011-01-01

    The ataxia-telangiectasia mutated (ATM) protein kinase is best known for its role in the DNA damage response, but recent findings suggest that it also functions as a redox sensor that controls the levels of reactive oxygen species in human cells. Here, we review the evidence supporting the conclusion that ATM can be directly activated by oxidation, as well as various observations from ATM-deficient patients and mouse models that point toward the importance of ATM in oxidative stress responses. We also discuss the roles of this kinase in regulating mitochondrial function and metabolic control through its action on tumor suppressor p53, AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and hypoxia-inducible factor-1 (HIF-1), and how the regulation of these enzymes may be affected in ATM-deficient patients and in cancer cells. PMID:22079189

  17. Noncanonical ATM Activation and Signaling in Response to Transcription-Blocking DNA Damage.

    PubMed

    Marteijn, Jurgen A; Vermeulen, Wim; Tresini, Maria

    2017-01-01

    Environmental genotoxins and metabolic byproducts generate DNA lesions that can cause genomic instability and disrupt tissue homeostasis. To ensure genomic integrity, cells employ mechanisms that convert signals generated by stochastic DNA damage into organized responses, including activation of repair systems, cell cycle checkpoints, and apoptotic mechanisms. DNA damage response (DDR) signaling pathways coordinate these responses and determine cellular fates in part, by transducing signals that modulate RNA metabolism. One of the master DDR coordinators, the Ataxia Telangiectasia Mutated (ATM) kinase, has a fundamental role in mediating DNA damage-induced changes in mRNA synthesis. ATM acts by modulating a variety of RNA metabolic pathways including nascent RNA splicing, a process catalyzed by the spliceosome. Interestingly, ATM and the spliceosome influence each other's activity in a reciprocal manner by a pathway that initiates when transcribing RNA polymerase II (RNAPII) encounters DNA lesions that prohibit forward translocation. In response to stalling of RNAPII assembly of late-stage spliceosomes is disrupted resulting in increased splicing factor mobility. Displacement of spliceosomes from lesion-arrested RNA polymerases facilitates formation of R-loops between the nascent RNA and DNA adjacent to the transcription bubble. R-loops signal for noncanonical ATM activation which in quiescent cells occurs in absence of detectable dsDNA breaks. In turn, activated ATM signals to regulate spliceosome dynamics and AS genome wide.This chapter describes the use of fluorescence microscopy methods that can be used to evaluate noncanonical ATM activation by transcription-blocking DNA damage. First, we present an immunofluorescence-detection method that can be used to evaluate ATM activation by autophosphorylation, in fixed cells. Second, we present a protocol for Fluorescence Recovery After Photobleaching (FRAP) of GFP-tagged splicing factors, a highly sensitive and

  18. 49 CFR 193.2059 - Flammable vapor-gas dispersion protection.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Flammable vapor-gas dispersion protection. 193.2059 Section 193.2059 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE...

  19. ATM and ATR play complementary roles in the behavior of excitatory and inhibitory vesicle populations.

    PubMed

    Cheng, Aifang; Zhao, Teng; Tse, Kai-Hei; Chow, Hei-Man; Cui, Yong; Jiang, Liwen; Du, Shengwang; Loy, Michael M T; Herrup, Karl

    2018-01-09

    ATM (ataxia-telangiectasia mutated) and ATR (ATM and Rad3-related) are large PI3 kinases whose human mutations result in complex syndromes that include a compromised DNA damage response (DDR) and prominent nervous system phenotypes. Both proteins are nuclear-localized in keeping with their DDR functions, yet both are also found in cytoplasm, including on neuronal synaptic vesicles. In ATM- or ATR-deficient neurons, spontaneous vesicle release is reduced, but a drop in ATM or ATR level also slows FM4-64 dye uptake. In keeping with this, both proteins bind to AP-2 complex components as well as to clathrin, suggesting roles in endocytosis and vesicle recycling. The two proteins play complementary roles in the DDR; ATM is engaged in the repair of double-strand breaks, while ATR deals mainly with single-strand damage. Unexpectedly, this complementarity extends to these proteins' synaptic function as well. Superresolution microscopy and coimmunoprecipitation reveal that ATM associates exclusively with excitatory (VGLUT1 + ) vesicles, while ATR associates only with inhibitory (VGAT + ) vesicles. The levels of ATM and ATR respond to each other; when ATM is deficient, ATR levels rise, and vice versa. Finally, blocking NMDA, but not GABA, receptors causes ATM levels to rise while ATR levels respond to GABA, but not NMDA, receptor blockade. Taken together, our data suggest that ATM and ATR are part of the cellular "infrastructure" that maintains the excitatory/inhibitory balance of the nervous system. This idea has important implications for the human diseases resulting from their genetic deficiency.

  20. Boosting ATM activity alleviates aging and extends lifespan in a mouse model of progeria

    PubMed Central

    Peng, Linyuan; Tang, Xiaolong; Meng, Fanbiao; Ao, Ying; Zhou, Mingyan; Wang, Ming; Cao, Xinyue; Qin, Baoming; Wang, Zimei; Zhou, Zhongjun; Wang, Guangming; Gao, Zhengliang; Xu, Jun

    2018-01-01

    DNA damage accumulates with age (Lombard et al., 2005). However, whether and how robust DNA repair machinery promotes longevity is elusive. Here, we demonstrate that ATM-centered DNA damage response (DDR) progressively declines with senescence and age, while low dose of chloroquine (CQ) activates ATM, promotes DNA damage clearance, rescues age-related metabolic shift, and prolongs replicative lifespan. Molecularly, ATM phosphorylates SIRT6 deacetylase and thus prevents MDM2-mediated ubiquitination and proteasomal degradation. Extra copies of Sirt6 extend lifespan in Atm-/- mice, with restored metabolic homeostasis. Moreover, the treatment with CQ remarkably extends lifespan of Caenorhabditis elegans, but not the ATM-1 mutants. In a progeria mouse model with low DNA repair capacity, long-term administration of CQ ameliorates premature aging features and extends lifespan. Thus, our data highlights a pro-longevity role of ATM, for the first time establishing direct causal links between robust DNA repair machinery and longevity, and providing therapeutic strategy for progeria and age-related metabolic diseases. PMID:29717979