National Library of Energy BETA

Sample records for admi nistra tor

  1. Plutonium_Disposition_Phase_2_TOR_082015_FINAL

    National Nuclear Security Administration (NNSA)

    AEROSPACE REPORT NO. TOR-2015-02671 Plutonium Disposition Study Options Independent Assessment Phase 2 Report August 20, 2015 Matthew J. Hart 1 , Nichols F. Brown 2 , Mark J. Rokey 1 , Harold J. Huslage 3 , J. Denise Castro-Bran 4 , Norman Y. Lao 5 , Roland J. Duphily 5 , Vincent M. Canales 2 , Joshua P. Davis 6 , Whitney L. Plumb-Starnes 7 , Jya-Syin W. Chien 5 1 Civil Applications Directorate, Civil and Commercial Programs Division 2 Schedule and Cost Analysis Department, Acquisition Analysis

  2. ATR/TOR-201X(XXXX)-XXXX

    National Nuclear Security Administration (NNSA)

    AEROSPACE REPORT NO. TOR-2015-01848 Plutonium Disposition Study Options Independent Assessment Phase 1 Report Option 1: MOX Fuel Option 4: Downblend April 13, 2015 Matthew J. Hart 1 , Nichols F. Brown 2 , Mark J. Rokey 1 , Harold J. Huslage 3 , Denise J. Castro-Bran 4 , Norman Y. Lao 5 , Roland J. Duphily 5 , Vincent M. Canales 2 , Joshua P. Davis 6 , Whitney L. Plumb-Starnes 7 , Jya-Syin W. Chien 5 1 Civil Applications Directorate, Civil and Commercial Programs Division 2 Schedule and Cost

  3. FK866-induced NAMPT inhibition activates AMPK and downregulates mTOR signaling in hepatocarcinoma cells

    SciTech Connect (OSTI)

    Schuster, Susanne; Penke, Melanie; Gorski, Theresa; Gebhardt, Rolf; Weiss, Thomas S.; Kiess, Wieland; Garten, Antje

    2015-03-06

    Background: Nicotinamide phosphoribosyltransferase (NAMPT) is the key enzyme of the NAD salvage pathway starting from nicotinamide. Cancer cells have an increased demand for NAD due to their high proliferation and DNA repair rate. Consequently, NAMPT is considered as a putative target for anti-cancer therapies. There is evidence that AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) become dysregulated during the development of hepatocellular carcinoma (HCC). Here, we investigated the effects of NAMPT inhibition by its specific inhibitor FK866 on the viability of hepatocarcinoma cells and analyzed the effects of FK866 on the nutrient sensor AMPK and mTOR complex1 (mTORC1) signaling. Results: FK866 markedly decreased NAMPT activity and NAD content in hepatocarcinoma cells (Huh7 cells, Hep3B cells) and led to delayed ATP reduction which was associated with increased cell death. These effects could be abrogated by administration of nicotinamide mononucleotide (NMN), the enzyme product of NAMPT. Our results demonstrated a dysregulation of the AMPK/mTOR pathway in hepatocarcinoma cells compared to non-cancerous hepatocytes with a higher expression of mTOR and a lower AMPKα activation in hepatocarcinoma cells. We found that NAMPT inhibition by FK866 significantly activated AMPKα and inhibited the activation of mTOR and its downstream targets p70S6 kinase and 4E-BP1 in hepatocarcinoma cells. Non-cancerous hepatocytes were less sensitive to FK866 and did not show changes in AMPK/mTOR signaling after FK866 treatment. Conclusion: Taken together, these findings reveal an important role of the NAMPT-mediated NAD salvage pathway in the energy homeostasis of hepatocarcinoma cells and suggest NAMPT inhibition as a potential treatment option for HCC. - Highlights: • FK866 increases cell death in p53-deficient hepatocarcinoma cells. • AMPK/mTOR signaling is dysregulated in hepatocarcinoma cells. • FK866-induced NAMPT inhibition activates AMPK

  4. RapTOR: Automated sequencing library preparation and suppression for rapid pathogen characterization ( 7th Annual SFAF Meeting, 2012)

    ScienceCinema (OSTI)

    Lane, Todd [SNL

    2013-02-11

    Todd Lane on "RapTOR: Automated sequencing library preparation and suppression for rapid pathogen characterization" at the 2012 Sequencing, Finishing, Analysis in the Future Meeting held June 5-7, 2012 in Santa Fe, New Mexico.

  5. Lithium protects against methamphetamine-induced neurotoxicity in PC12 cells via Akt/GSK3β/mTOR pathway

    SciTech Connect (OSTI)

    Wu, Jintao; Zhu, Dexiao; Zhang, Jing; Li, Guibao; Liu, Zengxun; Sun, Jinhao

    2015-09-25

    Methamphetamine (MA) is neurotoxic, especially in dopaminergic neurons. Long-lasting exposure to MA causes psychosis and increases the risk of Parkinson's disease. Lithium (Li) is a known mood stabilizer and has neuroprotective effects. Previous studies suggest that MA exposure decreases the phosphorylation of Akt/GSK3β pathway in vivo, whereas Li facilitates the phosphorylation of Akt/GSK3β pathway. Moreover, GSK3β and mTOR are implicated in the locomotor sensitization induced by psychostimulants and mTOR plays a critical role in MA induced toxicity. However, the effect of MA on Akt/GSK3β/mTOR pathway has not been fully investigated in vitro. Here, we found that MA exposure significantly dephosphorylated Akt/GSK3β/mTOR pathway in PC12 cells. In addition, Li remarkably attenuated the dephosphorylation effect of MA exposure on Akt/GSK3β/mTOR pathway. Furthermore, Li showed obvious protective effects against MA toxicity and LY294002 (Akt inhibitor) suppressed the protective effects of Li. Together, MA exposure dephosphorylates Akt/GSK3β/mTOR pathway in vitro, while lithium protects against MA-induced neurotoxicity via phosphorylation of Akt/GSK3β/mTOR pathway. - Highlights: • Lithium protects against methamphetamine-induced neurotoxicity in vitro. • Methamphetamine exposure dephosphorylates Akt/GSK3β/mTOR pathway. • Lithium attenuates methamphetamine-induced toxicity via phosphorylating Akt/GSK3β/mTOR pathway.

  6. MEMO RANUM FOR HUMAN RESOURCES DIRECTORS FROM: S~J\O~TOR OFFICE b:\HUMAN CAPITAL MANAGEMENT

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    0 MEMO RANUM FOR HUMAN RESOURCES DIRECTORS FROM: S~J\O~TOR OFFICE b:\HUMAN CAPITAL MANAGEMENT SUBJECT: GUIDANCE MEMORANDUM #13 REEMPLOYMENT PRIORITY LIST SELECTIONS This memorandum provides guidance for using the Department of Energy's (DOE) Reemployment Priority List (RPL). The DOE RPL is designed to provide priority consideration to employees who have lost their jobs through reduction in force. or who have fully recovered from a compensable injury after more than 1 year. Employees may only

  7. MicroRNA-101 mediates the suppressive effect of laminar shear stress on mTOR expression in vascular endothelial cells

    SciTech Connect (OSTI)

    Chen, Kui; Fan, Wendong; Wang, Xing; Ke, Xiao [Division of Cardiology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080 (China)] [Division of Cardiology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080 (China); Wu, Guifu, E-mail: eecpchina@yahoo.com.cn [Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080 (China)] [Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080 (China); Hu, Chengheng, E-mail: huchenghengpci@yahoo.com.cn [Division of Cardiology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080 (China)] [Division of Cardiology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080 (China)

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer Laminar shear stress upregulates miR-101 expression in vascular endothelial cells. Black-Right-Pointing-Pointer miR-101 represses mTOR expression through a specific 3 Prime UTR binding site. Black-Right-Pointing-Pointer Overexpression of miR-101 inhibits G1/S transition and endothelial cell proliferation. Black-Right-Pointing-Pointer Blockade of miR-101 attenuates the suppressive effect of laminar flow on mTOR expression. -- Abstract: Shear stress associated with blood flow plays an important role in regulating gene expression and cell function in endothelial cells (ECs). MicroRNAs (miRNAs) are highly conserved, small non-coding RNAs that negatively regulate the expression of target genes by binding to the mRNA 3 Prime -untranslated region (3 Prime UTR) at the posttranscriptional level involved in diverse cellular processes. This study demonstrates that microRNA-101 in response to laminar shear stress (LSS) is involved in the flow regulation of gene expression in ECs. qRT-PCR analysis showed that miR-101 expression was significantly upregulated in human umbilical vein endothelial cells (HUVECs) exposed to 12 dyn/cm{sup 2} laminar shear stress for 12 h. We found that transfection of miR-101 significantly decreased the luciferase activity of plasmid reporter containing the 3 Prime UTR of mammalian target of rapamycin (mTOR) gene. Western analysis revealed that the protein level of mTOR was significantly reduced in ECs transfected with miR-101. Furthermore, miR-101 overexpression induced cell cycle arrest at the G1/S transition and suppressed endothelial cell proliferation. Finally, transfection of miR-101 inhibitors attenuated the suppressive effects of LSS on mTOR expression, which identified the efficacy of loss-of-function of miR-101 in laminar flow-treated ECs. In conclusion, we have demonstrated that upregulation of miR-101 in response to LSS contributes to the suppressive effects of LSS on mTOR expression and EC

  8. A novel protoapigenone analog RY10-4 induces breast cancer MCF-7 cell death through autophagy via the Akt/mTOR pathway

    SciTech Connect (OSTI)

    Zhang, Xuenong; Wei, Han; Liu, Ziwei; Yuan, Qianying; Wei, Anhua; Shi, Du; Yang, Xian; Ruan, Jinlan

    2013-07-15

    Protoapigenone is a unique flavonoid and enriched in many ferns, showing potent antitumor activity against a broad spectrum of human cancer cell lines. RY10-4, a modified version of protoapigenone, manifested better anti-proliferation activity in human breast cancer cell line MCF-7. The cytotoxicity of RY10-4 against MCF-7 cells is exhibited in both time- and concentration-dependent manners. Here we investigated a novel effect of RY10-4 mediated autophagy in autophagy defect MCF-7 cells. Employing immunofluorescence assay for microtubule-associated protein light-chain 3 (LC3), monodansylcadaverine staining, Western blotting analyses for LC3 and p62 as well as ultrastructural analysis by transmission electron microscopy, we showed that RY10-4 induced autophagy in MCF-7 cells but protoapigenone did not. Meanwhile, inhibition of autophagy by pharmacological and genetic approaches significantly increased the viability of RY10-4 treated cells, suggesting that the autophagy induced by RY10-4 played as a promotion mechanism for cell death. Further studies revealed that RY10-4 suppressed the activation of mTOR and p70S6K via the Akt/mTOR pathway. Our results provided new insights for the mechanism of RY10-4 induced cell death and the cause of RY10-4 showing better antitumor activity than protoapigenone, and supported further evidences for RY10-4 as a lead to design a promising antitumor agent. - Highlights: We showed that RY10-4 induced autophagy in MCF-7 cells but protoapigenone did not. Autophagy induced by RY10-4 played as a promotion mechanism for cell death. RY10-4 induced autophagy in MCF-7 cell through the Akt/mTOR pathway. We provided new insights for the mechanism of RY10-4 induced cell death.

  9. ATR/TOR-201X(XXXX)-XXXX

    National Nuclear Security Administration (NNSA)

    ... The three product lines converge in MFFF, where it then undergoes aqueous processing, and is combined with depleted uranium oxide and fabricated into fuel pellets and ultimately ...

  10. Plutonium_Disposition_Phase_2_TOR_082015_FINAL

    National Nuclear Security Administration (NNSA)

    ... MOX Fuel because the fuel is more tolerant of impurities. ... in operations due to accident) would be to increase the ... nuclear reactors using uranium versus plutonium-based fuels. ...

  11. United States Environmental Protection Agency Environmental Monitoring

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ... Nevada, and Utah counties near the Nevada Test ... Admi.nistration Energy Research and Development ... Hydrological Monitoring Program meter minimum detectable ...

  12. a J. C. Clarke, Contract FEOM 8 J. P. Morgan, Assist tor, Pznduction...

    Office of Legacy Management (LM)

    ent No. 022-0141 Subprogram class-: 9120 Budget item : Inventory changes w Spe&.al Reactor M aterials 3. Basic provisions of Contract Nor w-7LO5 eng-14 and previous suppleanents ...

  13. MEMO RANUM FOR HUMAN RESOURCES DIRECTORS FROM: S~J\\O~TOR OFFICE...

    Broader source: Energy.gov (indexed) [DOE]

    0 MEMO RANUM FOR HUMAN RESOURCES DIRECTORS FROM: SJOTOR OFFICE b:HUMAN CAPITAL MANAGEMENT SUBJECT: GUIDANCE MEMORANDUM 13 REEMPLOYMENT PRIORITY LIST SELECTIONS This memorandum ...

  14. ATP-Competitive Inhibitors of the Mammalian Target of Rapamycin: Design and Synthesis of Highly Potent and Selective Pyrazolopyrimidines

    SciTech Connect (OSTI)

    Zask, Arie; Verheijen, Jeroen C.; Curran, Kevin; Kaplan, Joshua; Richard, David J.; Nowak, Pawel; Malwitz, David J.; Brooijmans, Natasja; Bard, Joel; Svenson, Kristine; Lucas, Judy; Toral-Barza, Lourdes; Zhang, Wei-Guo; Hollander, Irwin; Gibbons, James J.; Abraham, Robert T.; Ayral-Kaloustian, Semiramis; Mansour, Tarek S.; Yu, Ker

    2009-09-18

    The mammalian target of rapamycin (mTOR), a central regulator of growth, survival, and metabolism, is a validated target for cancer therapy. Rapamycin and its analogues, allosteric inhibitors of mTOR, only partially inhibit one mTOR protein complex. ATP-competitive, global inhibitors of mTOR that have the potential for enhanced anticancer efficacy are described. Structural features leading to potency and selectivity were identified and refined leading to compounds with in vivo efficacy in tumor xenograft models.

  15. Mammalian target of rapamycin is essential for cardiomyocyte survival and heart development in mice

    SciTech Connect (OSTI)

    Zhang, Pengpeng; Shan, Tizhong; Liang, Xinrong; Deng, Changyan; Kuang, Shihuan

    2014-09-12

    Highlights: mTOR is a critical regulator of many biological processes yet its function in heart is not well understood. MCK-Cre/Mtor{sup flox/flox} mice were established to delete Mtor in cardiomyocytes. The mTOR-mKO mice developed normally but die prematurely within 5 weeks after birth due to heart disease. The mTOR-mKO mice had dilated myocardium and increased cell death. mTOR-mKO hearts had reduced expression of metabolic genes and activation of mTOR target proteins. - Abstract: Mammalian target of rapamycin (mTOR) is a critical regulator of protein synthesis, cell proliferation and energy metabolism. As constitutive knockout of Mtor leads to embryonic lethality, the in vivo function of mTOR in perinatal development and postnatal growth of heart is not well defined. In this study, we established a muscle-specific mTOR conditional knockout mouse model (mTOR-mKO) by crossing MCK-Cre and Mtor{sup flox/flox} mice. Although the mTOR-mKO mice survived embryonic and perinatal development, they exhibited severe postnatal growth retardation, cardiac muscle pathology and premature death. At the cellular level, the cardiac muscle of mTOR-mKO mice had fewer cardiomyocytes due to apoptosis and necrosis, leading to dilated cardiomyopathy. At the molecular level, the cardiac muscle of mTOR-mKO mice expressed lower levels of fatty acid oxidation and glycolysis related genes compared to the WT littermates. In addition, the mTOR-mKO cardiac muscle had reduced Myh6 but elevated Myh7 expression, indicating cardiac muscle degeneration. Furthermore, deletion of Mtor dramatically decreased the phosphorylation of S6 and AKT, two key targets downstream of mTORC1 and mTORC2 mediating the normal function of mTOR. These results demonstrate that mTOR is essential for cardiomyocyte survival and cardiac muscle function.

  16. FNOV SEA-2015-01

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Admi nistrator, National Nuclear Security Administration Wash ington, DC 20585 VIA OVERNIGHT CARRIER Dr. Paul J. Hommert President Sandia Corporation 1515 Eubank SE July 13, 2015 Building 802 I Room 3180 Albuquerque, New Mexico 87123 SEA-2015-01 (FNOV) Dear Dr. Hommert: ///A *. .,~~~~ llV~~~ National Nuclear Security Administration Pursuant to section 234B of the Atomic Energy Act of 1954, as amended, (the Act) 42 U.S.C. § 2282b, and the Department of Energy (DOE) regulations at 10 C.F.R. Part

  17. I

    Office of Scientific and Technical Information (OSTI)

    ... During the late 1970s, breeder reactors using mixed ... 1000 MW(e) liquid-metal fast breeder reac- tors (LMFBR). ... versus standardized sodium hydroxide using multiple ...

  18. Buildings and Energy in the 1980's (TABLES)

    U.S. Energy Information Administration (EIA) Indexed Site

    in Residential Buildings, 1984 End Uses RSE Row Fac- tors All End Uses Space Heating Water Heating Air Conditioning Appliances Building Characteristics Buildings (thou- sand)...

  19. Buildings and Energy in the 1980's (TABLES)

    U.S. Energy Information Administration (EIA) Indexed Site

    in Residential Buildings, 1987 End Uses RSE Row Fac- tors All End Uses Space Heating Water Heating Air Conditioning Appliances Building Characteristics Buildings (thou- sand)...

  20. Effect of Doping on Surface Reactivity and Conduction Mechanism...

    Office of Scientific and Technical Information (OSTI)

    Univ. of Rome Tor Vergata (Italy) Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States) Science and Technology Facilities Council (STFC), Harwell Campus, Oxford (United ...

  1. Abbott, Joshua

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    U. Arcangeli, Caterina Centro NAST-ENEA, Italy Arruda, Thomas ORISE Aruta, Carmela U. ... Basoli, Francesco U. Roma Tor Vergata, Italy Bassim, Nabil Naval Research Laboratory ...

  2. Market Transformation Fact Sheet

    Broader source: Energy.gov (indexed) [DOE]

    ... Traditional backup power technologies used during power grid outages employ batteries or genera- tors that operate on diesel, propane, or gasoline. Although these systems are ...

  3. Disorder effects in the {ital t}-{ital J} model (Journal Article...

    Office of Scientific and Technical Information (OSTI)

    Authors: Caprara, S. 1 ; Dipartimento di Fisica, Universita Tor Vergata, Via della ... Dipartimento di Fisica, Universita La Sapienza, Piazzale Aldo Moro, 00185 Roma (Italy) ...

  4. SHELTER3 | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    acronym for Diverse, Urban, Resilient, and Adaptable. Learn More STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  5. Browse by Discipline -- E-print Network Subject Pathways: Energy...

    Office of Scientific and Technical Information (OSTI)

    ... Andrea (Andrea Marini) - Dipartimento di Fisica, Universit di Roma Tor Vergata ... Marko) - Departments of Biochemistry, Molecular Biology, and Cell Biology & Physics and ...

  6. Buildings and Energy in the 1980's (TABLES)

    U.S. Energy Information Administration (EIA) Indexed Site

    1982 End Uses RSE Row Fac- tors All End Uses Space Heating Water Heating Air Conditioning Appliances Building Characteristics Buildings (thou- sand) Consump- tion...

  7. Buildings and Energy in the 1980's (TABLES)

    U.S. Energy Information Administration (EIA) Indexed Site

    1980 End Uses RSE Row Fac- tors All End Uses Space Heating Water Heating Air Conditioning Appliances Building Characteristics Buildings (thou- sand) Consump- tion...

  8. Buildings and Energy in the 1980's (TABLES)

    U.S. Energy Information Administration (EIA) Indexed Site

    1981 End Uses RSE Row Fac- tors All End Uses Space Heating Water Heating Air Conditioning Appliances Building Characteristics Buildings (thou- sand) Consump- tion...

  9. From: Hooppell, Stuart

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    BY BPA FO 1A OFFICE THIS DATE: ?t'1 DUE DATE, Many thanks tor your time and consideration LOG ItW N '1 Best wishes Stuart Hooppell (University of Exeter Undergraduate Student)...

  10. Chapter 37 - Service Contracting | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    torEmployeeRolesintheFederalWorkplace0.pdf PDF icon 37.2PerformanceBasedServiceAcquisition0.pdf More Documents & Publications Microsoft Word - AcqGuide37pt1 binney Nov...

  11. Buildings and Energy in the 1980's

    U.S. Energy Information Administration (EIA) Indexed Site

    Table R8.82p. Total and Average Primaary Consumption and Expenditures for All Major Energy Sources in Residential Buildings, 1982 Total Average RSE Row Fac- tors Expenditures...

  12. Buildings and Energy in the 1980's

    U.S. Energy Information Administration (EIA) Indexed Site

    Table R8.90p. Total and Average Primary Consumption and Expenditures for All Major Energy Sources in Residential Buildings, 1990 Total Average RSE Row Fac- tors Expenditures...

  13. Buildings and Energy in the 1980's

    U.S. Energy Information Administration (EIA) Indexed Site

    Table R8.81p. Total and Average Primary Consumption and Expenditures for All Major Energy Sources in Residential Buildings, 1981 Total Average RSE Row Fac- tors Expenditures...

  14. Buildings and Energy in the 1980's

    U.S. Energy Information Administration (EIA) Indexed Site

    Table R8.84p. Total and Average Primary Consumption and Expenditures for All Major Energy Sources in Residential Buildings, 1984 Total Average RSE Row Fac- tors Expenditures...

  15. PLEASE RUSH

    Office of Legacy Management (LM)

    washers out of U v Beta metal slab on punch press. Re No ventilation in area. Oil pH pira tor worn. 1816 1433 BZ Same as 1815 - 32 washers stamp- .02 3 .06 ed in this ...

  16. Sandia Energy - Sandian Todd Lane's "Pond Crash Forensics" Project...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    team, as well as a very strong example of how a technology platform developed by the RapTOR grand challenge can have multiple applications, such as algal biofuels (and central to...

  17. Nonlinear

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    R. Gatto Universit di Roma "Tor Vergata", 00133 Rome, Italy P. W. Terry and D. A. Baver University of Wisconsin-Madison, Madison, Wisconsin 53706 Received 25 July 2005; ...

  18. Vote for Your Favorite Solar Decathlon House | Department of...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor Vergata entry in the 2015 Solar Decathlon, during team dinners that...

  19. EXEC-2010-017867 MEMORANDUM FOR CATHERINE R. ZOI ) Jj,J?- ACTING...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    DC 20585 Janunry 11, 20 I 1 EXEC-2010-017867 MEMORANDUM FOR CATHERINE R. ZOI ) Jj,J?- ACTING UNDER SECRETARY OF ENERGY - * INGRID KOLB, DIRE;TOR, OFFICE T PETER...

  20. AGGIE SOL | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    storms in a state that averages 27 tornadoes yearly. Learn More STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  1. INHOUSE | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    storms in a state that averages 27 tornadoes yearly. Learn More STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  2. EASI HOUSE | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    by embracing the city's sense of expansive greenery. Learn More STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  3. NEST HOME | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Random | Alphabetical | Rating (High to Low) | Rating (Low to High) STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  4. ALF HOUSE | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Random | Alphabetical | Rating (High to Low) | Rating (Low to High) STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  5. INDIGO PINE | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    storms in a state that averages 27 tornadoes yearly. Learn More STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  6. STILE | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor Vergata entry in the 2015 Solar Decathlon, during team dinners that...

  7. DURA URBAN HOUSE | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    University of New York (SUNY) team may change that. Learn More STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  8. SURE HOUSE | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Random | Alphabetical | Rating (High to Low) | Rating (Low to High) STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  9. CASA DEL SOL | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    their 2015 Solar Decathlon entry, dubbed "Indigo Pine." Learn More STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  10. GROW HOME | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Random | Alphabetical | Rating (High to Low) | Rating (Low to High) STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  11. INDIGO PINE | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Random | Alphabetical | Rating (High to Low) | Rating (Low to High) STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  12. DURA URBAN HOUSE | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    storms in a state that averages 27 tornadoes yearly. Learn More STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  13. DURA URBAN HOUSE | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    in nature: the golden poppy, California's state flower. Learn More STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  14. REFLECT HOME | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    storms in a state that averages 27 tornadoes yearly. Learn More STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  15. EASI HOUSE | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    fighting climate change with energy-saving innovations. Learn More STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  16. INHOUSE | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    pride in its identity to create its entry "Aggie Sol." Learn More STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  17. REFLECT HOME | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Random | Alphabetical | Rating (High to Low) | Rating (Low to High) STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  18. NEST HOME | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    storms in a state that averages 27 tornadoes yearly. Learn More STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  19. GROW HOME | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    their 2015 Solar Decathlon entry, dubbed "Indigo Pine." Learn More STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  20. SHELTER3 | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    and energy demand even as housing density increases. Learn More STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  1. SURE HOUSE | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    storms in a state that averages 27 tornadoes yearly. Learn More STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  2. EASI HOUSE | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    storms in a state that averages 27 tornadoes yearly. Learn More STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  3. SHELTER3 | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Random | Alphabetical | Rating (High to Low) | Rating (Low to High) STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  4. ALF HOUSE | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    storms in a state that averages 27 tornadoes yearly. Learn More STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  5. SURE HOUSE | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    to serve a family "from a full nest to an empty nest." Learn More STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  6. GROW HOME | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    by embracing the city's sense of expansive greenery. Learn More STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  7. REFLECT HOME | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Affordable, Solar, Innovation--or EASI--House. Learn More STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  8. AGGIE SOL | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Random | Alphabetical | Rating (High to Low) | Rating (Low to High) STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  9. CASA DEL SOL | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    storms in a state that averages 27 tornadoes yearly. Learn More STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  10. SHELTER3 | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    by embracing the city's sense of expansive greenery. Learn More STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  11. REFLECT HOME | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    to serve a family "from a full nest to an empty nest." Learn More STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  12. NEST HOME | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    pride in its identity to create its entry "Aggie Sol." Learn More STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  13. Vote for Your Favorite Solar Decathlon House | Department of...

    Broader source: Energy.gov (indexed) [DOE]

    their 2015 Solar Decathlon entry, dubbed "Indigo Pine." Learn More STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  14. EASI HOUSE | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Random | Alphabetical | Rating (High to Low) | Rating (Low to High) STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  15. GROW HOME | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    storms in a state that averages 27 tornadoes yearly. Learn More STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  16. DURA URBAN HOUSE | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Random | Alphabetical | Rating (High to Low) | Rating (Low to High) STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  17. INHOUSE | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Random | Alphabetical | Rating (High to Low) | Rating (Low to High) STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  18. AGGIE SOL | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    by embracing the city's sense of expansive greenery. Learn More STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  19. NEST HOME | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    in nature: the golden poppy, California's state flower. Learn More STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  20. INHOUSE | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    University of New York (SUNY) team may change that. Learn More STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  1. CASA DEL SOL | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Random | Alphabetical | Rating (High to Low) | Rating (Low to High) STILE The aroma of Italian cooking will waft from STILE, the West Virginia University and University of Roma Tor...

  2. Distorted spin dependent spectral function of {sup 3}He and semi...

    Office of Scientific and Technical Information (OSTI)

    (Russia) University of Rome, Rome (Italy); INFN-Roma (Italy) University of Rome (Italy); INFN-Tor Vergata (Italy) INFN-Roma (Italy) University of Perugia (Italy); INFN-Perugia ...

  3. Microsoft Word - 2005 Smooth Brome 032206 FINAL.doc

    Office of Environmental Management (EM)

    n i c a D ra w So uth Int erc ep tor Di tch W o m a n C re ek Smooth Brome Treatment Location Smooth Brome Weed Control Locations Figure 2 DATA SOURCE BASE FEATURES: Buildings,...

  4. OCEANS'13 MTS/IEEE SAN DIEGO, SEPTEMBER

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ... using the maximum desired emula- tor speed, maximum flow rate (computed from (1) and rated power), turbine radius and the optimal tip speed ratio as shown in equation (15). n em ...

  5. Letter Report for Analytical Results for Two Concrete and Three Soil Samples Associated with the Worcester Polytechnic Institute in Worcester Massachusetts

    SciTech Connect (OSTI)

    Ivey, Wade

    2013-10-07

    Oak Ridge Associated Universities (ORAU), under the Oak Ridge Institute tor Science and Education (ORISE) contract, received two concrete core and three soil samples on August 26, 2013 from the Worcester Polytechnic Institute in Worcester, Massachusetts. The samples were received in good condition. The samples were analyzed tor activation and fission products by gamma spectrometry. The sample collection data and identification numbers are tabulated and the gamma spectrometry data are presented. The pertinent procedure reference is included with the data table.

  6. The role of MAP4K3 in lifespan regulation of Caenorhabditiselegans

    SciTech Connect (OSTI)

    Khan, Maruf H.; Hart, Matthew J.; Rea, Shane L.

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Inhibition of MAP4K3 by RNAi leads to increased mean lifespan in Caenorhabditis elegans. Black-Right-Pointing-Pointer Mutation in the citron homology domain of MAP4K3 leads to increased mean lifespan. Black-Right-Pointing-Pointer Mutation in the kinase domain of MAP4K3 has no significant effect on mean lifespan. -- Abstract: The TOR pathway is a kinase signaling pathway that regulates cellular growth and proliferation in response to nutrients and growth factors. TOR signaling is also important in lifespan regulation - when this pathway is inhibited, either naturally, by genetic mutation, or by pharmacological means, lifespan is extended. MAP4K3 is a Ser/Thr kinase that has recently been found to be involved in TOR activation. Unexpectedly, the effect of this protein is not mediated via Rheb, the more widely known TOR activation pathway. Given the role of TOR in growth and lifespan control, we looked at how inhibiting MAP4K3 in Caenorhabditiselegans affects lifespan. We used both feeding RNAi and genetic mutants to look at the effect of MAP4K3 deficiency. Our results show a small but significant increase in mean lifespan in MAP4K3 deficient worms. MAP4K3 thus represents a new target in the TOR pathway that can be targeted for pharmacological intervention to control lifespan.

  7. WHC-SA-1619-FP

    Office of Scientific and Technical Information (OSTI)

    for the U.S. Department of Energy under Contract DE-AC06-87RL10930 Copyright LICSnso By ... tor the U.S Department of Energy under Contract DE-AC06-87RL10930 Copyright LIcsnso By ...

  8. Top-of-Rail lubricant

    SciTech Connect (OSTI)

    Alzoubi, M. F.; Fenske, G. R.; Erck, R. A.; Boparai, A. S.

    2000-07-14

    Analysis of the volatile and semivolatile fractions collected after use of the TOR lubricant indicated that other than contaminants in the collection laboratory, no compounds on the EPA's Target Compound Lists (Tables 2 and 5) were detected in these fractions. The data of these qualitative analyses, given in the various tables in the text, indicate only the relative amounts of the tentatively identified compounds. The authors recommend that quantitative analysis be performed on the volatile and semivolatile fractions to allow confirmation of the tentatively identified compounds and to obtain absolute amounts of the detected compounds. Additionally, the semivolatile fraction should be analyzed by liquid chromatography/mass spectrometry to identify compounds that are not chromatographable under the temperature program used for determination of semivolatile compounds. Introducing the top-of-rail (TOR) lubricant into the wheel/rail interface results in a reduction of almost 60% of lateral friction force over the forces encountered under dry conditions. This reveals good potential for energy savings, as well as wear reduction, for railroad companies. In TOR lubrication, an increase in the angle of attack and axle load results in increased lateral friction and rate of lubricant consumption. The most efficient TOR lubricant quantity to be used in the wheel/rail interface must be calculated precisely according to the number of cars, axle loads, train speed, and angle of attack.

  9. USDOE Top-of-Rail Lubricant Project

    SciTech Connect (OSTI)

    Mohumad F. Alzoubi; George R. Fenske; Robert A. Erck; Amrit S. Boparai

    2002-02-01

    Lubrication of wheel/rail systems has been recognized for the last two decades as a very important issue for railroads. Energy savings and less friction and wear can be realized if a lubricant can be used at the wheel/rail interface. On the other hand, adverse influences are seen in operating and wear conditions if improper or excessive lubrication is used. Also, inefficiencies in lubrication need to be avoided for economic and environmental reasons. The top-of-rail (TOR) lubricant concept was developed by Texaco Corporation to lubricate wheels and rails effectively and efficiently. Tranergy Corporation has been developing its SENTRAEN 2000{trademark} lubrication system for the last ten years, and this revolutionary new high-tech on-board rail lubrication system promises to dramatically improve the energy efficiency, performance, safety, and track environment of railroads. The system is fully computer-controlled and ensures that all of the lubricant is consumed as the end of the train passes. Lubricant quantity dispensed is a function of grade, speed, curve, and axle load. Tranergy also has its LA4000{trademark} wheel and rail simulator, a lubrication and traction testing apparatus. The primary task of this project was collecting and analyzing the volatile and semivolatile compounds produced as the lubricant was used. The volatile organic compounds were collected by Carbotrap cartridges and analyzed by adsorption and gas chromatography/mass spectrometry (GC/MS). The semivolatile fraction was obtained by collecting liquid that dripped from the test wheel. The collected material was also analyzed by GC/MS. Both of these analyses were qualitative. The results indicated that in the volatile fraction, the only compounds on the Environmental Protection Agency's (EPA) Superfund List of Analytes detected were contaminants either in the room air or from other potential contamination sources in the laboratory. Similarly, in the semivolatile fraction none of the detected

  10. OneTouch 4.0 Scanned Documents

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    4 The Population Status of The American Alligator on the Savannah River Plant, South Carolina by Thomas M. Murphy A Publication of the Savannah River Plant National Environmental Research Park Program United States Department of Energy April , 1981 , - - - - - -- - - NOTICE - - - - - - - - - , This re port w as pre pared as a n acco unt of work sponso red by the United Stales Government. Neither the Un ited Stales nor the United Stales Depart - ment of Energ y, no r an y of their contrac tors.

  11. LANL: AOT & LANSCE The Pulse February 2014

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    continued on page 3 2 From Alex's desk Celebrating service 4 New instrument aids fission-fragment yield measurements 5 Former Rosen Scholar named American Physical Society Fellow Seeking design rules for efficient lighting sources 6 Improved understanding of a semiconductor used in infrared detec- tors 7 Heads UP! Taking charge of electricity usage " With neutron diffraction, we can learn much more than where are the atoms. " A champion of neutrons for illuminating the properties and

  12. Nuclear PIM1 confers resistance to rapamycin-impaired endothelial proliferation

    SciTech Connect (OSTI)

    Walpen, Thomas; Kalus, Ina; Schwaller, Juerg; Peier, Martin A.; Battegay, Edouard J.; Zurich Center for Integrative Human Physiology , 8057 Zuerich ; Humar, Rok; Zurich Center for Integrative Human Physiology , 8057 Zuerich

    2012-12-07

    Highlights: Black-Right-Pointing-Pointer Pim1{sup -/-} endothelial cell proliferation displays increased sensitivity to rapamycin. Black-Right-Pointing-Pointer mTOR inhibition by rapamycin enhances PIM1 cytosolic and nuclear protein levels. Black-Right-Pointing-Pointer Truncation of Pim1 beyond serine 276 results in nuclear localization of the kinase. Black-Right-Pointing-Pointer Nuclear PIM1 increases endothelial proliferation independent of rapamycin. -- Abstract: The PIM serine/threonine kinases and the mTOR/AKT pathway integrate growth factor signaling and promote cell proliferation and survival. They both share phosphorylation targets and have overlapping functions, which can partially substitute for each other. In cancer cells PIM kinases have been reported to produce resistance to mTOR inhibition by rapamycin. Tumor growth depends highly on blood vessel infiltration into the malignant tissue and therefore on endothelial cell proliferation. We therefore investigated how the PIM1 kinase modulates growth inhibitory effects of rapamycin in mouse aortic endothelial cells (MAEC). We found that proliferation of MAEC lacking Pim1 was significantly more sensitive to rapamycin inhibition, compared to wildtype cells. Inhibition of mTOR and AKT in normal MAEC resulted in significantly elevated PIM1 protein levels in the cytosol and in the nucleus. We observed that truncation of the C-terminal part of Pim1 beyond Ser 276 resulted in almost exclusive nuclear localization of the protein. Re-expression of this Pim1 deletion mutant significantly increased the proliferation of Pim1{sup -/-} cells when compared to expression of the wildtype Pim1 cDNA. Finally, overexpression of the nuclear localization mutant and the wildtype Pim1 resulted in complete resistance to growth inhibition by rapamycin. Thus, mTOR inhibition-induced nuclear accumulation of PIM1 or expression of a nuclear C-terminal PIM1 truncation mutant is sufficient to increase endothelial cell proliferation

  13. Genome assortment, not serogroup, defines Vibrio cholerae pandemic strains

    SciTech Connect (OSTI)

    Brettin, Thomas S; Bruce, David C; Challacombe, Jean F; Detter, John C; Han, Cliff S; Munik, A C; Chertkov, Olga; Meincke, Linda; Saunders, Elizabeth; Choi, Seon Y; Haley, Bradd J; Taviani, Elisa; Jeon, Yoon - Seong; Kim, Dong Wook; Lee, Jae - Hak; Walters, Ronald A; Hug, Anwar; Colwell, Rita R

    2009-01-01

    Vibrio cholerae, the causative agent of cholera, is a bacterium autochthonous to the aquatic environment, and a serious public health threat. V. cholerae serogroup O1 is responsible for the previous two cholera pandemics, in which classical and El Tor biotypes were dominant in the 6th and the current 7th pandemics, respectively. Cholera researchers continually face newly emerging and re-emerging pathogenic clones carrying combinations of new serogroups as well as of phenotypic and genotypic properties. These genotype and phenotype changes have hampered control of the disease. Here we compare the complete genome sequences of 23 strains of V. cholerae isolated from a variety of sources and geographical locations over the past 98 years in an effort to elucidate the evolutionary mechanisms governing genetic diversity and genesis of new pathogenic clones. The genome-based phylogeny revealed 12 distinct V. cholerae phyletic lineages, of which one, designated the V. cholerae core genome (CG), comprises both O1 classical and EI Tor biotypes. All 7th pandemic clones share nearly identical gene content, i.e., the same genome backbone. The transition from 6th to 7th pandemic strains is defined here as a 'shift' between pathogenic clones belonging to the same O1 serogroup, but from significantly different phyletic lineages within the CG clade. In contrast, transition among clones during the present 7th pandemic period can be characterized as a 'drift' between clones, differentiated mainly by varying composition of laterally transferred genomic islands, resulting in emergence of variants, exemplified by V.cholerae serogroup O139 and V.cholerae O1 El Tor hybrid clones that produce cholera toxin of classical biotype. Based on the comprehensive comparative genomics presented in this study it is concluded that V. cholerae undergoes extensive genetic recombination via lateral gene transfer, and, therefore, genome assortment, not serogroup, should be used to define pathogenic V

  14. Nesfatin-1 inhibits ovarian epithelial carcinoma cell proliferation in vitro

    SciTech Connect (OSTI)

    Xu, Yang; Pang, Xiaoyan; Dong, Mei; Wen, Fang Zhang, Yi

    2013-11-01

    Highlights: Nesfatin-1 inhibits the proliferation and growth of HO-8910 cells by G1 phase arrest. Nesfatin-1 enhances HO-8910 cell apoptosis. Nesfatin-1 inhibits HO-8910 cell proliferation via mTOR and RhoA/ROCK signaling pathway. The first report of nesfatin-1-mediated proliferation in ovarian epithelial carcinoma. -- Abstract: Nesfatin-1, an 82-amino-acid peptide derived from a 396-amino-acid precursor protein nucleobindin 2 (NUCB2), was originally identified in hypothalamic nuclei involved in the regulation of food intake. It was recently reported that nesfatin-1 is a novel depot specific adipokine preferentially produced by subcutaneous tissue, with obesity- and food deprivation-regulated expression. Although a relation between ovarian cancer mortality and obesity has been previously established, a role of nesfatin-1 in ovarian epithelial carcinoma remains unknown. The aim of the present study is to examine the effect of nesfatin-1 on ovary carcinoma cells proliferation. We found that nesfatin-1 inhibits the proliferation and growth of HO-8910 cells by G1 phase arrest, this inhibition could be abolished by nesfatin-1 neutralizing antibody. Nesfatin-1 enhances HO-8910 cell apoptosis, activation of mammalian target of rapamycin (mTOR) and RhoA/ROCK signaling pathway block the effects of nesfatin-1-induced apoptosis, therefore reverses the inhibition of HO-8910 cell proliferation by nesfatin-1. In conclusion, the present study demonstrated that nesfatin-1 can inhibit the proliferation in human ovarian epithelial carcinoma cell line HO-8910 cells through inducing apoptosis via mTOR and RhoA/ROCK signaling pathway. This study provides a novel regulatory signaling pathway of nesfatin-1-regulated ovarian epithelial carcinoma growth and may contribute to ovarian cancer prevention and therapy, especially in obese patients.

  15. Microsoft Word - Science and Technology of Future Light Sources.doc

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    08/39 BNL-81895-2008 LBNL-1090E-2009 SLAC-R-917 Science and Technology of Future Light Sources A White Paper Report prepared by scientists from ANL, BNL, LBNL and SLAC. The coordinating team consisted of Uwe Bergmann, John Corlett, Steve Dierker, Roger Falcone, John Galayda, Murray Gibson, Jerry Hastings, Bob Hettel, John Hill, Zahid Hussain, Chi-Chang Kao, Janos Kirz, Gabrielle Long, Bill McCurdy, Tor Raubenheimer, Fernando Sannibale, John Seeman, Z.-X. Shen, Gopal Shenoy, Bob Schoenlein, Qun

  16. TITLE

    Office of Legacy Management (LM)

    Floodplains and Wetlands Survey Results for the Rulison and Rio Blanco Sites, Colorado December 1 993 Environmental Restoration Floodplains and Wetlands Survey Results tor the Rulison and Rio Blanco Sites, Colorado Prepared For: U.S. Department of Energy Environmental Restoration Division DOE Nevada Operations Office Las Vegas, Nevada 89 193-85 18 Prepared By: l T CORPORATION 4330 S. Valley View Blvd., Suite 114 Las Vegas, Nevada 89 103 Work Performed under Contract No: DE-AC08-92NV 10972

  17. Human Performance Modeling for Dynamic Human Reliability Analysis

    SciTech Connect (OSTI)

    Boring, Ronald Laurids; Joe, Jeffrey Clark; Mandelli, Diego

    2015-08-01

    Part of the U.S. Department of Energy’s (DOE’s) Light Water Reac- tor Sustainability (LWRS) Program, the Risk-Informed Safety Margin Charac- terization (RISMC) Pathway develops approaches to estimating and managing safety margins. RISMC simulations pair deterministic plant physics models with probabilistic risk models. As human interactions are an essential element of plant risk, it is necessary to integrate human actions into the RISMC risk framework. In this paper, we review simulation based and non simulation based human reliability analysis (HRA) methods. This paper summarizes the founda- tional information needed to develop a feasible approach to modeling human in- teractions in RISMC simulations.

  18. Water quality assessment in Ecuador

    SciTech Connect (OSTI)

    Chudy, J.P.; Arniella, E.; Gil, E.

    1993-02-01

    The El Tor cholera pandemic arrived in Ecuador in March 1991, and through the course of the year caused 46,320 cases, of which 692 resulted in death. Most of the cases were confined to cities along Ecuador's coast. The Water and Sanitation for Health Project (WASH), which was asked to participate in the review of this request, suggested that a more comprehensive approach should be taken to cholera control and prevention. The approach was accepted, and a multidisciplinary team consisting of a sanitary engineer, a hygiene education specialist, and an institutional specialist was scheduled to carry out the assessment in late 1992 following the national elections.

  19. Word Pro - Untitled1

    U.S. Energy Information Administration (EIA) Indexed Site

    Value of Fossil Fuel Imports Total, 1949-2011 By Fuel, 1949-2011 By Fuel, 2011 80 U.S. Energy Information Administration / Annual Energy Review 2011 1 In chained (2005) dollars, calculated by using gross domestic product implicit price defla- tors in Table D1. See "Chained Dollars" in Glossary. 2 See "Nominal Dollars" in Glossary. 3 Natural gas, coal, and coal coke. Source: Table 3.7. Crude Oil 1950 1960 1970 1980 1990 2000 2010 0 100 200 300 400 500 Billion Real (2005)

  20. Word Pro - Untitled1

    U.S. Energy Information Administration (EIA) Indexed Site

    Value of Fossil Fuel Exports Total, 1949-2011 By Fuel, 1949-2011 By Fuel, 2011 82 U.S. Energy Information Administration / Annual Energy Review 2011 104 16 7 2 Petroleum Coal Natural Gas Crude Oil 0 20 40 60 80 100 120 Billion Nominal Dollars² 1 In chained (2005) dollars, calculated by using gross domestic product implicit price defla- tors in Table D1. See "Chained Dollars" in Glossary. 2 See "Nominal Dollars" in Glossary. 3 Natural gas, crude oil, and coal coke. Source:

  1. Word Pro - Untitled1

    U.S. Energy Information Administration (EIA) Indexed Site

    Value of Fossil Fuel Production, Imports, and Exports Overview, 1949-2011 Production by Fuel, 1949-2011 Overview, 2011 70 U.S. Energy Information Administration / Annual Energy Review 2011 Production 1 In chained (2005) dollars, calculated by using gross domestic product implicit price defla- tors in Table D1. See "Chained Dollars" in Glossary. 2 See "Nominal Dollars" in Glossary. Sources: Tables 3.2, 3.7, and 3.8. 1950 1960 1970 1980 1990 2000 2010 0 25 50 75 100 125 150 175

  2. Word Pro - Untitled1

    U.S. Energy Information Administration (EIA) Indexed Site

    8 Crude Oil Domestic First Purchase Prices U.S. Average Prices, 1949-2011 Alaska North Slope, California, and Texas 1977-2011 160 U.S. Energy Information Administration / Annual Energy Review 2011 1 In chained (2005) dollars, calculated by using gross domestic product implicit price defla- tors in Table D1. See "Chained Dollars" in Glossary. 2 See "Nominal Dollars" in Glossary. 3 Alaska North Slope. Source: Table 5.18. Real¹ Nominal² 1950 1955 1960 1965 1970 1975 1980 1985

  3. Word Pro - Untitled1

    U.S. Energy Information Administration (EIA) Indexed Site

    1 Crude Oil Refiner Acquisition Costs, 1968-2011 Summary Composite Costs Domestic Costs Imported Costs 166 U.S. Energy Information Administration / Annual Energy Review 2011 1 See "Nominal Dollars" in Glossary. 2 In chained (2005) dollars, calculated by using gross domestic product implicit price defla- tors in Table D1. See "Chained Dollars" in Glossary. Source: Table 5.21. 1970 1975 1980 1985 1990 1995 2000 2005 2010 0 20 40 60 80 100 120 Nominal Dollars¹ per Barrel

  4. Office of Inspector General Annual Performance Plan 2011

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Performance Report FY 2010 Annual Performance Plan FY 2011 Office of Inspector General DOE/IG-APP012 Annual Performance Report FY 2010 Annual Performance Plan FY 2011 U.S. DEPARTMENT OF ENERGY OFFICE OF INSPECTOR GENERAL II DEPARTMENT OF ENERGY, OFFicE OF iNsPEcTOR GENERAl THIS PAGE INTENTIONALLY LEFT BLANK FY 2010 ANNUAl PERFORMANcE REPORT III Message from the Inspector General I am pleased to submit the Office of Inspector General's combined Fiscal Year 2010 Annual Performance Report and

  5. DOCUMENT RELEASE FORM

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    31 97 (2) Revision Number: 0 -- (3) Effective Date: 9/30/2009 (4) Document Type: E] Digital Image l Hard copy (a) Number of pages (including the DRF) or 84 0 POE E Video number of digital images (5) Release Type Z New 1:1 Cancel liiPage Change Elcomplete Revision (6) Document Title: 2009 Auto-TOR for Tank 241 -TY-1 05 (7) Change/Release Initial Issuance Description: (8) Change Initial Issuance Justification: (9) Associated (a) Structure Location: (c) Building Number: Structure, System, and

  6. DOCUMENT RELEASE FORM C

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    RELEASE FORM C (1) Document Number: RPP-RPT-431 74 (2) Revision Number: (3) Effective Date: 9/30/2009 (4) Document Type: El Digital Image El Hard copy (a) Number of pages (including the DRF) or 107 E PDF E] Video number of digital images (5) Release Type 0 New El Cancel El Page Change El complete Revision (6) Document Title: 2009 Auto-TOR for Tank 241 -T-204 (7) Change/Release Initial Issuance Description: (8) Change Initial Issuance Justification: (9) Associated (a) Structure Location: (c)

  7. OneTouch 4.0 Scanned Documents

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ....... ~~ ~~ -""~ - - - =-.- ~- ~ ----- ---- --- - - ~ - Stephen A. Whipple Lynn H. Wellman and Bill J. Good A Publication of the Savannah River Plant National Environmental Research Park Program United States Department of Energy a Th is report was prepared a s a n ac count of work sponsored by th e United States Governme nt. Neither the Un ited Slate s nor the United Sta les D~ - par trncnt of Energy. nor any of th eir co ntrac tors. su bco ntrac to rs. or th eir e mployees. mak es

  8. SIRT1 inactivation induces inflammation through the dysregulation of autophagy in human THP-1 cells

    SciTech Connect (OSTI)

    Takeda-Watanabe, Ai; Kitada, Munehiro; Kanasaki, Keizo; Koya, Daisuke

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer SIRT1 inactivation decreases autophagy in THP-1 cell. Black-Right-Pointing-Pointer Inhibition of autophagy induces inflammation. Black-Right-Pointing-Pointer SIRT1 inactivation induces inflammation through NF-{kappa}B activation. Black-Right-Pointing-Pointer The p62/Sqstm1 accumulation by impairment of autophagy is related to NF-{kappa}B activation. Black-Right-Pointing-Pointer SIRT1 inactivation is involved in the activation of mTOR and decreased AMPK activation. -- Abstract: Inflammation plays a crucial role in atherosclerosis. Monocytes/macrophages are some of the cells involved in the inflammatory process in atherogenesis. Autophagy exerts a protective effect against cellular stresses like inflammation, and it is regulated by nutrient-sensing pathways. The nutrient-sensing pathway includes SIRT1, a NAD{sup +}-dependent histone deacetylase, which is implicated in the regulation of a variety of cellular processes including inflammation and autophagy. The mechanism through which the dysfunction of SIRT1 contributes to the regulation of inflammation in relation to autophagy in monocytes/macrophages is unclear. In the present study, we demonstrate that treatment with 2-[(2-Hydroxynaphthalen-1-ylmethylene)amino]-N-(1-phenethyl)benzamide (Sirtinol), a chemical inhibitor of SIRT1, induces the overexpression of inflammation-related genes such as tumor necrosis factor (TNF)-{alpha} and interleukin (IL)-6 through nuclear factor (NF)-{kappa}B signaling activation, which is associated with autophagy dysfunction, as shown through p62/Sqstm1 accumulation and decreased expression of light chain (LC) 3 II in THP-1 cells. The autophagy inhibitor, 3-methyladenine, also induces inflammation-related NF-{kappa}B activation. In p62/Sqstm1 knockdown cells, Sirtinol-induced inflammation through NF-{kappa}B activation is blocked. In addition, inhibition of SIRT1 is involved in the activation of the mammalian target of rapamycin (mTOR) pathway and

  9. Secretary of Energy Advisory Board

    Office of Environmental Management (EM)

    Secretary of Energy Advisory Board Task Force Report to Support the Evaluation of New Funding Constructs for Energy R&D in the DOE March 28, 2014 U.S. Department of Energy Page 2 Report of the Task Force to Support the Evaluation of New Funding Constructs for Energy R&D in the DOE I. Introduction and Charge to the Task Force a. Terms of Reference The Terms of Reference (TOR) from the Secretary of Energy authorizing the creation of a Task Force to Support the Evaluation of New Funding

  10. LANL: AOT & LANSCE The Pulse April 2010

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    0 Los Alamos National Laboratory * Est. 1943 The Pulse-Newsletter of the Los Alamos Neutron Science Center and Accelerator Operations and Technology Division I N S I D E 2 KovalevsKy and Fisher receive post- doctoral awards nuclear cross sec- tions For accelera- tor production oF a therapy isotope 3 understanding the pathogenesis oF alzheimer's disease 4 heads up! Ultracold neutron accomplishments at LANSCE The weak nuclear force is one of the four fundamental forces in nature, along with

  11. I L

    Office of Legacy Management (LM)

    f- r a-.--+ _ . . .* i_ : CI r . : . . I . f" b" ? ' ,' ' , I L $.. . 0. .' ?, : _' . *r: :,: : .,: ' , . r:. i ' 3"' 3. L SURVEY F THE DITCHES AT THE ST t lJl@ ,bilRPORT STORAGE SITE, ' , :I (SLAPSS) .;' :: ,, .s . .I 1, :' ,., I,: AUGUST 1983 :' PARED FOR THE U.S.DEPARTME?W OF ENERGY &#$nEEi .Ct+TRACT NOa DE-ACOS-8 tOR20722 */, ? 8. ' By 8EGHi' El. NATIONAL, INC. NUGL&YAR FU& O%RAtlONS. .i -.- I 9.0, Box 360 t" OAK RI-. TN. 37830, jl c the united swee

  12. CONTINATIONSHEETREFERENCE NO. OF DOCUMENT BEING CONTINUED AEO

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    COTIUTINSHE DE-AC27-08RV14800/067 2G OF NAME OF OFFEROR OR CONTRACTOR WASHINGTON RIVER PROTECTION SOLUTIONS LLC ITEM NO. SUPPLIES/SERVICES QUANTITY UNIT UNIT PRICE AMOUNT (A) (B) (C) (D) (E) (F) -$1,000,000.00 New Total Obligated Amount tor this Award: $1, 180,251,170.41 incremental Funded Amount changed: from $1,181,251,170.41 to $1, 180,251,170.41 Account code: Reforming Treatability Fund 01250 Appr Year 2010 Allottee 34 Reporting Entity 421301 Object Class 25200 Program 1111412 Project

  13. The natural product peiminine represses colorectal carcinoma tumor growth by inducing autophagic cell death

    SciTech Connect (OSTI)

    Lyu, Qing; Tou, Fangfang; Su, Hong; Wu, Xiaoyong; Chen, Xinyi; Zheng, Zhi

    2015-06-19

    Autophagy is evolutionarily conservative in eukaryotic cells that engulf cellular long-lived proteins and organelles, and it degrades the contents through fusion with lysosomes, via which the cell acquires recycled building blocks for the synthesis of new molecules. In this study, we revealed that peiminine induces cell death and enhances autophagic flux in colorectal carcinoma HCT-116 cells. We determined that peiminine enhances the autophagic flux by repressing the phosphorylation of mTOR through inhibiting upstream signals. Knocking down ATG5 greatly reduced the peiminine-induced cell death in wild-type HCT-116 cells, while treating Bax/Bak-deficient cells with peiminine resulted in significant cell death. In summary, our discoveries demonstrated that peiminine represses colorectal carcinoma cell proliferation and cell growth by inducing autophagic cell death. - Highlights: • Peiminine induces autophagy and upregulates autophagic flux. • Peiminine represses colorectal carcinoma tumor growth. • Peiminine induces autophagic cell death. • Peiminine represses mTOR phosphorylation by influencing PI3K/Akt and AMPK pathway.

  14. The La-related protein 1-specific domain repurposes HEAT-like repeats to directly bind a 5'TOP sequence

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Lahr, Roni M.; Mack, Seshat M.; Heroux, Annie; Blagden, Sarah P.; Bousquet-Antonelli, Cecile; Deragon, Jean -Marc; Berman, Andrea J.

    2015-07-22

    La-related protein 1 (LARP1) regulates the stability of many mRNAs. These include 5'TOPs, mTOR-kinase responsive mRNAs with pyrimidine-rich 5' UTRs, which encode ribosomal proteins and translation factors. We determined that the highly conserved LARP1-specific C-terminal DM15 region of human LARP1 directly binds a 5'TOP sequence. The crystal structure of this DM15 region refined to 1.86 Å resolution has three structurally related and evolutionarily conserved helix-turn-helix modules within each monomer. These motifs resemble HEAT repeats, ubiquitous helical protein-binding structures, but their sequences are inconsistent with consensus sequences of known HEAT modules, suggesting this structure has been repurposed for RNA interactions. Amore » putative mTORC1-recognition sequence sits within a flexible loop C-terminal to these repeats. We also present modelling of pyrimidine-rich single-stranded RNA onto the highly conserved surface of the DM15 region. Ultimately, these studies lay the foundation necessary for proceeding toward a structural mechanism by which LARP1 links mTOR signalling to ribosome biogenesis.« less

  15. The La-related protein 1-specific domain repurposes HEAT-like repeats to directly bind a 5'TOP sequence

    SciTech Connect (OSTI)

    Lahr, Roni M.; Mack, Seshat M.; Heroux, Annie; Blagden, Sarah P.; Bousquet-Antonelli, Cecile; Deragon, Jean -Marc; Berman, Andrea J.

    2015-07-22

    La-related protein 1 (LARP1) regulates the stability of many mRNAs. These include 5'TOPs, mTOR-kinase responsive mRNAs with pyrimidine-rich 5' UTRs, which encode ribosomal proteins and translation factors. We determined that the highly conserved LARP1-specific C-terminal DM15 region of human LARP1 directly binds a 5'TOP sequence. The crystal structure of this DM15 region refined to 1.86 Å resolution has three structurally related and evolutionarily conserved helix-turn-helix modules within each monomer. These motifs resemble HEAT repeats, ubiquitous helical protein-binding structures, but their sequences are inconsistent with consensus sequences of known HEAT modules, suggesting this structure has been repurposed for RNA interactions. A putative mTORC1-recognition sequence sits within a flexible loop C-terminal to these repeats. We also present modelling of pyrimidine-rich single-stranded RNA onto the highly conserved surface of the DM15 region. Ultimately, these studies lay the foundation necessary for proceeding toward a structural mechanism by which LARP1 links mTOR signalling to ribosome biogenesis.

  16. The SuperB Accelerator: Overview and Lattice Studies

    SciTech Connect (OSTI)

    Biagini, M.E.; Boni, R.; Boscolo, M.; Drago, A.; Guiducci, S.; Preger, M.; Raimondi, P.; Tomassini, S.; Vaccarezza, C.; Zobov, M.; Cai, Y.; Fisher, A.; Heifets, S.; Novokhatski, A.; Pivi, M.T.; Seeman, J.; Sullivan, M.; Wienands, U.; Paoloni, E.; Marchiori, G.; Koop, I.; /Novosibirsk, IYF /Daresbury /LBL, Berkeley /CERN /Orsay, LAL /KEK, Tsukuba

    2011-11-22

    SuperB aims at the construction of a very high luminosity (10{sup 36} cm{sup -2} s{sup -1}) asymmetric e{sup +}e{sup -} Flavour Factory, with possible location at the campus of the University of Rome Tor Vergata, near the INFN Frascati National Laboratory. In this paper the basic principles of the design and details on the lattice are given. SuperB is a new machine that can exploit novel very promising design approaches: (1) large Piwinski angle scheme will allow for peak luminosity of the order of 10{sup 36} cm{sup -2} s{sup -1}, well beyond the current state-of-the-art, without a significant increase in beam currents or shorter bunch lengths; (2) 'crab waist' sextupoles will be used for suppression of dangerous resonances; (3) the low beam currents design presents reduced detector and background problems, and affordable operating costs; (4) a polarized electron beam can produce polarized {tau} leptons, opening an entirely new realm of exploration in lepton flavor physics. SuperB studies are already proving useful to the accelerator and particle physics communities. The principle of operation is being tested at DAFNE. The baseline lattice, based on the reuse of all PEP-II hardware, fits in the Tor Vergata University campus site, near Frascati. A CDR is being reviewed by an International Review Committee, chaired by J. Dainton (UK). A Technical Design Report will be prepared to be ready by beginning of 2010.

  17. INPP4B-mediated tumor resistance is associated with modulation of glucose metabolism via hexokinase 2 regulation in laryngeal cancer cells

    SciTech Connect (OSTI)

    Min, Joong Won; Kim, Kwang Il; Kim, Hyun-Ah; Kim, Eun-Kyu; Noh, Woo Chul; Jeon, Hong Bae; Cho, Dong-Hyung; Oh, Jeong Su; Park, In-Chul; Hwang, Sang-Gu; Kim, Jae-Sung

    2013-10-11

    Highlights: •HIF-1α-regulated INPP4B enhances glycolysis. •INPP4B regulates aerobic glycolysis by inducing HK2 via Akt-mTOR pathway. •Blockage of INPP4B and HK2 sensitizes radioresistant laryngeal cancer cells to radiation and anticancer drug. •INPP4B is associated with HK2 in human laryngeal cancer tissues. -- Abstract: Inositol polyphosphate 4-phosphatase type II (INPP4B) was recently identified as a tumor resistance factor in laryngeal cancer cells. Herein, we show that INPP4B-mediated resistance is associated with increased glycolytic phenotype. INPP4B expression was induced by hypoxia and irradiation. Intriguingly, overexpression of INPP4B enhanced aerobic glycolysis. Of the glycolysis-regulatory genes, hexokinase 2 (HK2) was mainly regulated by INPP4B and this regulation was mediated through the Akt-mTOR pathway. Notably, codepletion of INPP4B and HK2 markedly sensitized radioresistant laryngeal cancer cells to irradiation or anticancer drug. Moreover, INPP4B was significantly associated with HK2 in human laryngeal cancer tissues. Therefore, these results suggest that INPP4B modulates aerobic glycolysis via HK2 regulation in radioresistant laryngeal cancer cells.

  18. Pirarubicin induces an autophagic cytoprotective response through suppression of the mammalian target of rapamycin signaling pathway in human bladder cancer cells

    SciTech Connect (OSTI)

    Li, Kuiqing; Chen, Xu; Liu, Cheng; Gu, Peng; Li, Zhuohang; Wu, Shaoxu; Xu, Kewei; Lin, Tianxin; Huang, Jian

    2015-05-01

    Pirarubicin is widely used in intravesical chemotherapy for bladder cancer, but its efficacy is limited due to drug resistance; the mechanism has not been well studied. Emerging evidence shows that autophagy can be a novel target for cancer therapy. This study aimed to investigate the role of autophagy in pirarubicin-treated bladder cancer cells. Bladder cancer cells EJ and J82 were treated with pirarubicin, siRNA, 3-methyladenine or hydroxychloroquine. Cell proliferation and apoptosis were tested by cell survival assay and flow cytometric analysis, respectively. Autophagy was evaluated by immunoblotting before and after the treatments. The phosphorylated mammalian target of rapamycin, serine/threonine kinase p70 S6 kinase, and eukaryotic translation initiation factor 4E binding protein 1 were also investigated by immunoblotting. We found that pirarubicin could induce autophagy in bladder cancer cells. Inhibition of autophagy by 3-methyladenine, hydroxychloroquine or knockdown of autophagy related gene 3 significantly increased apoptosis in pirarubicin-treated bladder cancer cells. Pirarubicin-induced autophagy was mediated via the mTOR/p70S6K/4E-BP1 signaling pathway. In conclusion, autophagy induced by pirarubicin plays a cytoprotective role in bladder cancer cells, suggesting that inhibition of autophagy may improve efficacy over traditional pirarubicin chemotherapy in bladder cancer patients. - Highlights: • Pirarubicin induced autophagy in bladder cancer cells. • Inhibition of autophagy enhanced pirarubicin-induced apoptosis. • Pirarubicin induced autophagy through inhibition of mTOR signaling pathway.

  19. Improved DC Gun Insulator Assembly

    SciTech Connect (OSTI)

    Sah, R.; Dudas, A.; Neubauer, M. L.; Poelker, M.; Surles-Law, K. E.L.

    2010-05-23

    Many user fa­cil­i­ties such as syn­chrotron ra­di­a­tion light sources and free elec­tron lasers re­quire ac­cel­er­at­ing struc­tures that sup­port elec­tric fields of 10-100 MV/m, es­pe­cial­ly at the start of the ac­cel­er­a­tor chain where ce­ram­ic in­su­la­tors are used for very high gra­di­ent DC guns. These in­su­la­tors are dif­fi­cult to man­u­fac­ture, re­quire long com­mis­sion­ing times, and often ex­hib­it poor re­li­a­bil­i­ty. Two tech­ni­cal ap­proach­es to solv­ing this prob­lem will be in­ves­ti­gat­ed. First­ly, in­vert­ed ce­ram­ics offer so­lu­tions for re­duced gra­di­ents be­tween the elec­trodes and ground. An in­vert­ed de­sign will be pre­sent­ed for 350 kV, with max­i­mum gra­di­ents in the range of 5-10 MV/m. Sec­ond­ly, novel ce­ram­ic man­u­fac­tur­ing pro­cess­es will be stud­ied, in order to pro­tect triple junc­tion lo­ca­tions from emis­sion, by ap­ply­ing a coat­ing with a bulk re­sis­tiv­i­ty. The pro­cess­es for cre­at­ing this coat­ing will be op­ti­mized to pro­vide pro­tec­tion as well as be used to coat a ce­ram­ic with an ap­pro­pri­ate gra­di­ent in bulk re­sis­tiv­i­ty from the vac­u­um side to the air side of an HV stand­off ce­ram­ic cylin­der. Ex­am­ple in­su­la­tor de­signs are being com­put­er mod­elled, and in­su­la­tor sam­ples are being man­u­fac­tured and test­ed

  20. Fermilab F

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    F e r m i N a t i o n a l Ac celerato r L a b o r a tor y P . O . B o x 5 0 0 * B a t a v i a , I l . * 60510-0500 6 3 0 - 8 4 0 - 3 2 1 1 F A X 6 3 0 - 8 4 0 - 2 9 0 0 D i r e c t o r ' s O f f i c e April 15, 2004 Prof. Kevin McFarland Dept. of Physics & Astronomy University of Rochester Rochester NY 14627 Dr. Jorge Morfin Fermilab MS 220 Dear Kevin and Jorge, Thank you for your presentations to the Physics Advisory Committee (PAC). The presentations were well received, and the PAC

  1. ION EXCHANGE SUBSTANCES BY SAPONIFICATION OF ALLYL PHOSPHATE POLYMERS

    DOE Patents [OSTI]

    Kennedy, J.

    1959-04-14

    An ion exchange resin having a relatively high adsorption capacity tor uranyl ion as compared with many common cations is reported. The resin comprises an alphyl-allyl hydrogen phosphate polymer, the alphyl group being either allyl or a lower alkyl group having up to 5 carbon atoins. The resin is prepared by polymerizing compounds such as alkyl-diallyl phosphate and triallyl phosphate in the presence of a free radical generating substance and then partially hydrolyzing the resulting polymer to cause partial replacement of organic radicals by cations. A preferred free radical gencrating agent is dibenzoyl peroxide. The partial hydrolysis is brought about by refluxing the polymer with concentrated aqueous NaOH for three or four hours.

  2. Status of the SPARC Project

    SciTech Connect (OSTI)

    Alesini, D.; Bertolucci, S.; Bellaveglia, M.; Biagini, M.E.; Boni, R.; Boscolo, M.; Castellano, M.; Clozza, A.; Pirro, G.Di; Drago, A.; Esposito, A.; Ferrario, M.; Ficcadenti, L.; Filippetto, D.; Fusco, V.; Gallo, A.; Gatti, G.; Ghigo, A.; Guiducci, S.; Incurvati, M.; Ligi, C.; /Frascati /INFN, Milan /Milan U. /INFN, Rome /INFN, Rome /ENEA, Frascati /Milan, Polytechnic /UCLA /SLAC

    2006-01-25

    The SPARC project has entered its installation phase at the Frascati National Laboratories of INFN: its main goal, the promotion of an R&D activity oriented to the development of a high brightness photoinjector to drive SASE-FEL experiments, is being vigorously pursued by a collaboration among ENEA-INFN-CNR-Universita di Roma Tor Vergata-INFM-ST. In this paper we will report on the installation and test of some major components, like Ti:Sa laser system, RF gun and RF power system. Advancements in the control and beam diagnostics systems will also be reported, in particular on the emittance-meter device for beam emittance measurements in the drift space downstream the RF gun. Recent results on laser pulse shaping show the feasibility of producing 10 ps flat-top laser pulses in the UV with rise time below 1 ps. First FEL experiments have been proposed, using SASE, seeding and non-linear resonant harmonics.

  3. Structure-Based Design of Potent and Selective 3-Phosphoinositide-Dependent Kinase-1 (PDK1) Inhibitors

    SciTech Connect (OSTI)

    Medina, Jesus R.; Becker, Christopher J.; Blackledge, Charles W.; Duquenne, Celine; Feng, Yanhong; Grant, Seth W.; Heerding, Dirk; Li, William H.; Miller, William H.; Romeril, Stuart P.; Scherzer, Daryl; Shu, Arthur; Bobko, Mark A.; Chadderton, Antony R.; Dumble, Melissa; Gardiner, Christine M.; Gilbert, Seth; Liu, Qi; Rabindran, Sridhar K.; Sudakin, Valery; Xiang, Hong; Brady, Pat G.; Campobasso, Nino; Ward, Paris; Axten, Jeffrey M.

    2014-10-02

    Phosphoinositide-dependent protein kinase-1(PDK1) is a master regulator of the AGC family of kinases and an integral component of the PI3K/AKT/mTOR pathway. As this pathway is among the most commonly deregulated across all cancers, a selective inhibitor of PDK1 might have utility as an anticancer agent. Herein we describe our lead optimization of compound 1 toward highly potent and selective PDK1 inhibitors via a structure-based design strategy. The most potent and selective inhibitors demonstrated submicromolar activity as measured by inhibition of phosphorylation of PDK1 substrates as well as antiproliferative activity against a subset of AML cell lines. In addition, reduction of phosphorylation of PDK1 substrates was demonstrated in vivo in mice bearing OCl-AML2 xenografts. These observations demonstrate the utility of these molecules as tools to further delineate the biology of PDK1 and the potential pharmacological uses of a PDK1 inhibitor.

  4. Jnited States Government

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Jnited States Government Department of Energy memorandum OATE Ef:>L Y TO ~TTI\j OF UBJECT May 6, 198o ER-70 ~ Information on a Major N~w Initiativ~: Mapping and s~qu~ncing the Human G~nom~ TO Alvin W. Triv~lpi~r~, Dir~~tor Offir~ of En~rgy RPs~arch BACKGROUND: In thP ~arly 1970's Walt~r Gilb~rt, a form~r Harvard Univ~rsity physics prnf~ssor, and Fr~d Sang~r, a Cambridg~ biochemist, developPd important n~w approarhPs to DNA sequPnring. ThP m~thods, which allow rapid det~rminatinn of th~

  5. LANL: AOT & LANSCE The Pulse March 2010

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Los Alamos National Laboratory * Est. 1943 The Pulse-Newsletter of the Los Alamos Neutron Science Center and Accelerator Operations and Technology Division I N S I D E 2 Tajima receives DOe early career awarD 2 NeuTrON reflec- TOmeTry prOviDes firsT sub-NaNOmeTer visualizaTiON Of live cell aDhesiON 3 creaTiNg a high- efficieNcy cOmpacT iON acceleraTOr, aN alTerNaTive TO larger, mOre cOsTly sTruc- Tures 4 heaDs up! LANSCE beam reliability achieves "world class" ranking AOT has issued

  6. Platelet-derived growth factor regulates vascular smooth muscle phenotype via mammalian target of rapamycin complex 1

    SciTech Connect (OSTI)

    Ha, Jung Min; Yun, Sung Ji; Kim, Young Whan; Jin, Seo Yeon; Lee, Hye Sun; Song, Sang Heon; Shin, Hwa Kyoung; Bae, Sun Sik

    2015-08-14

    Mammalian target of rapamycin complex (mTORC) regulates various cellular processes including proliferation, growth, migration and differentiation. In this study, we showed that mTORC1 regulates platelet-derived growth factor (PDGF)-induced phenotypic conversion of vascular smooth muscle cells (VSMCs). Stimulation of contractile VSMCs with PDGF significantly reduced the expression of contractile marker proteins in a time- and dose-dependent manner. In addition, angiotensin II (AngII)-induced contraction of VSMCs was completely blocked by the stimulation of VSMCs with PDGF. PDGF-dependent suppression of VSMC marker gene expression was significantly blocked by inhibition of phosphatidylinositol 3-kinase (PI3K), extracellular signal-regulated kinase (ERK), and mTOR whereas inhibition of p38 MAPK had no effect. In particular, inhibition of mTORC1 by rapamycin or by silencing of Raptor significantly blocked the PDGF-dependent phenotypic change of VSMCs whereas silencing of Rictor had no effect. In addition, loss of AngII-dependent contraction by PDGF was significantly retained by silencing of Raptor. Inhibition of mTORC1 by rapamycin or by silencing of Raptor significantly blocked PDGF-induced proliferation of VSMCs. Taken together, we suggest that mTORC1 plays an essential role in PDGF-dependent phenotypic changes of VSMCs. - Graphical abstract: Regulation of VSMC phenotype by PDGF-dependent activation of mTORC1. - Highlights: • The expression of contractile marker proteins was reduced by PDGF stimulation. • PDGF-dependent phenotypic conversion of VSMCs was blocked by inhibition of mTOR. • PDGF-induced proliferation of VSMCs was attenuated by inhibition of mTORC1. • mTORC1 plays a critical role in PDGF-dependent phenotypic conversion of VSMCs.

  7. Arsenite induces cell transformation by reactive oxygen species, AKT, ERK1/2, and p70S6K1

    SciTech Connect (OSTI)

    Carpenter, Richard L.; Jiang, Yue; Jing, Yi; He, Jun; Rojanasakul, Yon; Liu, Ling-Zhi; Jiang, Bing-Hua

    2011-10-28

    Highlights: Black-Right-Pointing-Pointer Chronic exposure to arsenite induces cell proliferation and transformation. Black-Right-Pointing-Pointer Arsenite-induced transformation increases ROS production and downstream signalings. Black-Right-Pointing-Pointer Inhibition of ROS levels via catalase reduces arsenite-induced cell transformation. Black-Right-Pointing-Pointer Interruption of AKT, ERK, or p70S6K1 inhibits arsenite-induced cell transformation. -- Abstract: Arsenic is naturally occurring element that exists in both organic and inorganic formulations. The inorganic form arsenite has a positive association with development of multiple cancer types. There are significant populations throughout the world with high exposure to arsenite via drinking water. Thus, human exposure to arsenic has become a significant public health problem. Recent evidence suggests that reactive oxygen species (ROS) mediate multiple changes to cell behavior after acute arsenic exposure, including activation of proliferative signaling and angiogenesis. However, the role of ROS in mediating cell transformation by chronic arsenic exposure is unknown. We found that cells chronically exposed to sodium arsenite increased proliferation and gained anchorage-independent growth. This cell transformation phenotype required constitutive activation of AKT, ERK1/2, mTOR, and p70S6K1. We also observed these cells constitutively produce ROS, which was required for the constitutive activation of AKT, ERK1/2, mTOR, and p70S6K1. Suppression of ROS levels by forced expression of catalase also reduced cell proliferation and anchorage-independent growth. These results indicate cell transformation induced by chronic arsenic exposure is mediated by increased cellular levels of ROS, which mediates activation of AKT, ERK1/2, and p70S6K1.

  8. The multi-functional roles of GNMT in toxicology and cancer

    SciTech Connect (OSTI)

    Yen, Chia-Hung; Lin, Yu-Ting; Chen, Heng-Li; Chen, Shih-Yin; Chen, Yi-Ming Arthur

    2013-01-01

    Although glycine N-methyltransferase (GNMT) has been discovered for five decades, its function was not elucidated until recently. In this review, we discuss the multiple roles of GNMT in toxicology and cancer. Besides catalyzing the production of methylglycine (sarcosine) in one carbon metabolism pathway, GNMT was found to be able to bind a number of polycyclic aromatic hydrocarbons and inhibit DNA adducts formation. Moreover, GNMT exerts protective effects against the cytotoxicity and carcinogenicity of benzo(a)pyrene and aflatoxin B{sub 1} in vitro and in vivo. Occupational study showed that workers who had genotypes with higher GNMT promoter activity may have lower content of oxidative damaged DNA products in their urine. In terms of cancer, recent studies using GNMT knockout mouse models demonstrated that GNMT deficiency has high penetrance in inducing the development of steatohepatitis and hepatocellular carcinoma. In terms of the mechanism, besides dysregulation of epigenetic modification, insights have been provided by recent identification of two novel proteins interacting with GNMT-DEPTOR and NPC2. These studies suggest that GNMT not only is involved in mTOR signaling pathway, but also plays an important role in the intracellular trafficking of cholesterol. The implication of these findings to the preventive medicine and translational research will be discussed. -- Highlights: ► We discuss the critical roles of GNMT in toxicology and cancer biology. ► GNMT binds benzo(a)pyrene and aflatoxin and inhibits their DNA adduct formation. ► GNMT deficiency is related to liver tumorigenesis both in mice and human. ► GNMT deficiency results in epigenetic dysregulation and metabolic diseases. ► GNMT is involved in mTOR pathway and intracellular trafficking of cholesterol.

  9. Rictor regulates FBXW7-dependent c-Myc and cyclin E degradation in colorectal cancer cells

    SciTech Connect (OSTI)

    Guo, Zheng; Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Dadao Bei, Guangzhou 510515 ; Zhou, Yuning; Evers, B. Mark; Department of Surgery, The University of Kentucky, 800 Rose Street, Lexington, KY 40536 ; Wang, Qingding; Department of Surgery, The University of Kentucky, 800 Rose Street, Lexington, KY 40536

    2012-02-10

    Highlights: Black-Right-Pointing-Pointer Rictor associates with FBXW7 to form an E3 complex. Black-Right-Pointing-Pointer Knockdown of rictor decreases ubiquitination of c-Myc and cylin E. Black-Right-Pointing-Pointer Knockdown of rictor increases protein levels of c-Myc and cylin E. Black-Right-Pointing-Pointer Overexpression of rictor induces the degradation of c-Myc and cyclin E proteins. Black-Right-Pointing-Pointer Rictor regulation of c-Myc and cyclin E requires FBXW7. -- Abstract: Rictor (Rapamycin-insensitive companion of mTOR) forms a complex with mTOR and phosphorylates and activates Akt. Activation of Akt induces expression of c-Myc and cyclin E, which are overexpressed in colorectal cancer and play an important role in colorectal cancer cell proliferation. Here, we show that rictor associates with FBXW7 to form an E3 complex participating in the regulation of c-Myc and cyclin E degradation. The Rictor-FBXW7 complex is biochemically distinct from the previously reported mTORC2 and can be immunoprecipitated independently of mTORC2. Moreover, knocking down of rictor in serum-deprived colorectal cancer cells results in the decreased ubiquitination and increased protein levels of c-Myc and cyclin E while overexpression of rictor induces the degradation of c-Myc and cyclin E proteins. Genetic knockout of FBXW7 blunts the effects of rictor, suggesting that rictor regulation of c-Myc and cyclin E requires FBXW7. Our findings identify rictor as an important component of FBXW7 E3 ligase complex participating in the regulation of c-Myc and cyclin E protein ubiquitination and degradation. Importantly, our results suggest that elevated growth factor signaling may contribute to decrease rictor/FBXW7-mediated ubiquitination of c-Myc and cyclin E, thus leading to accumulation of cyclin E and c-Myc in colorectal cancer cells.

  10. Quantitative proteomic analysis of the inhibitory effects of CIL-102 on viability and invasiveness in human glioma cells

    SciTech Connect (OSTI)

    Teng, Chih-Chuan; Kuo, Hsing-Chun; Sze, Chun-I

    2013-11-01

    CIL-102 (1-[4-(furo[2,3-b]quinolin-4-ylamino)phenyl]ethanone), the major active agent of the alkaloid derivative, has been demonstrated to exert anticancer effects. Herein, we present an investigation focused on the identification of the target(s) of CIL-102's action and the mechanism of its action in apoptotic and anti-invasive pathways. Proteomic approaches were used to purify and identify the protein substrates using 2D difference gel electrophoresis (2D SDS-PAGE) to assess changes in the expression of relevant protein treatment with CIL-102 that resulted in the inhibition of viability and invasion. Our results demonstrate that CIL-102 treatment of U87 cells decreased cell proliferation and invasiveness. CIL-102 dose-dependent induction of apoptosis and inhibitory invasiveness were accompanied by sustained phosphorylation of JNK1/2 and p70S6K as well as generation of the reactive oxygen species. In addition, differential proteins displayed between CIL-102-treated and untreated U87 were determined and validated. There were 11 differentially expressed proteins between the CIL-102-treated and untreated groups. Furthermore, we demonstrated that CIL-102 inhibited cancer cell proliferation and reduced anti-invasion properties by up-regulating the levels of FUMH (Fumarate hydratase). The investigation demonstrated that there was an increase in the cellular levels of FUMH in the CIL-102 reduction in viability and invasion via the activation of JNK1/2 and mTOR signaling modules. NAC administration and shRNA FUMH conferred resistance to CIL-102-inhibited HIF1? and MMP-2 levels via inhibition of JNK1/2 and mTOR activation. We concluded that CIL-102-induced an apoptosis cascade and decreased aggressiveness in astrocytoma cells by modulation of mitochondria function, providing a new mechanism for CIL-102 treatment. - Highlights: We found the effect of CIL-102 on neuroblastoma cells. Fumarate hydratase as a CIL-102's target by proteomic differential displays. CIL-102

  11. SuperB Bunch-By-Bunch Feedback R&D

    SciTech Connect (OSTI)

    Drago, A.; Beretta, M.; Bertsche, K.; Novokhatski, A.; Migliorati, M.; /Rome U.

    2011-08-12

    The SuperB project has the goal to build in Italy, in the Frascati or Tor Vergata area, an asymmetric e{sup +}/e{sup -} Super Flavor Factory to achieve a peak luminosity > 10**36 cm{sup -2} s{sup -1}. The SuperB design is based on collisions with extremely low vertical emittance beams and high beam currents. A source of emittance growth comes from the bunch by bunch feedback systems producing high power correction signals to damp the beams. To limit any undesirable effect, a large R&D program is in progress, partially funded by the INFN Fifth National Scientific Committee through the SFEED (SuperB Feedback) project approved within the 2010 budget. The SuperB project [1] has the goal to build in Italy, in the Frascati or Tor Vergata area, an asymmetric e{sup +}/e{sup -} Super Flavor Factory to achieve a peak luminosity > 10**36 cm{sup -2} s{sup -1}. In the last and current years, the machine layout has been deeply modified, in particular the main rings are now shorter and an option with high currents has been foreseen. In the fig.1 the new SuperB layout is shown. From bunch-by-bunch feedback point of view, the simultaneous presence in the machine parameters, of very low emittance, of the order of 5-10 pm in the vertical plane, and very high currents, at level of 4 Ampere for the Low Energy Ring, asks for designing very carefully the bunch-by-bunch feedback systems. The parameter list is presented in Fig. 2. The bunch-by-bunch feedback design must take care of the risky and exciting challenges proposed in the SuperB specifications, but it should consider also some other important aspects: flexibility in terms of being able to cope to unexpected beam behaviours [2], [3] legacy of previous version experience [4], [5] and internal powerful diagnostics [6] as in the systems previously used in PEP-II and DAFNE [7].

  12. Reactive oxygen species mediate Cr(VI)-induced carcinogenesis through PI3K/AKT-dependent activation of GSK-3β/β-catenin signaling

    SciTech Connect (OSTI)

    Son, Young-Ok; Pratheeshkumar, Poyil; Wang, Lei; Wang, Xin; Fan, Jia; Kim, Dong-Hern; Lee, Ju-Yeon; Zhang, Zhuo; Lee, Jeong-Chae; Shi, Xianglin

    2013-09-01

    Cr(VI) compounds are known human carcinogens that primarily target the lungs. Cr(VI) produces reactive oxygen species (ROS), but the exact effects of ROS on the signaling molecules involved in Cr(VI)-induced carcinogenesis have not been extensively studied. Chronic exposure of human bronchial epithelial cells to Cr(VI) at nanomolar concentrations (10–100 nM) for 3 months not only induced cell transformation, but also increased the potential of these cells to invade and migrate. Injection of Cr(VI)-stimulated cells into nude mice resulted in the formation of tumors. Chronic exposure to Cr(VI) increased levels of intracellular ROS and antiapoptotic proteins. Transfection with catalase or superoxide dismutase (SOD) prevented Cr(VI)-mediated increases in colony formation, cell invasion, migration, and xenograft tumors. While chronic Cr(VI) exposure led to activation of signaling cascades involving PI3K/AKT/GSK-3β/β-catenin and PI3K/AKT/mTOR, transfection with catalase or SOD markedly inhibited Cr(VI)-mediated activation of these signaling proteins. Inhibitors specific for AKT or β-catenin almost completely suppressed the Cr(VI)-mediated increase in total and active β-catenin proteins and colony formation. In particular, Cr(VI) suppressed autophagy of epithelial cells under nutrition deprivation. Furthermore, there was a marked induction of AKT, GSK-3β, β-catenin, mTOR, and carcinogenic markers in tumor tissues formed in mice after injection with Cr(VI)-stimulated cells. Collectively, our findings suggest that ROS is a key mediator of Cr(VI)-induced carcinogenesis through the activation of PI3K/AKT-dependent GSK-3β/β-catenin signaling and the promotion of cell survival mechanisms via the inhibition of apoptosis and autophagy. - Highlights: • Chronic exposure to Cr(VI) induces carcinogenic properties in BEAS-2B cells. • ROS play an important role in Cr(VI)-induced tumorigenicity of BEAS-2B cells. • PI3K/AKT/GSK-3β/β-catenin signaling involved in Cr

  13. Nature of Catalytic Active Sites Present on the Surface of Advanced Bulk Tantalum Mixed Oxide Photocatalysts

    SciTech Connect (OSTI)

    Phivilay, Somphonh; Puretzky, Alexander A; Domen, Kazunari Domen; Wachs, Israel

    2013-01-01

    The most active photocatalyst system for water splitting under UV irradiation (270 nm) is the promoted 0.2%NiO/NaTaO3:2%La photocatalyst with optimized photonic efficiency (P.E.) of 56%, but fundamental issues about the nature of the surface catalytic active sites and their involvement in the photocatalytic process still need to be clarified. This is the first study to apply cutting edge surface spectroscopic analyses to determine the surface nature of tantalum mixed oxide photocatalysts. Surface analysis with HR-XPS (1-3nm) and HS-LEIS (0.3nm) spectroscopy indicates that the NiO and La2O3 promoters are concentrated in the surface region of the bulk NaTaO3 phase. The La2O3 is concentrated on the NaTaO3 outermost surface layers while NiO is distributed throughout the NaTaO3 surface region (1-3nm). Raman and UV-vis spectroscopy revealed that the bulk molecular and electronic structures, respectively, of NaTaO3 were not modified by the addition of the La2O3 and NiO promoters, with La2O3 resulting in a slightly more ordered structure. Photoluminescence (PL) spectroscopy reveals that the addition of La2O3 and NiO produces a greater number of electron traps resulting in the suppression of the recombination of excited electrons/holes. In contrast to earlier reports, the La2O3 is only a textural promoter (increasing the BET surface area ~7x by stabilizing smaller NaTaO3 particles), but causes a ~3x decrease in the specific photocatalytic TORs ( mol H2/m2/h) rate because surface La2O3 blocks exposed catalytic active NaTaO3 sites. The NiO promoter was found to be a potent electronic promoter that enhances the NaTaO3 surface normalized TORs by a factor of ~10-50 and TOF by a factor of ~10. The level of NiO promotion is the same in the absence and presence of La2O3 demonstrating that there is no promotional synergistic interaction between the NiO and La2O3 promoters. This study demonstrates the important contributions of the photocatalyst surface properties to the fundamental

  14. New photon science and extreme field physics: volumetric interaction of ultra-intense laser pulses with over-dense targets

    SciTech Connect (OSTI)

    Hegelich, Bjorn M [Los Alamos National Laboratory

    2010-11-24

    The constantly improving capabilities of ultra-high power lasers are enabling interactions of matter with ever extremer fields. As both the on target intensity and the laser contrast are increasing, new physics regimes are becoming accessible and new effects materialize, which in turn enable a host of applications. A first example is the realization of interactions in the transparent-overdense regime (TOR), which is reached by interacting a highly relativistic (a{sub 0} > 10), ultra high contrast laser pulse with a solid density, nanometer target. Here, a still overdense target is turned transparent to the laser by the relativistic mass increase of the electrons, increasing the skin depth beyond the target thickness and thus enabling volumetric interaction of the laser with the entire target instead of only a small interaction region at the critical density surface. This increases the energy coupling, enabling a range of effects, including relativistic optics and pulse shaping, mono-energetic electron acceleration, highly efficient ion acceleration in the break-out afterburner regime, the generation of relativistic and forward directed surface harmonics. In this talk we will show the theoretical framework for this regime, explored by multi-D, high resolution and high density PIC simulations as well as analytic theory and present measurements and experimental demonstrations of direct relativistic optics, relativistic HHG, electron acceleration, and BOA ion acceleration in the transparent overdense regime. These effects can in turn be used in a host of applications including laser pulse shaping, ICF diagnostics, coherent x-ray sources, and ion sources for fast ignition (IFI), homeland security applications and medical therapy. This host of applications already makes transparent-overdense regime one of general interest, a situation reinforced by the fact that the TOR target undergoes an extremely wide HEDP parameter space during interaction ranging from WDM conditions

  15. Developing an Innovative Field Expedient Fracture Toughness Testing Protocol for Concrete Materials

    SciTech Connect (OSTI)

    Wang, Jy-An John; Liu, Ken C; Naus, Dan J

    2008-09-01

    The Spiral Notch Torsion Fracture Toughness Test (SNTT) was developed recently to determine the intrinsic fracture toughness (KIC) of structural materials. The SNTT system operates by applying pure torsion to uniform cylindrical specimens with a notch line that spirals around the specimen at a 45? pitch. KIC values are obtained with the aid of a three-dimensional finite-element computer code, TOR3D-KIC. The SNTT method is uniquely suitable for testing a wide variety of materials used extensively in pressure vessel and piping structural components and weldments. Application of the method to metallic, ceramic, and graphite materials has been demonstrated. One important characteristic of SNTT is that neither a fatigue precrack or a deep notch are required for the evaluation of brittle materials, which significantly reduces the sample size requirement. In this paper we report results for a Portland cement-based mortar to demonstrate applicability of the SNTT method to cementitious materials. The estimated KIC of the tested mortar samples with compressive strength of 34.45 MPa was found to be 0.19 MPa m.

  16. High Accuracy Transistor Compact Model Calibrations

    SciTech Connect (OSTI)

    Hembree, Charles E.; Mar, Alan; Robertson, Perry J.

    2015-09-01

    Typically, transistors are modeled by the application of calibrated nominal and range models. These models consists of differing parameter values that describe the location and the upper and lower limits of a distribution of some transistor characteristic such as current capacity. Correspond- ingly, when using this approach, high degrees of accuracy of the transistor models are not expected since the set of models is a surrogate for a statistical description of the devices. The use of these types of models describes expected performances considering the extremes of process or transistor deviations. In contrast, circuits that have very stringent accuracy requirements require modeling techniques with higher accuracy. Since these accurate models have low error in transistor descriptions, these models can be used to describe part to part variations as well as an accurate description of a single circuit instance. Thus, models that meet these stipulations also enable the calculation of quantifi- cation of margins with respect to a functional threshold and uncertainties in these margins. Given this need, new model high accuracy calibration techniques for bipolar junction transis- tors have been developed and are described in this report.

  17. Wound Ballistics Modeling for Blast Loading Blunt Force Impact and Projectile Penetration

    SciTech Connect (OSTI)

    Taylor, Paul A.; Cooper, Candice Frances; Burnett, Damon J.

    2015-09-01

    Light body armor development for the warfighter is based on trial-and-error testing of prototype designs against ballistic projectiles. Torso armor testing against blast is virtually nonexistent but necessary to ensure adequate protection against injury to the heart and lungs. In this report, we discuss the development of a high-fidelity human torso model, it's merging with the existing Sandia Human Head-Neck Model, and development of the modeling & simulation (M&S) capabilities necessary to simulate wound injury scenarios. Using the new Sandia Human Torso Model, we demonstrate the advantage of virtual simulation in the investigation of wound injury as it relates to the warfighter experience. We present the results of virtual simulations of blast loading and ballistic projectile impact to the tors o with and without notional protective armor. In this manner, we demonstrate the ad vantages of applying a modeling and simulation approach to the investigation of wound injury and relative merit assessments of protective body armor without the need for trial-and-error testing.

  18. Super-B Project Overview

    SciTech Connect (OSTI)

    Biagini, M.E.; Boni, R.; Boscolo, M.; Demma, T.; Drago, A.; Guiducci, S.; Raimondi, P.; Tomassini, S.; Zobov, M.; Bertsche, K.; Donald, M.; Nosochkov, Y.; Novokhatski, A.; Seeman, J.; Sullivan, M.; Yocky, G.; Wienands, U.; Wittmer, W.; Koop, I.; Levichev, E.; Nikitin, S.; /Novosibirsk, IYF /KEK, Tsukuba /Pisa U. /CERN

    2010-08-26

    The SuperB project aims at the construction of an asymmetric very high luminosity B-Factory on the Frascati/Tor Vergata (Italy) area, providing a uniquely sensitive probe of New Physics in the flavour sector of the Standard Model. The luminosity goal of 10{sup 36} cm{sup -2} s{sup -1} can be reached with a new collision scheme with 'large Piwinski angle' (LPA) and the use of 'crab waist sextupoles' (CW). A LPA&CW Interaction Region (IR) has been successfully tested at the DA{Phi}NE {Phi}-Factory at LNF-Frascati in 2008. The LPA&CW scheme, together with very low {beta}*, will allow for operation with relatively low beam currents and reasonable bunch length, comparable to those of PEP-II and KEKB. In the High Energy Ring (HER), two spin rotators will bring longitudinally polarized beams into collision at the IP. The lattice has been designed with a very low intrinsic emittance and is quite compact, less than 2 km long. The tight focusing requires the final doublet quadrupoles to be very close to the IP and very compact. A Conceptual Design Report was published in March 2007, and beam dynamics and collective effects R&D studies are in progress in order to publish a Technical Design Report by the end of 2010.

  19. Rigorous theory of molecular orientational nonlinear optics

    SciTech Connect (OSTI)

    Kwak, Chong Hoon Kim, Gun Yeup

    2015-01-15

    Classical statistical mechanics of the molecular optics theory proposed by Buckingham [A. D. Buckingham and J. A. Pople, Proc. Phys. Soc. A 68, 905 (1955)] has been extended to describe the field induced molecular orientational polarization effects on nonlinear optics. In this paper, we present the generalized molecular orientational nonlinear optical processes (MONLO) through the calculation of the classical orientational averaging using the Boltzmann type time-averaged orientational interaction energy in the randomly oriented molecular system under the influence of applied electric fields. The focal points of the calculation are (1) the derivation of rigorous tensorial components of the effective molecular hyperpolarizabilities, (2) the molecular orientational polarizations and the electronic polarizations including the well-known third-order dc polarization, dc electric field induced Kerr effect (dc Kerr effect), optical Kerr effect (OKE), dc electric field induced second harmonic generation (EFISH), degenerate four wave mixing (DFWM) and third harmonic generation (THG). We also present some of the new predictive MONLO processes. For second-order MONLO, second-order optical rectification (SOR), Pockels effect and difference frequency generation (DFG) are described in terms of the anisotropic coefficients of first hyperpolarizability. And, for third-order MONLO, third-order optical rectification (TOR), dc electric field induced difference frequency generation (EFIDFG) and pump-probe transmission are presented.

  20. Fracture toughness determination using spiral-grooved cylindrical specimen and pure torsional loading

    DOE Patents [OSTI]

    Wang, Jy-An; Liu, Kenneth C.

    2003-07-08

    A method for determining fracture toughness K.sub.IC of materials ranging from metallic alloys, brittle ceramics and their composites, and weldments. A cylindrical specimen having a helical V-groove with a 45.degree. pitch is subjected to pure torsion. This loading configuration creates a uniform tensile-stress crack-opening mode, and a transverse plane-strain state along the helical groove. The full length of the spiral groove is equivalent to the thickness of a conventional compact-type specimen. K.sub.IC values are determined from the fracture torque and crack length measured from the test specimen using a 3-D finite element program (TOR3D-KIC) developed for the purpose. In addition, a mixed mode (combined tensile and shear stress mode) fracture toughness value can be determined by varying the pitch of the helical groove. Since the key information needed for determining the K.sub.IC value is condensed in the vicinity of the crack tip, the specimen can be significantly miniaturized without the loss of generality.

  1. Adaptation of HepG2 cells to a steady-state reduction in the content of protein phosphatase 6 (PP6) catalytic subunit

    SciTech Connect (OSTI)

    Boylan, Joan M.; Salomon, Arthur R.; Tantravahi, Umadevi; Gruppuso, Philip A.

    2015-07-15

    Protein phosphatase 6 (PP6) is a ubiquitous Ser/Thr phosphatase involved in an array of cellular processes. To assess the potential of PP6 as a therapeutic target in liver disorders, we attenuated expression of the PP6 catalytic subunit in HepG2 cells using lentiviral-transduced shRNA. Two PP6 knock-down (PP6KD) cell lines (90% reduction of PP6-C protein content) were studied in depth. Both proliferated at a rate similar to control cells. However, flow cytometry indicated G2/M cell cycle arrest that was accounted for by a shift of the cells from a diploid to tetraploid state. PP6KD cells did not show an increase in apoptosis, nor did they exhibit reduced viability in the presence of bleomycin or taxol. Gene expression analysis by microarray showed attenuated anti-inflammatory signaling. Genes associated with DNA replication were downregulated. Mass spectrometry-based phosphoproteomic analysis yielded 80 phosphopeptides representing 56 proteins that were significantly affected by a stable reduction in PP6-C. Proteins involved in DNA replication, DNA damage repair and pre-mRNA splicing were overrepresented among these. PP6KD cells showed intact mTOR signaling. Our studies demonstrated involvement of PP6 in a diverse set of biological pathways and an adaptive response that may limit the effectiveness of targeting PP6 in liver disorders. - Highlights: • Lentiviral-transduced shRNA was used to generate a stable knockdown of PP6 in HepG2 cells. • Cells adapted to reduced PP6; cell proliferation was unaffected, and cell survival was normal. • However, PP6 knockdown was associated with a transition to a tetraploid state. • Genomic profiling showed downregulated anti-inflammatory signaling and DNA replication. • Phosphoproteomic profiling showed changes in proteins associated with DNA replication and repair.

  2. Exposure to Ionizing Radiation Causes Long-Term Increase in Serum Estradiol and Activation of PI3K-Akt Signaling Pathway in Mouse Mammary Gland

    SciTech Connect (OSTI)

    Suman, Shubhankar; Johnson, Michael D.; Fornace, Albert J.; Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC ; Datta, Kamal

    2012-10-01

    Purpose: Exposure to ionizing radiation is an established risk factor for breast cancer. Radiation exposure during infancy, childhood, and adolescence confers the highest risk. Although radiation is a proven mammary carcinogen, it remains unclear where it acts in the complex multistage process of breast cancer development. In this study, we investigated the long-term pathophysiologic effects of ionizing radiation at a dose (2 Gy) relevant to fractionated radiotherapy. Methods and Materials: Adolescent (6-8 weeks old; n = 10) female C57BL/6J mice were exposed to 2 Gy total body {gamma}-radiation, the mammary glands were surgically removed, and serum and urine samples were collected 2 and 12 months after exposure. Molecular pathways involving estrogen receptor-{alpha} (ER{alpha}) and phosphatidylinositol-3-OH kinase (PI3K)-Akt signaling were investigated by immunohistochemistry and Western blot. Results: Serum estrogen and urinary levels of the oncogenic estrogen metabolite (16{alpha}OHE1) were significantly increased in irradiated animals. Immunostaining for the cellular proliferative marker Ki-67 and cyclin-D1 showed increased nuclear accumulation in sections of mammary glands from irradiated vs. control mice. Marked increase in p85{alpha}, a regulatory sub-unit of the PI3K was associated with increase in Akt, phospho-Akt, phospho-BAD, phospho-mTOR, and c-Myc in irradiated samples. Persistent increase in nuclear ER{alpha} in mammary tissues 2 and 12 months after radiation exposure was also observed. Conclusions: Taken together, our data not only support epidemiologic observations associating radiation and breast cancer but also, specify molecular events that could be involved in radiation-induced breast cancer.

  3. Fossil and Contemporary Fine Carbon Fractions at 12 Rural and Urban Sites in the United States

    SciTech Connect (OSTI)

    Schichtel, B; Malm, W; Bench, G; Fallon, S; McDade, C; Chow, J

    2007-03-01

    Fine particulate matter collected at two urban, four near-urban, and six remote sites throughout the United States were analyzed for total carbon (TC) and radiocarbon ({sup 14}C). Samples were collected at most sites for both a summer and winter season. The radiocarbon was used to partition the TC into fossil and contemporary fractions. On average, contemporary carbon composed about half of the carbon at the urban, {approx}70-97% at near-urban, and 82-100% at remote sites. At Phoenix, Arizona, and Seattle, Washington, one monitor was located within the urban center and one outside to assess the urban excess over background concentrations. During the summer the urban and rural sites had similar contemporary carbon concentrations. However, during the winter the urban sites had more than twice the contemporary carbon measured at the neighboring sites, indicating anthropogenic contributions to the contemporary carbon. The urban fossil carbon was 4-20 times larger than the neighboring rural sites for both seasons. Organic (OC) and elemental carbon (EC) from TOR analysis were available. These and the radiocarbon data were used to estimate characteristic fossil and contemporary EC/TC ratios for the winter and summer seasons. These ratios were applied to carbon data from the Interagency Monitoring of Protected Visual Environments network to estimate the fraction of contemporary carbon at mostly rural sites throughout the United States. In addition, the ratios were used to develop a semiquantitative, lower bound estimate of secondary organic carbon (SOC) contribution to fossil and contemporary carbon. SOC accounted for more than one-third of the fossil and contemporary carbon.

  4. Processes the Govern Helicity Injection in the SSPX Spheromak

    SciTech Connect (OSTI)

    Woodruff, S; Stallard, B W; Holcomb, C T; Cothran, C

    2002-10-08

    The physical processes that govern the gun-voltage and give rise to field generation by helicity injection are surveyed in the Sustained Spheromak Physics experiment (SSPX) using internal magnetic field probes and particular attention to the gun-voltage. SSPX is a gun-driven spheromak, similar in many respects to CTX, although differing substantially by virtue of a programmable vacuum field configuration. Device parameters are: diameter = 1m, I{sub tor}-400kA, T{sub e}{approx}120eV, t{sub pulse}{approx}3ms. SSPX is now in its third year of operation and has demonstrated reasonable confinement (core {chi}{sub e}{approx}30m{sup 2}/s), and evidence for a beta limit (<{beta}{sub e}>{sub vol}{approx}4%), suggesting that the route to high temperature is to increase the spheromak field-strength (or current amplification, A{sub I} = I{sub torr}/I{sub inj}). Some progress has been made to increase A{sub I} in SSPX (A{sub I} = 2.2), although the highest A{sub I} observed in a spheromak of 3 has yet to be beaten. We briefly review helicity injection as the paradigm for spheromak field generation. SSPX results show that the processes that give efficient injection of helicity are inductive, and that these processes rapidly terminate when the current path ceases to change. The inductive processes are subsequently replaced by ones that resistively dissipate the injected helicity. This result means that efficient helicity injection can be achieved by harnessing the inductive processes, possibly by pulsing the gun. A pulsed build-up scenario is presented which gives A{sub I} > 3 and emphasizes the need to maintain reasonable confinement while the field of the spheromak is being built.

  5. Controlled and Spontaneous Magnetic Field Generation in a Gun-Driven Spheromak

    SciTech Connect (OSTI)

    Woodruff, S; Cohen, B I; Hooper, E B; McLean, H S; Stallard, B W; Hill, D N; Holcomb, C T; Romero-Talamas, C; Wood, R D; Cone, G; Sovinec, C R

    2004-10-01

    In the Sustained Spheromak Physics Experiment, SSPX, progress has been made in understanding the mechanisms that generate fields by helicity injection. SSPX injects helicity (linked magnetic flux) from 1-m diameter magnetized coaxial electrodes into a flux-conserving confinement region. Control of magnetic fluctuations ({delta}B/B{approx}1% on the midplane edge) yields T{sub e} profiles peaked at > 200eV. Trends indicate a limiting beta ({beta}{sub e} {approx} 4-6%), and so we have been motivated to increase T{sub e} by operating with stronger magnetic field. Two new operating modes are observed to increase the magnetic field: (A) Operation with constant current and spontaneous gun voltage fluctuations. In this case, the gun is operated continuously at the threshold for ejection of plasma from the gun: stored magnetic energy of the spheromak increases gradually with {delta}B/B {approx}2% and large voltage fluctuations ({delta}V {approx} 1kV), giving a 50% increase in current amplification, I{sub tor}/I{sub gun}. (B) Operation with controlled current pulses. In this case, spheromak magnetic energy increases in a stepwise fashion by pulsing the gun, giving the highest magnetic fields observed for SSPX ({approx}0.7T along the geometric axis). By increasing the time between pulses, a quasi-steady sustainment is produced (with periodic good confinement), comparing well with resistive MHD simulations. In each case, the processes that transport the helicity into the spheromak are inductive and exhibit a scaling of field with current that exceeds those previously obtained. We use our newly found scaling to suggest how to achieve higher temperatures with a series of pulses.

  6. AQUEOUS HOMOGENEOUS REACTORTECHNICAL PANEL REPORT

    SciTech Connect (OSTI)

    Diamond, D.J.; Bajorek, S.; Bakel, A.; Flanagan, G.; Mubayi, V.; Skarda, R.; Staudenmeier, J.; Taiwo, T.; Tonoike, K.; Tripp, C.; Wei, T.; Yarsky, P.

    2010-12-03

    Considerable interest has been expressed for developing a stable U.S. production capacity for medical isotopes and particularly for molybdenum- 99 (99Mo). This is motivated by recent re-ductions in production and supply worldwide. Consistent with U.S. nonproliferation objectives, any new production capability should not use highly enriched uranium fuel or targets. Conse-quently, Aqueous Homogeneous Reactors (AHRs) are under consideration for potential 99Mo production using low-enriched uranium. Although the Nuclear Regulatory Commission (NRC) has guidance to facilitate the licensing process for non-power reactors, that guidance is focused on reactors with fixed, solid fuel and hence, not applicable to an AHR. A panel was convened to study the technical issues associated with normal operation and potential transients and accidents of an AHR that might be designed for isotope production. The panel has produced the requisite AHR licensing guidance for three chapters that exist now for non-power reactor licensing: Reac-tor Description, Reactor Coolant Systems, and Accident Analysis. The guidance is in two parts for each chapter: 1) standard format and content a licensee would use and 2) the standard review plan the NRC staff would use. This guidance takes into account the unique features of an AHR such as the fuel being in solution; the fission product barriers being the vessel and attached systems; the production and release of radiolytic and fission product gases and their impact on operations and their control by a gas management system; and the movement of fuel into and out of the reactor vessel.

  7. Identification of nucleosome assembly protein 1 (NAP1) as an interacting partner of plant ribosomal protein S6 (RPS6) and a positive regulator of rDNA transcription

    SciTech Connect (OSTI)

    Son, Ora; Kim, Sunghan; Shin, Yun-jeong; Kim, Woo-Young; Koh, Hee-Jong; Cheon, Choong-Ill

    2015-09-18

    The ribosomal protein S6 (RPS6) is a downstream component of the signaling mediated by the target of rapamycin (TOR) kinase that acts as a central regulator of the key metabolic processes, such as protein translation and ribosome biogenesis, in response to various environmental cues. In our previous study, we identified a novel role of plant RPS6, which negatively regulates rDNA transcription, forming a complex with a plant-specific histone deacetylase, AtHD2B. Here we report that the Arabidopsis RPS6 interacts additionally with a histone chaperone, nucleosome assembly protein 1(AtNAP1;1). The interaction does not appear to preclude the association of RPS6 with AtHD2B, as the AtNAP1 was also able to interact with AtHD2B as well as with an RPS6-AtHD2B fusion protein in the BiFC assay and pulldown experiment. Similar to a positive effect of the ribosomal S6 kinase 1 (AtS6K1) on rDNA transcription observed in this study, overexpression or down regulation of the AtNAP1;1 resulted in concomitant increase and decrease, respectively, in rDNA transcription suggesting a positive regulatory role played by AtNAP1 in plant rDNA transcription, possibly through derepression of the negative effect of the RPS6-AtHD2B complex. - Highlights: • Nucleosome assembly protein 1 (AtNAP1) interacts with RPS6 as well as with AtHD2B. • rDNA transcription is regulated S6K1. • Overexpression or down regulation of AtNAP1 results in concomitant increase or decrease in rDNA transcription.

  8. A NEW LOW MAGNETIC FIELD MAGNETAR: THE 2011 OUTBURST OF SWIFT J1822.3-1606

    SciTech Connect (OSTI)

    Rea, N.; Camero-Arranz, A.; Israel, G. L.; Esposito, P.; Burgay, M.; Possenti, A.; Pons, J. A.; Mignani, R. P.; Turolla, R.; Zane, S.; Oates, S. R.; Campana, S.; Enoto, T.; Goegues, E.; Goetz, D.; Makishima, K.; Mereghetti, S.; Palmer, D. M.; and others

    2012-07-20

    We report on the long-term X-ray monitoring with Swift, RXTE, Suzaku, Chandra, and XMM-Newton of the outburst of the newly discovered magnetar Swift J1822.3-1606 (SGR 1822-1606), from the first observations soon after the detection of the short X-ray bursts which led to its discovery, through the first stages of its outburst decay (covering the time span from 2011 July until the end of 2012 April). We also report on archival ROSAT observations which detected the source during its likely quiescent state, and on upper limits on Swift J1822.3-1606's radio-pulsed and optical emission during outburst, with the Green Bank Telescope and the Gran Telescopio Canarias, respectively. Our X-ray timing analysis finds the source rotating with a period of P = 8.43772016(2) s and a period derivative P-dot =8.3(2) Multiplication-Sign 10{sup -14} s s{sup -1}, which implies an inferred dipolar surface magnetic field of B {approx_equal} 2.7 Multiplication-Sign 10{sup 13} G at the equator. This measurement makes Swift J1822.3-1606 the second lowest magnetic field magnetar (after SGR 0418+5729). Following the flux and spectral evolution from the beginning of the outburst, we find that the flux decreased by about an order of magnitude, with a subtle softening of the spectrum, both typical of the outburst decay of magnetars. By modeling the secular thermal evolution of Swift J1822.3-1606, we find that the observed timing properties of the source, as well as its quiescent X-ray luminosity, can be reproduced if it was born with a poloidal and crustal toroidal fields of B{sub p} {approx} 1.5 Multiplication-Sign 10{sup 14} G and B{sub tor} {approx} 7 Multiplication-Sign 10{sup 14} G, respectively, and if its current age is {approx}550 kyr.

  9. Research in High Energy Physics at Duke University

    SciTech Connect (OSTI)

    Kotwal, Ashutosh V.; Goshaw, Al; Kruse, Mark; Oh, Seog; Scholberg, Kate; Walter, Chris

    2013-07-29

    This is the Closeout Report for the research grant in experimental elementary particle physics, carried out by the Duke University High Energy Physics (HEP) group. We re- port on physics results and detector development carried out under this grant, focussing on the recent three-year grant period (2010 to 2013). The Duke HEP group consisted of seven faculty members, two senior scientists, #12;ve postdocs and eight graduate students. There were three thrusts of the research program. Measurements at the energy frontier at CDF and ATLAS were used to test aspects of elementary particle theory described by the Stan- dard Model (SM) and to search for new forces and particles beyond those contained within the SM. The neutrino sector was explored using data obtained from a large neutrino detector located in Japan, and R & D was conducted on new experiments to be built in the US. The measurements provided information about neutrino masses and the manner in which neutri- nos change species in particle beams. Two years ago we have started a new research program in rare processes based on the Mu2E experiment at Fermilab. This research is motivated by the search for the #22; ! e transition with unprecedented sensitivity, a transition forbidden in the standard model but allowed in supersymmetric and other models of new physics. The high energy research program used proton and antiproton colliding beams. The experiments were done at the Fermilab Tevatron (proton-antiproton collisions at a center of mass energy of 1.96 TeV) and at the CERN Large Hadron Collider (proton-proton collisions at 7-8 TeV). The neutrino program used data obtained from the Super-Kamiokande detec- tor. This water-#12;lled Cherenkov counter was used to detect and measure the properties of neutrinos produced in cosmic ray showers, and from neutrino beams produced from acceler- ators in Japan. The Mu2E experiment will use a special stopped muon beam to be built at Fermilab.

  10. Human metastatic melanoma cell lines express high levels of growth hormone receptor and respond to GH treatment

    SciTech Connect (OSTI)

    Sustarsic, Elahu G.; Department of Biological Sciences, Ohio University, Athens, OH ; Junnila, Riia K.; Kopchick, John J.

    2013-11-08

    Highlights: Most cancer types of the NCI60 have sub-sets of cell lines with high GHR expression. GHR is highly expressed in melanoma cell lines. GHR is elevated in advanced stage IV metastatic tumors vs. stage III. GH treatment of metastatic melanoma cell lines alters growth and cell signaling. -- Abstract: Accumulating evidence implicates the growth hormone receptor (GHR) in carcinogenesis. While multiple studies show evidence for expression of growth hormone (GH) and GHR mRNA in human cancer tissue, there is a lack of quantification and only a few cancer types have been investigated. The National Cancer Institutes NCI60 panel includes 60 cancer cell lines from nine types of human cancer: breast, CNS, colon, leukemia, melanoma, non-small cell lung, ovarian, prostate and renal. We utilized this panel to quantify expression of GHR, GH, prolactin receptor (PRLR) and prolactin (PRL) mRNA with real-time RT qPCR. Both GHR and PRLR show a broad range of expression within and among most cancer types. Strikingly, GHR expression is nearly 50-fold higher in melanoma than in the panel as a whole. Analysis of human metastatic melanoma biopsies confirmed GHR gene expression in melanoma tissue. In these human biopsies, the level of GHR mRNA is elevated in advanced stage IV tumor samples compared to stage III. Due to the novel finding of high GHR in melanoma, we examined the effect of GH treatment on three NCI60 melanoma lines (MDA-MB-435, UACC-62 and SK-MEL-5). GH increased proliferation in two out of three cell lines tested. Further analysis revealed GH-induced activation of STAT5 and mTOR in a cell line dependent manner. In conclusion, we have identified cell lines and cancer types that are ideal to study the role of GH and PRL in cancer, yet have been largely overlooked. Furthermore, we found that human metastatic melanoma tumors express GHR and cell lines possess active GHRs that can modulate multiple signaling pathways and alter cell proliferation. Based on this data

  11. The Super-B Project Accelerator Status

    SciTech Connect (OSTI)

    Biagini, M.E.; Alesini, D.; Boni, R.; Boscolo, M.; Demma, T.; Drago, A.; Esposito, M.; Guiducci, S.; Marcellini, F.; Mazzitelli, G.; Preger, M.; Raimondi, P.; Sanelli, C.; Serio, M.; Stecchi, A.; Stella, A.; Tomassini, S.; Zobov, M.; Bertsche, K.; Brachmann, A.; Cai, Y.; /SLAC /Novosibirsk, IYF /Annecy, LAPP /LPSC, Grenoble /Orsay, LAL /Saclay /Pisa U. /CERN

    2011-08-17

    The SuperB project is an international effort aiming at building in Italy a very high luminosity e{sup +}e{sup -} (10{sup 36} cm{sup -2} sec{sup -1}) asymmetric collider at the Y(4S) energy in the CM. The accelerator design has been extensively studied and changed during the past year. The present design, based on the new collision scheme, with large Piwinski angle and the use of 'crab waist' sextupoles already successfully tested at the DA{Phi}NE {Phi}-Factory at LNF Frascati, provides larger flexibility, better dynamic aperture and spin manipulation sections in the Low Energy Ring (LER) for longitudinal polarization of the electron beam at the Interaction Point (IP). The Interaction Region (IR) has been further optimized in terms of apertures and reduced backgrounds in the detector. The injector complex design has been also updated. A summary of the project status will be presented in this paper. The SuperB collider can reach a peak luminosity of 10{sup 36} cm{sup -2} sec{sup -1} with beam currents and bunch lengths similar to those of the past and present e{sup +}e{sup -} Factories, through the use of smaller emittances and new scheme of crossing angle collision. The beams are stored in two rings at 6.7 GeV (HER) and 4.2 GeV (LER). Unique features of the project are the polarization of the electron beam in the LER and the possibility to decrease the energies for running at the {tau}/charm threshold. The option to reuse the PEP-II B-Factory (SLAC) hardware will allow reducing costs. The SuperB facility will require a big complex of civil infrastructure. The main construction, which will house the final part of the LINAC, the injection lines, the damping rings, and the storage rings, will be mainly underground. Two sites have been considered: the campus of Tor Vergata University near Frascati, and the INFN Frascati Laboratory. No decision has been made yet. A footprint of the possible SuperB layout on the LNF area is shown in Fig. 1.

  12. K20E, an oxidative-coupling compound of methyl caffeate, exhibits anti-angiogenic activities through down-regulations of VEGF and VEGF receptor-2

    SciTech Connect (OSTI)

    Pan, Chun-Hsu; Lin, Wen-Hsin; Chien, Yi-Chung; Liu, Fon-Chang; Sheu, Ming-Jyh; Kuo, Yueh-Hsiung; Wu, Chieh-Hsi

    2015-01-15

    Anti-angiogenesis is one of the most popular clinical interventions for cancer chemotherapy. A series of synthesized derivative of methyl caffeate were used to evaluate the anti-angiogenic activity and to investigate possible pharmacological mechanisms in the present study. The most potent anti-angiogenic compound was evaluated in the experiments of murine allograft tumor model and Matrigel plug assay as well as cell models in the human umbilical vascular endothelial cells (HUVECs) and the LLC1 lung cancer cells. Our results suggested that K20E suppressed the tumor growth in the allograft tumor model and exhibited anti-angiogenic activity in Matrigel plug assay. Besides, HUVEC viability was found to be significantly reduced by arresting cell cycle at G{sub 2}/M phase and apoptosis. Cell migration, invasion, and tube formation of the HUVECs were also markedly suppressed by K20E treatment. K20E largely down-regulated the intracellular and secreted vascular endothelial growth factor (VEGF) in the LLC1 cancer cells. Besides, VEGF receptor-2 (VEGFR-2) and its downstream signaling cascades (AKT-mTOR and MEK1/2-ERK1/2) as well as gelatinases were all evidently reduced in the HUVECs treated with K20E. Inversely, K20E can up-regulate the expression levels of p53 and p21 proteins in the HUVECs. Based on these results, our study suggested that K20E possessed inhibiting angiogenesis through regulation of VEGF/VEGFR-2 and its downstream signaling cascades in the vascular endothelial cells (VECs). - Highlights: • K20E is an oxidative-coupling compound of methyl caffeate. • K20E exhibits anti-tumor and anti-angiogenesis effects. • K20E suppresses the expressions of VEGF and VEGF receptor-2 (VEGFR-2) proteins. • K20E deactivates VEGFR-2-mediated downstream signaling pathways to inhibit angiogenesis. • K20E up-regulates p53-p21 pathway to induce apoptosis and cell arrest at G2/M phase.

  13. DNA–PKcs–SIN1 complexation mediates low-dose X-ray irradiation (LDI)-induced Akt activation and osteoblast differentiation

    SciTech Connect (OSTI)

    Xu, Yong; Fang, Shi-ji; Zhu, Li-juan; Zhu, Lun-qing; Zhou, Xiao-zhong

    2014-10-24

    Highlights: • LDI increases ALP activity, promotes type I collagen (Col I)/Runx2 mRNA expression. • LDI induces DNA–PKcs activation, which is required for osteoblast differentiation. • Akt activation mediates LDI-induced ALP activity and Col I/Runx2 mRNA increase. • DNA–PKcs–SIN1 complexation mediates LDI-induced Akt Ser-473 phosphorylation. • DNA–PKcs–SIN1 complexation is important for osteoblast differentiation. - Abstract: Low-dose irradiation (LDI) induces osteoblast differentiation, however the underlying mechanisms are not fully understood. In this study, we explored the potential role of DNA-dependent protein kinase catalytic subunit (DNA–PKcs)–Akt signaling in LDI-induced osteoblast differentiation. We confirmed that LDI promoted mouse calvarial osteoblast differentiation, which was detected by increased alkaline phosphatase (ALP) activity as well as mRNA expression of type I collagen (Col I) and runt-related transcription factor 2 (Runx2). In mouse osteoblasts, LDI (1 Gy) induced phosphorylation of DNA–PKcs and Akt (mainly at Ser-473). The kinase inhibitors against DNA–PKcs (NU-7026 and NU-7441) or Akt (LY294002, perifosine and MK-2206), as well as partial depletion of DNA–PKcs or Akt1 by targeted-shRNA, dramatically inhibited LDI-induced Akt activation and mouse osteoblast differentiation. Further, siRNA-knockdown of SIN1, a key component of mTOR complex 2 (mTORC2), also inhibited LDI-induced Akt Ser-473 phosphorylation as well as ALP activity increase and Col I/Runx2 expression in mouse osteoblasts. Co-immunoprecipitation (Co-IP) assay results demonstrated that LDI-induced DNA–PKcs–SIN1 complexation, which was inhibited by NU-7441 or SIN1 siRNA-knockdown in mouse osteoblasts. In summary, our data suggest that DNA–PKcs–SIN1 complexation-mediated Akt activation (Ser-473 phosphorylation) is required for mouse osteoblast differentiation.

  14. A Study Plan for Determining Recharge Rates at the Hanford Site Using Environmental Tracers

    SciTech Connect (OSTI)

    Murphy,, E. M.; Szecsody,, J. E.; Phillips,, S. J.

    1991-02-01

    This report presents a study plan tor estimating recharge at the Hanford Site using environmental tracers. Past operations at the Hanford Site have led to both soil and groundwater contamination, and recharge is one of the primary mechanisms for transporting contaminants through the vadose zone and into the groundwater. The prediction of contaminant movement or transport is one aspect of performance assessment and an important step in the remedial investigation/feasibility study (RI/FS) process. In the past, recharge has been characterized by collecting lysimeter data. Although lysimeters can generate important and reliable data, their limitations include 1) fixed location, 2) fixed sediment contents, 3) edge effects, 4) low rates, and 5) relatively short duration of measurement. These limitations impact the ability to characterize the spatial distribution of recharge at the Hanford Site, and thus the ability to predict contaminant movement in the vadose zone. An alternative to using fixed lysimeters for determining recharge rates in the vadose zone is to use environmental tracers. Tracers that have been used to study water movement in the vadose zone include total chloride, {sup 36}CI, {sup 3}H, and {sup 2}H/{sup 18}O. Atmospheric levels of {sup 36}CI and {sup 3}H increased during nuclear bomb testing in the Pacific, and the resulting "bomb pulse" or peak concentration can be measured in the soil profile. Locally, past operations at the Hanford Site have resu~ed in the atmospheric release of numerous chemical and isotopic tracers, including nitrate, {sup 129}I, and {sup 99}Tc. The radionuclides, in particular, reached a well-defined atmospheric peak in 1945. Atmospheric releases of {sup 129}I and {sup 99}Tc were greatly reduced by mid-1946, but nitrogen oxides continued to be released from the uranium separations facilities. As a result, the nitrate concentrations probably peaked in the mid-1950s, when the greatest number of separations facilities were operating

  15. Structural Health Monitoring for Impact Damage in Composite Structures.

    SciTech Connect (OSTI)

    Roach, Dennis P.; Raymond Bond; Doug Adams

    2014-08-01

    Composite structures are increasing in prevalence throughout the aerospace, wind, defense, and transportation industries, but the many advantages of these materials come with unique challenges, particularly in inspecting and repairing these structures. Because composites of- ten undergo sub-surface damage mechanisms which compromise the structure without a clear visual indication, inspection of these components is critical to safely deploying composite re- placements to traditionally metallic structures. Impact damage to composites presents one of the most signi fi cant challenges because the area which is vulnerable to impact damage is generally large and sometimes very dif fi cult to access. This work seeks to further evolve iden- ti fi cation technology by developing a system which can detect the impact load location and magnitude in real time, while giving an assessment of the con fi dence in that estimate. Fur- thermore, we identify ways by which impact damage could be more effectively identi fi ed by leveraging impact load identi fi cation information to better characterize damage. The impact load identi fi cation algorithm was applied to a commercial scale wind turbine blade, and results show the capability to detect impact magnitude and location using a single accelerometer, re- gardless of sensor location. A technique for better evaluating the uncertainty of the impact estimates was developed by quantifying how well the impact force estimate meets the assump- tions underlying the force estimation technique. This uncertainty quanti fi cation technique was found to reduce the 95% con fi dence interval by more than a factor of two for impact force estimates showing the least uncertainty, and widening the 95% con fi dence interval by a fac- tor of two for the most uncertain force estimates, avoiding the possibility of understating the uncertainty associated with these estimates. Linear vibration based damage detection tech- niques were investigated in the

  16. Discovery of the First Leaking Double-Shell Tank - Hanford Tank 241-AY-102

    SciTech Connect (OSTI)

    Harrington, Stephanie J.; Sams, Terry L.

    2013-08-15

    sample jar retrieval device for transportation of the material to the 222-S laboratory on the Hanford site for analysis. The subcontractor agency fabricated a remote underground sampler by modifying off-the-shelf robotics and parts. Limited testing of the sampler was conducted using a mock-up of the tank annulus and one simulated material type -a salt block. The mock-up testing indicated that the sampler would be able to maneuver within the confined space and that the device worked with full functionality. A total of six weeks had passed from initiation to implementation of the new sampler in the 241-AY-102 tank annulus. Initial sample material was obtained from the annulus floor using the Off-Riser Sampler System that has been used at Hanford tor years to obtain material from the primary tanks. This could be used at the location near Riser 83 since the material was collected directly from the annulus floor and not from a location on the wall or behind a pipe, as was needed from the two locations near Riser 90. After obtaining a small sample of the material on the annulus floor.this sampler sustained terminal damage due to conduit pipes it had to transverse in order to collect and recover material from this location. Several issues were also encountered during deployment of the new sampler into the annulus near Riser 90. These included: Difficulty fitting the sampler down the 12-inch riser into the annulus due to a small tolerance in the size of the sampler; Failure of sampler components and functions during deployment including the camera. pneumatics.and bearing seals; Delays in the field due to supporting equipment issues including cables. cameras. and scaffolding; and, Low recovery of sample material obtained for analysis. The complications that occurred during deployment and use of the new sampler during the sampling event ultimately resulted in lower recovery of material from these locations in the annulus than was obtained using the Off-Riser Sampler System and